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%