Cannabis

Prof Suleiman Olimat

Cannabis

الهندي القنبالحشيش نبات

Cannabis is a genus of flowering plant that includes one or more species The plant is believed to have originated in the mountainous regions just north-west of the Himalayas in India though it could also have come from Northern Africa It is also known as hemp although this term usually refers to Cannabis cultivated for non-drug use

Cannabis sppThere are three species known Cannabis sativa C indica and C rudelarisThe leaves are the most recognisable and well-

known aspect of the cannabis plant Despite the great degree of variation found naturally in local populations of cannabis the leaves do not alter greatly in appearance between varieties

Hemp

What is Marijuana

Marijuana is the dried mix of flowers and leaves form the female Cannabis Sativa plant

Hashish is the resin or sap harvested from the plant

Hashish oil is the essential oil of the female Cannabis Sativa plant

Marijuana ndash History of Use

bull Cannabis ndash native to central Asia

bull Chinese ndash first to use employed for fabric medicines

bull India ndash country where first used for hallucinogenic properties

bull Africa ndash introduced through Arab traders used as medicine

bull Europe ndash became popular in 1800s

bull USA ndash 1900s -- use proscribed outlawed

bull End of 20th century ndash contentious debate regarding merits of legalization

HempvsMarijuana-1

bull The word hempis English for a number of varieties of the Cannabisplant particularly the varieties like industrial hemp that were bred over time for industrial uses such as fuel fiber paper seed food oil etc

HempvsMarijuana-2

bull The term marijuanais of Spanish derivation and was primarily used to describe varieties of Cannabisthat were more commonly bred over time for medicinal and recreational purposes like Cannabisindica and certain strains of Cannabissativa

HempvsMarijuana-3

bull Two cannabinoids are preponderant in Cannabis

bull THC CBDbull psychoactive ingredient antipsychoactive ingredient

Marijuana Hempbull (leaves and flowers of the female plant)

bull High in THC High in CBDbull Low in THCbull Low in CBD

Cannabis BiologyMajor Drug Component ndash delta-trans-tetrahydrocannabinol (THC)

- binds to specific receptors in brain

THC- produced in glands on leaves and flowers

-- female plants produce more glands

-- gland production stimulated by heat sunlight drought

-- sinsemilla (sin = without semilla = seeds) ndash particularly strong

Hashish ndash product - relatively pure resin

Glands THC

Chemical constituents of Cannabis

bull Cannabinoids (66)bull Nitrogenous compounds (27)bull Amino acids(18)bull Proteins enzymes (11)bull Sugars (34)bull Hydrocarbons (50)bull Simple alcohols (7)bull Simple aldehydes (12)bull Simple ketones (13)bull Simple acids (21)bull Fatty acids (22)bull Simple esterslactones (13)bull Steroids (11)bull Terpenes (20)bull Non-cannabinoid phenols (25)bull Flavoroids (21)bull Vitamins (1)bull Pigments (2)bull Elements (9) bull Total known compounds (483)

What is a cannabinoid

bullInitially compounds extracted by Cannabis spp producing characteristic psychoactivity

bullLater compounds with a characteristic terpenoid structure

bullCurrently most any compound that produces cannabinoid psychoactivity natural or synthetic

bullOccasionally just compounds that will interact with cannabinoid receptors

What are cannabinoidsbull Group of gt60 dibenzopyran chemicals found in

leaves and flowering tops of female cannabis plant (Cannabis sativa and Cannabis indica)

bull Some common cannabinoids are

In the plantIn your body (endogenous)

Synthetic

Δ9 ndash THC 2-arichidonyl glycerol (2 ndash AG)

CP 55940

Δ8 ndash THC anandamideHU ndash 210

cannabidiol and cannabinol

Natural cannabinoids

Representative cannabinoids

Classical cannabinoids Non-classical cannabinoid Aminoalkylindole

CB1 antagonists

Endogenous cannabinoids

Receptors suggest endogenous ligandsTwo main families identifiedBoth arachidonic acid derivativesPrecursors in membranes

ldquoMade on demandrdquoAmides (anandamide)

Esters (2-AG)

bull Significant differences

ndash Routes of synthesis ndash Mode of degradation

(FAAH vs MAGL)ndash Efficacy

Endocannabinoids

bull Anandamide (Sanskrit ananda inner bliss) is one endocannabinoid It is found in chocolate (though there is some controversy over whether the small quantity has any effect on the body) It is about as potent as THC

Structure of THC and synthetic analogs

Lipophilic side chain Most potent analog 100s

times more potent than THC

with 4 major cannabinoids in the plant

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

THC

bull Variedly aromatic ring (C Ring)

O

O

H

11rsquo-di-methyl-pyrane ring (B ring)

Variedly unsaturated cyclohexyl ring (A ring)

Results of SAR

bull Psychoactive properties are (-) trans-enatioselective

bull Length lipophilicity C3 alkyl chain

bull Phenolic hydroxyl-group

bull C9 substitute

O

O

H

Modes of Absorption

bull The most common method of absorption is smoking Either in a loosely rolled cigarette called a joint or through a pipe or water pipe

Smoking and the Body

THC enters the body through the Lungs

The smoke is inhaled and held in the lungsAll affect how much THC will enter the plasmaTHC crosses the blood barrier through the capillaries in the lungs

After inhalation THC can reach the brain in about 14 seconds

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Cannabis

الهندي القنبالحشيش نبات

Cannabis is a genus of flowering plant that includes one or more species The plant is believed to have originated in the mountainous regions just north-west of the Himalayas in India though it could also have come from Northern Africa It is also known as hemp although this term usually refers to Cannabis cultivated for non-drug use

Cannabis sppThere are three species known Cannabis sativa C indica and C rudelarisThe leaves are the most recognisable and well-

known aspect of the cannabis plant Despite the great degree of variation found naturally in local populations of cannabis the leaves do not alter greatly in appearance between varieties

Hemp

What is Marijuana

Marijuana is the dried mix of flowers and leaves form the female Cannabis Sativa plant

Hashish is the resin or sap harvested from the plant

Hashish oil is the essential oil of the female Cannabis Sativa plant

Marijuana ndash History of Use

bull Cannabis ndash native to central Asia

bull Chinese ndash first to use employed for fabric medicines

bull India ndash country where first used for hallucinogenic properties

bull Africa ndash introduced through Arab traders used as medicine

bull Europe ndash became popular in 1800s

bull USA ndash 1900s -- use proscribed outlawed

bull End of 20th century ndash contentious debate regarding merits of legalization

HempvsMarijuana-1

bull The word hempis English for a number of varieties of the Cannabisplant particularly the varieties like industrial hemp that were bred over time for industrial uses such as fuel fiber paper seed food oil etc

HempvsMarijuana-2

bull The term marijuanais of Spanish derivation and was primarily used to describe varieties of Cannabisthat were more commonly bred over time for medicinal and recreational purposes like Cannabisindica and certain strains of Cannabissativa

HempvsMarijuana-3

bull Two cannabinoids are preponderant in Cannabis

bull THC CBDbull psychoactive ingredient antipsychoactive ingredient

Marijuana Hempbull (leaves and flowers of the female plant)

bull High in THC High in CBDbull Low in THCbull Low in CBD

Cannabis BiologyMajor Drug Component ndash delta-trans-tetrahydrocannabinol (THC)

- binds to specific receptors in brain

THC- produced in glands on leaves and flowers

-- female plants produce more glands

-- gland production stimulated by heat sunlight drought

-- sinsemilla (sin = without semilla = seeds) ndash particularly strong

Hashish ndash product - relatively pure resin

Glands THC

Chemical constituents of Cannabis

bull Cannabinoids (66)bull Nitrogenous compounds (27)bull Amino acids(18)bull Proteins enzymes (11)bull Sugars (34)bull Hydrocarbons (50)bull Simple alcohols (7)bull Simple aldehydes (12)bull Simple ketones (13)bull Simple acids (21)bull Fatty acids (22)bull Simple esterslactones (13)bull Steroids (11)bull Terpenes (20)bull Non-cannabinoid phenols (25)bull Flavoroids (21)bull Vitamins (1)bull Pigments (2)bull Elements (9) bull Total known compounds (483)

What is a cannabinoid

bullInitially compounds extracted by Cannabis spp producing characteristic psychoactivity

bullLater compounds with a characteristic terpenoid structure

bullCurrently most any compound that produces cannabinoid psychoactivity natural or synthetic

bullOccasionally just compounds that will interact with cannabinoid receptors

What are cannabinoidsbull Group of gt60 dibenzopyran chemicals found in

leaves and flowering tops of female cannabis plant (Cannabis sativa and Cannabis indica)

bull Some common cannabinoids are

In the plantIn your body (endogenous)

Synthetic

Δ9 ndash THC 2-arichidonyl glycerol (2 ndash AG)

