21st Century Street Drug Pharmacology: New Drugs

J. Randall Webber, MPH, CADCPrincipal Consultant

JRW Behavioral Health Serviceswww.randallwebber.com

Herbal Incense

• Crushed, non-psychoactive herbal/plant matter treated with one or more synthetic cannabinoids

– First Generation: “K2”, “Spice”, “Black Mamba”, “Red Dragon”

– Second Generation: “K3”, “Splice”, “Apocalypse”, “Destiny”, “Cloud Ten”, “Head Trip”, house mixes

Current Legal Status of "first generation" Herbal Incense

• The federal Drug Enforcement Administration (DEA) has used its emergency scheduling authority to temporarily control five chemicals (JWH-018, JWH-073, JWH-200, CP-47,497, and cannabicyclohexanol) that were used to make “herbal incense” products

• Possessing/selling these synthetic substances or products in which they are contained now illegal for at least one year

• Over next year DEA and the United States Department of Health and Human Services (DHHS) will study whether these chemicals and products should be permanently controlled

Banned Herbal incense Brands

• Frequently marketed as “incense” under a variety of names:– K2– Spice/Spice Gold– Arctic Synergy– Black Mamba– Yucatan Fire– Red Dragon– Genie– Blaze– Red X – Dawn

BANNED HERBAL INCENSE PRODUCTS

LEGAL HERBAL INCENSE PRODUCTS

New Herbal Incense Brands

• K2• K3• Destiny • Splice• Apocalypse• Cloud Ten• Head Trip• “House Blends”

Apocalypse Flavors

• BLUEBERRY

• STRAWBERRY

• JUNGLE JUICE

• CHERRY               COTTON CANDY

• COCONUT             

• LEMON

• LIME.

• SPEARMINT     

• ROOT BEER

•  BANANA    

• BUBBLE GUM

• ORANGE

• COCA COLA

• ”JOOSY FRUIT”

• RASPBERRY

• PEACH               

• APPLE

• CHOCOLATE                        

• GRAPE

• WATERMELON                     

• PINEAPPLE

• MANGO           

AM-HI-C “Atomic Bomb”

DROBUDROLL YOUR OWN

Herbal incense Pharmacology

• To date, hundreds of synthetic cannabinoids (similar to both 9-THC and endogenous cannabinoids) have been created

• Potency ranges from hundreds of times more potent than THC to over 1000x less potent

• Most common psychoactive ingredient in herbal incense was JWH-018 (1-pentyl-3-[1-naphthoyl]indole)

• Synthesized in 1995 by Dr. John W. Huffman at Clemson University

DEA Analysis of “New Grass”

Herbal incense Pharmacology

• Research supported by NIDA

• Two cannabinoid receptors in the human brain, CB1 and CB2

• CB2 affects inflammatory pain and was the focus of NIDA study

• JWH-018 targets both receptors

• Huffman: “JWH-018 easiest to make outside a lab, requiring only two steps involving commercial products”

• Transferring the JWH to the botanical product involves using acetone

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Herbal incense Pharmacology

• Research supported by NIDA

• Two cannabinoid receptors in the human brain, CB1 and CB2

• CB2 affects inflammatory pain and was the focus of NIDA study

• JWH-018 targets both receptors

• Huffman: “JWH-018 easiest to make outside a lab, requiring only two steps involving commercial products”

• Transferring the JWH to the botanical product involves using acetone

A Historical Perspective

• All drugs currently illicit in the U.S. have started out as legal (uncontrolled) substances– Heroin– Cocaine – Marijuana– MDMA (“ecstasy”)– LSD– Amphetamine

• Many of these “sat on the shelf” for years before becoming popular intoxicants

• A mixture of rumor, myth and science have all contributed to changes in the legal status of these substances

Herbal incense

• Street drugs– Psychoactive substances – Inconsistent ingredients– Unregulated manufacture– Multiple slang names– Often difficult to specify effects– Inflated prices

• Herbal incense has many of these characteristics

Drug Testing

• Many laboratories have a test for some of the first generation JWH chemicals

• In February, 2011 Redwood Laboratories announced a saliva based test that tests for JWH-018, JWH-073 and JWH-250

• Unknown if saliva/urine tests exist for the other cannabinoids in newer products

Herbal Incense in the Popular Press

• Sales of “K2” products increased significantly in Chicago following news of its impending status as a controlled substance

• Following an August 2008 report on “herbal incense” in Germany, ER visits ↑ significantly

• How do we inform the public of new drugs without setting of an epidemic of use?

Herbal Incense Pharmacology:The Scientific Literature

At present, almost nothing is known about the pharmacology, toxicology and safety profile of such compounds in humans*, except the opinions of consumers in internet forums.

Mustata, C; Torrens, M; Pardo, R; Perez, C; Farre, M. (2009).

a/k/a “human guinea pigs”

Herbal Incense: Typical Effects

• Cannabis-like intoxication

• Dreaminess

• Euphoria

• Introspective mood

• Hilarity

• Forgetfulness

• Heightened sensory perception

THESE ARE THE EFFECTS MOST COMMONLY THESE ARE THE EFFECTS MOST COMMONLY REPORTED BY USERSREPORTED BY USERS

Calls to Poison Control Centers

• Data from the American Association of Poison Control Centers’ “National Poison Data Center”

• 2010: 2,874 calls• As of April 6, 2011: 1,387• Total will be 5,548 calls if current trend

continues

Herbal Incense:Other Possible Effects

• Severe anxiety (may persist after herbal incense use is discontinued)

• Panic attacks• Dissociation (e.g., derealization)• Racing thoughts• Hallucinations• Rapid pulse (tachycardia)• Death/Suicide (?)

User Report # 1

• This is the worst experience I’ve ever had• The most anxiogenic substance I've ever

used • Nausea, vomiting, heart pounding like I’m

going to have a heart attack• Not sure whether I just said that, thought it

or read it• 2 hours later: Will never take this again

User Report #2: "Apocalypse"

• 3 individual “hits” from a small pipe• “organic” taste/no chemical odor or taste • 5 minutes: Feels like Cannabis• 10 minutes: Like an intense cannabis high• More than 3 puffs might be too much

Why the Discrepancy in Reported Effects?

• Use of other drugs (including alcohol) with herbal incense

• Varying potency

• “Hot spots”

• Overdose

• Presence of different cannabinoids

• “Knock-offs”

• User/environmental characteristics:

– Setting

– Set

Why the Discrepancy in Reported Effects?

• User/environmental characteristics:

– Set• Age

• Psychological stability

• Previous experience with psychoactive drugs

• Immediate support system

• Sensationalism (some reports taken out of context)

• Anti- Pro-drug attitudes

• Agency funding/Visibility

Overview

• Herbal incense contains a cannabinoid closely related to THC/marijuana

• No quality control• Manufacturing process may be associated

with adverse effects• Subjective effects most commonly

resemble those of extremely powerful marijuana

Overview

• Other reported effects range from intense euphoria and pleasant hallucinations to abject terror and near-psychotic reactions

• Almost complete lack of scientific study

• Street information is very inconsistent

Currently Available Legal Substances

• Herbal Incense

• “Bath Salts”

• Kratom

• Salvia

• “Lazy Cakes”

“Not for Human Consumption”

Kratom

Kratom• Mitragyna speciosa• Used in

Malaysia Thailand Indonesia

Local names: ithang biak biak Ketum Kakuam Thom

KRATOM CAPSULES

DRIED KRATOM LEAF

Young Kratom Tree

Kratom Leaf

Kratom Pharmacology

• 7-hydroxymitragynin

• Mitragynine

• Structural similar to some psychedelics

• No psychedelic activity or effects

• Interacts with the opioid receptors

Mitragynine

• Low doses Attaches to delta (Δ) opioid

receptors• Higher doses

“Crossover” to mu opioid receptors

7-hydroxymitragynine

• Recently identified as main active ingredient. • Animal research: Potent opiate agonist• Ceiling effect: limits respiratory depression and euphoria. •No fatal overdose of kratom known to have

occurred.

History of Kratom as a Treatment for Opiate Dependence

•1897: Europeans first noted that that the leaves of Mitragyna speciosa were a cure for opium dependence. •Currently used for methadone dependence detox in some countries (e.g., New Zealand) and by heroin addicts in Thailand to detox and manage withdrawal symptoms

Kratom Pharmacology

• Used for:– Prevention or delay of opiate withdrawal

symptoms “Recreational Purposes”

Kratom

• Seems to be:– Stimulant in lower doses (mitragynine)

– Sedative in higher doses (7-hydroxymitragynine)

•  Often produces a mixed effect

• Onset: Five to ten minutes

• Duration of action: Several hours

Kratom: Side Effects

• Short-term (immediate) Dry mouth Increased or decreased urination loss of appetite Nausea and/or vomiting.

• Side effects (Intermediate)– Anorexia/weight loss– Insomnia– Dependence (addiction)

Kratom: Side Effects

• Long term health risks :– Currently unknown

Khat

Khat

• Native to tropical East Africa and the Arabian Peninsula

• Fresh leaves/tops chewed or consumed as tea

• Stimulation and euphoria• Part of social culture in many countries

(coffee, tea, coca or khat?)

Khat cultivation in Yemen

Khat chewing

Women in Somalia Selling Khat/Quat

2006: Bundles of khat seized by the DEA

Khat

• Coca--------Cocaine • Khat---------Cathinone (Schedule I)• Cathinone: Structure similar to

amphetamines– Euphoria

– Anorexia

– Stimulation

– Dilated pupils

– Hypnagogic hallucinations when wearing off

Khat

• Withdrawal– Depression

– Irritability

– Lethargy

– Nightmares

– Hand tremor

Methcathinone (Schedule I)

• First synthesized in 1928

• 1930s: Used in the Soviet Union as an anti-depressant.

• 1960s: Began to be used as recreational drug in (former) Soviet Union

• More powerful than cathinone

• Effects similar to amphetamines/cocaine

• 1990s: Appeared in U.S. as “cat”

• Little current use

BATH SALTS

• States that have taken emergency action to ban at least two chemicals used in designer drugs labeled as “bath salts” (pink)

• States with current laws banning at least one so-called “bath salts” designer drug chemical (lavender)

• States with pending legislation to ban at least one so-called “bath salts” designer drug chemical (purple)

“Bath Salts”A/K/A “Plant Food”

– Energizing Aromatherapy

– Down2Earth White Horse

– Kamikaze

– Ivory Wave

– Purple Wave

– Red Dove

– Blue Silk

– Vanilla Sky

– White Blizzard

– Fake Cocaine

Aromatherapy Bath Salts

“White Blizzard”

“Plant Food”“NoveltyCollector’s Item

Possible Substances in “Bath Salts”

• 3,4 – Methylenedioxypyrovalerone (MDPV)

• 4 – Methylmethcathinone (Mephedrone, M-Cat, Meow, 4-MMC)

• 3,4 – Methylenedioxymethcathinone (Methylone, MDMC)

• 4 – Fluoromethcathinone (Flephedrone, 4-FMC)

• 3 – Fluoromethcathinone (3-FMC)

Mephedrone

• Onset: – Oral: 15–45 minutes

– Insufflation (nasal/“snorting): 10 minutes

– i.v. injection (rare): 30 minutes

• Duration: – Oral/Nasal: 2-3 hours

– Intravenous: 30 minutes

Mephedrone Research

• Dutch study:– 58%: overall pleasant experience

– 12 %: unpleasant experience.

• UK Study:– Users w/ previous cocaine experience:

• Better quality and longer lasting high

• Less addictive

Mephadrone

• Intended Effects: (Similar to MDMA/”ecstasy”, amphetamines and/or cocaine)– Euphoria

– Stimulation

– Enhanced music appreciation

– Decreased hostility

– Improved mental function

– Mild sexual stimulation

Mephadrone

• Unintended (Side) Effects: – Dilated pupils

– Poor concentration

– Bruxism (teeth grinding)

– Problems focusing visually

– Poor short-term memory

– Hallucinations

– Delusions

Mephedrone

• 4-methylmethcathinone (4-MMC, M-Cat, Meow)

• 4-methylephedrone

• Effects similar to MDMA/”ecstasy” BUT– No formal published studies effects on humans

– No animals studies that could be applied to humans

• Controlled under federal analog act if for human consumption

• Not controlled if “not for human consumption)

M-CAT

4-Methylmethcathinone & Caffeine:

MDMA, caffeine & 4-Methylmethcathinone

4-Methylmethcathinone & Caffeine 4-Methylmethcathinone & Methylone

Methylone

• 3,4-methylenedioxy-N-methylcathinone– M1

– bk-MDMA

• Structure similar to MDMA/”ecstasy”

Methylone

• Central Nervous System Stimulation

• Euphoria or dysphoria,

• Anxiolysis or Anxiogenesis

• Increase in sociability.

• Insomnia

• Restlessness

• Derealization/depersonalization

• Hallucinations

• Psychosis

Methylone• Tachycardia (rapid pulse)

• Hypertension (high BP)

• Hyperthermia

• Sweating

• Dilated pupils

• Nystagmus

• Trismus (inability to open the mouth)

• Bruxism (Tooth grinding)

• Anorexia

• Nausea and vomiting

Sold as methylone

Methylone

Sold as ecstasy (Sold as M1) Methylone, bk-MBDB

(Sold as Dragonfly Pokeball) Methylone, Caffeine

Plant Food“Piperazine Free”

• The piperazines are a category of substances

• Used in medicine to kill parasites

• Some have psychoactive properties and are often substituted for MDMA in “ecstasy”– BZP (Benzylpiperazine )

BMP Products

“Charge” “Extreme Jet”

BMP Characteristics

• Appears to have mild to moderate addiction potential

• Tolerance appears to develop quickly

• Potential for short-term toxicity moderate

• Potential for long-term toxicity unknown

• Potential for acute psychiatric impairment appears moderate at the least

• Potential for persistent psychiatric impairment unknown

BMP Effects

• Dosage ranges from 50-200 mg

• Former amphetamine addicts could not discriminate between BMP and amphetamine when injected i.v.

