Cannabichromene (CBC) Cannabinol (CBN) … · A Gateway drug is defined as “one that apparently...

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Tetrahydrocannabinol (THC)

Cannabichromene (CBC)

Cannabidiol (CBD)

(THCA)(THCV)

Beta-myrcene

Justin Sinclair

Research Fellow, NICM (Western Sydney University)

[email protected]

www.tmconsultancy.com.au

What is Medicinal

Cannabis? The facts and the fiction.

Mental Health and Drug & Alcohol Nurses’ Forum

September 2017.

Alpha-pinene

Cannabinol (CBN)

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Justin Sinclair

(Pharmacognosist)

MHerbMed (USyd) BHSc (UNE) ND

DBM DNut FNHAA MICRS MSCC

• Research Fellow – NICM

(Western Sydney University)

• Scientific Advisory Board

Member – Bioceuticals

• Chief Scientist,

Scientific Advisory

Council – United in

Compassion (Registered

Charity)

• Lecturer – Endeavour

Disclosures

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Family: Cannabaceae (AHP 2014)

Botanical nomenclature: (AHP 2014)

Cannabis sativa (L)

Cannabis indica (Lam)

Cannabis ruderalis (Janisch)

Common names: (AHP 2014)

Pot, weed, cannabis, ganja, marijuana,

hemp, reefer.

Part used:

Medicinally:

Dried unfertilised female inflorescence,

Resin glands (aka hashish), leaves

Industry:

Seeds (i.e. oil, protein) and fibre (i.e.

Textiles, paper, building material)

Figure 1: Graphic representation of Cannabis

sativa (L), showing seeds, stamens, leaves,

ovaries and inflorescence. Photo from Kohler

(1887)

Cannabis Botany

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Figure 3: Graphic representation of present day ranges of various Cannabis biotypes. As seen in Clarke & Merlin 2013.

BLD – Broad Leaf Drug: Cannabis indica ssp.

afghanica

NLD – Narrow Leaf Drug: Cannabis indica ssp. indica

BLH – Broad Leaf Hemp: Cannabis indica ssp.

chinensis

NLH – Narrow Leaf Hemp: Cannabis sativa ssp.

sativa

Cannabis Origins

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Figure 2: The short, broad leaf exhibited

by Cannabis indica, or what is also

being described as a broad-leaf drug

variety.

Figure 3: The long, narrow leaf seen in

Cannabis sativa.

Acuminate apex

Cannabis Morphology

Serrated leaf margin

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Figure 4: The androecium, or “male place” of

the Cannabis plant comprised of filaments and

anthers, collectively known as stamens.

Figure 5: The female inflorescence made up of

many smaller florets and populated with

pistils/stigmas

Stamens

Pollen

Cannabis Morphology

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Figure 7: Magnified glandular trichomes on

Cannabis plant.

Pistils / Stigmas Glandular trichomes

Figure 6: The covering of glandular trichomes

on a female Cannabis plant.

Cannabis Morphology

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Figure 9: Hashish can be sifted or hand rubbed.

The hand rubbed product is known as charas.

Photo by Pierre Arnoud-Chouvy

Figure 8: The compressed glandular trichomes

of the Cannabis plant, known commonly as

hashish or hash.

Cannabis Morphology

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Figure 10: The covering of glandular trichomes

on a specific strain of Cannabis known as

“Bubba Kush”. This is crude herb that can be

smoked, vaporized or used to make edible

products (THC:@11-17% / CBD:

< @ 0.4%)

Figure 11: Another broad leaf drug variety

known as “Afghani Kush” obtained from a

licensed Medical Cannabis dispensary.

Cannabis Morphology

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Figure 12: Cannabis plant in vegetative growth stage...note the absence of flowers or buds forming

as yet.

Cannabis Morphology

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Figure 13: Cannabis plants under indoor lighting in vegetative growth stage.

Cannabis Morphology

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Figure 14: Outdoor Cannabis plants just starting the flowering stage...notice the Cola buds forming

at the end of the stems.

Cannabis Morphology

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Figure 15: The seeds of Cannabis, a

great nutritional source of oil and

protein.

Figure 16: The fibre obtained from Cannabis

stalks, used throughout human history for

millennia.

Cannabis Morphology

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Tetrahydrocannabinol (THC) Structure

Cannabidiol (CBD) StructureFigure 17: A large Cannabis

inflorescence nearing maturity and

harvest.