CP 55940

Δ8 ndash THC anandamideHU ndash 210

cannabidiol and cannabinol

Natural cannabinoids

Representative cannabinoids

Classical cannabinoids Non-classical cannabinoid Aminoalkylindole

CB1 antagonists

Endogenous cannabinoids

Receptors suggest endogenous ligandsTwo main families identifiedBoth arachidonic acid derivativesPrecursors in membranes

ldquoMade on demandrdquoAmides (anandamide)

Esters (2-AG)

bull Significant differences

ndash Routes of synthesis ndash Mode of degradation

(FAAH vs MAGL)ndash Efficacy

Endocannabinoids

bull Anandamide (Sanskrit ananda inner bliss) is one endocannabinoid It is found in chocolate (though there is some controversy over whether the small quantity has any effect on the body) It is about as potent as THC

Structure of THC and synthetic analogs

Lipophilic side chain Most potent analog 100s

times more potent than THC

with 4 major cannabinoids in the plant

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

THC

bull Variedly aromatic ring (C Ring)

O

O

H

11rsquo-di-methyl-pyrane ring (B ring)

Variedly unsaturated cyclohexyl ring (A ring)

Results of SAR

bull Psychoactive properties are (-) trans-enatioselective

bull Length lipophilicity C3 alkyl chain

bull Phenolic hydroxyl-group

bull C9 substitute

O

O

H

Modes of Absorption

bull The most common method of absorption is smoking Either in a loosely rolled cigarette called a joint or through a pipe or water pipe

Smoking and the Body

THC enters the body through the Lungs

The smoke is inhaled and held in the lungsAll affect how much THC will enter the plasmaTHC crosses the blood barrier through the capillaries in the lungs

After inhalation THC can reach the brain in about 14 seconds

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Cannabis is a genus of flowering plant that includes one or more species The plant is believed to have originated in the mountainous regions just north-west of the Himalayas in India though it could also have come from Northern Africa It is also known as hemp although this term usually refers to Cannabis cultivated for non-drug use

Cannabis sppThere are three species known Cannabis sativa C indica and C rudelarisThe leaves are the most recognisable and well-

known aspect of the cannabis plant Despite the great degree of variation found naturally in local populations of cannabis the leaves do not alter greatly in appearance between varieties

Hemp

What is Marijuana

Marijuana is the dried mix of flowers and leaves form the female Cannabis Sativa plant

Hashish is the resin or sap harvested from the plant

Hashish oil is the essential oil of the female Cannabis Sativa plant

Marijuana ndash History of Use

bull Cannabis ndash native to central Asia

bull Chinese ndash first to use employed for fabric medicines

bull India ndash country where first used for hallucinogenic properties

bull Africa ndash introduced through Arab traders used as medicine

bull Europe ndash became popular in 1800s

bull USA ndash 1900s -- use proscribed outlawed

bull End of 20th century ndash contentious debate regarding merits of legalization

HempvsMarijuana-1

bull The word hempis English for a number of varieties of the Cannabisplant particularly the varieties like industrial hemp that were bred over time for industrial uses such as fuel fiber paper seed food oil etc

HempvsMarijuana-2

bull The term marijuanais of Spanish derivation and was primarily used to describe varieties of Cannabisthat were more commonly bred over time for medicinal and recreational purposes like Cannabisindica and certain strains of Cannabissativa

HempvsMarijuana-3

bull Two cannabinoids are preponderant in Cannabis

bull THC CBDbull psychoactive ingredient antipsychoactive ingredient

Marijuana Hempbull (leaves and flowers of the female plant)

bull High in THC High in CBDbull Low in THCbull Low in CBD

Cannabis BiologyMajor Drug Component ndash delta-trans-tetrahydrocannabinol (THC)

- binds to specific receptors in brain

THC- produced in glands on leaves and flowers

-- female plants produce more glands

-- gland production stimulated by heat sunlight drought

-- sinsemilla (sin = without semilla = seeds) ndash particularly strong

Hashish ndash product - relatively pure resin

Glands THC

Chemical constituents of Cannabis

bull Cannabinoids (66)bull Nitrogenous compounds (27)bull Amino acids(18)bull Proteins enzymes (11)bull Sugars (34)bull Hydrocarbons (50)bull Simple alcohols (7)bull Simple aldehydes (12)bull Simple ketones (13)bull Simple acids (21)bull Fatty acids (22)bull Simple esterslactones (13)bull Steroids (11)bull Terpenes (20)bull Non-cannabinoid phenols (25)bull Flavoroids (21)bull Vitamins (1)bull Pigments (2)bull Elements (9) bull Total known compounds (483)

What is a cannabinoid

bullInitially compounds extracted by Cannabis spp producing characteristic psychoactivity

bullLater compounds with a characteristic terpenoid structure

bullCurrently most any compound that produces cannabinoid psychoactivity natural or synthetic

bullOccasionally just compounds that will interact with cannabinoid receptors

What are cannabinoidsbull Group of gt60 dibenzopyran chemicals found in

leaves and flowering tops of female cannabis plant (Cannabis sativa and Cannabis indica)

bull Some common cannabinoids are

In the plantIn your body (endogenous)

Synthetic

Δ9 ndash THC 2-arichidonyl glycerol (2 ndash AG)

CP 55940

Δ8 ndash THC anandamideHU ndash 210

cannabidiol and cannabinol

Natural cannabinoids

Representative cannabinoids

Classical cannabinoids Non-classical cannabinoid Aminoalkylindole

CB1 antagonists

Endogenous cannabinoids

Receptors suggest endogenous ligandsTwo main families identifiedBoth arachidonic acid derivativesPrecursors in membranes

ldquoMade on demandrdquoAmides (anandamide)

Esters (2-AG)

bull Significant differences

ndash Routes of synthesis ndash Mode of degradation

(FAAH vs MAGL)ndash Efficacy

Endocannabinoids

bull Anandamide (Sanskrit ananda inner bliss) is one endocannabinoid It is found in chocolate (though there is some controversy over whether the small quantity has any effect on the body) It is about as potent as THC

Structure of THC and synthetic analogs

Lipophilic side chain Most potent analog 100s

times more potent than THC

with 4 major cannabinoids in the plant

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

THC

bull Variedly aromatic ring (C Ring)

O

O

H

11rsquo-di-methyl-pyrane ring (B ring)

Variedly unsaturated cyclohexyl ring (A ring)

Results of SAR

bull Psychoactive properties are (-) trans-enatioselective

bull Length lipophilicity C3 alkyl chain

bull Phenolic hydroxyl-group

bull C9 substitute

O

O

H

Modes of Absorption

bull The most common method of absorption is smoking Either in a loosely rolled cigarette called a joint or through a pipe or water pipe

Smoking and the Body

THC enters the body through the Lungs

The smoke is inhaled and held in the lungsAll affect how much THC will enter the plasmaTHC crosses the blood barrier through the capillaries in the lungs

After inhalation THC can reach the brain in about 14 seconds

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Cannabis sppThere are three species known Cannabis sativa C indica and C rudelarisThe leaves are the most recognisable and well-

known aspect of the cannabis plant Despite the great degree of variation found naturally in local populations of cannabis the leaves do not alter greatly in appearance between varieties

Hemp

What is Marijuana

Marijuana is the dried mix of flowers and leaves form the female Cannabis Sativa plant

Hashish is the resin or sap harvested from the plant

Hashish oil is the essential oil of the female Cannabis Sativa plant

Marijuana ndash History of Use

bull Cannabis ndash native to central Asia

bull Chinese ndash first to use employed for fabric medicines

bull India ndash country where first used for hallucinogenic properties

bull Africa ndash introduced through Arab traders used as medicine

bull Europe ndash became popular in 1800s

bull USA ndash 1900s -- use proscribed outlawed

bull End of 20th century ndash contentious debate regarding merits of legalization

HempvsMarijuana-1

bull The word hempis English for a number of varieties of the Cannabisplant particularly the varieties like industrial hemp that were bred over time for industrial uses such as fuel fiber paper seed food oil etc

HempvsMarijuana-2

bull The term marijuanais of Spanish derivation and was primarily used to describe varieties of Cannabisthat were more commonly bred over time for medicinal and recreational purposes like Cannabisindica and certain strains of Cannabissativa

HempvsMarijuana-3

bull Two cannabinoids are preponderant in Cannabis

bull THC CBDbull psychoactive ingredient antipsychoactive ingredient

Marijuana Hempbull (leaves and flowers of the female plant)

bull High in THC High in CBDbull Low in THCbull Low in CBD

Cannabis BiologyMajor Drug Component ndash delta-trans-tetrahydrocannabinol (THC)

- binds to specific receptors in brain

THC- produced in glands on leaves and flowers

-- female plants produce more glands

-- gland production stimulated by heat sunlight drought

-- sinsemilla (sin = without semilla = seeds) ndash particularly strong

Hashish ndash product - relatively pure resin

Glands THC

Chemical constituents of Cannabis

bull Cannabinoids (66)bull Nitrogenous compounds (27)bull Amino acids(18)bull Proteins enzymes (11)bull Sugars (34)bull Hydrocarbons (50)bull Simple alcohols (7)bull Simple aldehydes (12)bull Simple ketones (13)bull Simple acids (21)bull Fatty acids (22)bull Simple esterslactones (13)bull Steroids (11)bull Terpenes (20)bull Non-cannabinoid phenols (25)bull Flavoroids (21)bull Vitamins (1)bull Pigments (2)bull Elements (9) bull Total known compounds (483)

