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What are the kids using?Inhalants, CCCs, Dextromethorphan and
other Hallucinogens
Kirk Moberg, MD, PhD, FASAMMedical Director, Illinois Institute for Addiction Recovery
Clinical Professor, Departments of Internal Medicine and Psychiatry and Behavioral Medicine
University of Illinois College of MedicineIllinois Alcohol and other Drug Abuse Professional Certification Association, Inc.
March 17, 2016
Agenda
• Statistics
• Inhalants
• Dissociatives
• Hallucinogens
• Cold remedies
• Miscellaneous
• Synthetic Cannabinoids
STATISTICS
Let’s start with some statistics
Monitoring the Future StudyUniversity of Michigan44,892 students382 public and private schoolsFunding Source: National Institute on Drug Abuse
Prevalence among past year drug use among 12th graders
Drug Prevalence
Alcohol 58.2
Marijuana/Hashish 34.9
Hookah 19.8
Small cigars 15.9
Amphetamines* 7.7
Adderall* 7.5
Snus 5.8
Narcotics o/t Heroin* 5.4
Synthetic Cannabinoids 5.2
Tranquilizers* 4.7
Cough Medicine* 4.6
Vicodin* 4.4
Hallucinogens 4.2
OxyContin* 3.7
Sedatives* 3.6
MDMA (Ecstasy) 3.6
LSD 2.9
Hall other than LSD 2.9
Cocaine (any form) 2.5
Ritalin* 2.0
Inhalants 1.9
Salvia 1.9
* Nonmedical use Categories not mutually exclusive
Tobacco
e-cigarette risk
e-cigarette substance
Tobacco vs. Cannabis
Cannabis
Cannabis
Cannabis Risk
Synthetic Cannabinoids
Prescription Opioids
Prescription Opioids
Heroin
INHALANTS
Inhalants
Inhalants
• Volatile hydrocarbons
– Solvents
– Adhesives
– Paint removers
– Etc.
• Nitrous oxide
• Alkyl nitrites
Three classifications
Aerosol
Volatile hydrocarbons
Gas phase
Volatile hydrocarbons
ButaneEther
Adhesives and thinners
Diflouroethane
Alkyl nitrites
Poppers
Uses: vasodilator (heart disease); cyanide poisoning; euphoria (especially with cocaine and MDMA); enhancesexual experience
Chloroethane
Mechanism of action?
• GABA-A
• NMDA
• Acetyl choline
DISSOCIATIVES
Dissociative drugsNMDA receptor antagonists
The trail to dextromethorphan
Racemethorphan
Dextromethorphan (DXM)
Levomethorphan
AntitussiveDissociative
OpioidAnalgesic
Dextrorphan (DXO)
Dextromethorphan Dextrophan
LevomethorphanLevorphanol
DXO pharmacology
• N-Methyl-D-Aspartate receptor antagonist
• m, k receptor agonist
Nitrous oxide
PhencyclidineSchedule II
OralIntravenousInhalationIntranasal
Clinical Presentation
• Rage• Erythema• Dilated Pupils
• Delusions• Amnesia• Nystagmus• Excitation• Skin Dryness
Receptors
• NMDA receptor antagonist
• Dopamine-2 receptor partial agonist
HALLUCINOGENS
Hallucinogens
MDMA
Salvia divinorum
Dimethyltryptamine (DMT)
Psylocybin
Serotonin receptors
Mescaline3, 4, 5-trimethoxyphenethylamine
PeyoteLophophora williamsii
Results
• Altered thinking
• Altered sense of time and self awareness
• Color brilliance and intensity
• Distortions and kaleidoscope forms
• Flattening of three dimensional objects
Psylocybin
More
• 200 species mushrooms
• Psylocybin Psilocin
• Human usage dates back thousands of years
• Serotonin agonist
Effects
• Euphoria
• Visual hallucinations
• Distorted sense of time
• Changes in perception
Dimethyltryptamine
50 plants4 animals
Hallucinogenic toads
5-methoxy-N, N-dimethyltryptamineBufotenin (N, N,-dimethylserotonin)
Lysergic Acid Diethylamide
Methylenedioxymethamphetamine (MDMA)
• Ecstasy
• XTC
• Adam
• Clarity
• Lover’s speed
• Molly
Two sterioisomers
• (l) isomer
– hallucinogenic
– indirect serotonergic agent
• (d) isomer
– stimulant
– indirect sympathomimetic agent
Molly, Mandy or Ecstasy?
• Mandy = Molly (Mandy is a UK term)
• Molly can be defined in two ways
– MDMA that is “pure”
– Methylone: a synthetic cathinone synthesized in 1996 for use as an antidepressant (b, k MDMA)
Methylone
Structural comparison
MDMA
methamphetamine
Methylone (b, k MDMA)
Pleasurable effects
• Energetic
• Peaceful
• Empathetic
• “Gooey”
• “A six hour orgasm”
NBOMe compoundsSchedule I
PhenylethylamineThe base compound
1st generation
2C-C 2C-B 2C-I
1-(4-chloro-2,5-dimethoxyphenyl)-2-aminoethane
2nd generation
25I-NBOMe
25C-NBOMe
25B-NBOMe
High affinity, high potencyKyriakou et al., 2015.
