CLUB DRUGS Nothing to Rave About

1. CLUB DRUGS Nothing to Rave About Cynthia C. Haith, M.D. Department of Pediatrics May 12, 2004

2. Goals • To familiarize you with various aspects of rave culture • To alert you to the dangers associated with club drugs • To illustrate the role of the Internet • To help you better educate your patients and their families and hopefully prevent future use of club drugs

3. RAVES • All-night dance parties • Characterized by loud, pulsating, techno music and visual effects with strobe and laser lights

4. RAVES • Originated in England in the late 1980s • Attended largely by adolescents and promoted by a small group of disc jockeys • Initially were underground, often held in large warehouses or stadiums • Logistical information sent out at the last minute; spread by word of mouth • Associated with illicit use of drugs and alcohol

5. RAVES • British authorities became aware and ultimately made them illegal • By the late 1980s rave culture then migrated to the United States • By the mid-1990s explosive growth of dance club scene popularized by youth

6. RAVES • Now have become more mainstream and commercialized • Concert promoters sponsor raves (legally) at prominent venues in most major cities • Advertised via flyers, posters, telephone, radio, and the Internet • Many events advertised as “alcohol free”

7. Raves and Drugs • Ravers’ Motto: • P.L.U.R.Message of peace, love, unity, and respect • Photo below depicts a rave “enhanced” by Ectasy

8. Raves and Drugs • World Wide Internet and dance club growth paralleled the rise of club drug abuse • Raves promoted as a “safe event” because no alcohol is sold • However, alcohol is NOT the drug of choice • Raves typically last all night • Drugs help participants stay up all night and come down at dawn • Drugs used to maintain energy levels and facilitate prolonged dancing

9. Raves and Drugs • Serve to intensify the sensory experience of the lights and the music • Lowers inhibitsions • Helps participants dismiss classic social barriers and connect to peers regardless of sex, ethnic background or social class

10. Raves and Drugs • Common misconception - these drugs provide a “safe high” • Relatively inexpensive • Readily available

11. Rave Paraphernalia • Surgical Masks • Vicks Vapor Rub and Menthol nasal inhalers • Glow Sticks • Skittles, M&M’s and other candies Lollipops and Pacifiers

12. Common Club Drugs • MDMA (Ecstasy) • Gamma-hydroxybutyrate (GHB) • Ketamine • Rohypnol • Metamphetamine • Lysergic acid diethylamide (LSD)

13. Club Drugs • Club Drugs are not safe • 2 mechanisms contributing to club drug toxicity: • “Cafeteria” Drug Use • adolescents sample whatever drugs are available for sale at a venue • Adulterated or diluted drugs • Adulterated Drugs • May contain other substances with little or none of the intended drug • Dilution attenuates the effect • Forces users to use repeated doses to achieve desired effect - “stacking” • Successive redosing can lead to OD and toxicity

14. Epidemiology • Monitoring the Future Study • Implemented in 1975 • Funded by National Institute of Drug Abuse (NIDA) and conducted by the University of Michigan’s Institute for Social Research • An ongoing study of the behaviors, attitudes, and values of American secondary school students, college students, and young adults. • Surveys 50,000 8th, 10th and 12th graders • Collects data on past month, past year, and lifetime drug use

15. Epidemiology • According to the 29th annual study conducted in 2003 • Percentages of illicit drug use has declined among 8th and 10th graders • Ecstasy use has also declined in each grade • 8th graders: from 2.9 to 2.1 percent • 10th graders: from 4.9 to 3.0 percent • 12th graders: from 7.4 to 4.5 percent • However according to the DEA • Ecstasy use is on the rise in NC • LSD use has increased in Charlotte

16. Epidemiology

17. Epidemiology

18. Epidemiology • Drug Abuse Warning Network (DAWN) • DAWN is a national surveillance system operated by the federal government that monitors trends in drug-related emergency department visits and deaths.