What is a cannabinoid

bullInitially compounds extracted by Cannabis spp producing characteristic psychoactivity

bullLater compounds with a characteristic terpenoid structure

bullCurrently most any compound that produces cannabinoid psychoactivity natural or synthetic

bullOccasionally just compounds that will interact with cannabinoid receptors

What are cannabinoidsbull Group of gt60 dibenzopyran chemicals found in

leaves and flowering tops of female cannabis plant (Cannabis sativa and Cannabis indica)

bull Some common cannabinoids are

In the plantIn your body (endogenous)

Synthetic

Δ9 ndash THC 2-arichidonyl glycerol (2 ndash AG)

CP 55940

Δ8 ndash THC anandamideHU ndash 210

cannabidiol and cannabinol

Natural cannabinoids

Representative cannabinoids

Classical cannabinoids Non-classical cannabinoid Aminoalkylindole

CB1 antagonists

Endogenous cannabinoids

Receptors suggest endogenous ligandsTwo main families identifiedBoth arachidonic acid derivativesPrecursors in membranes

ldquoMade on demandrdquoAmides (anandamide)

Esters (2-AG)

bull Significant differences

ndash Routes of synthesis ndash Mode of degradation

(FAAH vs MAGL)ndash Efficacy

Endocannabinoids

bull Anandamide (Sanskrit ananda inner bliss) is one endocannabinoid It is found in chocolate (though there is some controversy over whether the small quantity has any effect on the body) It is about as potent as THC

Structure of THC and synthetic analogs

Lipophilic side chain Most potent analog 100s

times more potent than THC

with 4 major cannabinoids in the plant

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

THC

bull Variedly aromatic ring (C Ring)

O

O

H

11rsquo-di-methyl-pyrane ring (B ring)

Variedly unsaturated cyclohexyl ring (A ring)

Results of SAR

bull Psychoactive properties are (-) trans-enatioselective

bull Length lipophilicity C3 alkyl chain

bull Phenolic hydroxyl-group

bull C9 substitute

O

O

H

Modes of Absorption

bull The most common method of absorption is smoking Either in a loosely rolled cigarette called a joint or through a pipe or water pipe

Smoking and the Body

THC enters the body through the Lungs

The smoke is inhaled and held in the lungsAll affect how much THC will enter the plasmaTHC crosses the blood barrier through the capillaries in the lungs

After inhalation THC can reach the brain in about 14 seconds

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Hemp

What is Marijuana

Marijuana is the dried mix of flowers and leaves form the female Cannabis Sativa plant

Hashish is the resin or sap harvested from the plant

Hashish oil is the essential oil of the female Cannabis Sativa plant

Marijuana ndash History of Use

bull Cannabis ndash native to central Asia

bull Chinese ndash first to use employed for fabric medicines

bull India ndash country where first used for hallucinogenic properties

bull Africa ndash introduced through Arab traders used as medicine

bull Europe ndash became popular in 1800s

bull USA ndash 1900s -- use proscribed outlawed

bull End of 20th century ndash contentious debate regarding merits of legalization

HempvsMarijuana-1

bull The word hempis English for a number of varieties of the Cannabisplant particularly the varieties like industrial hemp that were bred over time for industrial uses such as fuel fiber paper seed food oil etc

HempvsMarijuana-2

bull The term marijuanais of Spanish derivation and was primarily used to describe varieties of Cannabisthat were more commonly bred over time for medicinal and recreational purposes like Cannabisindica and certain strains of Cannabissativa

HempvsMarijuana-3

bull Two cannabinoids are preponderant in Cannabis

bull THC CBDbull psychoactive ingredient antipsychoactive ingredient

Marijuana Hempbull (leaves and flowers of the female plant)

bull High in THC High in CBDbull Low in THCbull Low in CBD

Cannabis BiologyMajor Drug Component ndash delta-trans-tetrahydrocannabinol (THC)

- binds to specific receptors in brain

THC- produced in glands on leaves and flowers

-- female plants produce more glands

-- gland production stimulated by heat sunlight drought

-- sinsemilla (sin = without semilla = seeds) ndash particularly strong

Hashish ndash product - relatively pure resin

Glands THC

Chemical constituents of Cannabis

bull Cannabinoids (66)bull Nitrogenous compounds (27)bull Amino acids(18)bull Proteins enzymes (11)bull Sugars (34)bull Hydrocarbons (50)bull Simple alcohols (7)bull Simple aldehydes (12)bull Simple ketones (13)bull Simple acids (21)bull Fatty acids (22)bull Simple esterslactones (13)bull Steroids (11)bull Terpenes (20)bull Non-cannabinoid phenols (25)bull Flavoroids (21)bull Vitamins (1)bull Pigments (2)bull Elements (9) bull Total known compounds (483)

What is a cannabinoid

bullInitially compounds extracted by Cannabis spp producing characteristic psychoactivity

bullLater compounds with a characteristic terpenoid structure

bullCurrently most any compound that produces cannabinoid psychoactivity natural or synthetic

bullOccasionally just compounds that will interact with cannabinoid receptors

What are cannabinoidsbull Group of gt60 dibenzopyran chemicals found in

leaves and flowering tops of female cannabis plant (Cannabis sativa and Cannabis indica)

bull Some common cannabinoids are

In the plantIn your body (endogenous)

Synthetic

Δ9 ndash THC 2-arichidonyl glycerol (2 ndash AG)

CP 55940

Δ8 ndash THC anandamideHU ndash 210

cannabidiol and cannabinol

Natural cannabinoids

Representative cannabinoids

Classical cannabinoids Non-classical cannabinoid Aminoalkylindole

CB1 antagonists

Endogenous cannabinoids

Receptors suggest endogenous ligandsTwo main families identifiedBoth arachidonic acid derivativesPrecursors in membranes

ldquoMade on demandrdquoAmides (anandamide)

Esters (2-AG)

bull Significant differences

ndash Routes of synthesis ndash Mode of degradation

(FAAH vs MAGL)ndash Efficacy

Endocannabinoids

bull Anandamide (Sanskrit ananda inner bliss) is one endocannabinoid It is found in chocolate (though there is some controversy over whether the small quantity has any effect on the body) It is about as potent as THC

Structure of THC and synthetic analogs

Lipophilic side chain Most potent analog 100s

times more potent than THC

with 4 major cannabinoids in the plant

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

THC

bull Variedly aromatic ring (C Ring)

O

O

H

11rsquo-di-methyl-pyrane ring (B ring)

Variedly unsaturated cyclohexyl ring (A ring)

Results of SAR

bull Psychoactive properties are (-) trans-enatioselective

bull Length lipophilicity C3 alkyl chain

bull Phenolic hydroxyl-group

bull C9 substitute

O

O

H

Modes of Absorption

bull The most common method of absorption is smoking Either in a loosely rolled cigarette called a joint or through a pipe or water pipe

Smoking and the Body

THC enters the body through the Lungs

The smoke is inhaled and held in the lungsAll affect how much THC will enter the plasmaTHC crosses the blood barrier through the capillaries in the lungs

After inhalation THC can reach the brain in about 14 seconds

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

What is Marijuana

Marijuana is the dried mix of flowers and leaves form the female Cannabis Sativa plant

Hashish is the resin or sap harvested from the plant

Hashish oil is the essential oil of the female Cannabis Sativa plant

Marijuana ndash History of Use

bull Cannabis ndash native to central Asia

bull Chinese ndash first to use employed for fabric medicines

bull India ndash country where first used for hallucinogenic properties

bull Africa ndash introduced through Arab traders used as medicine

bull Europe ndash became popular in 1800s

bull USA ndash 1900s -- use proscribed outlawed

bull End of 20th century ndash contentious debate regarding merits of legalization

HempvsMarijuana-1

bull The word hempis English for a number of varieties of the Cannabisplant particularly the varieties like industrial hemp that were bred over time for industrial uses such as fuel fiber paper seed food oil etc

HempvsMarijuana-2

bull The term marijuanais of Spanish derivation and was primarily used to describe varieties of Cannabisthat were more commonly bred over time for medicinal and recreational purposes like Cannabisindica and certain strains of Cannabissativa

HempvsMarijuana-3

bull Two cannabinoids are preponderant in Cannabis

bull THC CBDbull psychoactive ingredient antipsychoactive ingredient

Marijuana Hempbull (leaves and flowers of the female plant)

bull High in THC High in CBDbull Low in THCbull Low in CBD

Cannabis BiologyMajor Drug Component ndash delta-trans-tetrahydrocannabinol (THC)

