The Designer Drug – What You Always Wanted to Know Steven Kipnis MD, FACP, FASAM

1. The Designer Drug – What You Always Wanted to Know Steven Kipnis MD, FACP, FASAM Medical Director, NYS OASAS

2. Thanks to: Paul L. Cary Toxicology Laboratory University of Missouri Steve Hanson Acting Associate Commissioner - NYSOASAS

3. CASE A healthy 48-year-old man has a generalized convulsion after ingesting a powder he purchased through the Internet. The powder was sold with the wording “not for human consumption” listed on the packaging. The seizures continue in the pre-hospital setting, as well as in the ED, for approximately 15 minutes in total before ceasing after administration of lorazepam 4 mg IV. Initial vital signs after cessation of his seizures include a blood pressure of 140/88 mm Hg; pulse, 106 beats/min; respiratory rate, 22 breaths/min; temperature, 37.7°C. Physical examination is notable for mydriasis and diaphoresis with 5 beats of myoclonus in the bilateral lower extremities. Shortly after arrival in the ED, the patient is intubated for airway control. Finding on noncontrast CT of the brain are unremarkable, and EEG results are normal. Initial pertinent laboratory values include normal electrolyte, creatinine, and glucose levels. His creatine phosphokinase level is elevated, at 2,500 U/L. Toxicology screening does not detect acetaminophen, ethanol, or salicylates

4. CASE A healthy 48-year-old man has a generalized convulsion after ingesting a powder he purchased through the Internet. The powder was sold as “research grade JWH-018 – synthetic cannabinoid,” with the wording “not for human consumption” listed on the packaging. The seizures continue in the prehospital setting, as well as in the ED, for approximately 15 minutes in total before ceasing after administration of lorazepam 4 mg IV. Initial vital signs after cessation of his seizures include a blood pressure of 140/88 mm Hg; pulse, 106 beats/min; respiratory rate, 22 breaths/min; temperature, 37.7°C. Physical examination is notable for mydriasis and diaphoresis with 5 beats of myoclonus in the bilateral lower extremities. Shortly after arrival in the ED, the patient is intubated for airway control. Finding on noncontrast CT of the brain are unremarkable, and EEG results are normal. Initial pertinent laboratory values include normal electrolyte, creatinine, and glucose levels. His creatine phosphokinase level is elevated, at 2,500 U/L. Toxicology screening does not detect acetaminophen, ethanol, or salicylates

5. A 36-year-old male in the Netherlands became acutely agitated and enraged after ingesting mephedrone along with cocaine, and subsequently lost consciousness and died despite resuscitation efforts. • A 29-year-old male found unresponsive at a nightclub died of cerebral edema and brainstem herniation. Serum sodium was • noted to be 125 mmol/L, later suggested by laboratory data to have resulted from water intoxication. • The first synthetic cathinone-related death in the United States, described in the scientific literature, involved a 22-year-old male who was found unresponsive and subsequently died at the receiving hospital. • One case of mephedrone-related myocarditis has also been reported in the literature. A 19-year-old male presented with crushing chest pain after ingesting mephedrone sold as ‘‘not for-human-consumption’’ plant food.

6. Drive to Get High • People will seek any means to alter their state of consciousness

8. The Story of Designer Drugs

9. Designer Drugs: Created (or reformulated, if the drug already existed) to get around existing drug laws (Controlled Substance Act), usually by modifying the molecular structures of existing drugs to varying degrees.

10. Designer Drugs: • Second International Opium Convention in 1925 which specifically banned alternative esters of morphine • 1960s - 1970s, new synthetic hallucinogens (modifications of LSD & PCP) • “Designer drug” was first coined by law enforcement in the 1980s • 1980s - 1990s, design of MDMA (ecstasy) & methcathinone • 2000 - 2005, derivatives of psilocybin & mescaline, anabolic steroids • European authorities have identified 41 new psychoactive drugs in 2010 alone

11. What Drives the Production Designer Drugs ? • Consumer preferences • Law enforcement control

12. An agonist is a chemical that binds to a receptor and triggers a response – often mimicking the action of a naturally occurring substance. Receptor Drug (agonist)

13. Why Change the Key? • Prolong the effect of the drug • Increase the potency of the drug • “Select” the desired effect • Make the drug more difficult to detect • Avoid patent infringement • Make an illegal drug “legal” Drug

14. Spice/K2 and Synthetic Cannabinoids(HMA – Herbal Marijuana Alternatives)

15. No! We’re not talking about this!

16. We’re talking about this! There are hundreds of synthetic cannabinoids.

17. Brand Names of Common HMA’s • Spice • K2 • Tai Fun (Blackberry, Vanilla, Orange) • Exclusive (Original, Mint, Cherry) • Chill Zone (Berry, Mint, Original) • Chill Out (Cherry, Mint, Original) • Sensation (Vanilla, Orange, Bkberry) • Chaos (Mint, Original, Cherry) • Zen • Zen Ultra

20. What’s in these “incense” products?

21. “Listed” Ingredients in Spice Canavalia rosea: beach bean or bay bean Nymphaea caerulea: Blue Egyptian water lily Scutellaria nana: Dwarf skullcap Pedicularis densiflora: Indian warrior Leonotis leonurus: Lion's Tail and Wild Dagga Cannabis – like effect Zornia latifolia: is a perennial herb Nelumbo nucifera: Lotus Leonurus sibiricus: Honeyweed or Siberian motherwort Vanilla Honey

