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Will They Turn You into a Zombie? What You Need to Know about Synthetic Drugs Presented by: Gary Seech Educational Objectives At the end of this presentation, participants will be able to: 1. Identify the key characteristics and effects of synthetic drugs, most notably synthetic cannabinoids and synthetic cathinones. 2. Describe the current information available on the availability and patterns of synthetic drug use in the United States. 3 “Tales of Bath Salts and Zombie Cannibalism” Bath Salts made headlines in summer 2012 when a story of possible cannibalism was reported in Miami, FL The Miami-Dade Medical Examiner found no traces of bath salts, LSD, or synthetic marijuana in the perpetrator's system The sole psychoactive substance detected was cannabis (marijuana) 4 Substance Use Continuum Dependence with Addiction Substance Abuse At Risk Use Non-problem Use Abstinence “At Risk” Substance Use Definition: Planned use to intoxication/disinhibition Generally rare adverse consequences Use remains within peer group norms Substance Abuse Definition: ABUSE is a maladaptive pattern of substance use, leading to clinically significant impairment or distress as manifested by one or more behavioral based criteria: failure to carry out obligations at home or work use even when physically dangerous legal problems resulting from use use despite the development of social and interpersonal problems Physical Dependence Definition: PHYSICAL DEPENDENCE is a state of adaptation that is manifested by a drug class specific withdrawal syndrome that can be produced by abrupt cessation, rapid dose reduction, decreasing blood level of the drug, and/or administration of an antagonist. Some Additional Important Terminology Psychological craving Tolerance Withdrawal symptoms 9 Psychological Craving Psychological craving is a strong desire or urge to use drugs. Cravings are most apparent during drug withdrawal. 10 Tolerance Tolerance is a state in which a person no longer responds to a drug as they did before, and a higher dose is required to achieve the same effect. 11 Withdrawal The following symptoms may occur when drug use is reduced or discontinued: Tremors, chills Cramps Emotional problems Cognitive and attention deficits Hallucinations Convulsions Death 12 Addiction is simply: compulsive use despite adverse consequences Addiction: A Vicious Cycle What drives this never ending cycle? Addiction: A Vicious Cycle The Drivers: Addiction: A Vicious Cycle The Drivers: Neurotransmitters and Addictive Drugs of Abuse Neurotransmitter is mimicked by…. Drug of Abuse Acetylcholine Nicotine Serotonin LSD Dopamine Amphetamine Endorphin Morphine GABA Alcohol Natural Rewards Elevate Dopamine Levels 200 % of Basal DA Output NAc shell 150 100 Empty 50 Box Feeding SEX 200 150 100 15 10 5 0 0 0 60 120 180 Time (min) ScrScr BasFemale 1 Present Sample1 2 3 4 5 6 7 8 Number Scr Scr Female 2 Present 9 10 11 12 13 14 15 16 17 Mounts Intromissions Ejaculations Source: Di Chiara et al. Source: Fiorino and Phillips Copulation Frequency DA Concentration (% Baseline) FOOD Accumbens 1100 1000 900 800 700 600 500 400 300 200 100 0 AMPHETAMINE Much greater Activity than any DA Other drug ofDOPAC abuse HVA -causes neurotoxicity 250 NICOTINE 200 Accumbens Caudate 150 100 Accumbens COCAINE DA DOPAC HVA 300 200 100 0 5 hr 250 % of Basal Release 1 2 3 4 Time After Amphetamine % of Basal Release 400 0 % of Basal Release % of Basal Release Effects of Drugs on Dopamine Release 0 1 2 3 4 Time After Cocaine Accumbens 5 hr ETHANOL Dose (g/kg ip) 200 0.25 0.5 1 2.5 150 100 0 0 1 2 3 hr Time After Nicotine 0 0 Source: Di Chiara and Imperato 1 2 3 Time After Ethanol 4hr Dopamine and The Brain’s Reward Circuit Neuroanatomic Substrates of Drug Action How Psychoactive Substances Work Because of their chemical structure, alcohol and drugs have dramatic effects on neurotransmitters in CNS. Effects on: Mental processes Behavior Perception Alertness 22 Commonly Used Psychoactive Substances SUBSTANCE EFFECTS Alcohol (liquor, beer, wine) euphoria, stimulation, relaxation, lower inhibitions, drowsiness Cannabinoids (marijuana, hashish) euphoria, relaxations, slowed reaction time, distorted perception Opioids (heroin, opium, many pain meds) euphoria, drowsiness, sedation Stimulants (cocaine, methamphetamine) exhilaration, energy Club Drugs (MDMA/Ecstasy, GHB) hallucinations, tactile sensitivity, lowered inhibition Dissociative Drugs (Ketamine, PCP, DXM) feel separated from body, delirium, impaired motor function Hallucinogens (LSD, Mescaline) hallucinations, altered perception SOURCE: National Institute on Drug Abuse. 23 “Designer” Psychoactive Substances 24 A Review of Synthetic Cannabinoids and Synthetic Cathinones 25 Synthetic Drugs Not really “Spice,” “Bath Salts,” or “Incense” Chemically-based; not plant derived Complex chemistry Constantly changing to “stay legal” Need to prove “intended to use” to convict in some areas 26 Marijuana (Cannabis) Often called pot, grass, reefer, MJ, weed, A mixture of the dried, shredded leaves, stems, seeds, and flowers of Cannabis sativa— the hemp plant Most commonly used drug in the U.S. Delta-9-tetrahydrocannabinol (THC) is the main active ingredient in marijuana Common effects include: euphoria, relaxation, heightened sensory perception, laughter, altered perception of time, and increased appetite May also produce anxiety, fear, distrust, or panic, and can lead to severe mental health problems for some users. 27 herb Synthetic Cannabinoids (a.k.a. Spice) Wide variety of herbal mixtures Marketed as “safe” alternatives to marijuana Brand names include: K2, fake weed, Yucatan Fire, Skunk, Moon Rocks Labeled “not for human consumption” Contain dried, shredded plant material and chemical additives that are responsible for their psychoactive effects. 28 Synthetic Cannabinoids (Spice) Mainly abused by smoking (alone or with marijuana); may also be prepared as an herbal infusion for drinking. The five active chemicals most frequently found in “Spice” products have been classified by the DEA as Schedule I controlled substances, making them illegal to buy, sell, or possess. 29 Timeline of Synthetic Cannabinoids and Spice Products SOURCE: Fattore & Fratta. (2011). Frontiers in Behavioral Neuroscience, 5(60), 1-12. 30 Factors Associated with Spice Products’ Popularity They induce psychoactive effects They are readily available in retail stores and online The packaging is highly attractive They are perceived as safe drugs They are not easily detectable in urine and blood samples SOURCE: Fattore & Fratta. (2011). Frontiers in Behavioral Neuroscience, 5(60), 1-12. 31 Synthetic Cathinones: “Bath Salts” Could be MDPV, 4-MMC, mephedrone, or methylone Sold on-line with little info on ingredients, dosage, etc. Advertised as legal highs, legal meth, cocaine, or ecstasy Taken orally or by inhaling Serious side effects include tachycardia, hypertension, confusion or psychosis, nausea, convulsions Labeled “not for human consumption” to get around laws prohibiting sales or possession 32 Actual Product Names “Ivory Wave” “Purple Wave” “Vanilla Sky” “Bliss” “White Lightening” “Blizzard” “Hurricane Charlie” Also known as “PLANT FOOD” 33 What Is The Experience Like? Agitation Paranoia Hallucinations Chect Pains Suicidal Thoughts Muscle Spasms Increased blood pressure/pulse 34 Treating M.D.’s Comment “If you take the very worst of some of the other drugs – LSD and Ecstasy with their hallucinations/delusional type properties, PCP with the extreme agitation, superhuman strength and competiveness, as well as the stimulant properties of cocaine and meth and take them all together, this is what you get. It is absolutely ugly.” 35 Sources and Continuing Availability A number of synthetic marijuana and bath salt products appear to originate overseas and are manufactured in the absence of quality controls and devoid of governmental regulatory oversight. The large profits from sales, plus the fact that these chemicals can be easily synthesized to stay one step ahead of control, indicate there is no incentive to discontinue retail distribution of synthetic cannabinoid products under the current statutory and regulatory scheme. 