- binds to specific receptors in brain

THC- produced in glands on leaves and flowers

-- female plants produce more glands

-- gland production stimulated by heat sunlight drought

-- sinsemilla (sin = without semilla = seeds) ndash particularly strong

Hashish ndash product - relatively pure resin

Glands THC

Chemical constituents of Cannabis

bull Cannabinoids (66)bull Nitrogenous compounds (27)bull Amino acids(18)bull Proteins enzymes (11)bull Sugars (34)bull Hydrocarbons (50)bull Simple alcohols (7)bull Simple aldehydes (12)bull Simple ketones (13)bull Simple acids (21)bull Fatty acids (22)bull Simple esterslactones (13)bull Steroids (11)bull Terpenes (20)bull Non-cannabinoid phenols (25)bull Flavoroids (21)bull Vitamins (1)bull Pigments (2)bull Elements (9) bull Total known compounds (483)

What is a cannabinoid

bullInitially compounds extracted by Cannabis spp producing characteristic psychoactivity

bullLater compounds with a characteristic terpenoid structure

bullCurrently most any compound that produces cannabinoid psychoactivity natural or synthetic

bullOccasionally just compounds that will interact with cannabinoid receptors

What are cannabinoidsbull Group of gt60 dibenzopyran chemicals found in

leaves and flowering tops of female cannabis plant (Cannabis sativa and Cannabis indica)

bull Some common cannabinoids are

In the plantIn your body (endogenous)

Synthetic

Δ9 ndash THC 2-arichidonyl glycerol (2 ndash AG)

CP 55940

Δ8 ndash THC anandamideHU ndash 210

cannabidiol and cannabinol

Natural cannabinoids

Representative cannabinoids

Classical cannabinoids Non-classical cannabinoid Aminoalkylindole

CB1 antagonists

Endogenous cannabinoids

Receptors suggest endogenous ligandsTwo main families identifiedBoth arachidonic acid derivativesPrecursors in membranes

ldquoMade on demandrdquoAmides (anandamide)

Esters (2-AG)

bull Significant differences

ndash Routes of synthesis ndash Mode of degradation

(FAAH vs MAGL)ndash Efficacy

Endocannabinoids

bull Anandamide (Sanskrit ananda inner bliss) is one endocannabinoid It is found in chocolate (though there is some controversy over whether the small quantity has any effect on the body) It is about as potent as THC

Structure of THC and synthetic analogs

Lipophilic side chain Most potent analog 100s

times more potent than THC

with 4 major cannabinoids in the plant

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

THC

bull Variedly aromatic ring (C Ring)

O

O

H

11rsquo-di-methyl-pyrane ring (B ring)

Variedly unsaturated cyclohexyl ring (A ring)

Results of SAR

bull Psychoactive properties are (-) trans-enatioselective

bull Length lipophilicity C3 alkyl chain

bull Phenolic hydroxyl-group

bull C9 substitute

O

O

H

Modes of Absorption

bull The most common method of absorption is smoking Either in a loosely rolled cigarette called a joint or through a pipe or water pipe

Smoking and the Body

THC enters the body through the Lungs

The smoke is inhaled and held in the lungsAll affect how much THC will enter the plasmaTHC crosses the blood barrier through the capillaries in the lungs

After inhalation THC can reach the brain in about 14 seconds

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Marijuana ndash History of Use

bull Cannabis ndash native to central Asia

bull Chinese ndash first to use employed for fabric medicines

bull India ndash country where first used for hallucinogenic properties

bull Africa ndash introduced through Arab traders used as medicine

bull Europe ndash became popular in 1800s

bull USA ndash 1900s -- use proscribed outlawed

bull End of 20th century ndash contentious debate regarding merits of legalization

HempvsMarijuana-1

bull The word hempis English for a number of varieties of the Cannabisplant particularly the varieties like industrial hemp that were bred over time for industrial uses such as fuel fiber paper seed food oil etc

HempvsMarijuana-2

bull The term marijuanais of Spanish derivation and was primarily used to describe varieties of Cannabisthat were more commonly bred over time for medicinal and recreational purposes like Cannabisindica and certain strains of Cannabissativa

HempvsMarijuana-3

bull Two cannabinoids are preponderant in Cannabis

bull THC CBDbull psychoactive ingredient antipsychoactive ingredient

Marijuana Hempbull (leaves and flowers of the female plant)

bull High in THC High in CBDbull Low in THCbull Low in CBD

Cannabis BiologyMajor Drug Component ndash delta-trans-tetrahydrocannabinol (THC)

- binds to specific receptors in brain

THC- produced in glands on leaves and flowers

-- female plants produce more glands

-- gland production stimulated by heat sunlight drought

-- sinsemilla (sin = without semilla = seeds) ndash particularly strong

Hashish ndash product - relatively pure resin

Glands THC

Chemical constituents of Cannabis

bull Cannabinoids (66)bull Nitrogenous compounds (27)bull Amino acids(18)bull Proteins enzymes (11)bull Sugars (34)bull Hydrocarbons (50)bull Simple alcohols (7)bull Simple aldehydes (12)bull Simple ketones (13)bull Simple acids (21)bull Fatty acids (22)bull Simple esterslactones (13)bull Steroids (11)bull Terpenes (20)bull Non-cannabinoid phenols (25)bull Flavoroids (21)bull Vitamins (1)bull Pigments (2)bull Elements (9) bull Total known compounds (483)

What is a cannabinoid

bullInitially compounds extracted by Cannabis spp producing characteristic psychoactivity

bullLater compounds with a characteristic terpenoid structure

bullCurrently most any compound that produces cannabinoid psychoactivity natural or synthetic

bullOccasionally just compounds that will interact with cannabinoid receptors

What are cannabinoidsbull Group of gt60 dibenzopyran chemicals found in

leaves and flowering tops of female cannabis plant (Cannabis sativa and Cannabis indica)

bull Some common cannabinoids are

In the plantIn your body (endogenous)

Synthetic

Δ9 ndash THC 2-arichidonyl glycerol (2 ndash AG)

CP 55940

Δ8 ndash THC anandamideHU ndash 210

cannabidiol and cannabinol

Natural cannabinoids

Representative cannabinoids

Classical cannabinoids Non-classical cannabinoid Aminoalkylindole

CB1 antagonists

Endogenous cannabinoids

Receptors suggest endogenous ligandsTwo main families identifiedBoth arachidonic acid derivativesPrecursors in membranes

ldquoMade on demandrdquoAmides (anandamide)

Esters (2-AG)

bull Significant differences

ndash Routes of synthesis ndash Mode of degradation

(FAAH vs MAGL)ndash Efficacy

Endocannabinoids

bull Anandamide (Sanskrit ananda inner bliss) is one endocannabinoid It is found in chocolate (though there is some controversy over whether the small quantity has any effect on the body) It is about as potent as THC

Structure of THC and synthetic analogs

Lipophilic side chain Most potent analog 100s

times more potent than THC

with 4 major cannabinoids in the plant

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

THC

bull Variedly aromatic ring (C Ring)

O

O

H

11rsquo-di-methyl-pyrane ring (B ring)

Variedly unsaturated cyclohexyl ring (A ring)

Results of SAR

bull Psychoactive properties are (-) trans-enatioselective

bull Length lipophilicity C3 alkyl chain

bull Phenolic hydroxyl-group

bull C9 substitute

O

O

H

Modes of Absorption

bull The most common method of absorption is smoking Either in a loosely rolled cigarette called a joint or through a pipe or water pipe

Smoking and the Body

THC enters the body through the Lungs

The smoke is inhaled and held in the lungsAll affect how much THC will enter the plasmaTHC crosses the blood barrier through the capillaries in the lungs

After inhalation THC can reach the brain in about 14 seconds

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

HempvsMarijuana-1

bull The word hempis English for a number of varieties of the Cannabisplant particularly the varieties like industrial hemp that were bred over time for industrial uses such as fuel fiber paper seed food oil etc

HempvsMarijuana-2

bull The term marijuanais of Spanish derivation and was primarily used to describe varieties of Cannabisthat were more commonly bred over time for medicinal and recreational purposes like Cannabisindica and certain strains of Cannabissativa

HempvsMarijuana-3

bull Two cannabinoids are preponderant in Cannabis

bull THC CBDbull psychoactive ingredient antipsychoactive ingredient

Marijuana Hempbull (leaves and flowers of the female plant)

bull High in THC High in CBDbull Low in THCbull Low in CBD

Cannabis BiologyMajor Drug Component ndash delta-trans-tetrahydrocannabinol (THC)

- binds to specific receptors in brain

THC- produced in glands on leaves and flowers

-- female plants produce more glands

-- gland production stimulated by heat sunlight drought

-- sinsemilla (sin = without semilla = seeds) ndash particularly strong

Hashish ndash product - relatively pure resin

Glands THC

Chemical constituents of Cannabis

bull Cannabinoids (66)bull Nitrogenous compounds (27)bull Amino acids(18)bull Proteins enzymes (11)bull Sugars (34)bull Hydrocarbons (50)bull Simple alcohols (7)bull Simple aldehydes (12)bull Simple ketones (13)bull Simple acids (21)bull Fatty acids (22)bull Simple esterslactones (13)bull Steroids (11)bull Terpenes (20)bull Non-cannabinoid phenols (25)bull Flavoroids (21)bull Vitamins (1)bull Pigments (2)bull Elements (9) bull Total known compounds (483)