Cannabis Phytochemistry

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(Andre, Hausman & Guerriero 2016)


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(Giacoppo et al. 2014; AHP 2014)



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Psychoactive

Non Psychoactive



Cannabigerolic acid (CBGA) Cannabidiolic acid (CBDA)Δ9-Tetrahydrocannabinolic acid (THCA)

Cannabichromic acid (CBCA) Cannabielsoinic acid

THCA THC

non-enzymatic

decarboxylation (heat)

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Tetrahydrocannabinol (THC) Structure Cannabidiol (CBD) Structure

Pharmacological actions attributed to CBD

Anticonvulsant (Jones et al. 2010)

Antagonizes effects of THC (Pertwee 2008)

Analgesic (Davis & Hartoum, 1983)

Anti-inflammatory (Booz, 2011)

Antiemetic / Antinausea (Rock et al. 2010)

Anxiolytic (Russo et al. 2005; Campos & Guimares, 2008)

Antioxidant (Hampson et al. 1998)

Neuroprotective (Hampson et al. 1998)

Pharmacological actions attributed to THC *

Analgesic (Rahn & Hohmann, 2009)

Antiemetic (Haney et al. 2007; Hollister 1971; Machado et al. 2008)

Anti-inflammatory (Hampson et al. 1998)

Antipruritic (Neff et al. 2002)

Bronchodilator (Williams et al. 1976)

Muscle relaxant (Kavia et al. 2010)

Antioxidant, Neuroprotective (Hampson et al. 1998)

symptoms of Alzheimer’s (Eubanks et al. 2006)

(Russo 2011; AHP 2014) * Denotes psychoactivity


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Cannabichromene

Weak analgesic (Turner et al. 1980)

Anti-inflammatory (Davis & Hatoum, 1983)

Antimicrobial (Turner & ElSohly, 1981)

Cannabigerol

Analgesic (Cascio et al. 2010)

Anti-inflammatory

Antifungal (ElSohly et al. 1982)

Antipsoriatic (Wilkinson & Williamson 2007)

Cannabidivarin

Anticonvulsant (Hill et al. 2010)

Tetrahydocannabivarin

THC antagonist (Pertwee et al. 2007)

Anticonvulsant (Hill et al. 2010)

Improved glucose tolerance (Wargent et al.

2010)

Delta-8-Tetrahydrocannabinol *

Appetite stimulant (Avraham et al. 2004)

Less psychoactive then Delta-9-THC

Binds to CB1 receptors in the brain like

Delta-9

Antiemetic and analgesic

Cannabinol

Antipsoriatic (Wilkinson & Williamson 2007)

Sedative (Musty et al. 1976)

Antimicrobial against MRSA (Appendino et

al. 2008)

(Russo 2011; AHP 2014)


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(Russo 2011; AHP 2014)

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Limonene

Anxiolytic (Carvahlo-Freitas & Costa, 2002)

Immunostimulant if inhaled (Komori et al.

1995)

Antioxidant

Apoptosis of breast cancer (Viguishin et al.

1998)

Beta-Myrcene

Anti-inflammatory (Lorenzetti et al. 1991)

Analgesic (Rao et al. 1990)

Sedative & hypnotic (do Vale et al. 2002)

Muscle relaxant (do Vale et al. 2002)

Alpha-pinene

Anti-inflammatory (Gil et al. 1989)

Bronchodilatory (Falk et al. 1980)

(Russo 2011; AHP 2014)

CBD

CBD

THC

CBD

THC

Terpene Phytochemistry

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(Russo 2011; AHP 2014)

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(AHP 2014)

Flavonoids

Polysaccharides

Phenols

Coumarins

Glycosides

Alcohols

Steroids

Flavones

Flavonols


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Dosage Form Pros Cons

Smoking Quick onset of effect; Cheap;

easy to adjust dosing

Smoke can irritate the lungs;

Pulmonary disease effect

Vaporising Quick onset of effect; better for

lung health than smoking

Vaporising units can be

expensive.

Edibles Long lasting effect; option for

those that do not smoke

Longer onset of action; can be

stronger effect.

Juicing Rich in THCA; non-

psychoactive

Not a great deal of evidence to

support this form.

Tinctures / Oils Easy to control dosage;

palatable; Good for children

Slower than smoking in onset.

Capsules Long lasting effect; option for

those that do not smoke

Longer onset of action;

Excipient ingestion.

Suppositories Absorbed quickly; Long lasting

effect

Difficult to administer; Needs

refrigeration

Topically Can be used for local skin

conditions; Not psychoactive

Not a great deal of evidence to

support this form.

Cannabis Dosage Forms

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Cannabis phytochemical Interaction

Cannabidiol (CBD) Can potently inhibit CYP3A4, CYP3A5

and CYP2D6 enzymes

Tetrahydrocannabinol

(THC)

In-vitro inhibition of CYP2C9 has been

observed (Cannabis smoke)

Cannabidiol (CBD) In-vitro inhibition of CYP2C9 has been


Cannabinol (CBN) In-vitro inhibition of CYP2C9 has been


Cannabis specific drug interactions

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28How did we get here?

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Cannabis may cause short term memory impairment whilst under the influence.

This is considered reversible upon cessation...not permanent.

Certain Cannabis phytochemicals such as Cannabidiol (CBD) actually exhibit neuroprotective activity.

Animal studies are now showing the possibility of specific Cannabis phytochemistry assisting in:

Foetal hypoxia (Alvarez et al. 2008)

Multiple sclerosis

Hypoxic brain injury (Ischaemicstroke)

Alzheimer’s Disease (Ramirez et al. 2005)

Figure 18: The female inflorescence (bud) of

“Super Silver Haze”, one of hundreds of

different Cannabis strains.

Cannabis lowers your IQ?

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32Cannabis lowers your IQ?

