Methamphetamine: New Knowledge and Effective Treatment Approaches Thomas Freese, PhD Beth Rutkowski, MPH Pacific Southwest Addiction Technology Transfer Center UCLA Integrated Substance Abuse Programs Alhambra, CA December 9, 2005 Speed • • • It is methamphetamine powder ranging in color from white, yellow, orange, pink, or brown. Color variations are due to differences in chemicals used to produce it and the expertise of the cooker. Other names: shabu, crystal, crystal meth, crank, tina, yaba Ice High purity methamphetamine crystals or coarse powder ranging from translucent to white, sometimes with a green, blue, or pink tinge. Primary Amphetamine/Methamphetamine TEDS Admission Rates: 1992 (per 100,000 aged 12 and over) SOURCE: 2002 SAMHSA Treatment Episode Data Set (TEDS). > 58 35 - 58 12 - 35 < 12 No data Primary Amphetamine/Methamphetamine TEDS Admission Rates: 1997 (per 100,000 aged 12 and over) SOURCE: 2002 SAMHSA Treatment Episode Data Set (TEDS). > 58 35 - 58 12 - 35 < 12 No data Primary Amphetamine/Methamphetamine TEDS Admission Rates: 2002 (per 100,000 aged 12 and over) < 12 12 - 35 35 -58 58-99 100-149 SOURCE: 2002 SAMHSA Treatment Episode Data Set (TEDS). 150-199 200 or more Percentage of Arrestees Testing Positive for Methamphetamine 2002 45 40 Salt Lake City San Jose 35 Portland 30 25 20 15 10 5 0 San Diego Sacramento Males Spokane Females SOURCE: National Institute of Justice, Arrestee Drug Abuse Monitoring Program (ADAM), 2003. IHS-Wide RPMS PCC Outpatient Encounters for Amphetamine Related Visit by Calendar Year Percent (%) of all Admissions Trends in LA County Treatment Admissions by Primary Substance of Abuse 50 45 40 35 30 25 20 15 10 5 0 1H00 2H00 1H01 2H01 1H02 2H02 1H03 2H03 1H04 2H04 Alcohol Marijuana Cocaine/Crack Methamphetamine SOURCE: ADP, California Alcohol and Drug Data System, 2005. Heroin Poison Control Center Calls for Major Substances of Abuse: 2000-2004 Los Angeles County Total Number of Calls 120 100 80 60 40 20 0 2000 Cocaine Meth/Amph 2001 2002 Heroin Ecstasy SOURCE: California Poison Control System, 2004. 2003 LSD GHB 2004* PCP DAWN Major Substances of Abuse: Los Angeles County, CY 2004 Amphetamines N=8,982 326 Meth 909 Marijuana 1,067 Heroin 712 Cocaine 2,348 Alcohol Only (<21) 531 Alcohol 3,307 0 500 1,000 1,500 2,000 2,500 Number of Reports SOURCE: DAWN, OAS, SAMHSA, updated 4/13-14/2005. 3,000 3,500 NFLIS Illicit Drug Items: LA County, Jan-Dec 2004 Heroin 4.1% Cannabis 22.8% PCP 0.5% N=53,972 Other 0.6% Cocaine 39.0% Meth 32.9% SOURCE: DEA, National Forensic Laboratory Information System (NFLIS), 2004. Methamphetamine in Los Angeles County Indicators of Use/Abuse Percentage of All Treatment Admissions Value/Percent 23.4% () Most Commonly Used Secondary Drugs Marijuana (29%) Alcohol (24%) Preferred Route of Administration Smoking (70%) Presence in DAWN (2004) 909 (10%) Poison Control Calls (1/03-6/04) 87 (23%) Midlevel Price (per ounce) Retail Price (per 1/8 and 1/16 oz) $450 – 550 $100 – $120/$60 Methamphetamine Lab Equipment SOURCE: www.stopdrugs.org Methamphetamine: A Growing Menace in Rural America • • • • In 1998, rural areas nationwide reported 949 methamphetamine labs. Last year, 9,385 were reported. This year, 4,589 rural labs had been reported as of July 26. Source: El Paso Intelligence Center (EPIC), U.S. DEA Lab Seizure Locations Desert 3% Shed Business 3% 3% Motel/Hotel 3% • Storage 3% Apartment 11% Garage 8% Mobile Home 11% Trailer 5% • Vehicle 8% House 42% Most common meth lab facilities were singlefamily houses, followed by apartments, mobile homes, vehicles in traffic stops, garages, trailers, motels/hotels, businesses, desert, and storage. Toxic Effects of Methamphetamine • • • Manufacturing Abuse Fetal exposure Clandestine Meth Lab Clandestine Meth Lab Drug Endangered Children High Incidence of Domestic Violence in MA-Abusing Homes • • Threatening notes Dangerous & stressful environment for children Children • • Children who live in and around the area of the meth lab become exposed to the drug and its toxic precursors and byproducts. 