Designer Drugs:

1. Designer Drugs: drugs, which are created (or reformulated, if the drug already existed) to get around existing drug laws CSA (controlled substance act), usually by modifying the molecular structures of existing drugs to varying degrees

2. Sources of Incense Products: • internet/on-line sources • “head” shops/alternative medicine stores / convenience stores/flea markets • 1-(800) phone ordering services • individual distributors

3. Preparation of the “incense”: • Botanical plants/herbs are sprayed with liquid preparations of: • HU-210 • HU-211 • CP 47,497 • JWH-018 • JWH-073 • JWH-250 • JWH-081 • JWH-210 • XLR-11, UR-144 • And many more

4. Origins of Synthetic Cannabinoids • CP 47,497 - developed by Pfizer in 1980 as an analgesic (pain reliever) • HU-210 & HU-211 - synthesized at Hebrew University, Israel in 1988. HU-210 is an anti-inflammatory; HU-211 as an anesthetic • JWH-018 & JWH-073 - synthesized by a researcher at Clemson (1995) for use in THC receptor research - John W. Huffman • more than 200 different synthetic cannabinoids have been created

5. How K2/Spice works:Synthetic Cannabinoids act as THC agonists -An agonist is a chemical that binds to a receptor and triggers a response – often mimicking the action of the naturally occurring substance. Receptor Drug (agonist)

6. Why Change the Key? • prolong the effect of the drug • increase the potency of the drug • “select” the desired effect • avoid patent infringement • make the drug more difficult to detect • make an illegal drug “legal” Drug

7. Pharmacological Effects of Synthetic Cannabinoids are Similar to THC • increase heart rate & blood pressure • altered state of consciousness, mild euphoria • relaxation, perceptual alterations (time distortion) • intensification of sensory experiences • pronounced cognitive effects • impaired short-term memory • reduction in motor skill acuity • increase in reaction times • Sickness • kidney damage

8. Reported Effects of Synthetic Cannabinoids are different to THC • production inconsistencies • herbal incense blends are harsher to inhale • effect on appetite is non-existent • increased restlessness & aggressive behavior • herbal incense produces a shorter “high” (perceptual alterations & sensory effects are limited) • doesn’t mix well with alcohol (hangovers) • incense costs more than marijuana?

9. Cannabis vs. Cannabinoids: Effects Seen in Clinical Cases Most symptoms aresimilar to cannabisintoxication: Symptoms nottypically seen aftercannabis intoxication: – Seizures– Potassium deficiency– Hypertension– Nausea/vomiting– Agitation– Violent behavior– Coma -Abnormally rapid heart rate– Reddened eyes– Anxiousness– Mild sedation– Hallucinations– Acute psychosis– Memory deficits SOURCES: Hermanns-Clausen et al . (In Press), Addiction; Rosenbaum et al . (2012). Journal of Medical Toxicology; Forrester et al. (2011). Journal of Addictive Disease; Schneir et al . (2011). Journal of Emergency Medicine.

10. Drug Testing: Synthetic THC / K2 • Rapid, onsite instant test (as of 3/1/12) • Laboratory-based screening test (limited) • Most Laboratories are employing LC/MS/MS technology • Primarily via urine, however some labs can test via oral fluid and blood • $$$ varies greatly • Onsite vs Lab is very different testing methodology

11. On-site vs Laboratory testing for K2 On-site K2 Laboratory K2 JWH-018, 073, plus *17 other synthetic cannabinoid structures JWH-019, 081, 122, 200, 203, 210, 250, 398, AM2201, MAM2201, RCS4, RCS8, AM-694, AM-1248, AKB-48,UR-144, XLR-11 Cut-off 1ng/ml or less Testing for hydroxy acid & other components/metabolites Detecting presence Confirmatory technology *Redwood Toxicology Laboratory • JWH-018 & JWH-073 primarily • Cut-off at 25 or 50ngs/ml • Testing limited metabolites • Much higher threshold to trigger positive • Screening technology

12. Issues of Concern • What synthetic compounds (or metabolites) are being tested by the laboratories? • no standardized urine cutoff levels • no standardized methods (LC/MS/MS) • tests detect metabolites • no independent quality control materials • no proficiency testing • keeping up with molecular changes

13. Detection Window ??? • testing for metabolites • educated guess - same as real marijuana? • many labs advertise “up to 72 hours” • limited studies • passive inhalation? • fact is - we don’t know all the answers