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The psychoactivity of cannabis

is largely dependent on the

phytochemistry exhibited in the

specific strain of the plant.

There exist numerous strains of

Cannabis that have been

selectively bred to be low in

THC, but higher in other

phytochemicals such as CBD.

Individual dosing (titration) and

appropriate Cannabis strain

selection is key to reducing

psychoactive effects.

Figure 19: Harlequin, is rich in CBD and has much lower levels of THC (the main psychoactive

cannabinoid) than most recreationally used varieties. Phytochemical profile produced with

permission from Steep Hill (Halent) Laboratories (USA).

All Cannabis gets you “high”?

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(Anthony, Warner & Kessler 1994).

Cannabis is a drug of dependence?

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Cannabis dependency

does exist but is also

dependent on the

individual.

Factors such as

individual polymorphic

expression, individual

variability, the strain of

Cannabis being utilised

and the dosage taken

are also important

contributing factors.

(Anthony, Warner & Kessler 1994).


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We are

both legal


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A Gateway drug is

defined as “one that

apparently can lead to

the use of harder,

more addictive or

dangerous drugs”.

Examples of hard

drugs may include:

Heroine

Methamphetamine

Cocaine

(Reiman 2009)

Cannabis is a gateway drug?

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Type of substitution # of Participants % of Participants

EtOH substitute n = 134 40%

Illicit drug substitute n= 87 26%

Prescription drug substitute n= 219 65.8%

Table 1: Percent of sample reporting using cannabis as a substitute.

0

50

100

150

200

250

Alcohol (EtOH)substitute

Illicit drug substitute Prescription drugsubstituteNumber of study participants

(Reiman 2009)


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Reasons for using cannabis as a substitute

Less adverse side effects(n=197)

Less withdrawal potential(n=103)

Ability to obtain Cannabis(n=54)

Greater socialacceptance (n=36)

Better symptommanagement (n=174)

(Reiman 2009)


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Psychosis is an inability to distinguish what is real and can include delusions and hallucinations.

Psychosis can be a brief episode or longer term as seen in psychiatric conditions such as schizophrenia.

The exact cause of psychosis is unknown but likely involves a complex interplay of physical, genetic, psychological and environmental factors.

(Ksir & Hart 2016)

KEYWORDS:

How to join PubMed Commons

PubMed Commons home

Curr Psychiatry Rep. 2016 Feb;18(2):12. doi: 10.1007/s11920-015-0657-y.

Cannabis and Psychosis: a Critical Overview of the Relationship.

Ksir C , Hart CL .

Abstract

Interest in the relationship between cannabis use and psychosis has increased dramatically in

recent years, in part because of concerns related to the growing availability of cannabis and

potential risks to health and human functioning. There now exists a plethora of scientific articles

addressing this issue, but few provide a clear verdict about the causal nature of the cannabis-

psychosis association. Here, we review recent research reports on cannabis and psychosis, giving

particular attention to how each report provides evidence relating to two hypotheses: (1) cannabis

as a contributing cause and (2) shared vulnerability. Two primary kinds of data are brought to bear

on this issue: studies done with schizophrenic patients and studies of first-episode psychosis.

Evidence reviewed here suggests that cannabis does not in itself cause a psychosis disorder.

Rather, the evidence leads us to conclude that both early use and heavy use of cannabis are more

likely in individuals with a vulnerability to psychosis. The role of early and heavy cannabis use as a

prodromal sign merits further examination, along with a variety of other problem behaviors (e.g.,

early or heavy use of cigarettes or alcohol and poor school performance). Future research studies

that focus exclusively on the cannabis-psychosis association will therefore be of little value in our

quest to better understand psychosis and how and why it occurs.

Cognition; Marijuana; Mental illness; Psychotic disorder; Schizophrenia; THC

PMID: 26781550 [PubMed - in process]

PubMed Commons

0 comments

Abstract

1 2,3,4,5

Author information

LinkOut - more resources

Full text links

PubMed

Cannabis can cause psychosis?

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In this UK study,

it was estimated

that to prevent

one case of

psychosis

approximately

2000 young men

would need to

stop using

Cannabis.


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1%

25%

50%

75%

100%

1970 1980 1990 2010 Now200019601950

Years of Cannabis use (International)


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Statistics regarding Cannabis

causing harm are skewed as

they often involve multiple

other drugs such as alcohol.

Data specifically relating to

Cannabis overdose or toxicity

is difficult to find.

Cannabis related harm is more

likely, such as operating motor

vehicles or predisposing to

mental illness or accident.

Figure 20: An example of an old United

States Pharmacopoeia Fluid extract of

Cannabis.

Cannabis use is harmful?

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0

1000

2000

3000

4000

5000

6000

7000

80007060

1944

9801270

21.8

636192

LD50 mg/kg in rats (oral)

LD50 mg/kg in rats (oral)

Cannabis use is harmful?

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50Cannabis use is harmful?

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51How much Cannabis to cause death?

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52Cannabis hyperemesis syndrome

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“Truth is

always the

first casualty

of war”

- Aeschylus (523-456BCE)

To conclude.

Figure 21: Aeschylus (523-456 BCE)

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