What are the kids using? Inhalants, CCCs, Dextromethorphan and other Hallucinogens Kirk Moberg, MD, PhD, FASAM Medical Director, Illinois Institute for Addiction Recovery Clinical Professor, Departments of Internal Medicine and Psychiatry and Behavioral Medicine University of Illinois College of Medicine Illinois 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 Study University of Michigan 44,892 students 382 public and private schools Funding 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 Gas phase Volatile hydrocarbons Aerosol Volatile hydrocarbons Adhesives and thinners Diflouroethane Ether Butane Alkyl nitrites Uses: vasodilator (heart disease); cyanide poisoning; euphoria (especially with cocaine and MDMA); enhance sexual experience Poppers Chloroethane Mechanism of action? • GABA-A • NMDA • Acetyl choline DISSOCIATIVES Dissociative drugs NMDA receptor antagonists The trail to dextromethorphan Antitussive Dissociative Dextromethorphan (DXM) Racemethorphan Opioid Analgesic Levomethorphan Dextrorphan (DXO) Dextromethorphan Dextrophan Levorphanol Levomethorphan DXO pharmacology • N-Methyl-D-Aspartate receptor antagonist • m, k receptor agonist Nitrous oxide Phencyclidine Schedule II Oral Intravenous Inhalation Intranasal Clinical Presentation • Rage • Erythema • Dilated Pupils • Delusions • Amnesia • Nystagmus • Excitation • Skin Dryness Receptors • NMDA receptor antagonist • Dopamine-2 receptor partial agonist HALLUCINOGENS Hallucinogens MDMA Dimethyltryptamine (DMT) Salvia divinorum Psylocybin Serotonin receptors Mescaline 3, 4, 5-trimethoxyphenethylamine Peyote Lophophora 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 plants 4 animals Hallucinogenic toads 5-methoxy-N, N-dimethyltryptamine Bufotenin (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 methamphetamine MDMA Methylone (b, k MDMA) Pleasurable effects • Energetic • Peaceful • Empathetic • “Gooey” • “A six hour orgasm” NBOMe compounds Schedule I Phenylethylamine The base compound 1st generation 2C-C 2C-B 2C-I 1-(4-chloro-2,5-dimethoxyphenyl)-2-aminoethane 2nd generation 25C-NBOMe 2-(4-chloro-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine 25B-NBOMe 25I-NBOMe High affinity, high potency Kyriakou et al., 2015. Effects 5-H2A receptor agonist • Paranoia • Dystonia and clonus • Confusion • Seizures • Syncope • Shaking • Vasoconstriction • Scrambled • Nausea communication • Yawning • Tunnel vision • Insomnia • Time dilation • Tachycardia • 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 agonist partial 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 Acetaminophen; dextromethorphan; doxylamine Acetaminophen; chlorpheniramine; Dextromethorphan; guaifenesin dextromethorphan Acetaminophen; chlorpheniramine 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 Acetaminophen; dextromethorphan; doxylamine Acetaminophen; chlorpheniramine; Dextromethorphan; guaifenesin dextromethorphan Acetaminophen; chlorpheniramine 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 100-800x more potent Anti-emetic; analgesic No psychoactive effects Pfizer CB reverse agonist CB reverse agonist Weak metabolite of THC Prototype of JWH Full agonist Partial agonist Raphael Mechoulam—1960s Professor of Medicinal Chemistry The Hebrew University Pfizer—1979 John W. Huffman—1984 Professor Emeritus, Organic Chemistry Clemson University Washington Post August 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 Anandamide ananda=joy (Sanskrit) Activates m opioid and GABA receptors which increase dopamine and serotonin Acetaminophen metabolized to AM404 which is a potent agonist at TRPV1 receptor (analgesia); also may act as reuptake inhibitor for anandamide. JWH-018 Full agonist Potency: 5x THC 2002: circulated as “spice” 2008: banned in Germany after discovering the presence of the compound JWH-073 Partial agonist Discovered in circulation 4 weeks after JWH-018 ban HU-210 Hebrew University Difficult to synthesize 100-800x 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 Mamba University of Colorado, 2014 Questions? 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