1. Designer Drugs – What You Need to Know The Fundamentals By: Paul L. Cary Toxicology Laboratory University of Missouri

2. March 1, 2011 DEA “ Banned ” Five Synthetic Cannabinoids n synthetic cannabinoids covered under the DEA’s new rule includes the following: u JWH-018 * u JWH-073 * u JWH-200 u CP-47,497 u CP-47,497 (C-8 homologue)

3. On October 21, 2011, the Drug Enforcement Administration (DEA) “ banned ” three synthetic cathinones by placing them into Schedule I of the Controlled Substances Act (CSA) n mephedrone n 3,4 methylenedioxypyrovalerone (MDPV) n methylone Bath Salts

4. DEA Actions: n DEA took action - imminent hazard to the public safety n imposes criminal sanctions and regulatory controls of Schedule I substances under the CSA n covers the manufacture, distribution, possession, importation, and exportation n RAMIFICATIONS?

5. The Story of Designer Drugs

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

7. 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)

8. Why Change the Key? prolong the effect of the drugprolong the effect of the drug increase the potency of the drugincrease the potency of the drug “select” the desired effect“select” the desired effect make the drug more difficult to detectmake the drug more difficult to detect avoid patent infringementavoid patent infringement make an illegal drug “legal”make an illegal drug “legal”

9. Spice/K2 and Synthetic Cannabinoids

10. Preparation of the “ incense ” : n botanicals are sprayed with liquid preparations of: u HU-210 u HU-211 u CP 47,497 u JWH-018 u JWH-073

11. Origins of Synthetic Cannabinoids n HU-210 & HU-211 - synthesized at Hebrew University, Israel in 1988. HU-210 is an anti- inflammatory; HU-211 as an anesthetic n CP 47,497 - developed by Pfizer in 1980 as an analgesic n JWH-018 & JWH-073 - synthesize by a researcher at Clemson (1995) for use in THC receptor research - John W. Huffman n more than 100 different synthetic cannabinoids have been created

12. Smoking Cannabinoids n BG: motor control, learning n Hippo: memory, spatial navigation n CB: cognitive functions - attention, language, emotions What does CB 1 receptor control?

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

14. Public Perception of “Legal Highs” Synthetic cannabinoids are as safe as marijuana.

15. Forensic Science Review Volume: Twenty-Six Number One January 2014 25 pages

16. Synthetic Cannabinoids: Physical Effects n n kidney damage (XLR-11) n n pulmonary effects (lung dysfunction) n n cardiovascular issues (tachycardia), increases in blood pressure n n GI problems (pain, nausea, vomiting) n n seizures (6 cases) n n chemically-induced psychosis ** n n DUID (12 reported cases) ** n n three reported deaths (cardiac, suicide, OD)

17. More dangerous than we first thought?

18. Synthetic Cannabinoids: Physical Effects n n kidney damage (XLR-11) n n pulmonary effects (lung dysfunction) n n cardiovascular issues (tachycardia), increases in blood pressure n n GI problems (pain, nausea, vomiting) n n seizures (6 cases) n n chemically-induced psychosis ** n n DUID (12 reported cases) ** n n three reported deaths (cardiac, suicide, OD)

19. Evolutionary Landscape n appearing & disappearing what ’ s popular today cycles out to be replaced by new synthetic THC analogs what ’ s popular today cycles out to be replaced by new synthetic THC analogs n labs testing for common compounds a few months ago may not be testing for same chemicals now n on-site, POC devices cannot keep pace

20. Lab-Based Drug Testing (2010):

21. Lab-Based Drug Testing (2012):

22. Acknowledgment: Dr. Barry Logan National Medical Services Willow Grove, PA

23. July – December 2010 Prevalence – 2010

24. Oct 2011 – April 2012 Prevalence – 2012

25. Evolutionary Landscape

26. Ingenuity of Designer Chemists:

27. Drug Testing for Synthetic Cannabinoids

28. Drug Testing – On-Site: n rapid, instant, POC tests n testing for JWH-018/JWH-073 n cutoff 50-75 ng/mL n lab testing - cutoff 0.5 ng/mL n false negatives

29. Drug Testing – Laboratory: n rapidly changing landscape n constantly updating menus n lack of standards n some labs developing screening tests n not all lab-based testing is equal

30. Unresolved Issues of Concern: n what synthetic compounds (or metabolites) are being tested by these laboratories? n no standardized urine cutoff levels n no standardized methods (LC/MS/MS) n tests detect metabolites n no independent quality control materials n no proficiency testing n detection window unknown

31. More dangerous than we first thought?

32. Designer Stimulants (Novelty Powders)

33. Designer Stimulants: n bath salts/bath bubbles n plant foods/plant vitamins n glass cleaners/pond cleaners n soft drink additive “ novelty collectors item ” “ novelty collectors item ”

34. MDPV: n Methylenedioxypyrovalerone (MDPV) - a psychoactive drug with stimulant properties which acts as both a norepinephrine- dopamine reuptake inhibitor (NDRI). n often snorted - similar to cocaine n considered extremely addictive n adverse medical/psychiatric ramifications

35. n designer drug chemically similar to cathinone n first synthesized in 1929 n amphetamine-like properties n powerful synthetic stimulant n adverse medical/psychiatric ramifications Methylmethcathinone (Mephedrone)

37. DMAA Methylhexanamine (1,3-dimethylamylamine)

38. February, 2014 - Bath Salt Data

39. Growth of Designer Drugs What ’ s different today then in the 1970 ’ s when the drug Ecstasy (MDMA) was popularized? What ’ s different today then in the 1970 ’ s when the drug Ecstasy (MDMA) was popularized? What has changed to fuel the rapid development and distribution of designer drugs? What has changed to fuel the rapid development and distribution of designer drugs?

40. 3 billion users The Internet!

41. Average 58 million per day 1.2 billion users

42. What does the Internet offer? n improved accessibility n increased affordability n n enhanced anonymity

43. Unfortunate Truisms: n legal controls that prohibit designer drugs will always lag behind their production n drug detection methods for the identification of designer drugs may also not be available when these compounds become popular

44. Legal Status of Control Strategies

45. Federal & State Law: Scheduled Drugs Federal Analog Statutes n substantially chemically similar n equivalent pharmacological activity n intended for human consumption

46. New Legal Approach: n Deceptive Trade Practices Act u false & misleading u deceptive sales n rather that criminal charges n large civil monetary fines

47. Outlook for the 2014 and Beyond

48. Trend lines?

51. August, 2013

52. Two Web Sites You Need to Know

53. www.erowid.org

54. www.designerdrugtrends.org

56. email address: carypl@health.missouri.edu