What is a cannabinoid

bullInitially compounds extracted by Cannabis spp producing characteristic psychoactivity

bullLater compounds with a characteristic terpenoid structure

bullCurrently most any compound that produces cannabinoid psychoactivity natural or synthetic

bullOccasionally just compounds that will interact with cannabinoid receptors

What are cannabinoidsbull Group of gt60 dibenzopyran chemicals found in

leaves and flowering tops of female cannabis plant (Cannabis sativa and Cannabis indica)

bull Some common cannabinoids are

In the plantIn your body (endogenous)

Synthetic

Δ9 ndash THC 2-arichidonyl glycerol (2 ndash AG)

CP 55940

Δ8 ndash THC anandamideHU ndash 210

cannabidiol and cannabinol

Natural cannabinoids

Representative cannabinoids

Classical cannabinoids Non-classical cannabinoid Aminoalkylindole

CB1 antagonists

Endogenous cannabinoids

Receptors suggest endogenous ligandsTwo main families identifiedBoth arachidonic acid derivativesPrecursors in membranes

ldquoMade on demandrdquoAmides (anandamide)

Esters (2-AG)

bull Significant differences

ndash Routes of synthesis ndash Mode of degradation

(FAAH vs MAGL)ndash Efficacy

Endocannabinoids

bull Anandamide (Sanskrit ananda inner bliss) is one endocannabinoid It is found in chocolate (though there is some controversy over whether the small quantity has any effect on the body) It is about as potent as THC

Structure of THC and synthetic analogs

Lipophilic side chain Most potent analog 100s

times more potent than THC

with 4 major cannabinoids in the plant

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

THC

bull Variedly aromatic ring (C Ring)

O

O

H

11rsquo-di-methyl-pyrane ring (B ring)

Variedly unsaturated cyclohexyl ring (A ring)

Results of SAR

bull Psychoactive properties are (-) trans-enatioselective

bull Length lipophilicity C3 alkyl chain

bull Phenolic hydroxyl-group

bull C9 substitute

O

O

H

Modes of Absorption

bull The most common method of absorption is smoking Either in a loosely rolled cigarette called a joint or through a pipe or water pipe

Smoking and the Body

THC enters the body through the Lungs

The smoke is inhaled and held in the lungsAll affect how much THC will enter the plasmaTHC crosses the blood barrier through the capillaries in the lungs

After inhalation THC can reach the brain in about 14 seconds

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

HempvsMarijuana-2

bull The term marijuanais of Spanish derivation and was primarily used to describe varieties of Cannabisthat were more commonly bred over time for medicinal and recreational purposes like Cannabisindica and certain strains of Cannabissativa

HempvsMarijuana-3

bull Two cannabinoids are preponderant in Cannabis

bull THC CBDbull psychoactive ingredient antipsychoactive ingredient

Marijuana Hempbull (leaves and flowers of the female plant)

bull High in THC High in CBDbull Low in THCbull Low in CBD

Cannabis BiologyMajor Drug Component ndash delta-trans-tetrahydrocannabinol (THC)

- binds to specific receptors in brain

THC- produced in glands on leaves and flowers

-- female plants produce more glands

-- gland production stimulated by heat sunlight drought

-- sinsemilla (sin = without semilla = seeds) ndash particularly strong

Hashish ndash product - relatively pure resin

Glands THC

Chemical constituents of Cannabis

bull Cannabinoids (66)bull Nitrogenous compounds (27)bull Amino acids(18)bull Proteins enzymes (11)bull Sugars (34)bull Hydrocarbons (50)bull Simple alcohols (7)bull Simple aldehydes (12)bull Simple ketones (13)bull Simple acids (21)bull Fatty acids (22)bull Simple esterslactones (13)bull Steroids (11)bull Terpenes (20)bull Non-cannabinoid phenols (25)bull Flavoroids (21)bull Vitamins (1)bull Pigments (2)bull Elements (9) bull Total known compounds (483)

What is a cannabinoid

bullInitially compounds extracted by Cannabis spp producing characteristic psychoactivity

bullLater compounds with a characteristic terpenoid structure

bullCurrently most any compound that produces cannabinoid psychoactivity natural or synthetic

bullOccasionally just compounds that will interact with cannabinoid receptors

What are cannabinoidsbull Group of gt60 dibenzopyran chemicals found in

leaves and flowering tops of female cannabis plant (Cannabis sativa and Cannabis indica)

bull Some common cannabinoids are

In the plantIn your body (endogenous)

Synthetic

Δ9 ndash THC 2-arichidonyl glycerol (2 ndash AG)

CP 55940

Δ8 ndash THC anandamideHU ndash 210

cannabidiol and cannabinol

Natural cannabinoids

Representative cannabinoids

Classical cannabinoids Non-classical cannabinoid Aminoalkylindole

CB1 antagonists

Endogenous cannabinoids

Receptors suggest endogenous ligandsTwo main families identifiedBoth arachidonic acid derivativesPrecursors in membranes

ldquoMade on demandrdquoAmides (anandamide)

Esters (2-AG)

bull Significant differences

ndash Routes of synthesis ndash Mode of degradation

(FAAH vs MAGL)ndash Efficacy

Endocannabinoids

bull Anandamide (Sanskrit ananda inner bliss) is one endocannabinoid It is found in chocolate (though there is some controversy over whether the small quantity has any effect on the body) It is about as potent as THC

Structure of THC and synthetic analogs

Lipophilic side chain Most potent analog 100s

times more potent than THC

with 4 major cannabinoids in the plant

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

THC

bull Variedly aromatic ring (C Ring)

O

O

H

11rsquo-di-methyl-pyrane ring (B ring)

Variedly unsaturated cyclohexyl ring (A ring)

Results of SAR

bull Psychoactive properties are (-) trans-enatioselective

bull Length lipophilicity C3 alkyl chain

bull Phenolic hydroxyl-group

bull C9 substitute

O

O

H

Modes of Absorption

bull The most common method of absorption is smoking Either in a loosely rolled cigarette called a joint or through a pipe or water pipe

Smoking and the Body

THC enters the body through the Lungs

The smoke is inhaled and held in the lungsAll affect how much THC will enter the plasmaTHC crosses the blood barrier through the capillaries in the lungs

After inhalation THC can reach the brain in about 14 seconds

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

HempvsMarijuana-3

bull Two cannabinoids are preponderant in Cannabis

bull THC CBDbull psychoactive ingredient antipsychoactive ingredient

Marijuana Hempbull (leaves and flowers of the female plant)

bull High in THC High in CBDbull Low in THCbull Low in CBD

Cannabis BiologyMajor Drug Component ndash delta-trans-tetrahydrocannabinol (THC)

- binds to specific receptors in brain

THC- produced in glands on leaves and flowers

-- female plants produce more glands

-- gland production stimulated by heat sunlight drought

-- sinsemilla (sin = without semilla = seeds) ndash particularly strong

Hashish ndash product - relatively pure resin

Glands THC

Chemical constituents of Cannabis

bull Cannabinoids (66)bull Nitrogenous compounds (27)bull Amino acids(18)bull Proteins enzymes (11)bull Sugars (34)bull Hydrocarbons (50)bull Simple alcohols (7)bull Simple aldehydes (12)bull Simple ketones (13)bull Simple acids (21)bull Fatty acids (22)bull Simple esterslactones (13)bull Steroids (11)bull Terpenes (20)bull Non-cannabinoid phenols (25)bull Flavoroids (21)bull Vitamins (1)bull Pigments (2)bull Elements (9) bull Total known compounds (483)

What is a cannabinoid

bullInitially compounds extracted by Cannabis spp producing characteristic psychoactivity

bullLater compounds with a characteristic terpenoid structure

bullCurrently most any compound that produces cannabinoid psychoactivity natural or synthetic

bullOccasionally just compounds that will interact with cannabinoid receptors

What are cannabinoidsbull Group of gt60 dibenzopyran chemicals found in

leaves and flowering tops of female cannabis plant (Cannabis sativa and Cannabis indica)

bull Some common cannabinoids are

In the plantIn your body (endogenous)

Synthetic

Δ9 ndash THC 2-arichidonyl glycerol (2 ndash AG)

CP 55940

Δ8 ndash THC anandamideHU ndash 210

cannabidiol and cannabinol

Natural cannabinoids

Representative cannabinoids

Classical cannabinoids Non-classical cannabinoid Aminoalkylindole

CB1 antagonists

Endogenous cannabinoids

Receptors suggest endogenous ligandsTwo main families identifiedBoth arachidonic acid derivativesPrecursors in membranes

ldquoMade on demandrdquoAmides (anandamide)