• Acts as both a stimulant and a hallucinogen

• perceptions such as taste, color or music may be subjectively enhanced.

• Duration of action = 4-6 hours/rarely 8 hours

• Mixed with TFMPP produces a similar effects as MDMA

BMP Effects

• Feelings of euphoria, wonder, amazement, well-being, energy and elation

• Rapid mood elevation • Enhanced sociability • Enhanced appreciation of music • Increased desire to move, also slight increase in

stereotypy • Skin tingling • Decreased appetite • Repetitive thought patterns • Actual and perceived changes in body temperature

BMP Effects

• Mild jaw clenching/bruxism

• Increased heart rate

• Dilation of pupils

• Nausea

• Flushing

• Mild xerostomia (dry mouth)

• Slight urinary incontinence, often described as "leaking" a small amount of urine after urinating (not due to loss of bladder control)

BMP Effects• Later Effects:

– Mild headache– Nausea – Hang-like symptoms (common with high doses) – Fatigue– Indigestion/heartburn hunger/thirst– Insomnia– Confusion– Depression (more pronounced with

frequent/long-term use)

BMP Side Effects

• dilated pupils• blurred vision • dryness of the mouth • extreme alertness • pruritis• confusion • Tremor• Agitation• Extrapyramidal symptoms (dystonia, akathisia

BMP Side Effects

• Headache

• Dizziness

• Anxiety

• Insomnia

• Vomiting

• Chest pain

• Hallucinations• Paresthesia• Tachycardia• Hypertension

BMP Side Effects

• Palpitations• Hyperventilation• Sweating• Hyperthermia• Psychosis or adverse psychiatric events• renal toxicity• Respiratory failure• Seizures

Trifluoromethylphenylpiperazine TFMMP

Trifluoromethylphenylpiperazine TFMMP

• “Legal X”• Rarely used by itself• Produces aversive effects in animals rather

than self-administration• Not a controlled substance• More commonly co-administered with BZP

Trifluoromethylphenylpiperazine TFMMP

• “Crash” syndrome:– Insomnia– Loss of appetite– Headache– Alcohol-like hangover

Packaging50 to 500 milligram packets.

Price 25 to $50 per 50 milligram packet

Reported Effects

• Stimulant euphoria

• ↑ Energy

• Reversal of fatigue/Insomnia

• Agitation

• Hallucinations

• Irritability

Salvia: One name-many plants

Salvia: One name-many plants

• Plants in the Mint family

• Sage

• Common Sage

• Mexican Bush Sage

• White Sage

• Greek Sage

• Diviner's Sage (Salvia Divinorum)

Meadow Sage

Salvia divinorum/Herba de Maria

Salvia Divinorum

• Grows primarily in the Sierra Mazateca (Oaxaca, Mexico)

• Commonly used by Mazateca shamans

Sierra Mazateca

Salvia Divinorum

• Grows primarily in the Sierra Mazateca (Oaxaca, Mexico)

• Commonly used by Mazateca shamans• Low addiction potential (kappa opioid

agonist)• Psychoactive component = Salvinorin A

(most potent natural hallucinogen)

0.5 gm of salvia divinorum extract

Salvia Divinorum:Recreational Use

• Smoked• Unnoticeable or light effects from dry leaf • More intense effects from higher doses

– Uncontrollable laughter

– Past memories, such as revisiting places from childhood memory

– Sensations of motion, or being pulled or twisted by forces

Salvia Divinorum:Recreational Use

• Smoked• Unnoticeable or light effects from dry leaf • More intense effects from higher doses

– Visions of membranes, films and various two-dimensional surfaces

– Merging with or becoming objects

– Overlapping realities, such as the perception of being in several locations at once

After effects produced by SalviaN=500

Positive NegativeIncreased insight: 47% Decreased insight: 1.8%

Improved mood: 44.8% Worsened mood: 4.0%

Increased connection with universe or nature: 39.8%

Decreased connection with universe or nature: 5.4%

Increased sweating: 28.2% Decreased sweating: 1.6%

Body felt warm or hot: 25.2% Body felt cold: 6.4%

Increased self-confidence: 21.6% Decreased self-confidence: 2.4%