Modified by:Patrick Clay, PharmD

UNT System College of PharmacyPatrick.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

Recreational Drugs, HIV, and

Antiretroviral Therapy

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.

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“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 Circuit Party

All night parties involving loud music, laser light shows, and marathon dancing.

Most commonly held in large open areas such as old warehouses.

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. White tabletB. Pink capsuleC. 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

UNIVERSITY OF KENTUCKY COLLEGE OF PHARMACYUNIVERSITY OF KENTUCKY COLLEGE OF PHARMACY

UNIVERSITY OF KENTUCKY COLLEGE OF PHARMACYUNIVERSITY OF KENTUCKY COLLEGE OF PHARMACY

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. XB. Kit KatC. PoppersD. 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**

MethamphetamineCrystal, Tina, glassSpeed, Meth, Crank

Historical AspectsWorldwide

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 AspectsUnited 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 UseMansergh 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 UseMansergh 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 Risk Stimulant

2.99

‘Poppers’

3.89

PDE 3.443 drugs 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 q72hTadalafil: 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. “An individual should be drug free for one month before they can start antiretroviral therapy.”

B. “An individual should be drug free for three months before they can start antiretroviral therapy.”

C. “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.