Esters (2-AG)

bull Significant differences

ndash Routes of synthesis ndash Mode of degradation

(FAAH vs MAGL)ndash Efficacy

Endocannabinoids

bull Anandamide (Sanskrit ananda inner bliss) is one endocannabinoid It is found in chocolate (though there is some controversy over whether the small quantity has any effect on the body) It is about as potent as THC

Structure of THC and synthetic analogs

Lipophilic side chain Most potent analog 100s

times more potent than THC

with 4 major cannabinoids in the plant

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

THC

bull Variedly aromatic ring (C Ring)

O

O

H

11rsquo-di-methyl-pyrane ring (B ring)

Variedly unsaturated cyclohexyl ring (A ring)

Results of SAR

bull Psychoactive properties are (-) trans-enatioselective

bull Length lipophilicity C3 alkyl chain

bull Phenolic hydroxyl-group

bull C9 substitute

O

O

H

Modes of Absorption

bull The most common method of absorption is smoking Either in a loosely rolled cigarette called a joint or through a pipe or water pipe

Smoking and the Body

THC enters the body through the Lungs

The smoke is inhaled and held in the lungsAll affect how much THC will enter the plasmaTHC crosses the blood barrier through the capillaries in the lungs

After inhalation THC can reach the brain in about 14 seconds

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Cannabis BiologyMajor Drug Component ndash delta-trans-tetrahydrocannabinol (THC)

- binds to specific receptors in brain

THC- produced in glands on leaves and flowers

-- female plants produce more glands

-- gland production stimulated by heat sunlight drought

-- sinsemilla (sin = without semilla = seeds) ndash particularly strong

Hashish ndash product - relatively pure resin

Glands THC

Chemical constituents of Cannabis

bull Cannabinoids (66)bull Nitrogenous compounds (27)bull Amino acids(18)bull Proteins enzymes (11)bull Sugars (34)bull Hydrocarbons (50)bull Simple alcohols (7)bull Simple aldehydes (12)bull Simple ketones (13)bull Simple acids (21)bull Fatty acids (22)bull Simple esterslactones (13)bull Steroids (11)bull Terpenes (20)bull Non-cannabinoid phenols (25)bull Flavoroids (21)bull Vitamins (1)bull Pigments (2)bull Elements (9) bull Total known compounds (483)

What is a cannabinoid

bullInitially compounds extracted by Cannabis spp producing characteristic psychoactivity

bullLater compounds with a characteristic terpenoid structure

bullCurrently most any compound that produces cannabinoid psychoactivity natural or synthetic

bullOccasionally just compounds that will interact with cannabinoid receptors

What are cannabinoidsbull Group of gt60 dibenzopyran chemicals found in

leaves and flowering tops of female cannabis plant (Cannabis sativa and Cannabis indica)

bull Some common cannabinoids are

In the plantIn your body (endogenous)

Synthetic

Δ9 ndash THC 2-arichidonyl glycerol (2 ndash AG)

CP 55940

Δ8 ndash THC anandamideHU ndash 210

cannabidiol and cannabinol

Natural cannabinoids

Representative cannabinoids

Classical cannabinoids Non-classical cannabinoid Aminoalkylindole

CB1 antagonists

Endogenous cannabinoids

Receptors suggest endogenous ligandsTwo main families identifiedBoth arachidonic acid derivativesPrecursors in membranes

ldquoMade on demandrdquoAmides (anandamide)

Esters (2-AG)

bull Significant differences

ndash Routes of synthesis ndash Mode of degradation

(FAAH vs MAGL)ndash Efficacy

Endocannabinoids

bull Anandamide (Sanskrit ananda inner bliss) is one endocannabinoid It is found in chocolate (though there is some controversy over whether the small quantity has any effect on the body) It is about as potent as THC

Structure of THC and synthetic analogs

Lipophilic side chain Most potent analog 100s

times more potent than THC

with 4 major cannabinoids in the plant

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

THC

bull Variedly aromatic ring (C Ring)

O

O

H

11rsquo-di-methyl-pyrane ring (B ring)

Variedly unsaturated cyclohexyl ring (A ring)

Results of SAR

bull Psychoactive properties are (-) trans-enatioselective

bull Length lipophilicity C3 alkyl chain

bull Phenolic hydroxyl-group

bull C9 substitute

O

O

H

Modes of Absorption

bull The most common method of absorption is smoking Either in a loosely rolled cigarette called a joint or through a pipe or water pipe

Smoking and the Body

THC enters the body through the Lungs

The smoke is inhaled and held in the lungsAll affect how much THC will enter the plasmaTHC crosses the blood barrier through the capillaries in the lungs

After inhalation THC can reach the brain in about 14 seconds

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Chemical constituents of Cannabis

bull Cannabinoids (66)bull Nitrogenous compounds (27)bull Amino acids(18)bull Proteins enzymes (11)bull Sugars (34)bull Hydrocarbons (50)bull Simple alcohols (7)bull Simple aldehydes (12)bull Simple ketones (13)bull Simple acids (21)bull Fatty acids (22)bull Simple esterslactones (13)bull Steroids (11)bull Terpenes (20)bull Non-cannabinoid phenols (25)bull Flavoroids (21)bull Vitamins (1)bull Pigments (2)bull Elements (9) bull Total known compounds (483)

What is a cannabinoid

bullInitially compounds extracted by Cannabis spp producing characteristic psychoactivity

bullLater compounds with a characteristic terpenoid structure

bullCurrently most any compound that produces cannabinoid psychoactivity natural or synthetic

bullOccasionally just compounds that will interact with cannabinoid receptors

What are cannabinoidsbull Group of gt60 dibenzopyran chemicals found in

leaves and flowering tops of female cannabis plant (Cannabis sativa and Cannabis indica)

bull Some common cannabinoids are

In the plantIn your body (endogenous)

Synthetic

Δ9 ndash THC 2-arichidonyl glycerol (2 ndash AG)

CP 55940

Δ8 ndash THC anandamideHU ndash 210

cannabidiol and cannabinol

Natural cannabinoids

Representative cannabinoids

Classical cannabinoids Non-classical cannabinoid Aminoalkylindole

CB1 antagonists

Endogenous cannabinoids

Receptors suggest endogenous ligandsTwo main families identifiedBoth arachidonic acid derivativesPrecursors in membranes

ldquoMade on demandrdquoAmides (anandamide)

Esters (2-AG)

bull Significant differences

ndash Routes of synthesis ndash Mode of degradation

(FAAH vs MAGL)ndash Efficacy

Endocannabinoids

bull Anandamide (Sanskrit ananda inner bliss) is one endocannabinoid It is found in chocolate (though there is some controversy over whether the small quantity has any effect on the body) It is about as potent as THC

Structure of THC and synthetic analogs

Lipophilic side chain Most potent analog 100s

times more potent than THC

with 4 major cannabinoids in the plant

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

THC

bull Variedly aromatic ring (C Ring)

O

O

H

11rsquo-di-methyl-pyrane ring (B ring)

Variedly unsaturated cyclohexyl ring (A ring)

Results of SAR

bull Psychoactive properties are (-) trans-enatioselective

bull Length lipophilicity C3 alkyl chain

bull Phenolic hydroxyl-group

bull C9 substitute

O

O

H

Modes of Absorption

bull The most common method of absorption is smoking Either in a loosely rolled cigarette called a joint or through a pipe or water pipe

Smoking and the Body

THC enters the body through the Lungs

The smoke is inhaled and held in the lungsAll affect how much THC will enter the plasmaTHC crosses the blood barrier through the capillaries in the lungs

After inhalation THC can reach the brain in about 14 seconds

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

What is a cannabinoid

bullInitially compounds extracted by Cannabis spp producing characteristic psychoactivity

bullLater compounds with a characteristic terpenoid structure

bullCurrently most any compound that produces cannabinoid psychoactivity natural or synthetic

bullOccasionally just compounds that will interact with cannabinoid receptors

What are cannabinoidsbull Group of gt60 dibenzopyran chemicals found in

leaves and flowering tops of female cannabis plant (Cannabis sativa and Cannabis indica)

bull Some common cannabinoids are

In the plantIn your body (endogenous)

Synthetic

Δ9 ndash THC 2-arichidonyl glycerol (2 ndash AG)

CP 55940

Δ8 ndash THC anandamideHU ndash 210

cannabidiol and cannabinol

Natural cannabinoids

Representative cannabinoids

Classical cannabinoids Non-classical cannabinoid Aminoalkylindole

CB1 antagonists

Endogenous cannabinoids

Receptors suggest endogenous ligandsTwo main families identifiedBoth arachidonic acid derivativesPrecursors in membranes

ldquoMade on demandrdquoAmides (anandamide)

Esters (2-AG)

bull Significant differences

ndash Routes of synthesis ndash Mode of degradation

(FAAH vs MAGL)ndash Efficacy

Endocannabinoids

bull Anandamide (Sanskrit ananda inner bliss) is one endocannabinoid It is found in chocolate (though there is some controversy over whether the small quantity has any effect on the body) It is about as potent as THC

