K2, BATH SALTS & BEYOND

K2, BATH SALTS & BEYOND "The U.S. has encountered over 200 new substances over the past four years," "Our chemists are finding multiple drugs, multiple compounds when we make purchases of these drugs. John Scherbenske DEA Synthetic Drugs & Chemicals section Classification Difficulties K2/Spice Bath Salts Herbal Highs Legal Highs Designer Drugs Synthetics Research Chemicals New Psychoactive Substances Novel Psychoactive Substances Objectives Identify current trends in psychoactive substance abuse Explain the pharmacology of new psychoactive substances Describe potential clinical effects and medical interventions related to new psychoactive substance toxicity Identify regulatory challenges posed by the new psychoactive substances 1

"It was the best of times, it was the worst of times Charles Dickens A Very Incomplete History of Cannabinoids Heaven and Hell Wolf in Sheep's Clothing... Better than Weed! First Time Very Impressed It was a terrifying. Blissful trip. Violently Puking and Delirious Hallucinations Terrifying, Will Never Touch It Again High on a Wave on a Dream The Night I Killed My Friends From mildly pleasant to fear of death First Time A fantastic cannabinoid Blonde (vaporized) made me feel a full on weed high Brain melting pain just isn't worth it The fear, visuals, and tremors continued The battle between good and evil in my head Cannabis medical and recreational use dates back to B.C. 1619 Jamestown farmers required to grow hemp 1850 1942 Cannabis listed in United States Pharmacopeia 1906 1937 Local, state, and federal regulation of cannabis enacted 1906 present Local, state, and federal efforts to end regulation initiated 1964 Δ 9 Tetrahydrocannabinol (THC) identified 1970 classified as schedule I controlled substance in U.S. 1970s present R&D of novel synthetic cannabimimetic agents 1985 FDA approves synthetic THC pharmaceutical agent dronabinol Late 1980s/Early 1990s endocannabinoid system defined THC Endocannabinoid System Basics CB1 receptors Distributed throughout the brain Activation affects the release of acetylcholine, L glutamate, γ aminobutyric acid, noradrenaline, dopamine and serotonin Responsible for clinical effects on regulation of cognition, memory, motor activities, nociception, and nausea and vomiting CB2 receptors Located peripherally in immune system tissues, B lymphocytes, peripheral nerve terminals, and the vas deferens. Believed to participate in the regulation of immune responses and inflammatory reactions. Goldfrank s Toxicologic Emergencies, 9 th edition Proposed Therapeutic Uses for Cannabinoids Anxiety Asthma Depression Epilepsy Glaucoma Traumatic head injury Insomnia Migraine headaches Multiple sclerosis Muscle spasticity and spasms Neurological disorders Pain Parkinson disease Tourette syndrome Anorexia cachexia syndrome secondary to AIDS * Resistant nausea and vomiting associated with cancer chemotherapy** *FDA approved indication for dronabinol **FDA approved indication for dronabinol & nabilone THC Synthetic Cannabinoids HU-210, HU-211 JWH-018, JWH-073 CP 47,497 WIN 55,212-2 AM-2201 Raphael Mechoulam, Ph.D. Hebrew University John W. Huffman Ph.D. Clemson University Charles Pifzer Pharmaceutical Company Sterling Winthrop Pharmaceuticals Alexandros Markiyannis Ph.D. Northeastern University Synthetic Cannabinoids Initially marketed as 100s of different brand name products disguised as incense, potpourri, herbal smoke blends Commonly sold in sachets contain 3 grams of vegetable matter which are treated with one or more synthetic cannabinoids (but not always vegetable matter in appearance) Most commonly smoked, but reports of ingestion, insufflation, rectal and parenteral use. Cost of 3 grams is between $20 50, utilized dose varies from user to user Original labeling listed multiple herbal compounds and always with some wording of not for human consumption JWH 018 CP 47,497 HU 210 AM 2201 2