19. Epidemiology • According to DAWN • Most frequent ED mentions of club drugs • Methamphetamine, MDMA, GHB, LSD, Ketamine • Most ED visits involving club drugs also involve other drugs • Particularly alcohol and marijuana

20. Epidemiology

21. MDMA (Ecstasy) • 3,4-Methylenedioxymethamphetamine • Structurally resembles both the stimulant amphetamine and the hallucinogen mescaline • Street names • Ecstasy, Adam, Bean, XTC, E, X, Hug Drug, Lovers’ Speed

22. History of MDMA • Synthesized in 1912 in Germany by Merck and patented in 1914 as an appetite suppressant • Secretly studied by the U.S. military/CIA in the 1950s as a possible truth serum • Became popular in the 1970s among psychotherapists as an adjunct to therapy • enhanced communication and improved self-esteem

23. History of MDMA • During this time (late 1970s) MDMA became available on the streets • By the mid-1980s it was becoming more widely abused • In 1985 the Drug Enforcement Agency classified MDMA a Schedule I drug • declaring it a substance with high abuse potential, no accepted medical uses, and illegal to possess

24. MDMA • History cont. • Initial popularity faded and usage declined in the mid-1980s after it was classified as a Schedule I drug • In the 1990s MDMA abuse escalated corresponding with the growing popularity of raves

25. MDMA • Availability • Produced primarily in Europe, smuggled to US, and sold illegally • Synthesis is relatively simple • “How-to” instructions available on Internet • Usually ingested in tablet form • can also be crushed and snorted, injected or used as suppository • Costs $0.02-$0.50 per tablet to produce • Sells for $15 to $50 per tablet in the U.S.

26. MDMA • Tablets come in a variety of colors and are commonly imprinted with popular culture icons

27. MDMA • Usual recreational dose is 100-150 mg • Although some users “stack” MDMA • Not standardized or regulated • Concentration can range from 0 to 200 mg • Many other drugs (adulterants) combined with MDMA and marketed as Ecstasy

28. Methamphetamine Phencyclidine (PCP) Ketamine Methylenedioxy-ampethamine (MDA or “Love Drug”) Methylenedioxy- ethamphetamine (MDEA or “Eve”) Dextromethorphan Acetaminophen Caffeine Ephedrine/Pseudo-ephedrine Aspirin Drugs Found in “Ecstasy”

29. MDMA • Metabolism • Demethylenation to DHMA or MDA • Partially metabolized in the liver by the CYP2D6 isoenzyme of cytochrome P-450 • 50-70% of MDMA is excreted unchanged in the urine • Pharmacokinetics • Onset of action: 20 to 40 minutes • Duration of action: 2 to 6 hours

30. MDMA • Mechanism of Action • Indirect sympathomimetic • Acts primarily by releasing excess serotonin from presynaptic neurons - up to 80% of stores • releases dopamine and norepinephrine to a lesser extent • Inhibits reuptake of serotonin

31. Review of Neurotransmitters • Serotonin - involved in regulation of a variety of behavioral functions • mood, anxiety, aggression, appetite, and sleep • Dopamine • motivational processes - reward and reinforcement • Norepinephrine • important roles in the processes of attention and arousal

32. MDMA and Serotonin

33. Why Take Ecstasy? • Referred to as an “Enactogen” • means “touching within” • Produces euphoria and a sense of well-being or inner peace • Heightens energy, empathy towards others, emotional warmth and desire to socialize

34. Why Take Ecstasy? • Mental stimulation • Heightens sexual arousal • Enhances sensory perception • Causes sensory distortion and illusion, but not overt hallucinations

35. Adverse Effects • Nonspecific effects • diaphoresis, mydriasis, blurred vision, nausea, dry mouth, decreased appetite and thirst • can cause sexual dysfunction in men • Cardiovascular • Tachycardia, vasoconstriction, hypertension • Muscular • Trismus (tightening of jaw muscles) and bruxism (jaw-clenching), muscle tension and spasms, muscle aches, motor tics • Neurologic • headache, tremor, ataxia

