Welcome to a discussion of SYNTHETIC DRUGS, synthetic drug culture and some of

1. Welcome to a discussion of SYNTHETIC DRUGS, synthetic drug culture and some of the unique problems Teens bring with them…

2. Your local resources: Dr. Thomas Walters, MD, Medical Director Don Hassett, MA, CASAC, CPP, Director of Prevention CASA Council on Alcohol and Substance Abuse of Livingston County

3. Sources: We gratefully acknowledge the following institutions and sources: NFLIS, National Forensic Laboratory Information System DEA Upstate New York Poison Center NCADD, Rochester DAWN Drug Abuse Warning Network With specific public material originally developed by: • Alexander Garrard, PharmD • Clinical Toxicologist • Upstate New York Poison Center

4. Issue:Language-With the hundreds of new drugs (or are they “chemicals”) of abuse in use in various regions of this and other countries we will mostly be looking at these 2 categories of mind altering substances, as teens understand them: • BATH SALTS/ • HERBAL INCENSE Spice/ K-2, K-3 and The remarketing via street names is already changing and expanding even this basic classification.

5. Note: At the end of this presentation you will find a comprehensive list of chemical names along with their sexy street names , understand that the formulations will continually change.

6. We will cover: • Synthetics –specifically, spice & bath salts • Their origins • Chemical make up & derivations • Prevention and management Issues relevant to: • language & terminology • drug purity • cultural appeal for teens • a couple of Case presentation, management • Regional to NY, varieties & names • How synthetics fit teen culture • How they fit into the addiction paradigm • Do we know enough to judge how addictive these chemicals are? • Does addictiveness depend on social & genetic factors? • Some of the grass roots marketing strategy • Handouts: # 1 drug street names; #2 packaging & pictures; #3 simplified text on Spice, suitable for parent/student information.

7. As if terminology isn’t enough of an obfuscation, consider: Very few street drugs are 100% pure  Many are adulterated or contaminated  Most discussion will be over pure presentation 

8. Shrub to Bath Salts?

9. Catha Edulis

10. Khat plant geography

11. What is khat? Cathinone active alkaloid in khat leaves  Chewing popular in middle east  Produces amphetamine-like  sympathomimetic symptoms

12. What are bath salts? Synthetic cathinone derivatives  Synthesized as early as 1928 and studied for  medical use Methcathinone  Mephedrone  Bupropion only cathinone with medical  indication MDPV, mephedrone, buphedrone,  pentedrone, methylone, 4MEC, 4MePPP, α- PVP, etc

13. Structures!

14. Pharmacology Similar to amphetamines  Affect dopamine, serotonin, and norepinephrine  Neuronal stimulation due to increased post-  synaptic catecholamines Increased release of catecholamines  Blockade of pre-synaptic uptake and storage  Reduced MAO activity  Indirect glutamate pathway stimulation  End result: increased chemicals in the synapse  causing increased effects

15. How supplied? Powder, capsules, and tablets  Insufflation, ingestion, IV use, and rectal use  Mephedrone: 100 – 200 mg  MDPV: 10 – 15 mg  Effects within 30 mins; lasts up to 7+ hours 

16. Patient Case 30 yo male admits to using 1 – 2 grams of  bath salts daily x 2 months VS: 187/93 P129 R12-16 T 98  Presents to ED “shaky and anxious” and  hallucinating Administered lorazepam  Patient returns to baseline 24 hours later 

17. Patient Case 26 yo male presents to ED after injecting bath  salts Found agitated, altered, violent and  combative and foaming at the mouth by EMS VS: 148/66 P175 T 106.3 (rectally)  Patient intubated with RSI and aggressive  cooling measures instituted CK peaked at 235,377 U/L (normal < 170 U/L) 

18. Patient Case 40 yo male injected unknown amount of  “bath salts” Became aggressive, uncontrollable,  delusional, removed all his clothing, and violent behavior Tazed by police and had be physically  restrained by EMS VS: P 164 131/72 R24 rectal temp 105.4  Declared brain dead 42 hours after  presentation after complicated ICU stay

19. Clinical Manifestations Agitation (53.3%)  Tachycardia (40%)  Hypertension (20%)  Seizures (20%)  Palpitations (13.3%)  Hallucinations/delusions  Paranoia  Renal failure?  Cannibalism?  Death 

20. Clinical Manifestations 45% of patients  experience symptoms beyond 24 hours post exposure 30% have symptoms >  48 hours post exposure Are there adulterants  present or contaminants?

