Recreational Drugs, HIV, and Antiretroviral Therapy Modified by: Patrick Clay, PharmD UNT System College of Pharmacy Patrick.Clay@unthsc.edu O: (817) 735-2798 Originally designed and developed by: Frank Romanelli, Pharm.D., MPH, BCPS Professor of Pharmacy, Medicine, & Health Sciences Associate Dean for Education, University of Kentucky Objectives Define the term “club drugs.” List potential clinical and toxic effects of club and recreational drugs. Describe potential effects of recreational drug use upon ARV therapy. Discuss HIV specific adverse consequences of recreational drug use. ICE m&m “CLUB DRUGS” ‘Recreational Drugs’ *SOCIAL LUBRICANTS* Substances used in a recreational fashion to enhance social experiences. Club Drugs Not all recreational drugs are considered ‘Club Drugs’ Produce dis-inhibition Common substances of abuse at bars, circuit parties, raves Rave All night parties involving loud music, laser light shows, and marathon dancing. Most commonly held in large open areas such as old warehouses. Circuit Party Most commonly three day weekend events centered in large urban areas. Attendees pay one lump sum to attend multiple events throughout the weekend culminating in one final large party. Club Drugs Methylenedioxymethamphetamine (MDMA) “Ecstasy” Gammahydroxybutyric Acid (GHB) “G” Ketamine “Special K” Amyl and Butyl Nitrites “Poppers” Methamphetamine “Crystal” “Tina” Methylenedioxymethamphetamine Amphetamine derivative which leads to exaggerated levels of neurotransmitters throughout the CNS. • Ecstasy, E, XTC • M and M • Hug Drug Epidemiology Within the US, National Drug Intelligence Center now equates MDMA use to that of heroin and cocaine. MDMA estimated to be one of the fastest growing drug of abuse in the US. 2000: 1.4 million HS seniors used MDMA. 2005: 2.5% of HS seniors reported ‘ever-use.’ Availability Amsterdam – “Ecstasy Capitol of the World” Commonly manufactured in clandestine laboratories High level of impurities and contaminants (DM, ASA, Pseudoephedrine) What does “Hug Drug” look like? Audience Participation time! A. B. C. White tablet Pink capsule Never scored History of Abuse Created in 1914 for appetite control Used in 1970s as a means of enhancing behavior therapy Entered club scene in 1980s Classified as a C-I 2001, FDA approval of trial involving post-traumatic stress disorder Street Sales Sold in tablet form Typical tablet contains 50-150mg of active ingredient Cost: $20-40.00 per tablet Pharmacology Structurally related to the stimulant methamphetamine and hallucinogen mescaline Increases levels of all NTs within CNS synapses Inhibition of MAO Clinical Effects Increased energy Talkative, open-minded Intimacy Distorted senses Decreased fear, aggression, defensiveness Hallucinations Teeth grinding Club Drug Paraphernalia Gamma-hydroxybutyrate Naturally occurring fatty acid derivative of CNS neurotransmitter GABA Liquid E Gib, GBH, Grievous Bodily Harm, Georgia Home Boy, “G” Soap, Scoop, Salty Water Easy Lay Availability Controlled substance C-I Internet recipes available Gammabutyrolactone (GBL) 1,4-butanediol (1,4-BD) History of Abuse Early 1990s - Dietary supplement purported to increase muscle mass, increase libido, metabolize fat Mid-1990’s - Popularity increased, euphoric effects recognized Late 1990’s – Established club and date rape drug, FDA ban on OTC sales History of Abuse 2000 – C-I status in US Early 2000 - GBL and 1,4-BD become popular precursor sources of GHB FDA issues warning letters re: GBL and 1,4-BD Commonly imported from Europe Manufactured from internet recipes and clandestine labs Street Sales Oral dosage form Typical dose “one capful” Often admixed into water bottles $5.00-$10.00/dose Pharmacology Normally 1/1000th the concentrations of GABA within CNS GHB endogenous CNS chemical Mediates: sleep cycles, temperature, memory Gets in your head easily (lipophilic, crosses BBB rapidly) Impacts levels of growth hormone Clinical Effects Dose-related CNS depression Amplification with ethanol or other CNS depressants Often ingested to counteract euphoric effects of ecstasy What rec drug was found in the characters portrayed in the movie, Armageddon A. B. C. D. X Kit Kat Poppers Ice Ketamine Derivative of phencyclidine (PCP), introduced in the 1960s and used as a dissociative anesthetic Special K, “K”, Kit-Kat, Super K Jet, Super Acid Availability C-III - Injectable prescription formulation (Ketalar®) Use has dwindled with advent of safer, more effective anesthetics Common vet agent Difficult to manufacture and most often acquired through diversion of the Rx product History of Abuse Believed to have entered rave scene in mid-1980s Originally may have been an adulterant of MDMA tablets As abusers became familiar with the effects of ketamine, its use as a sole agent emerged Street Sales Injection product (IV or IM) Ingestion Smoking Snorting $80.00/gram Pharmacology High bioavailability by both IV or IM route Oral doses not as well absorbed and undergo first pass metabolism Interacts with and inhibits NMDA channels (PCP) Clinical Effects Analgesic effects at lower doses, with amnestic effects at increasing doses Dramatic feelings of dissociation “floating over one’s body” into “K-land” or “K-holes” Visual hallucinations and lack of coordination are common Many abusers report effects dependent upon the setting within which the drug is abused Amyl and Butyl Nitrites Volatile nitrite and nitrate derivatives originally intended to produce vasodilatory effects on patients with coronary artery disease. Poppers Availability Originally crushable, mesh enclosed pearls RX product until 1960 when moved to OTC status 1969 FDA re-instated RX status subsequent to reports of abuse Banned in 1988 Street Sales Inhalation Sold in small amber glass ampoules Typical unit dose for sale contains 10-30 cc of drug Cost: $10-20 per ampoule Clinical Effects Feelings of a “rush”, warmth, dizziness Reduce anal sphincter tone Increased sexual intensity Methemeglobinemia Early association with HIV and KS Interaction with PDEs** Methamphetamine Crystal, Tina, glass Speed, Meth, Crank Historical Aspects Worldwide Synthesized in late 1800s and studied in the 1930s First epidemic occurred during and after WWII (1945-1957) By 1948 - 5% of Japanese aged 16-25 were users, restrictions enacted in 1951 Gradual west to east movement of MA use from Japan, to Hawaii, to the US west coast (motorcycle gangs) Historical Aspects United States 1950s: inhalational products available OTC 1960s: popular use of MA/MA derivatives for obesity 1970s: restrictions and underground production increases 1980s: shifts to college students, females, young professionals 1990s: clandestine labs emerge 1996: Comprehensive Methamphetamine Control Act 2000s: enhanced enforcement and regulation; greater international (Mex) trafficking – reductions in Mom & Pop production? Epidemiology MA now the most widely abused substance in world following cannabis 35 million estimated MA abusers versus 15 million cocaine abusers Estimated 5% of US residents have used MA at least once Epidemiology In US from 1992-2002, MA-related admissions to treatment programs rose from 10 to 52/100K persons Extent of MA abuse seems to be concentrated in West, Midwest, and South Subpopulations: MSM, homeless, rural areas Clandestine labs “Meth Labs” Utilize readily available and inexpensive chemical products and internet recipes to produce MA Meth labs carry toxic and explosive risk and considered hazardous waste sites by authorities = costly clean-up Usually designed to be mobile (trailers, automobile trunks, hotel/motel rooms) Chemistry beakers, mason jars, coffee filters Methamphetamine Labs Cost Compared to other illicit drugs: inexpensive $25 per 1/4 gram $100 per gram $1,700 per ounce Clinical Effects - Acute “rush” or “flash” Flight or fight response Increased HR, BP, body temperature Euphoria, alertness, energy Enhanced sense of well-being/self-esteem Increased libido and pleasure from sexual activity Clinical Effects - Chronic Pilot study Subjects: 65 active MA abusers (by urine screen) Control: 80 non-abusers Poor memory (p=0.03) Manual manipulation of information (p=0.001) Cho A, et al. J Addic Dis 2002; 21:21-34. Adverse Effects - Chronic Emotional liability (insomnia?) Paranoid psychosis (insomnia?) Memory loss (grey matter loss) Cognitive dysfunction (grey matter loss) Dermatologic pathology (“crank bugs”) Burns Poor dentition – “meth mouth” Withdrawal/Tachyphylaxis “meth mouth” “crank bugs” “meth sores” “meth-decay” “meth decay” HIV Recreational Drugs Crossroads Recreational Drug Use (MA) Halkitis PN, et al. J Urban Health 2005; 18-25. 450 MSM/bisexual men 293 (65%) reported MA use in the previous 4 month time-span AA men less likely to report MA use (p<0.001) Mean age of MA users: 33±7.9 years Recreational Drug Use Mansergh G, et al. Am J Pub Health 2001. Cross-sectional study of 295 gay and bisexual males in SF Bay Area who attended a circuit party in previous year. 75% reported use of MDMA 58% reported use of Ketamine 25% reported use of GHB 49% reported having had protected anal sex and 28% unprotected Recreational Drug Use Mansergh G, et al. Klitzman RL, et al. Am J Psychiatry 2000. Pilot study of 169 gay and bisexual men at three NYC clubs. One-third of all respondents reported use of MDMA at least monthly. Use of MDMA was statistically significantly correlated with recent and repeated unprotected anal sex. Recreational Drug Use Colfax GN, et al. J Acquir Immune Defic Syndr 2001. Cross-sectional study of gay and bisexual males in SF to examine prevalence of club drug use and high risk sex practices during circuit parties. 80% reported use of MDMA 66% reported use of Ketamine 29% reported use of GHB 21% of HIV+ and 9% of HIV- persons reported having unprotected anal sex. Recreational Drug Use Mattison AM, et al. Journal of Substance Abuse 2001. Non-random sample of 1169 circuit party attendees in 3 separate venues. 