A Very Incomplete History of Cathinone Catha edulis (Khat, Qat) native to east Africa & Arabian Peninsula contains the phenethylamine alkaloid cathinone Centuries old history of use for its stimulant and mild euphoria effects Library of synthetic compounds derived from base structure, majority not fully investigated due to toxicities seen in early testing Mechanism of action postulated to involve varying degrees of release and blocked reuptake of dopamine, norepinephrine and serotonin 96 Hours of Fun Hell Anxiety and Insanity Stimulated, Alert, Socially Loose Most Devilish Powdered evil I Went to Hell and I Saw the Abyss Vivid Hallucinations and Intense Paranoia Better than Meth Social Withdrawal, Stereotypy and Psychosis Seemingly Real Paranoid Hallucination Hell Structural Similarity of Amphetamines and Cathinones Neurotransmission Drug action at presynaptic reuptake transporters results in increased cleft concentrations of dopamine, norepinephrine and/or serotonin by either blocking reuptake (cocaine) or serving as a transporter substrate resulting in decreased uptake and increased monoamine release (amphetamine) DAT (dopamine active transporter) NET (norepinephrine transporter) SERT (serotonin transporter) DA, NE & 5HT Dopamine, serotonin and norepinephrine in the brain can become mind altering, where: Dopamine is associated with reward systems, alertness, and motor function Serotonin is associated with our mood, perception, temperature regulation, and motor and sexual function. Norepinephrine is associated with concentration and responding actions (fight orflight response) Synthetic Cathinones Initially marketed as 100s of different brand name products disguised as bath salts, plant food, or research chemicals Commonly sold in small jars or sachets containing 500 mg of white or brown powders. Most commonly insufflated or ingested, but reports of rectal and parenteral use. Cost of 500 mg is between $20 50, utilized dose varies from user to user and from one specific agent to another Labeling typically with some wording of not for human consumption 3

Why are they called Bath Salts? Legal Highs Coming to America Savvy Entrepreneurs Media Hysteria and Hype, or Cause for Concern? Fake Weed "K2" Can Cause Hallucinations Study Also Says Vomiting, Seizures Among Possible Reactions to Synthetic Drug After Indianola teen's suicide, Iowa officials set sights on banning K2 Doctors concerned over possible link of K2, heart damage Killing "spice" before it kills again Students Hospitalized After Smoking Synthetic Marijuana Synthetic drugs send thousands to ER "CDC does not know of a virus or condition that would reanimate the dead (or one that would present zombie like symptoms)," CDC spokesman David Daigle YEAR Number of Synthetic Cannabinoid Calls 2010 2,906 2011 6,968 2012 5,230 2013 2,222 (as of Oct 31) YEAR Number of Synthetic Cathinone Calls 2010 306 2011 6,137 2012 2,691 2013 833 (as of Oct 31) 4

User Demographic K2 Bath Salts Arkansas Designer Drug Workgroup Statewide Surveillance K2 Product Testing Human Specimens Compiling Clinical Data & Samples Testing of Human Specimens State Regulations Translational Science Quantitative Study Different Products Basic Research Poison Control Center Quantitative Study Same Product, Different Lot Hot Spots 5

Forensic Summary No quality control Deceptive labeling Compounds vary from product to product Concentrations of the compounds vary within the package Hot Spots Concentrations of the compounds vary between different lots of the same products Adulterants New compounds ever emerging Federal Analog Act of 1986 U.S. Regulatory Timeline 1 st state (Kansas) designates JWH-018 & JWH-073 Schedule I DEA temporarily schedules 5 specific SC as schedule I 1 st state (Louisiana) designates 6 synthetic cathinones Schedule I Synthetic Drug Abuse Prevention Act of 2012 permanent schedules 15 specific SC, cannabimimetics, MDPV, MMC and nine 2C series schedule I March 2010 July 2010 January 2011 March 2011 October 2011 July 2012 April 2013 AR Board of Health makes sale of synthetic marijuana products a misdemeanor CSA = Controlled Substance Act (Federal) SC = synthetic cannabinoid MDPV = methylenedioxypyrovalerone MMC = methylmethcathinone AR Act 751 schedules 7 SC schedule VI and 6 cathinones schedule I DEA schedules of MDPV, MMC, & methylone as schedule I DEA schedules UR144, AKB48, & XLR11 as schedule I People like to take drugs and will pay good money for the opportunity to do so and [these drugs are difficult to regulate] because chemists are generally a lot smarter than lawmakers. William Fantegrossi, Ph.D. Behavioral pharmacologist 6