22. Preparation of the “incense”: • Botanicals (vegetable matter) are sprayed with liquid preparations of: • HU-210 • HU-211 • CP 47,497 • JWH-018 • JWH-073

23. Origins of Synthetic Cannabinoids • CP 47,497 - developed by Pfizer in 1980 as an analgesic • 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 - synthesize by a researcher at Clemson (1995) for use in THC receptor research - John W. Huffman • more than 100 different synthetic cannabinoids have been created

24. Usage • Very little known about the extent of use • 2009 Survey in Frankfurt • Surveyed 1463 students aged between 15 and 18 at schools providing general and vocational training. • Prevalence of use was 6% of respondents reported using Spice at least once • National Poison Data System in 2010 (Aurora, CO) • During the 9 month study period, there were 1898 exposures reported with a mean age of 22.5 years old • Most cases reported were in men. • Community Epidemiologic Work Group (CEWG) noted K2 epidemic in Midwest US in 2010 • Appears to be shifting from marijuana to synthetics

25. Usage • Mode of use: • Smoked • Drink as an infusion/herbal tea

26. Availability • Sold in metal-foil sachets • Typically contain 3 g of smoking mixture sufficient for 8 joints • Typical cost is 20 – 60 dollars per pack • Sold in: • Internet sites • Tobacco stores • Head shops • Some gas stations • Often sold as “incense” labeled with disclaimer: not for human consumption

27. Smoking Cannabinoids What does CB1 receptor control? • Basal Ganglia: motor control, learning • Hippocampus: memory, spatial navigation • Cerebrum: cognitive functions - attention, language, emotions *CB2 found in blood cells, immune tissue and spleen. ? in CNS

28. Dual effects: • Herbs (very little medical literature of effects) • Synthetic cannabinoid

29. Pharmacological Effects of Synthetic Cannabinoids are Similar to THC • Mental (these affects predominate): • Altered state of consciousness • Mild euphoria and relaxation • Perceptual alterations (time distortion) • Intensification of sensory experiences • Pronounced cognitive effects • Impaired short-term memory • Anxiety • Paranoia • Avoidant eye contact • Agitation • Delusions (paranoid, grandiose) • Psychosis

30. Pharmacological Effects of Synthetic Cannabinoids are Similar to THC • Physical: • Increase heart rate & blood pressure • Dry eyes • Diaphoresis • Mild decrease in potassium • Seizures • Reduction in motor skill acuity • Increase in reaction times

31. DependenceSyndrome Similar to Marijuana • Withdrawal: • “Inner unrest” • Drug craving • Nightmares • Profuse sweating • Nausea • Tremor • Headache • Hypertension • Increased HR

32. Reported Effects of Synthetic Cannabinoids are Different Than 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

33. Synthetic Cannabinoid Data

34. Percentage of U.S. 12th Grade Students Reporting Past Year Use of Drugs* Other Than Alcohol and Tobacco, 2011(N=approximately 14,900) • Marijuana and synthetic marijuana are the most prevalent illicit drugs used by 12th graders, according to recent data from the 2011 Monitoring the Future (MTF) survey. Slightly more than one-third (36.4%) of high school seniors reported using marijuana in the past year, including 11.4% who reported using synthetic marijuana, compared with less than 10% for all other illicit drugs.

35. Legal Status of Synthetic Cannabinoids (DEA) • March 1, 2011, the DEA, issued final notice to temporarily place five synthetic cannabinoids into the Controlled Substances Act (CSA) for at least one year • Synthetic cannabinoids treated as Schedule 1 drugs • A drug that has a high potential for abuse • A drug that has no currently accepted medical use in treatment in the United States • There is a lack of accepted safety for use of the drug under medical supervision

36. Legal Status of Synthetic Cannabinoids (DEA) • DEA took action - imminent hazard to the public safety • Imposes criminal sanctions and regulatory controls of Schedule I substances under the CSA • Covers the manufacture, distribution, possession, importation, and exportation • US Senate considering a bill permanently banning these drugs

37. State Laws • Some states have passed their own laws banning the substance • New York has pending legislation

38. Synthetic Cannabinoids “Banned” by the (DEA) • Synthetic cannabinoids covered under the DEA’s new rule includes the following: • JWH-018 * • JWH-073 * • JWH-200 • CP-47,497 • CP-47,497 (C-8 homologue)

40. Can synthetic THC chemicals be detected by drug testing?

41. Drug Testing: • New on-site, rapid, instant tests • Numerous laboratories employing LC/MS/MS technology • $$$ per sample • Many unknowns regarding this testing

42. While parent drugs are detectable, metabolites of synthetic cannabinoids may be the only detectable compounds found • Can use blood and urine as sample

43. Unresolved Issues of Concern: • What synthetic compounds (or metabolites) are being tested by these laboratories? • No standardized urine cutoff levels • No standardized methods (LC/MS/MS) • Tests detect metabolites • No independent quality control materials • No proficiency testing • Detection window unknown • May be 48 – 72 hours

44. What to test for ? ? ?

45. More dangerous than we first thought?

46. Management • No pharmacolgically specific antidote • Supportive care • Benzodiazepines for agitation and anxiety • Intubation in one case for decreased respiratory rate • Duration of effects???

47. Bath Salts

48. Bath Salts: • Ivory Wave • Ivory Pure • Ivory Coast • Purple Wave • Vanilla Sky

49. Appealing Product?

50. Not talking about this: