21st century street drug pharmacology new drugs of the 2nd decade
DESCRIPTION
This presentation was delivered at the Northwest Conference on Alcohol, July 18, 2011, Scottsdale, AZTRANSCRIPT
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%