A Characterization of Synthetic Cannabinoid Exposures Reported to the National Poison Data System in 2010 (Hoyte CO, et. Ann Emerg Med 2012 May 8. [Epub ahead of print]) Symptom N=1,353 (%) Tachycardia 541 (40) Agitation/irritability 317 (23.4) Vomiting 207 (15.3) Drowsiness/lethargy 183 (13.5) Confusion 164 (12) Nausea 139 (10) Hallucination/delusion 127 (9.4) Hypertension 110 (8.1) Dizziness/vertigo 99 (7.3) Chest pain 64 (4.7) Seizure 52 (3.8) Treatment N=1,353 (%) IV fluid administration 343 (25.3) Benzodiazepines 217 (16) Supplemental oxygen 79 (5.8) Antiemetic 64 (4.7) Duration of clinical effects N=907 (%) Less than 8 hours 711 (78.4) Between 8 and 24 hours 151 (16.6) More than 24 hours 44 (4.9) Comparison of Acute Clinical Toxicity following recreational dose K2/Spice Marijuana Increased Heart Rate Increased Heart Rate Altered mental status Altered mental status Anxiety Ataxia Agitation Nausea/vomiting Decreased capacity to do Tremor complex tasks Vs. Pallor Injected conjunctiva Hallucinations Seizures (infrequent) Dysrhythmia (infrequent) Renal failure (rare) Myocardial infarct (rare) K2 vs. THC Dose Response Relationships are not Equal K2 THC Synthetic Cannabinoid Treatment Considerations De escalation techniques (if indicated) ABCs Benzodiazepines Correct fluid/electrolytes Supportive care Contact regional poison center 1 800 222 1222 Laboratory CMP, CBC EKG UA ABG? Standard urine tox screen? Specialized urine tox screen??? Characterization of Bath Salt exposures reported to select U.S. Poison Centers SYMPTOMS Spiller HA, et al. (KY and LA) N= 236 Murphy CM, et al. (NC) N=409 Forrester MB, et al. (TX) N=292 Agitation 194 (82.2%) 206 (50.4%) (37.3%) Tachycardia 132 (55.9%) 218 (53.3%) (45.5%) Hallucinations 94 (39.8%) 109 (26.7%) (17.8%) Confusion 83 (35.2%) (12.3%) Hypertension 41 (17.3%) 103 (25.2%) (19.2%) Chest pain 40 (16.9%) (7.5%) Mydriasis 31 (13.1%) CPK elevation 22 (9.3%) Vomiting (9.4%) TREATMENTS Benzodiazepine 125 (53%) 188 (46%) (38.4%) Sedation antipsychotic = 47 (19.9%) 55 (13.4%) (6.8%) propofol =10 (4.2%) haloperidol = 40 (9.8%) Alkalinization 16 (3.9%) Antihistamine 17 (4.2%) Intubation 15 (3.7%) Designer Stimulant Clinical Concerns Tachycardia/Dysrhythmia Hypertension Mydriasis Fever Chest pain Agitation Hallucinations Fluid/Electrolyte balance Dystonia/Myoclonus/Catatonia Seizures Extreme paranoia/delusions (may be prolonged >7 days) Rhabdomyolysis Sleep deprivation 7