Structure of THC and synthetic analogs

Lipophilic side chain Most potent analog 100s

times more potent than THC

with 4 major cannabinoids in the plant

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

THC

bull Variedly aromatic ring (C Ring)

O

O

H

11rsquo-di-methyl-pyrane ring (B ring)

Variedly unsaturated cyclohexyl ring (A ring)

Results of SAR

bull Psychoactive properties are (-) trans-enatioselective

bull Length lipophilicity C3 alkyl chain

bull Phenolic hydroxyl-group

bull C9 substitute

O

O

H

Modes of Absorption

bull The most common method of absorption is smoking Either in a loosely rolled cigarette called a joint or through a pipe or water pipe

Smoking and the Body

THC enters the body through the Lungs

The smoke is inhaled and held in the lungsAll affect how much THC will enter the plasmaTHC crosses the blood barrier through the capillaries in the lungs

After inhalation THC can reach the brain in about 14 seconds

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

What are cannabinoidsbull Group of gt60 dibenzopyran chemicals found in

leaves and flowering tops of female cannabis plant (Cannabis sativa and Cannabis indica)

bull Some common cannabinoids are

In the plantIn your body (endogenous)

Synthetic

Δ9 ndash THC 2-arichidonyl glycerol (2 ndash AG)

CP 55940

Δ8 ndash THC anandamideHU ndash 210

cannabidiol and cannabinol

Natural cannabinoids

Representative cannabinoids

Classical cannabinoids Non-classical cannabinoid Aminoalkylindole

CB1 antagonists

Endogenous cannabinoids

Receptors suggest endogenous ligandsTwo main families identifiedBoth arachidonic acid derivativesPrecursors in membranes

ldquoMade on demandrdquoAmides (anandamide)

Esters (2-AG)

bull Significant differences

ndash Routes of synthesis ndash Mode of degradation

(FAAH vs MAGL)ndash Efficacy

Endocannabinoids

bull Anandamide (Sanskrit ananda inner bliss) is one endocannabinoid It is found in chocolate (though there is some controversy over whether the small quantity has any effect on the body) It is about as potent as THC

Structure of THC and synthetic analogs

Lipophilic side chain Most potent analog 100s

times more potent than THC

with 4 major cannabinoids in the plant

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

THC

bull Variedly aromatic ring (C Ring)

O

O

H

11rsquo-di-methyl-pyrane ring (B ring)

Variedly unsaturated cyclohexyl ring (A ring)

Results of SAR

bull Psychoactive properties are (-) trans-enatioselective

bull Length lipophilicity C3 alkyl chain

bull Phenolic hydroxyl-group

bull C9 substitute

O

O

H

Modes of Absorption

bull The most common method of absorption is smoking Either in a loosely rolled cigarette called a joint or through a pipe or water pipe

Smoking and the Body

THC enters the body through the Lungs

The smoke is inhaled and held in the lungsAll affect how much THC will enter the plasmaTHC crosses the blood barrier through the capillaries in the lungs

After inhalation THC can reach the brain in about 14 seconds

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Natural cannabinoids

Representative cannabinoids

Classical cannabinoids Non-classical cannabinoid Aminoalkylindole

CB1 antagonists

Endogenous cannabinoids

Receptors suggest endogenous ligandsTwo main families identifiedBoth arachidonic acid derivativesPrecursors in membranes

ldquoMade on demandrdquoAmides (anandamide)

Esters (2-AG)

bull Significant differences

ndash Routes of synthesis ndash Mode of degradation

(FAAH vs MAGL)ndash Efficacy

Endocannabinoids

bull Anandamide (Sanskrit ananda inner bliss) is one endocannabinoid It is found in chocolate (though there is some controversy over whether the small quantity has any effect on the body) It is about as potent as THC

Structure of THC and synthetic analogs

Lipophilic side chain Most potent analog 100s

times more potent than THC

with 4 major cannabinoids in the plant

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

THC

bull Variedly aromatic ring (C Ring)

O

O

H

11rsquo-di-methyl-pyrane ring (B ring)

Variedly unsaturated cyclohexyl ring (A ring)

Results of SAR

bull Psychoactive properties are (-) trans-enatioselective

bull Length lipophilicity C3 alkyl chain

bull Phenolic hydroxyl-group

bull C9 substitute

O

O

H

Modes of Absorption

bull The most common method of absorption is smoking Either in a loosely rolled cigarette called a joint or through a pipe or water pipe

Smoking and the Body

THC enters the body through the Lungs

The smoke is inhaled and held in the lungsAll affect how much THC will enter the plasmaTHC crosses the blood barrier through the capillaries in the lungs

After inhalation THC can reach the brain in about 14 seconds

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Representative cannabinoids

Classical cannabinoids Non-classical cannabinoid Aminoalkylindole

CB1 antagonists

Endogenous cannabinoids

Receptors suggest endogenous ligandsTwo main families identifiedBoth arachidonic acid derivativesPrecursors in membranes

ldquoMade on demandrdquoAmides (anandamide)

Esters (2-AG)

bull Significant differences

ndash Routes of synthesis ndash Mode of degradation

(FAAH vs MAGL)ndash Efficacy

Endocannabinoids

bull Anandamide (Sanskrit ananda inner bliss) is one endocannabinoid It is found in chocolate (though there is some controversy over whether the small quantity has any effect on the body) It is about as potent as THC

Structure of THC and synthetic analogs

Lipophilic side chain Most potent analog 100s

times more potent than THC

with 4 major cannabinoids in the plant

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

THC

bull Variedly aromatic ring (C Ring)

O

O

H

11rsquo-di-methyl-pyrane ring (B ring)

Variedly unsaturated cyclohexyl ring (A ring)

Results of SAR

bull Psychoactive properties are (-) trans-enatioselective

bull Length lipophilicity C3 alkyl chain

bull Phenolic hydroxyl-group

bull C9 substitute

O

O

H

Modes of Absorption

bull The most common method of absorption is smoking Either in a loosely rolled cigarette called a joint or through a pipe or water pipe

Smoking and the Body

THC enters the body through the Lungs

The smoke is inhaled and held in the lungsAll affect how much THC will enter the plasmaTHC crosses the blood barrier through the capillaries in the lungs

After inhalation THC can reach the brain in about 14 seconds

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Endogenous cannabinoids

Receptors suggest endogenous ligandsTwo main families identifiedBoth arachidonic acid derivativesPrecursors in membranes

ldquoMade on demandrdquoAmides (anandamide)

Esters (2-AG)

bull Significant differences

ndash Routes of synthesis ndash Mode of degradation

(FAAH vs MAGL)ndash Efficacy

Endocannabinoids

bull Anandamide (Sanskrit ananda inner bliss) is one endocannabinoid It is found in chocolate (though there is some controversy over whether the small quantity has any effect on the body) It is about as potent as THC

Structure of THC and synthetic analogs

Lipophilic side chain Most potent analog 100s

times more potent than THC

with 4 major cannabinoids in the plant

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

THC

bull Variedly aromatic ring (C Ring)

O

O

H

11rsquo-di-methyl-pyrane ring (B ring)

Variedly unsaturated cyclohexyl ring (A ring)

Results of SAR

bull Psychoactive properties are (-) trans-enatioselective

bull Length lipophilicity C3 alkyl chain

bull Phenolic hydroxyl-group

bull C9 substitute

O

O

H

Modes of Absorption

bull The most common method of absorption is smoking Either in a loosely rolled cigarette called a joint or through a pipe or water pipe

Smoking and the Body

THC enters the body through the Lungs

The smoke is inhaled and held in the lungsAll affect how much THC will enter the plasmaTHC crosses the blood barrier through the capillaries in the lungs

After inhalation THC can reach the brain in about 14 seconds

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Endocannabinoids

bull Anandamide (Sanskrit ananda inner bliss) is one endocannabinoid It is found in chocolate (though there is some controversy over whether the small quantity has any effect on the body) It is about as potent as THC

Structure of THC and synthetic analogs

Lipophilic side chain Most potent analog 100s

times more potent than THC

with 4 major cannabinoids in the plant

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

THC

bull Variedly aromatic ring (C Ring)

O

O

H

11rsquo-di-methyl-pyrane ring (B ring)

Variedly unsaturated cyclohexyl ring (A ring)

Results of SAR

bull Psychoactive properties are (-) trans-enatioselective

bull Length lipophilicity C3 alkyl chain

bull Phenolic hydroxyl-group

bull C9 substitute

O

O

H

Modes of Absorption

bull The most common method of absorption is smoking Either in a loosely rolled cigarette called a joint or through a pipe or water pipe

Smoking and the Body

THC enters the body through the Lungs

The smoke is inhaled and held in the lungsAll affect how much THC will enter the plasmaTHC crosses the blood barrier through the capillaries in the lungs

After inhalation THC can reach the brain in about 14 seconds

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Structure of THC and synthetic analogs

Lipophilic side chain Most potent analog 100s

times more potent than THC

with 4 major cannabinoids in the plant

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

THC

bull Variedly aromatic ring (C Ring)