2-(4-chloro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine
Effects5-H2A receptor agonist
• Paranoia
• Confusion
• Syncope
• Vasoconstriction
• Nausea
• Yawning
• Insomnia
• Tachycardia
• Dystonia and clonus
• Seizures
• Shaking
• Scrambled communication
• Tunnel vision
• Time dilation
• Dilated pupils
DEATH…with as little as one drop
Overdose or Trauma
Expert Committee on Drug Dependence, WHO, 2014.DEA, Drug and Chemical Diversion Section, 2013.
Salvia divinorum
salvinorin A
k opioid agonistpartial D2 agonist
Salvia divinorum—pharmacology
• Ingested by – Chewing
– Drinking juice
– Smoking
– Inhaling vapor
• Effects– Hallucinations
– Psychosis
• Duration– Few minutes
Salvia divinorum—legal status
• Federal—Controlled substance act doesn’t apply
• Illegal in many states—Illinois, Minnesota
• Wisconsin—illegal to grow and sell but legal to possess
COLD REMEDIES
Lots to choose from
Dextromethorphan; chlorpheniramine
Dextromethorphan; guaifenesinAcetaminophen; chlorpheniramine;dextromethorphan
Acetaminophen; chlorpheniramine
Acetaminophen; dextromethorphan;doxylamine
Ingredients
• Acetaminophen—analgesic—not mind altering
• Chlorpheniramine—antihistamine—sedative
• Doxylamine—antihistamine—sedative
• Dextromethorphan—antitussive—dissociative
• Guaifenesin—expectorant—sedative
The key?
The key?
Guaifenesin causes nausea
Lots to choose from
Dextromethorphan; chlorpheniramine
Dextromethorphan; guaifenesinAcetaminophen; chlorpheniramine;dextromethorphan
Acetaminophen; chlorpheniramine
Acetaminophen; dextromethorphan;doxylamine
MISCELLANEOUS
Codeine and Promethazine
• Children who are CYP2D6 rapid metabolizersoverdose
• Codeine + promethazine + soda pop and/or Jolly Rancher = “Sizzurp,” “Lean,” “Purple Drank,” “Syrup.”
• Promethazine in opioid addicts
• Mepergan = meperidine + promethazine
Alcohol sanitizer
• Best ethyl alcohol on the market is 70%
• A few comparisons
– Beer—4-5%
– Wine—12-14%
– Vodka, whiskey, gin—45%
But if you want you want to drink it
Add salt
SYNTHETIC CANNABINOIDS
Synthetic cannabinoids
No psychoactive effects
CB reverse agonist
Anti-emetic; analgesic100-800x more potent
Prototype of JWH
Pfizer
Partial agonist
Full agonistWeak metabolite of THC
CB reverse agonist
Raphael Mechoulam—1960sProfessor of Medicinal Chemistry
The Hebrew University
Pfizer—1979
John W. Huffman—1984 Professor Emeritus, Organic Chemistry
Clemson University
Washington PostAugust 9,2015
Alexandros Makriyannis—2001 Director of Center for Drug Discovery,
Northeastern University
Classes
• HU series—Raphael Mechoulam at Hebrew University
• CP series—Charles Pfizer
• JWH series—John W. Huffman
• AM series—Alexandros Makriyannis
Debruyne & Le Boisselier, 2015
Anandamideananda=joy (Sanskrit)
Activates m opioid and GABA receptors which increase dopamine and serotonin
Acetaminophen metabolized to AM404 which is a potent agonist at TRPV1receptor (analgesia); also may act as reuptake inhibitor for anandamide.
JWH-018
Full agonistPotency: 5x THC
2002: circulated as “spice”2008: banned in Germany after discovering the presence of the compound
JWH-073
Partial agonistDiscovered in circulation 4 weeks after JWH-018 ban
HU-210Hebrew University
Difficult to synthesize100-800x as potent as THC
Seely et al., 2012
XLR-11
Cannabis vs. cannabinoids
• Most symptoms similar to cannabis intoxication– Tachycardia– Reddened eyes– Anxiety– Mild sedation– Hallucinations, acute psychosis– Memory deficits
• Symptoms not typically seen after cannabis intoxication—clenbuterol– Seizures – Hypokalemia – Metabolic acidosis – Hypertension (?)– Nausea/vomiting– Coma – Agitation/violent behavior
Seely et al., 2011
Effects increasing in frequency
• Tachycardia followed by bradycardia
• Seizures
• Stroke
• Cardiac toxicity
• Altered mental status
Three demographic groups
• Marijuana smokers
• Occasional drug users seeking to avoid legal consequences
• Drug naïve, curious experimenters
Seely et al., 2012
Black MambaUniversity of Colorado, 2014
Questions?