Designer Stimulant Treatment Considerations ABCs De escalation techniques (if indicated) Benzodiazepines Benzodiazepines Benzodiazepines Benzodiazepines Antipsychotics?? Propofol??? Diphenhydramine (for clonus) External cooling Correct fluid/electrolytes Supportive care Contact regional poison center (1 800 222 1222) Laboratory CMP, CBC CK, Troponins? EKG UA ABG? Standard urine tox screen? Specialized urine tox screen??? Pitfalls and Caveats Product confusion Variation in dose of active agent Combination products Coingestants & adulterants Acute vs. Chronic vs. Acute on Chronic January 2012 Situation Report Cases reported to poison centers decreasing Access/availability not as open Analytic testing improved but of limited value No understanding of long term complications Active compounds continued to change and significant risk in assuming active compounds based on route of use, physical form, name, or past experience. Phenazepam USSR 1974 developed benzodiazepine Never marketed in the U.S. Not specifically listed on U.S. CSA Schedule I substance in AR & LA ~60 hour t ½ Texarkana, spring 2012 Phenazepam Classic BZD toxicity profile (cns depression, ataxia, confusion.respiratory depression unlikely) Coingestion with other depressants significantly increases risk of respiratory depression Symptomatic and supportive care DO NOT utilize flumazenil due to risk of precipitation of withdrawal or unmasked other coingested agents toxicity Educate patient on prolonged duration of action and need to avoid all CNS depressants for prolonged period following use 8

United Nations Office on Drugs and Crime www.drugs-forum.com http://www.mixmag.net/words/features/mixmags global drug survey the results http://www.mixmag.net/words/features/mixmags global drug survey the results Dark Web TOR Project: Anonymity Online 9

Hydra Effect Arkansas Forensic Investigation Jan 2010 Dec 2012 3871 Items 1536 Cases 47 Synthetic Cannabinoids 18 Designer Stimulants 7 Designer Hallucinogens Seely KA, Patton AL, Moran CL, et al. Forensic Sci Int [in press] 10

Non cathinone Phenethylamines MDMA 2C series NBOMe s MDMA 3,4 methylenedioxymethamphetamine ecstasy, molly, E, XTC MoA: like amphetamines, but much more potent for 5HT than DA or NE Originally synthesized 1890s, gained popularity starting in the 1980s as one of the most popular club drugs PO, sold as tablets Most common 75 125mg $10 25 per dose Onset 20 90min, duration 3 5hrs, hangover up to 72hrs Erwoid.org MDMA Desired effects: Empathogenic/Entactogenic effects, increased awareness of senses, euphoria Negative effects Muscle tension, insomnia, teeth grinding, tongue/cheek chewing, hyperthermia, dehydration, hyponatremia, N/V, posttrip crash Warnings Substrate/inhibitor of CYP 2D6 (might influence toxicity) Case report of death due to interaction w/ ritonavir Some individuals react more sensitively Balance dehydration vs. over hydrating hyponatremia Intensive Care Med (2012) 38:1239 1240. Ecstasydata.org MDMA $40 for pressed tabs sold as ecstasy, $100 for anything else 2-3 weeks, results posted on website Data for 2013: only 34.3% of products sold as ecstasy contained MDMA by itself, and 44.5% contained no MDMA at all 2004, PSE and methamphetamine 2008, Diphenhydramine, ketamine, MDMA 2013, APAP, caffeine, MDMA 2013, MDMA Erwoid.org 11

Alexander Shulgin Ph.D. chemist/pharmacologist Godfather of Psychedelics Credited with introducing MDMA to psychiatry in the 70s Created >200 psychoactive compounds Published PiHKAL in 1991 2C E 2C Series Phenethylamines (2,5 dimethoxy (whatever) phenethylamine) 2C B 2C F 2C T 32 2C Series Phenethylamines 5 HT2A receptor agonists 2C B, 2C C, 2C D, 2C E, 2C I Synthesized in 1970s and gained popularity in mid 1990s in Europe after MDMA made illegal Many 2C compounds are DEA schedule 1 in U.S. (2012) Sold as tabs or powder, $10 30/dose Dose 10 40mg Onset 45 75min (slower if full stomach) Duration 4 8hrs 2C Series Desired effects Euphoria, feelings of empathy, closed and open eye visuals, body tripping Less dissociative than LSD, but less directed than MDMA Negative effects N/V, increased mucus production, insomnia, sweating/chills, paranoia/panic, hallucinations Toxicity delirium, hyperthermia, seizures Pharm World Sci. 2004 Apr;26(2):110 3 Erwoid.org J Med Toxicol. 2013 Jun;9(2):172 8 Erwoid.org NBOMe s N Bomb potent 5HT2A agonist NOT TO BE CONFUSED W/ 2C SERIES N (2 methoxy)benzyl derivatives 25B NBOMe, 25I NBOMe, etc No history of human use prior to 2010 SL on blotter paper or insufflated Onset 0 15min (shorter if insufflated) Duration 4 8hrs Active at microgram dose (50 250 mcg threshold dose) 25C NBOMe and 25I NBOMe added to Arkansas schedule I controlled list in 2013, but is not specifically listed at the federal level A little NBOME Math $90 200/gram (Silk Road 09/13) 340 grams in 12 oz $30,600 $68,000/12 oz 50 250 mcg threshold dose 6.8 million 1.36 million doses/12 oz $0.0045 $0.0225/dose @ $90/g $0.01 0.05/dose @ $200/g Erwoid.org 12

NBOMe s Desired effects Open/closed eye visuals, euphoria, life changing spiritual experiences Negative effects Nausea, insomnia, panic/fear/paranoia, unwanted and overwhelming feelings Toxicity stimulant and serotoninergic features Tachycardia, hypertension, agitation, aggression, seizures, and hyperthermia Multiple reported fatalities in the US Piperazines Broad class of therapeutic compounds which include antihelmintics, antivertigo agents, erectile dysfunction agents, and several stimulants Three piperazines used as NPS: BZP N benzylpiperazine* TFMPP Trifluoromethyhlphenylpiperazine mcpp Chlorophenylpiperazine *BZP is a Schedule I substance on US CSA Erwoid.org BZP, TFMPP, & mcpp Increase dopamine and norepinephrine concentrations via reuptake inhibition Increase serotonin concentrations by stimulation of release and inhibition of reuptake TFMPP & mcpp also act as serotonin agonist BZP and TFMPP typically used in combination as TFMPP has limited effect when taken alone BZP, TFMPP, & mcpp Beneficial 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 Toxicity/Symptoms dilated pupils, blurred vision, dryness of the mouth, pruritus, confusion, agitation, tremor, extrapyramidal symptoms, headache, dizziness, anxiety, insomnia, vomiting, chest pain, hallucinations, tachycardia, hypertension, palpitations, hyperventilation, sweating The more severe toxic effects include psychosis or adverse psychiatric events, arrhythmia, seizures, hyperthermia, serotonin syndrome, rhabdomyolysis and renal dysfunction. Tryptamines Natural and synthetic hallucinogens Serotonin receptor agonists and reuptake inhibitors 1997, 55 compounds 13