21. Management Protect yourself!  Difficult to manage patients and unpredictable  behavior ABCs  No antidote  GI decon?  BZDs, BZDs, and more BZDs for agitation  DPH likely won’t be effective  Haloperidol could be problematic 

22. Management All BZDs work the same  Increase frequency of chloride channel opening  leading to hyperpolarization Only works in conjunction with GABA  Diazepam Midazolam Lorazepam Onset Quick (min) Quick (min) 5 – 20 min IV Unpredictable 5 – 10 min 20 – 30 min IM Duration Short Short Long Single dose Long Intermediate Long Repeated Doses

23. Management What if BZDs do not work?  No real ceiling to BZD doses  Respiratory depression  Haloperidol  Anticholinergic  QTc prolongation  Risk vs benefits  Bring product into ED 

24. Synthetic Cannabinoids

25. Where did it come from? 1960s: research into THC-like compounds  Analgesic and anti-inflammatory minus  psychotropic effects Recognized as drugs of abuse in early 2000’s  in Europe Dr. JW Huffman researched THC analogues  for use in cancer and AIDS patients Developer of JWH compounds  HU-210 from Hebrew University 

26. What are they? Synthetic cannabinoids which work on the  CB1 and CB2 receptor like THC Marketed as herbal incense, herbal smoking  blends, potpourri, etc. Spice, K2, Mr. Nice Guy, Legal Funk, Tai Fun, Zen  Ultra, Smoke, Chaos Mint, etc. Misleading packaging  Not for human consumption  Commonly smoked 

27. What’s in them?

28. Pharmacology Effects likely from mixture of herbs and actual  synthetic compounds Baybean, Beach bean, Dwarf skullcap, red clover,  vanilla, honey, wild dagga and more Affects CB1 and CB2 receptors found in CNS/PNS  Responsible for elevating mood, anxiety, cognition  Responsible for reducing inflammation induced pain  HU-210 100-800x more potent than THC 

29. Patient Case 21 yo male smoked some K2 earlier in  evening Presents to ED tachycardic, dilated pupils and  with myoclonic jerking Given BZDs and symptoms resolved over 8  hours

30. Patient Case 48 yo man had generalized seizure within 30  minutes of ingesting a synthetic marijuana- like product Initial vital signs were: pulse, 106/min; BP,  140/88 mmHg; respirations, 22/min GCMS confirmed substance to be JWH-018 

31. Patient Case 35 yo male admits to smoking legal weed 90  minutes ago C/o chest pain and dizziness  Supportive care instituted  Patient leaves AMA 

32. Clinical Manifestation Most information from case reports and case  series Psychiatric effects predominate  Anxiety, paranoia, agitation, delusions, and  psychosis Physical manifestations  Tachycardia, HTN, diaphoresis, seizures, and ???? 

33. The good ol’ standard addictive drugs are still here. We don’t yet fully understand how the new drugs fit the user’s needs. It is clear that they fit the network of illegal drug trade and electronic marketing of chemicals both illegal & legal. NFLIS analyzes drug samples. Here is what they are finding by region…

34. NFLIS drug samples analyzed1,660,216 drug reports were submitted to State and local forensiclaboratories in the United States from January 1 through December 31, 2011 • Nationally, in 2011 • Cannabis/THC was the most frequently identified drug (536,630 reports), • followed by: • Cocaine (333,645 reports), • Methamphetamine (160,960 reports), • and Heroin (119,765 reports). • More recently from 2010 to 2011, reports of clonazepam, buprenorphine, and amphetamine increased significantly at the national level. • Regionally, • reports of oxycodone, hydrocodone, alprazolam, and clonazepam increased • significantly in all four U.S. census regions from the period of 2001 through 2011. • Reports of buprenorphine increased significantly in the Midwest, and amphetamine reports increased significantly in the Midwest, Northeast, and South.

35. NFLIS data contd.Some current, partial, context for what we should be seeing in clinics. • From 2010 to 2011, reports increased significantly In the Northeast • oxycodone , • buprenorphine • Amphetamin • BUT Cannabis/THC and cocaine reports decreased significantly • In 2011, more than 70% of narcotic analgesic reports were oxycodone or hydrocodone. (while) • Alprazolam accounted for 52% of identified tranquilizers and depressants. • Among identified/Hallucinogens, MDMA accounted for 23% of reports.

36. 2001 – 2011 (long term Trends) • Reports of cocaine decreased significantly from the period of 2001 through 2011 in all four U.S. census regions. While cannabis/THC reports increased significantly in the Northeast.