36. Acute Complications • Toxicity not necessarily dose dependent • In one case a person attempted suicide with an overdose of Ecstasy. After taking 47 pills he had a resultant plasma MDMA level of 7.72 mcg/ml, but displayed only tachycardia and hypertension.3 • There are reports of others who have died with much lower MDMA levels from 0.05 to 1.26 mcg/ml.12

37. Acute Complications • Hyperthermia • multifactorial • serotonergic effects on thermoregulatory center • hot rave environment • prolonged dancing ->excessive heat production • temperatures as high as 43o C (>109o F) • may lead to DIC, rhabdomyolysis, myoglobinuria, and acute renal failure • Treatment with dantrolene is controversial

38. Acute Complications • Hyponatremia • two proposed mechanisms • SIADH - MDMA leads to increased levels of arginine vasopressin (ADH) • water intoxication - dehydration associated with massive water intake • Hepatotoxicity • proposed mechanisms • injury secondary to hyperthermia • production of hepatotoxic metabolites

39. Acute Complications • Drug Interactions • Antiretrovirals • Reported fatality in 1996 of a HIV-positive person who had recently started taking ritanovir* • This person ingested 180 mg MDMA and the resultant blood level was 4.56 mcg/ml (higher than expected) • Ritonavir inhibits hepatic isoenzyme CYP2D6, which is required to metabolize MDMA

40. Chronic Complications • Long-term neurotoxicity • Memory and cognitive impairment • Psychological difficulties • confusion, depression, insomnia, drug craving, anxiety and paranoia • may last days to weeks after ingestion • Animal studies have shown: • reductions in brain levels of serotonin and its metabolite 5-hydroxyindoleacetic acid (5-HIAA) • reductions in the serotonin transporter • degeneration of serotonin terminals

41. Chronic Complications • One study by Hatzidimitriou et al10 • demonstrated neurotoxic effects of MDMA in monkeys persisting up to 7 years after administration • there was evidence of some regrowth of axons, but that it may be abnormal and incomplete

42. Chronic Complications

43. Chronic Complications • Human Studies • dose-dependent decreases of 5-HIAA in CSF • PET scans have shown decreased serotonin receptor binding11

44. Is MDMA Addictive? • Most users believe that it is not • However, it can be addictive for some • psychological dependence • With repeated dosing, tolerance develops to the desired effects • due to serotonin depletion • tolerance does not develop to the adverse effects

45. Methamphetamine • N-methyl homolog of amphetamine • Street names • Crank, Chalk, Crystal, Meth, Ice, Glass, Fire Speed, Yaba

46. Methamphetamine • History • Amphetamine first synthesized in 1887 • Used as a nasal decongestant (Benzedrine) and bronchial inhaler in 1930s • Supplied as stimulants for soldiers and prisoners of war in WWII • From 1950 to 1970, sporadic periods of widespread use and abuse • Controlled Substance Act of 1970 listed it as Schedule II

47. Methamphetamine • Limited medical indications • narcolepsy • attention deficit hyperactivity disorder • short-term treatment of obesity

48. Methamphetamine • Forms • white, odorless powder - dissolves in waterclear, • chunky crystals • small, brightly colored tablets (Yaba) • Can be injected intravenously, smoked, snorted or taken orally

49. Methamphetamine • Primarily produced in clandestine laboratories in California and Mexico • Yaba - most often produced in Southeast Asia • Easily synthesized in home labs using OTC products - pseudoephedrine • home meth lab raided yesterday in Charlotte

50. Methamphetamine • Injection or smoking • immediately causes a “rush” or “flash” • described as extremely pleasurable • lasts only a few minutes • Oral or intranasal use • produces euphoria - a high, but not a rush • onset 3 to 5 minutes for intranasal; 15 to 20 minutes for oral