14. Wet Marijuana • Embalming Fluid-Soaked Marijuana: smoking marijuana soaked in embalming fluid is gaining popularity throughout the United States. The syndrome of intoxication looks nearly identical to that seen following phencyclidine (PCP) use, with agitation, disorganized speech, and thoughts, and diminished attention. This new trend in drug use involving marijuana also presents a resurgence in PCP use. • Soaked in water – uneven burn • Mixed with PCP: wet, fry, crystal joint, supergrass • Mixed with codeine containing cough syrup • Mixed with methamphetamines

15. What’s in Bath Salts: • MDPV (Methylenedioxypyrovalerone) - a psychoactive drug with powerful stimulant properties which acts as both a norepinephrine & dopamine reuptake inhibitor (NDRI). “A two for” • usually snorted like cocaine • duration of effect 2-3 hours /adverse effect 6-8 hrs • MDPV - no history of FDA approved medical use • Sold as a “research chemical” • adverse medical or psychiatric ramifications

16. Mephedrone (Methylmethcathinone) • amphetamine-like properties, powerful stimulant • “rediscovered” by synthetic chemists in 2003 • reformulation of cathinone, a chemical found in the khat plant of Eastern Africa • khat existence traced to 15th C. Ethiopia • khat is banned in the U.S.

17. Methylone (3,4-methylenedioxy-N-methylcathinone) • very similar to MDMA • stimulant • phenethylamine, amphetamine, and cathinone properties • euphoria and increased sociability • insomnia and restlessness • hallucinations and psychosis

18. Bath Salts and beyond!!!Expanded Synthetic Stimulant Panel α-PVP BZP Butylon Buphedrone   Cathinone     Ethylone Flephedrone MBDB      mCPP MDA MDEA  MDMA MDPV Mephedrone  Methcathinone 4-Methylethcathinone  Methylone Pentedrone Pentylone Pyrrolidinopentiophenone TFMPP

19. Synthetic Seizures & Cathinone Varieties (through 8/27/12) SOURCE: U.S. DEA, Office of Diversion Control,NFLIS data, 2012

20. MDMA – Molly / Ecstasy - Molly is not new, exactly. - MDMA, or 3,4-methylenedioxy-N-methylamphetamine, was patented by Merck pharmaceuticals in 1914 - did not make much news until the 1970s, when psychotherapists began giving it to patients to get them to open up. -arrived at New York nightclubs in the late 1980s, and by the early ’90s - Ecstasy was quickly embraced by Wall Street traders and Chelsea gallerinas. as demand increased, so did the adulterants in each pill (caffeine, speed, ephedrine, ketamine, LSD, talcum powder and aspirin, to name a few), and by the new millennium, the drug’s reputation had soured. - in the last decade, it returned to clubs as Molly, a powder or crystalline form of MDMA that implied greater purity and safety: Ecstasy re-branded as a gentler, more approachable drug. (Molly for molecule) - thanks in part to that new friendly moniker, MDMA has found a new following in a generation of conscientious professionals who have never been to a rave and who are known for making careful choices in regard to their food, coffee and clothing. - -

21. Molly - continued • common side effects, include teeth grinding, dehydration, anxiety, insomnia, fever and loss of appetite. • more dangerous ones include hyperthermia, uncontrollable seizures, high blood pressure and depression caused by a sudden drop in serotonin levels in the days after use, nicknamed Suicide Tuesdays. • capsules sell for $8 to $40. • the most common Molly additives are bath salts, including methylone and mephedrone. Bath salts are chemically similar to MDMA. • A report recently released by the DEA's New York division highlighted the results of 143 lab tests over the past four years of substances suspected of being Molly. Only 13% of the drugs were MDMA, while 41% were 4-MEC, a type of bath salt, and 20% were methylone. • Veteran MDMA users say they ask that drugs be tested before they buy them, using kits that can be bought online. "If I'm getting more than a gram, they'll test it right in front of you," said a 27-year-old ad salesman from Oakland, Calif. DanceSafe, an organization that promotes safety at raves, sets up testing tables at some events.

22. Pharmacological Effects of “Bath Salts”: • increase heart rate & blood pressure • pupil dilation, rapid speech • hyperactivity, arousal, & over stimulation • increased energy & motivation • euphoria - agitation • dizziness, nausea • hallucinations, seizures, convulsions • breathing difficulties!!! • diminished perception of the requirement for food and sleep • death

23. Testing for Bath Salts??Yes! However: • No on-site, rapid, instant tests • No laboratory-based screening tests • Laboratories employing GC/MS and LC/MS/MS technologies • Detection times remain unknown • Best procedure for detecting metabolites vs parent drug unknown

24. 2C-INicknamed “Smiles” • popular among teens, responsible for dozens of overdoses and deaths especially in Midwest. • white crystalline powder, typically snorted or ingested. • High & Effects can last a few hours to a few days, described as being a “roller coaster through hell” • a combination of MDMA and LSD, only more intense. • 2C-I is being made by dealers and “hobbyists,” • chemicals can be obtained over the internet • 2C-I overdoses can cause seizures, kidney failure, and fatally high blood pressure.

25. Pharmacological Effects • Dilated pupils • Sweating • Dry mouth • Rapid speech • Rapid/frequent mood swings • Hyperactivity/ Elevated BP • Hair standing on end • Nasal passage irritation

26. Erowid.com“Documenting the complex relationships between humans and psychoactives” • Great resource for information • Take with a grain of salt • Your clients are probably aware of this site as well

27. The Opiate Family Opiates: Heroin Morphine Codeine Hydrocodone - (Vicodin, Loratab) Hyrdomorphone -(Dilaudid) Oxycodone – (Oxycontin, Percocet, Roxicodone) Oxymorphone - (Opana)

28. Heroin Makes a Comeback This Time, Small Towns are Increasingly Beset by Addiction, Drug-Related Crimes Thursday, August 8, 2013 - WSJ ELLENSBURG, Wash.—This small city east of the Cascade Mountains is known for its hay farms, rodeos and, increasingly, something more sinister: a growing heroin problem. The fatal overdose of a state trooper's son in May convulsed the town—especially when the two men arrested and charged with selling him heroin turned out to be a county official's sons. Heroin use in the U.S. is soaring, especially in rural areas, amid ample supply and a shift away from costlier prescription narcotics that are becoming tougher to acquire. Much of the heroin that reaches smaller towns such as Ellensburg comes from Mexico, where producers have ramped up production in recent years, drug officials say. Heroin seizures at the Southwest border, from Texas to California, ballooned to 1,989 kilograms in fiscal 2012 from 487 kilograms in 2008, according to figures from the Drug Enforcement Administration. The heroin scourge has been driven largely by a law-enforcement crackdown on illicit use of prescription painkillers such as oxycodone and drug-company reformulations that make the pills harder to crush and snort, drug officials say. That has pushed those who were addicted to the pills to turn to heroin, which is cheaper and more plentiful. A 21-year-old recovering addict said she made the switch from pain pills to heroin after her dealer one day held out both options in his hands and encouraged her to choose the cheaper one Drug experts say the heroin sold today is generally purer and thereby more potent than the varieties prevalent in past decades, increasing the risk of overdose. A baggie "may be 15% pure one day, and the next day it's 60%," said Skip Holbrook, the police chief in Huntington, W.Va., which sits in an area of Appalachia where heroin is spreading. "It's like playing Russian roulette."

29. Opana Information • Opana is more potent, per milligram, than Oxy • Users vulnerable to O.D, kidney failure, death • Street names: "stop signs," ”Obomb,”new blues” • crushed - either snorted or injected. • Endo Pharmaceuticals, announced in Dec 2011 that it would reformulate Opana. The new pill is being manufactured • Old form of Opana is still available -$90 per bill • Opana ER (Extended Release) • Small blood clots under the skin/cause blood disorders

30. Take away comments • If positive on an Opiate screening test – an Opiate family member most likely detected • If confirmed for 6-AM (6-Acetylmorphine )at the Lab: • Heroin use • If confirmed positive just for Morphine • Metabolized heroine to morphine and or • morphine use i.e. from a prescription, • poppy seed use

31. Suboxone-Buprenorphine • FDA approved in 2002 • used to treat opiate addiction • alternative to methadone • partial agonist (ceiling) • in pill, film, patch • 2mg & 8mg doses • will not test positive on an opiate test • significant diversion • contains naloxone- guard against misuse • Individuals will get high on this stuff

32. What’s the attraction to Bup? • user’s experience a euphoria effect • if taken in conjunction with other sedative drugs like alcohol, sleeping pills(ambien) or benzodiazepines (clonopin)- extreme sedation, drowsiness, unconscious, or even death may occur • Method of ingestion – typically sublingual (under the tongue), pill format going away, reports of snorting • injected? • only test positive if specifically testing for buprenorphine

33. Thank you for your time. Presented by: Vinnie HappRedwood Toxicology LaboratoryAn Alere Companyvhapp@redwoodtoxicology.com