Tryptamines Tryptamines DMT 5 MeO DMT Beneficial Effects immersive experiences intense open eye visuals and kaleidoscopic patterning powerful "rushing" of sensation radical perspective shifting profound life changing spiritual experiences Load Universe into Cannon. Aim at Brain. Fire. Toxicity/Symptoms overly intense experiences Nausea and vomiting difficulty integrating experiences overwhelming fear Onset and intensity can lead to self harm elevated blood pressure, heart rate, pupil diameter, and rectal temperature Seizures (rare) 5 MeO DIPT Psilocybin 5 MeO DALT & 5 MeO DiPT 5 methoxy diisopropyltryptamine (5 MeO DiPT) Foxy/Foxy Methoxy Oral/insufflation/smoked Tablets, capsules and powders Onset 30 min, Peak 60 90 min, Duration 3 6 hr NFLIS reports increased from 72 in 2010 to 3,271 in 2011 N,N diallyl methoxytryptamine (5 Meo DALT) Not specifically listed on US CSA Management of Hallucinogenic Exposures ABCs De escalation techniques Supportive measures mainstay of care Rapid sedation, fluid resuscitation and cooling for patients with excited delirium Benzodiazepines Neuroleptics Ketamine? Propofol? Acetylfentanyl (Desmethylfentanyl) Opioid analgesic 5 times more potent that heroin, but less potent than fentanyl Analgesia, alteration in mood, euphoria, drowsiness, respiratory depression, suppression of cough reflex, constriction of pupils (miosis), and impaired gastrointestinal motility Very minor process impurity in the synthesis of fentanyl Acetylfentanyl (Desmethylfentanyl) May 2013, Montreal Police report seizure of 12,000 tablets and another 1,500 kg of powder Acetylfentanyl is not currently scheduled under the Controlled Substance Act (CSA). However, if intended for human consumption, acetylfentanyl may be treated as a controlled substance analogue 14

Acetylfentanyl (Desmethylfentanyl) MMWR Morbidity and Mortality Weekly Report. 2013 Aug 30;62(34):703 4 14 confirmed deaths in Rhode Island between March and May 2013. 50 confirmed deaths in Pennsylvania in 2013 October 2013, Jefferson Parrish, LA officials link 5 deaths to acetylfentanyl Acetylfentanyl (Desmethylfentanyl) Should be suspected in the setting of classic opioid triad CDC request all fentanyl positive screens have subsequent GC/MS investigation for acetylfentanyl Symptomatic and supportive care May require large than typical dose of naloxone to obtain clinical response CDC hints at increasing naloxone inventory Breaking Worse: Desomorphine KROKODIL "A heroin addict has a chance to become cured of his or her addiction it is possible in 3 of 100 cases. Desomorphine kills all of its victims and it kills them very quickly. A heroin addict may live up to six or seven years. The life of a desomorphine addict is much shorter two years maximum. Dr. Anatoly Berestov Desomorphine KROKODIL Patented in 1932 in the US 8 10 times more potent than morphine Rapid onset, effects last ~2 3 hours Produced via crude clandestine process using codeine as a precursor Notoriously impure and contaminated with toxic substances (solvents, lye, HCL, Iodine, Phosphorus) Schedule I under US CSA Poorer Man s Heroin Economic alternative to heroin Reports of use in Russia date back to 2003. In 2010 estimated that up to 1 million people in Russia used krokodil. Arizona Sept 2013, First alleged US report Multiple ongoing US investigations Desomorphine Beneficial Effects Euphoria Pain relief Sedation Toxicity/Symptoms Skin necrosis turning the skin scaly and green, like a crocodile, at injection site Abscesses Sepsis Gangrene and amputations are common Respiratory depression High abuse potential 15

