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Lisa Marzilli, PharmD, CDOE Clinical Pharmacist Research and Education Synthetic Cannabinoids (SC) • Stimulants • •Natural khat plant •Synthetic • Bath Salts/Ivory Wave • Psychedelic stimulants (2CE, 2CB, 2CI…) Salvia • Kratom • Various other chemicals/substances • 1 Designer drug is a term used to describe drugs which are created in order to get around existing laws by: Modifying the molecular structures of existing drugs Developing drugs with entirely different chemical structures that produce similar effects to illegal recreational drugs Quest for ‘Legal High’ Chemists Outfox Law, Wall Street Journal Original Modified Legal • Ritalin™ • (methylphenidate) Ritalin™ • Nopaine • (ethylphenidate) • “Nopaine‐‐‐every bit as good as actual cocaine” says Mr. Llewellyn Nopaine 2 Spice, K2, Genie, Yucatan Fire, Spice Gold, Plant food Mixture of herbal plant products, sprayed with synthetic cannabinoids ◦ Sold as aromatic incense, potpourri, plant food…”smoking blend” ◦ Often contaminated with unidentified toxic ◦ “Natural” →››› misconception of safety Marketing ◦ Similar in appearance to marijuana ◦ Sold in variety of colors/flavors ◦ $30‐45 per 3Gm 3 Compounds developed for research ◦ Efforts to separate psychoactive & therapeutic effects ◦ CB1 vs. CB2 ◦ JWH‐018 & JWH‐073 THERE ARE OVER 100 KNOWN SYNTHETIC ◦ JWH‐250, CP‐47, 497 CANNABINOIDS ◦ HU‐210 Dr. John W. Huffman, Clemson University professor, synthesized many novel cannabinoids as part of research for National Institute for Drug Abuse (NIDA) on endogenous cannabinoid receptors‐‐‐‐had never been tested on humans, nor approved by FDA Shipped in from China, Asia Dosing the plant material ◦ May result in “hot spots” or inconsistencies 4 • Similar euphoric high as THC • Higher affinity for receptor •Duration of action 6‐12hr?? •Detection times blood/urine ?? • FAR MORE toxic than phytocannabinoids •Since 2010, estimated 6,000 ER visits per year and climbing!! ◦ Unknown ingredients added to mixture over time……… Cannabinoid Adulteration 5 Number of Exposures Per Year Synthetic Marijuana Exposure Cases Per Year 6968 5228 4377 3682 2915 2010 2668 2011 2012 2013 2014 2015 (July 6, 2015) • July 2012 – President signs Synthetic Drug Abuse Prevention Act of 2012 into law; 15 specific molecules •May 2013 • DEA emergency scheduled 3 new molecules UR‐144, XLR11, and AKB48 •Feb 2014 • 4 compounds added as Schedule I…… 6 As substances are added to Schedule I and “bans” implemented…. How Do Sales continue???? 7 8 • Life threatening issues • Supportive measures • Stabilize organ function • Acute anxiety reaction • Talk‐down technique • HPPD or Hallucinogen Persisting Perception Disorder • Use of clonazepam • Marijuana like reaction • Physical and emotional dependence • Physical w/d‐‐‐‐ sleep & appetite disturbance, HA, irritability, anxiety, depression, muscle discomfort Bath Salts, Ivory Wave, Plant Food, Cloud 9, MTV, Super Coke • Synthetic stimulants (SS) • Modeled after natural plant product, Khat • MDPV (methylene‐dioxy‐pyro‐valerone) • Mephedrone (MMC, MCAT, Meow‐meow) • Methylone • Similar molecular structure to amphetamines • Product labeling • “Not for human consumption” loop hole to Federal analog Act • Cost $20‐30 per packet 9 Chemical Structures Production ◦ Illicit laboratories Bulk packaging (powder) imported from China and Asia Packages are often mislabeled to pass Customs Warehouse distribution centers in USA, product “cut” ◦ ↑ effects vs. plant ↑ potency, ↑ ↑ ↑ ill effects Route of ingestion ◦ Snorting most common ◦ Can be smoked or swallowed 