50% of respondents reported using MDMA within last 30 days Use of MDMA and ketamine were associated with high risk sexual practices. Most common reason for attending circuit party was “to have uninhibited sex.” Recreational Drug Use Ostrow D, Plankey M, Cox C, et al. JAIDS 2009;51:349-55. MACS cohort of HIV-seronegative MSM 1998-2008 (n=6,972 males) Reporting use of both PDEs and other recreational drugs (n=1,667) Results Ostrow D, Plankey M, Cox C, et al. JAIDS 2009;51:349-55. HIV + (n=57) HIV – (1610) No drug use 33% 60% 2 or + URASP 21% 5% Poppers +/- PDEs 33% 23% Stimulants 33% 16% Ethanol (low-mod) 60% 68% Ethanol (mod- high) 25% 23% Risk of seroconversion increased from: 2.99 (single drug) [95% CI 1.02-8.76] 8.45 (3 drugs (MDMA, ‘poppers’, PDEs) [95% CI 2.67-26.71] Results Ostrow D, Plankey M, Cox C, et al. JAIDS 2009;51:349-55. Agent Stimulant ‘Poppers’ PDE 3 drugs Risk 2.99 3.89 3.44 8.45 Recreational Drug Use Semple SJ, Strathdee sa, Zians J, et al. BMC Public Health 2010;10:1-6. 321 participants in a safer-sex intervention surveyed Survey: drug use and sexual behavior Cohort split into groups based on preferred sexual venue: private (home); commercial (bathhouse); public (restroom) Recreational Drug Use Semple SJ, Strathdee sa, Zians J, et al. BMC Public Health 2010;10:1-6. Commercial: > gay, better educated, ↑ club drugs High risk sex greatest in commercial and public groups Public group: > alcohol use, heavier overall drug use, ↑ depression Mean 4.2-7.3 gm of MA in last 30 d Implications Rec drugs inc high risk sexual encounters inc rate of STIs. Potential for fatal interactions in HIV seropositive patients using rec/club drugs. Potential effects of club drug use on adherence to antiretrovirals? Potential deleterious disease-related effects withstanding issues surrounding other STIs and ARV adherence -PEARLS ‘Respect ritonavir’ Start low and have friends nearby Don’t neglect ethanol (ddI, ABC) Sildenafil: 25 mg q48h Vardenafil: 2.5 mg q72h Tadalafil: 10 mg q 72h Adherence to ARVs, ancillary meds, appointments, etc. Don’t forget the needles Patients use recreational drugs … just ask … Why Adopt a Broad View of Adherence? A broad view of adherence: – recognizes that adherence is not only about taking one’s medications – actively engages patients in health care and treatment – values the health impacts of “non-medical” interventions, including controlled drug use, stable housing, social supports, harm reduction, and good nutrition – improves patients’ self-efficacy – provides more opportunities for success Adherence: defined Any action that improves, supports, or promotes the health of a person living with HIV with respect to HIV treatment and care, including physical, mental, and psychosocial well-being. Adherence through HP “..helping a patient who uses drugs adhere to a complex medical regimen can support an upward spiral of self-esteem and the adoption of healthier practices.” Why focus on adherence in substance abusers? There is systemic discrimination against substance users – Less access to care – Less access to ART – Slower decline in morbidity and mortality Providers often lack training in the care of substance users and may have negative attitudes towards them Poor Adherence = … (audience participation time!) HIV resistance:adherence Audience poll: A. B. C. “An individual should be drug free for one month before they can start antiretroviral therapy.” “An individual should be drug free for three months before they can start antiretroviral therapy.” “An individual should be drug free for six months before they can start therapy.” Correct answer: Yes. Adherence & Drug of Choice Heroin: use may be more regimented – Users may have an easier time w/ adherence Cocaine/Crack: use may be more sporadic – Intense mood swings may interfere with adherence Methamphetamine: unclear, but use may be more sporadic and interfere with adherence Alcohol: may have most negative impact on adherence due to blackouts and memory loss HIV, Psyche, Substance Abuse Up to 50% to 80% of HIV-infected persons are affected by mental illness. Triple diagnosis of HIV, substance use, and mental illness is common. Up to 80% of HIV-infected patients in methadone maintenance require psychiatric consultation for mental illness. Untreated depression can compromise medication adherence and make HIV infection more disabling. Health Promotion I Taking all antiretrovirals, on time exactly as prescribed Taking meds to prevent opportunistic infections Keeping regular medical appointments Eating a nutritious diet Exercising regularly Health Promotion II Participating in a drug treatment program Controlling drug use or sobriety Practicing safer sex and drug injection Taking a multivitamin Stopping smoking Connecting with a support network Take Home Points Individualize treatment plans to each patient’s needs. Recognize the specific challenges of working with HIV infected substance users. Use knowledge and tools to overcome these challenges and to advocate for patients. Consider the boundaries for non-medical providers offering HIV adherence and health promotion counseling. Explore opportunities to link with providers across disciplines to strengthen adherence support.