O

O

H

11rsquo-di-methyl-pyrane ring (B ring)

Variedly unsaturated cyclohexyl ring (A ring)

Results of SAR

bull Psychoactive properties are (-) trans-enatioselective

bull Length lipophilicity C3 alkyl chain

bull Phenolic hydroxyl-group

bull C9 substitute

O

O

H

Modes of Absorption

bull The most common method of absorption is smoking Either in a loosely rolled cigarette called a joint or through a pipe or water pipe

Smoking and the Body

THC enters the body through the Lungs

The smoke is inhaled and held in the lungsAll affect how much THC will enter the plasmaTHC crosses the blood barrier through the capillaries in the lungs

After inhalation THC can reach the brain in about 14 seconds

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

with 4 major cannabinoids in the plant

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

THC

bull Variedly aromatic ring (C Ring)

O

O

H

11rsquo-di-methyl-pyrane ring (B ring)

Variedly unsaturated cyclohexyl ring (A ring)

Results of SAR

bull Psychoactive properties are (-) trans-enatioselective

bull Length lipophilicity C3 alkyl chain

bull Phenolic hydroxyl-group

bull C9 substitute

O

O

H

Modes of Absorption

bull The most common method of absorption is smoking Either in a loosely rolled cigarette called a joint or through a pipe or water pipe

Smoking and the Body

THC enters the body through the Lungs

The smoke is inhaled and held in the lungsAll affect how much THC will enter the plasmaTHC crosses the blood barrier through the capillaries in the lungs

After inhalation THC can reach the brain in about 14 seconds

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

THC

bull Variedly aromatic ring (C Ring)

O

O

H

11rsquo-di-methyl-pyrane ring (B ring)

Variedly unsaturated cyclohexyl ring (A ring)

Results of SAR

bull Psychoactive properties are (-) trans-enatioselective

bull Length lipophilicity C3 alkyl chain

bull Phenolic hydroxyl-group

bull C9 substitute

O

O

H

Modes of Absorption

bull The most common method of absorption is smoking Either in a loosely rolled cigarette called a joint or through a pipe or water pipe

Smoking and the Body

THC enters the body through the Lungs

The smoke is inhaled and held in the lungsAll affect how much THC will enter the plasmaTHC crosses the blood barrier through the capillaries in the lungs

After inhalation THC can reach the brain in about 14 seconds

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Results of SAR

bull Psychoactive properties are (-) trans-enatioselective

bull Length lipophilicity C3 alkyl chain

bull Phenolic hydroxyl-group

bull C9 substitute

O

O

H

Modes of Absorption

bull The most common method of absorption is smoking Either in a loosely rolled cigarette called a joint or through a pipe or water pipe

Smoking and the Body

THC enters the body through the Lungs

The smoke is inhaled and held in the lungsAll affect how much THC will enter the plasmaTHC crosses the blood barrier through the capillaries in the lungs

After inhalation THC can reach the brain in about 14 seconds

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Modes of Absorption

bull The most common method of absorption is smoking Either in a loosely rolled cigarette called a joint or through a pipe or water pipe

Smoking and the Body

THC enters the body through the Lungs

The smoke is inhaled and held in the lungsAll affect how much THC will enter the plasmaTHC crosses the blood barrier through the capillaries in the lungs

After inhalation THC can reach the brain in about 14 seconds

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Smoking and the Body

THC enters the body through the Lungs

The smoke is inhaled and held in the lungsAll affect how much THC will enter the plasmaTHC crosses the blood barrier through the capillaries in the lungs

After inhalation THC can reach the brain in about 14 seconds

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

After a 6 min smoking period peak blood levels reached at about 7 min (100 ngml plasma)

Most THC is absorbed from the blood within 30 min

Moves rapidly into the brain and across the bloodbrainplacental barrier Because fatty chains make it very lipid soluble

Half-life is about 19 hours Can store in fat cells

Established physiological effects are dose related

Lethal dose for THC use has now been studied and no human deaths have been reported due to intoxication from cannabis

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Metabolites

bull Radioactively labeled delta-9-THC has been found to persist in the body as an active metabolite as long as 8 days after use

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Primary metabolite has a half-life of 50 hours The complete elimination of the drug can take as long as 6 weeks

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

23 of metabolites are excreted in feces13 of metabolites are excreted in urine

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Cannabis Pharmacology

Primary Cannabinoids from Cannabis are

bull Cannabinol (CBN) Cannabidiol (CBD) and Tetrahydrocannabinol (THC)

bull THC (-9-THC ) is the only one with significant psychoactive properties

bull CBN - 110 th activity of THC CBD - none

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

bull 2 isomers a trans-delta-9-THC and a delta-8-THC

bull A cannabidiol (the 2nd most abundant psychoactive ingredient after THC)

bull A cannabinol a decomposition product of THC that accumulates as cannabis samples age

After ingestion delta-9 is converted in the liver to 11-Hydroxy THC which is equally as potent and active

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Therapeutic

bull Antiemeticbull Reduction of intra-ocular tensionbull Analgesicbull Muscle relaxant bull Anti-convulsant bull Anti-inflammatory appetite ldquothe munchiesrdquo It is one of the most well-known effects of marijuana the

powerful surge in appetite many users feel after smoking or ingesting the drug colloquially known as the munchies

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Marinol

THC in a sesame oil suspension

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Cannabinoid ReceptorsBeforethe 1980s it was often speculated that

cannabinoids produced their effects through non specific interaction with cell membranes instead of interacting with specific receptors

The discovery of the first cannabinoid receptors in the 1980s helped to resolve this debate These receptors are common in animals and have been found in mammals birds fishes and reptiles

There are currently two known types of cannabinoid receptors CB1 and CB2

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

CB1 ReceptorsFound primarily in the brain (specifically basal ganglia limbic

system including the hippocampus and cerebellum)1048766Most dense in brain regions involved with thinking and memory

attention and control of movement1048766Also present in both male and female reproductive systems as

well as in the lungs liver and kidneys1048766Appear to be responsible for the euphoric and anticonvulsive

effects of Cannabis1048766Essentially absent in the medulla oblongata the part of the brain

that is responsible for respiratory and cardiovascular functions

Thus there is no risk of respiratory or cardiovascular failure as there is with many other drugs

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

CB2 Receptor

CB2 receptors are almost exclusively found in the immune system (T cells macrophages B cells) with the greatest density in the spleen

1048766CB2 receptors appear to be responsible for the anti-inflammatory and possible other therapeutic effects of Cannabis

1048766Also expressed on peripheral nerve terminals

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Cannabis and Δ9- (THC) for weight loss

bull Obesity is one of the highest preventable causes of morbidity and mortality in the developed world It has been well known for a long time that exposure to cannabis produces an increase of appetite (a phenomenon referred to as the munchies) This phenomenon led to an exploration of the role of the endocannabinoid system in the regulation of obesity and associated metabolic syndrome This effort subsequently led to the development of a successful therapeutic approach for obesity that consisted of blocking the cannabinoid CB1 receptors using ligands such as Rimonabant in order to produce weight loss and improve metabolic profile

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

What is obesity

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Obesity is characterized by an abnormal accumulation of body fat usually 20 percent or more over an individuals ideal body weight Obesity results when the size or number of fat cells in a persons body increases When a person gains weight these fat cells first increase in size and later in number When a person starts losing weight the cells decreas ein size but their number generally stays the same This is part of the reason that once you gain a significant amount of weight it is more difficult to lose it

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

The clinical definition of obesity is a body mass index(BMI)of 30 or higher BMI = Weight (in kg) Height (in meters) Squared

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Rimonabant

bull Acompliareg(Sanofi-Aventis)

launched in Europe in 2006 for

oral treatment of obesity at 20 mg

once daily

Selective blocker of central

and peripheral CB1 receptors

It reduces food intake and improves lipid and glucose metabolism

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Rimonabant

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48

Despite being efficacious Rimonabant was associated with increased rates of depression and anxiety and therefore removed from the market

• Cannabis
• Slide 2
• Slide 3
• Cannabis spp
• Slide 5
• Slide 6
• Hemp
• What is Marijuana
• Marijuana ndash History of Use
• HempvsMarijuana-1
• HempvsMarijuana-2
• HempvsMarijuana-3
• Cannabis Biology
• Chemical constituents of Cannabis
• What is a cannabinoid
• What are cannabinoids
• Natural cannabinoids
• Slide 18
• Representative cannabinoids
• Slide 20
• Endocannabinoids
• Structure of THC and synthetic analogs
• Slide 23
• Slide 24
• THC
• Results of SAR
• Modes of Absorption
• Smoking and the Body
• Slide 29
• Slide 30
• Metabolites
• Slide 32
• Slide 33
• Cannabis Pharmacology
• Slide 35
• Therapeutic
• Marinol
• Cannabinoid Receptors
• CB1 Receptors
• CB2 Receptor
• Cannabis and Δ9- (THC) for weight loss
• What is obesity
• Slide 43
• Slide 44
• Rimonabant
• Slide 46
• Slide 47
• Slide 48