37. Foxy Methoxy: Tryptamines Will Not Fade Away 5-methoxy-N,N­diisopropyltryptamine (5-MeO-DIPT) was ranked among the 25 most frequently identified drug samples • Foxy Methoxy: Tryptamines Will Not Fade Away • In 2011, for the first time ever, 5-methoxy-N,N­diisopropyltryptamine (5-MeO-DIPT) was ranked among the 25 most frequently identified drugs in NFLIS. With over 3,000 estimated drug reports, it was the only Tryptamine to make the list. In addition to the NFLIS State and local data, 5-MeO-DIPT was one of the top 10 drugs reported by the DEA. • Abused for its hallucinogenic-like effects, 5-MeO-DIPT is often administrated orally as tablets, capsules, or powder forms at doses ranging from 6 to 20 milligrams. Other routes of administration include smoking and snorting. It produces subjective effects with an onset of about 20 to 30 minutes, a peak at about 1 to 1.5 hours, and a duration of about 3 to 6 hours. • Subjects who have been administered 5-MeO-DIPT are talkative and disinhibited with dilated pupils. High doses of 5-MeO-DIPT produce nausea, jaw clenching, muscle tension, and overt hallucinations with both auditory and visual distortions. • The abuse of hallucinogenic substances in all-night dance parties (raves) and other venues was a major problem in the United States in the late 1990s and early 2000s. As DEA controlled various Phenethylamines and tryptamines, more designer drugs would appear. Sold as “Foxy” or “Foxy Methoxy,” the abuse of 5-MeO-DIPT began to spread in 1999. For the next four years, it was encountered by law enforcement agencies in several States. • In 2003, DEA temporarily added 5-MeO-DIPT to Schedule I of the CSA to avoid imminent hazard to public safety. In 2004, this action was made permanent. Between 2010 and 2011, the number of 5-MeO-DIPT reports increased nearly 36-fold. From • 2009 to 2011, the change was 56-fold. It has been found in combination with N-benzylpiperazine (BZP); 1-(3-trifluoromethylphenyl)-piperazine (TFMPP); 3,4-methylenedioxymethamphetamine (MDMA); and various synthetic cathinones. More intelligence gathering will be needed to discover why 5-MeO-DIPT has made such a resurgence.

38. About: Bath salts, research chemicals, plant food • May have originated in China and India • In foreign use for about two years • Powder • Snorted, smoked or injected • Made of MDPV – • Methylenedioxyprovalerone • Methylone • Mephedrone

39. Not your Mum’s Bath Salts? • So – what are Bath Salts anyway? They are a man-made, chemical (as opposed to organic) stimulant drug. Generally, stimulants are a class of drugs that elevate mood, increase feelings of well-being and increase energy and alertness. Amphetamines, or speed, are an example of stimulant drugs. • The technical term for Bath Salts is “substituted cathinone.” Khat is a plant that is cultivated and used in East Africa and the Middle East. It has a stimulant effect on the user and can be quite dangerous. Substituted cathinones are synthetic, concentrated versions of the stimulant chemical in Khat. Methylenedioxypyrovalerone (MDPV), mephedrone and methylone are the chemicals most often found in “Bath Salts.” • They can be ingested orally or snorted through the nose.

40. Bath Salts are also called… • Zoom lady bubbles • Tranquility dove • Ivory wave vanilla sky • Bliss • White Girl is good for cooking like crack • Tranquility, better when smoked in powder form • NRG not good cooked, better placed in mouth, tastes like vanilla

41. Roch/Buff/Syracuse markets: • Molly an analogue of MDMA • Believed on the street to be “pure MDMA” • Manufactured in Europe and Asia for US

42. Begin by looking at why kids might choose Salts… • • For energy / alternative to illegal stimulants • Perceived to be legal • • Not picked up on standard drug tests • • Available at retail outlets: convenience stores; head shops; online • …they are trying to stay as legal as possible! • Prevention messages, parental messages have been aimed at avoiding illegal behavior, and this is now a driver for synthetics.

43. It’s “New & Improved”… • Drugs such as synthetics, not known to be used by addicts can be used “off label” with out incurring the social stigma usually associated with street drugs such as cocaine or even alcohol. • So no stigma and doesn’t attract any attention from parents. • Actually Tide has been a ingredient in drug manufacturing for several years.

44. Product labeling “legal, not for human consumption” means you can’t be busted for holding. • Dilemma: when, in an “underground culture” mind altering drugs are relabeled as insecticide (to allow for legal importation and retail sales), young adults realistically could assume any insecticide might get them high?

45. Again, the Effects of “Bath Salts” would look like: • • Very severe paranoia that sometimes causes users to harm themselves or others. • • Speed of onset – 15 minutes; Length of high – 4-6 hours • Long term effects: Unknown • • Effects reported to Poison Control Centers – Suicidal thoughts – Agitation; Combative/Violent; • Confusion – Hallucinations / psychosis – Increased heart rate; Hypertension; Chest Pain – Death or serious injury users can’t know except via trial or reputation, contents or dosage

46. Calls To Poison Control Centers for Human Exposure to Bath Salts, 2010 to January 2012

47. Poison control centers show dramatic increase in ingestion over very short period for bath salts –but beginning to flatten out. • In 2010, poison centers received 304 calls about exposures to Bath Salts. That number rose dramatically in 2011 when poison centers received 6,138 calls. In early 2011, calls closed in each month* spiked through June, then gradually declined and was level in November and December 2011 and January 2012.

48. Synthetic Marijuana = Spice, K-2,and analogues • K2 or "Spice" is a mixture of herbs or dried, shredded plant material that is typically sprayed with chemicals that are similar to THC, the psychoactive ingredients in marijuana. • JWJ-018 (or J dub) Name refers to a key ingredient research chemical

49. Synthetic (420) marijuana also known locally as: • K 2 blaze • Spice red dawn • Genie 420 • blue

50. More signs of use • • Loss of physical control • • Lack of pain response • • Increased agitation • • Pale skin • • Seizures • Vomiting • • Profuse sweating • • Uncontrolled / spastic body movements • • Elevated blood pressure, heart rate, and palpitations