10 • Pharmacology • NE/DA reuptake inhibitor • Duration: 6‐8hrs…24hr? • Effects • Rush, ↑ HR/BP • ↑ energy, insomnia • Hallucination, psychosis • Violent behavior • Seizure, kidney failure → death • Permanent neuronal damage? Indigenous to East Africa ◦ Catha edulis bush, referred to as“African Salad” Harvested all year Centuries of traditional use ◦ Captain Phillips movie starring Tom Hanks and others depict use 11 Main Constituents: cathinone, cathine Ingested via: Chew Extracted for tincture, teas Crystallized and smoked CNS stimulant, similar to methamphetamine & MDMA (Ecstasy) MDMA White to light brown crumbly powder MDPV May cause seizures, panic attacks, or psychosis 12 • • • MMC, MCAT, Meow‐meow, Drone, Plant Food Synthetic derivative amphetamine/cathinone Jan 2010 most popular “club drug” UK Methylone (bk-MDMA) Ecstasy (MDMA) Note: Molly of late 1990’s and early 2000 MDMA Molly of 2006 contained BZP/TFMPP stimulants Many current Molly products contain methylone, other cathinones--- cheaper to produce 13 Gravel, Flakka $5 or less a vial Reports‐ surge in FL, Feb 2015 alpha-PVP MDPV • Primary concerns •Lethality •Not detectable with routine drug screens • Medical treatment •Restraints, intravenous benzos for seizures •High dose iv sedatives (2+2 lorazepam/haloperidol) •Fluids and assess for rhabdomyolysis •Monitor and treat morbid hyperthermia promptly 14 Synthetic Cathinone Exposure Per Year Number of Exposures 6137 2691 995 2011 2012 2013 582 2014 267 2015 (June 30, 2015) DEA temporary ban Sept 8, 2011 o Scheduled I as of Oct 8, 2011 MDPV, Mephedrone, Methylone Synthetic Drug Abuse Prevention Act of 2012 o Bans 31 specific compounds oOnly included 3 synthetic stimulant o 9 hallucinogenic compounds, 18 synthetic cannabinoids o Conviction/penalties for sale or possession‐punishable for up to 20yrs in prison 15 • “Cosmic Blast” or naphyrone • Derived from pyrovalerone • Currently very little data on safety/toxicity • Pentedrone • Related to pyrovalerone and mephedrone • No reliable information as yet • • 3‐Flouromethcathinone4‐Fluoromethcathinone Other common “street names” • Jewelry Cleaner, Glass Cleaner • Pump‐It Powder • Plant Food…. Cathinone Adulteration 16 Other Stimulants of Concern… Phenethylamine hallucinogens ◦ Amphetamine‐like PLUS Psychedelic activity Hallucinations Paranoia ◦ 2CB, 2CI, 2CT, 2CE, Bromo‐ DragonFLY ◦ Marketed as Eros, Nexus, Smiles… 17 Chemical Name Street Name 2C‐T‐7 Tripstasy, Blue Mystic 2C‐B Nexus 2C‐I Smiles (also 2C‐E, ‐I, 25‐I & 25b‐Nbome) 5‐methoxy diisopropyltryptamine Foxy, Methoxy Alpha methyltryptamine Spirals N‐benxylpiperazine BZP Dimethyltryptamine DMT Bromobenzodifuranylpropylamine Bromo‐DragonFly COMMON & BRAND NAMES The Bomb, N‐Bomb, NBOMe, 25’s Blotters are placed between the gums and cheek, one on top and one on the bottom lip Powder form is often snorted DEA Report Jan 2011‐ Aug 2015 43 states 4,680 usage/incidence reports 18 19 Indigenous to Mexico Diviner’s Sage Used for centuries in healing rituals Mazatec Indian Shamans Kappa‐opioid receptor agonist Partial agonist dopamine receptor (D2) Hallucinogen ◦ Psychotomimetic, dysphoric ◦ Fast onset, duration 30‐60min (user experience days ‐‐‐ weeks) ◦ No activity 5‐HT2A serotonin receptor (site of action LSD) Low risk dependence, low toxicity 20 Laughter, evokes childhood memories Sensation of motion, merging, overlapping realities S‐A‐L‐V‐I‐A ubtle effects, relaxation ltered perception ight, colors ivid visionary states, “encapsulation” mmaterial existence, dissociation mnesia A Drug Enforcement Administration study is still pending to