Methoxetamine MXE, Mexxy, special M Dissociative anesthetic, NMDA receptor antagonist Insufflated, SL, or IM all very tentative Duration 2 7hrs, onset 10 90min, after effects 2 48hrs Dose ranges from 10 100mg 1 st use reported in 2010 DEA unscheduled Methoxetamine Desired effects Euphoria, calmness/serenity, open/closed eye visuals, distortion of sensory perceptions Negative effects Severe dissociation, confusion, blacking out (forgetting having taken drug), severe sensory distortion, N/V, loss of consciousness Toxicity dissociative and sympathomimetic bladder safe alternative to ketamine (unproven) PLoS One. 2013; 8(3): e59334 Erowid.org References Nelson, LS, et. al. (2010) Goldfrank s Toxicologic Emergencies, 9th Edition. New York: McGraw Hill Advisory Council on the Misuse of Drugs (2009), Consideration of the major cannabinoid agonists. Advisory Council on the Misuse of Drugs, Home Office, London. Available at: http://www.homeoffice.gov.uk/publications/agencies public bodies/acmd1/acmd report agonists European Monitoring Centre on Drugs and Drug Addiction. Thematic Paper. Understanding the Spice phenomenon. Available at: http://www.emcdda.europa.eu/attachements.cfm/att_80086_en_spice%20thematic%20paper%20 %20final%20version.pdf Advisory Council on the Misuse of Drugs (2010), Consideration of the cathinones, 31 March. Advisory Council on the Misuse of Drugs, Home Office, London. Available at: http://www.homeoffice.gov.uk/publications/drugs/acmd1/acmd cathinodes report 2010 Whalen J. In Quest for Legal High, Chemists Outfox Law. The Wall Street Journal. October 29, 2010. at: http://online.wsj.com/article/sb10001424052748704763904575550200845267526.html European Monitoring Centre on Drugs and Drug Addiction. Drug profiles. Available at: http://www.emcdda.europa.eu/drug profiles References European Monitoring Centre on Drugs and Drug Addiction. Drug profile on synthetic cannabinoids. Available at: http://emcdda.europa.eu/publications/drug profiles/synthetic cannabinoids European Monitoring Centre on Drugs and Drug Addiction. Drug profile on synthetic cathinones. Available at: http://www.emcdda.europa.eu/publications/drug profiles/synthetic cathinones Fattore L, Fratta W. Beyond THC: The New Generation of Cannabinoid Designer Drugs. Front Behav Neurosci. 2011; 5:60. DOI:: 10.3389/fnbeh.2011.00060 Spiller HA, et al. Clinical experience with and analytical confirmation of bath salts and legal highs (synthetic cathinones) in the United States. Clin Toxicol 2011 Jul;49;499 505. Olives TD, et al. Bath Salts: The Ivory Wave of Trouble. West J Emerg Med. 2012 Feb;13:58 62. Murphy CM, et al. Bath Salts and Plant Food Products: the Experience of One Regional US Poison Center. J Med Toxicol 2012. DOI: 10.1007/s13181 012 0243 1 Forrester MB, Leung L, Kleinschmidt K. Comparison of synthetic cathinone and methylendioxymethamphetamine (MDMA) exposures. [abstract 293]. Clin Toxicol 2012; 50:706. University of Michigan, 2012 Monitoring the Future Study. www.drugabuse.gov/relatedtopics/trends statistics/monitoring future References Hoyte CO, et al. A Characterization of Synthetic Cannabinoid Exposures Reported to the National Poison Data System in 2010. Ann Emerg Med. 2012 May 8. S. 3187. Food and Drug Administration Safety and Innovation Act. 112th United States of America Congress, 2011 2012. Available at: http://www.govtrack.us/congress/bills/112/s3187/text Act 751. Act 751. An Act Regarding Substances in Schedule I and Schedule VI; To Declare an Emergency; and for other purposes. 88th General Assembly of the State of Arkansas legislature. Available at: http://www.arkleg.state.ar.us/assembly/2011/2011r/acts/act751.pdf American Association of Poison Control Centers press releases and data. Available at: www.aapcc.org www.deadiversion.usdoj.gov/drug_chem_info/index.html www.unodc.org/documents/scientific/nps_2013_smart.pdf www.erowid.org www.aapcc.org References www.torproject.org www.ecstasydata.org www.drugs forum.com www.bryanlewissaunders.org/drugs/ www.emcdda.europa.eu www.gov.uk/government/organisations/advisory council on the misuse of drugs http://www.mixmag.net/words/features/mixmags global drug survey the results Shulgin, Alexander; Ann Shulgin (September 1991). PiHKAL: A Chemical Love Story. Berkeley, California Power, Mike (January 2013) Drugs 2.0: The Web Revolution That s Changing How the World Gets High Seely KA, Patton AL, Moran CL et. al. Forensic investigation of K2, Spice, and bath salt commercial preparations: A three year study of new designer drug products containing synthetic cannabinoid, stimulant, and hallucinogenic compounds. Forensic Sci Int [in press] 16