36 Federal Efforts to Ban Synthetic Drugs Mar 2011: Five synthetic cannabinoids were temporarily categorized as Schedule I substances under the CSA. Oct 2011: DEA exercised its emergency scheduling authority to control some of the synthetic substances used to manufacture bath salts; these synthetic stimulants are now designated as Schedule I substances. Dec 2011: House of Representatives approves the Synthetic Drug Control Act (HR 1254). July 2012: Congress passed and President Obama signed the Synthetic Drug Abuse Prevention Act. 37 Texas Poison Control Exposures and Effect of Controls Synthetic Cannabis Synthetic Cathinones 38 39 “People high on these drugs can get very agitated and violent, exhibit psychosis, and severe behavior changes…some have been admitted to psychiatric hospitals and have experienced continued neurological and psychological effects.” (Dr. Rick Dart, AAPCC President) 40 Cannabis vs. Cannabinoids: Effects Seen in Clinical Cases Most symptoms are similar to cannabis intoxication: Symptoms not typically seen after cannabis intoxication: Tachycardia Seizures Reddened eyes Hypokalemia Anxiousness Hypertension Mild sedation Nausea/vomiting Hallucinations Agitation Acute psychosis Violent behavior Memory deficits Coma 41 Clinical Symptoms of Synthetic Cathinone Use in Patients Admitted to the Emergency Department (N=236) Agitation 82% Combative/Violent behavior 57% Tachycardia 56% Hallucinations 40% Paranoia 36% Confusion 34% Myoclonus/Movement disorders 19% Hypertension 17% Chest pain 17% CPK elevations 9% 42 The Epidemiology of Synthetic Drug Use 43 Calls Received by U.S. Poison Control Centers for Human Exposure to Synthetic Marijuana The number of calls in 2011 were more than double that in 2010 6,959 3,821 2,906 2010 2011 Jan-July 2012 44 45 Calls Received by U.S. Poison Control Centers for Human Exposure to Bath Salts, 2010 to July 2012 The number of calls in 2011 were over 20 times that in 2010 6,138 2,078 304 2010 2011 Jan-July 2012 46 Challenges with Chromatography Screening Lack of availability of the reference standard for new drugs Variable quality of reference standards Lack of purity and labeled internal standards Chemical similarity of new drugs within a class requires great care with identification Sensitivity (correctly IDs the drug) 47 Other Notable Synthetic Drugs – “New And Old” 48 MDMA (Ecstasy) 3, 4-methylenedioxy-methamphetamine Street terms: Adam, E, X, XTC, love drug, Molly A synthetic, psychoactive drug with both stimulant and hallucinogenic properties similar to methamphetamine and mescaline Adverse effects: enhanced physical activity, sweating, lack of coordination, mental confusion, jaw clenching, hyperthermia, and agitation 49 2C-Phenethylamine A broad range of compounds that share a common phenylethan-2-amine structure. Some are naturally occurring neurotransmitters (Dopamine and Epinephrine), while others are psychoactive stimulants (Amphetamine), entactogens (MDMA), or hallucinogens (the 2C-X series of compounds). 2 C-X can be snorted or dissolved into a liquid and placed on blotter paper under the tongue. May last 6-10 hours; onset takes 15 min-120 to 2 hours. Reports of seizures and renal failure. 50 Piperazines Frenzy, Bliss, Charge, Herbal ecstasy, A2, Legal Z, Legal E. Mainly available over internet and sold as ecstasy pills that are “safe.” Two classes: (1) benzylpiperazines (BZP) and (2) phenylpiperazines (TFMPP). Mimics effects of ecstasy (MDMA); dangerous with seizure disorders, psychiatric illness, or coronary disease. Adverse events included hypertension, reduced consciousness, psychotic episode, hallucinations, tachycardia, hyperthermia, coma. Could be toxic if combined with MDMA or amphetamines. 51 A Few Other Psychoactive Substances to Throw in the Mix… Kratom – opioid-like effects Salvia divinorum – hallucinogenic effects Methoxetamine – “legal ketamine” 52 Phencyclidine PCP, Angel Dust, Killer Weed Dissolved in embalming fluid (“Fry,” “Amp,” “Water, Water”) Swallowed, sniffed, smoked on joints dipped in “Fry” Users report out-of-body strength 53 DXM What is ? Dextromethorphan is a psychoactive drug found in common over the counter cough medicines. 54 Dextromethorphan (DXM) Dextromethorphan’s slang names include “Robo”. At high doses, may produce dissociative hallucinations (distance from reality, visual effects with eyes open and closed; perceptual changes, drug liking, mystical-type experiences similar to use of psilocybin. Can also produce tachycardia, hypertension, agitation, ataxia, and psychosis at high doses. Users of DXM engage in “dose dependent” behaviors in which they try to gauge the amount of the drug they take to produce the desired effects, which they call “plateaus”. Plateau is the mildest effect and the 5th plateau will guarantee a trip to the hospital. 55 56 Sample Clinical Treatment Protocol for Synthetic Cannabinoid Users Direct individual to emergency room via ambulance Consult a regional Poison Control Center Acute management consists of: Supportive care with the use of benzodiazepines, if needed, to control agitation and anxiety Observe until resolution of abnormal vital signs, vomiting, and psychiatric symptoms 57 Sample Clinical Treatment Protocol for Synthetic Cathinone Users Supportive care Aggressive sedation with benzodiazepines (for agitation, seizures, tachycardia, and hypertension) Significant hyperthemia may require passive or active cooling. Lab studies including electrolytes, renal and liver function tests, cardiac markers, and creatine kinase should be considered. 58 What do you do if someone has taken a Spice Product or Bath Salts? Call your local poison center at 1-800-222-1222 57 poison centers around the country have experts waiting to answer your call. Experts can help you decide whether someone can be treated at home, or whether he or she must go to a hospital. Dial 9-1-1 immediately if they: Stop breathing Collapse Have a seizure …or if they have taken one of these and are having physical symptoms or behaving in a way that is concerning to you 59 In Summary: Key Points Despite widespread Internet availability and use among certain populations, health care providers remain largely unfamiliar with Spice products and Bath Salts. Research is needed to better understand the side effects and long-term consequences associated with the use of synthetic cannabinoids and synthetic cathinones More toxicological identification of these new drugs, more information on the sources of them, as well as their distribution and patterns of use is needed to curtail future increases in use. 60 In Summary: Key Points Despite widespread Internet availability and use among certain populations, health care providers remain largely unfamiliar with Spice products and Bath Salts. Research is needed to better understand the side effects and long-term consequences associated with the use of synthetic cannabinoids and synthetic cathinones More toxicological identification of these new drugs, more information on the sources of them, as well as their distribution and patterns of use is needed to curtail future increases in use. 61 Resources for Continued Learning American Association of Poison Control Centers, www.aapcc.org Drug Enforcement Administration, www.dea.usdoj.gov European Monitoring Centre for Drugs and Drug Addiction, www.emcdda.europa.eu National Institute on Drug Abuse, www.nida.nih.gov Office of National Drug Control Policy, www.ondcp.org Refer to the Synthetic Drugs Reference List** 62