determine the 8 point criteria to place Salvia on the Federal Controlled Substance Act o Salvia is illegal in 27 States and US Military o Controlled in some manner in Australia, Belgium, Canada, Finland, and Italy 21 Kakuam, Ithang, Thom, Kekum Kratom is a tropical tree indigenous to Thailand, Malaysia, and other areas of South East Asia Botanical Classification ◦ Genus : Mitragyna ◦ Species : speciosa ◦ Coffee in species!! ◦ Active compounds:7-hydroxymitragynine, speciogynine Description ◦ Leaves contain MG (SG) and are chewed as an opiate substitute and stimulant in Thailand and South‐East Asia, primarily among the working class ◦ Relatively long history of human use 22 • Stimulant effects at low dose • Yohimbe‐like effect • Increased alertness, physical energy, talkative and sociable • Similar effect as 1‐2 cups of coffee • Mu‐opioid receptor agonist • Analgesia, euphoria, cough suppression • CNS depressant ≡ sedation • Quick onset and lasts ~ 1‐3hr • Similar side effects as other opioids •Opioid‐like, full physical addiction Sold ◦ Raw or crushed leaves •Various commercial concentrations 15X ‐‐‐‐ 250x extracts Ingestion ◦ Chew; extract and brew tea or tincture ◦ Heat decreases potency so usually not smoke Potencies and strains vary ◦ $15 to $50 per five‐gram packet ◦ $18 to $25 for about 50 capsules ◦ Doses generally 2‐10 grams. 23 Alleged 15X Concentrated mitragynine and 7-hydroxymitragynine extracted from Kratom leaves 24 • Kratom is not controlled under the Controlled Substances Act, but considered an herbal drug of abuse Banned in Thailand, Malaysia, other areas “Dirty” cousin of morphine • Khanka, tar‐like substance • Desmorphine produced from codeine and mixed w gasoline, paint thinner, ioidine, oils..… • “Recipes” posted on web • Epidemic in Russia • Seize rate ↑↑↑ 23‐fold 2009‐present • Few user’s survive 2 years • Rotting at injection site, gangrene, amputation • Significant and prompt jaw degeneration 25 Used for sedation, anesthesia, and muscle relaxation in horse and cattle • Prevalent use in Puerto Rico • Combination use • • Cocaine speedball • “Cut” heroin • Ingestion • IV • Insufflation • May have severe cardiac effects Human or Animal excrement fermented to methane gas said to be a ~ psychedelic? 26 • Hallucinogens • Psilocybin • “Shrums” • Disrupts natural functioning of SE system • Dissociatives • DXM, Robo‐ ataxia, slurred speech How many mgs of DXM are in 4oz Robitussin? 360 mg • PCP‐ paranoia, aggression, hallucination • Ketamine • Diverted from hospital and veterinary stock rooms abused as a dissociative/psychedelic • Dissociative anesthetic Baker’s Brew 27 Banned in many States, new replacement is Vapotini at Hookah Bars Images from KCTV via New York Times and Nub TV via YouTube Videos 28 Approved by U.S. Alcohol and Tobacco tax and Trade Bureau in early 2014 but rescinded its approval on 4/21/14 Alcohol Extraction “Ear Wax” or Wax Butane Extraction or CO2 Extraction “Honey Oil” Cold Water Extraction 29 • Contain higher percent of THC • Use some type of solvent to extract THC 1. CO2---$$$ safer 2. Butane---$ dangerous • Not all solvent is removed Wax • Whipping hash oil during purging process • Easier to manipulate Oil • Sticky like honey • Used in “vape pens” 30 Shatter • • • • Refined version of Hash Oil Pressure vacuum utilized Semi-transparent Yellow or amber color Dab • Technique for consuming concentrates • Place “dab” on heated surface • Inhale the vapors • ↑ 90% THC New Age Vape Products 31 • Erowid (.org) • Grasscity (.com) • Psychonaut (.com) • Shoomery (.org) • Spice University (.org) [email protected] 32