80-90% of children found in homes where there are meth labs test positive for exposure to meth. Some are as young as 19 months old. Children • Children can test positive for methamphetamine by: Having inhaled fumes during the manufacturing process Coming into direct contact with the drug Through second-hand smoke. Children • • Hundreds of children are neglected by parents who are meth cooks. Nationally, over 20% of the seized meth labs in 2002 had children present. In Washington State, the counties of Grays Harbor, Spokane, Thurston, and Klickitat all reported that children were found at half the labs seized in 2002. In Lewis County, children were found at 60-70 %, and in ClarkSkamania, 35%. Children • • In 2002, a total of 142 children were present at lab seizures in Riverside and San Bernardino Counties. Most children reported as being present during a seizure were school age. Children • Social workers now accompany law enforcement during lab seizures with children involved. Parents are often charged with second-degree criminal mistreatment, along with manufacturing charges. Allowing children to live in a toxic environment where additional risks of explosion and fire are high is considered to be neglect at best to child abuse. Children are not small adults! • Different diet • Growing & developing rapidly • Higher metabolic & respiratory rate • Developing nervous system • • Unusual habits (hand-to-mouth behaviors; close to floor, contact with many surfaces, at risk for all poisonings) Biologic & developmental vulnerability DEC RESPONSE TEAM • CORE TEAM MEMBERS: • LAW ENFORCEMENT (24/7) CHILD PROTECTIVE SERVICES (24/7) DISTRICT ATTORNEY’S OFFICE (24/7) MEDICAL PERSONNEL (24/7) “AUXILIARY” TEAM MEMBERS: MENTAL HEALTH & THERAPEUTIC PERSONNEL FOR CHILDREN ENVIRONMENTAL SERVICES, FIRE, & PUBLIC HEALTH DRUG TREATMENT PROVIDERS FOR PARENTS AND FAMILY MEMBERS WWW.NATIONALDEC.ORG WWW.NATIONALDEC.ORG Methamphetamine Addiction The brains of people addicted to Methamphetamine are different than those of non-addicts Natural Rewards Elevate Dopamine Levels 200 % of Basal DA Output NAc shell 150 100 Empty 50 Box Feeding SEX 200 150 100 15 10 5 0 0 0 60 120 Time (min) 180 ScrScr BasFemale 1 Present Sample 1 2 3 4 5 6 7 8 Number Scr Scr Female 2 Present 9 10 11 12 13 14 15 16 17 Mounts Intromissions Ejaculations Source: Di Chiara et al. Source: Fiorino and Phillips Copulation Frequency DA Concentration (% Baseline) FOOD Accumbens 1100 1000 900 800 700 600 500 400 300 200 100 0 AMPHETAMINE Accumbens % of Basal Release 400 DA DOPAC HVA 0 1 2 3 4 250 200 100 0 5 hr 0 NICOTINE Accumbens Caudate 150 100 0 0 1 2 3 hr Time After Nicotine 1 Accumbens 250 % of Basal Release 200 COCAINE DA DOPAC HVA 300 Time After Amphetamine % of Basal Release % of Basal Release Effects of Drugs on Dopamine Levels 2 3 4 Time After Cocaine 5 hr MORPHINE Dose (mg/kg) 0.5 1.0 2.5 10 200 150 100 0 0 Source: Di Chiara and Imperato 1 2 3 4 Time After Morphine 5hr PET Scan of Long-Term Impact of Methamphetamine on the Brain Decreased dopamine transporter binding in METH users resembles that in Parkinson’s Disease patients %ID/cc 0.030 0.015 0.000 Control Meth PD Source: McCann U.D.. et al.,Journal of Neuroscience, 18, pp. 8417-8422, October 15, 1998. Methamphetamine Abuser p < 0.0002 Dopamine Transporter Bmax/Kd Normal Control Dopamine Transporter (Bmax/Kd) Dopamine Transporters in Methamphetamine Abusers Motor Activity 2.0 1.8 1.6 1.4 1.2 1.0 7 8 9 10 11 12 13 Time Gait (seconds) Memory 2 1.8 1.6 1.4 1.2 1 16 14 12 10 8 6 Delayed Recall (words remembered) 4 Cognitive Impairment in Individuals Currently Using Methamphetamine Sara Simon, Ph.D. VA MDRU Matrix Institute on Addictions LAARC Differences between Stimulant and Comparison Groups on tests requiring perceptual speed Stimulant (n=80) Comparison (n=80 Mean Scores 100 80 60 40 20 0 Digit Symbol** Trail Making A* Trail Making B** Memory Difference between Stimulant and Comparison Groups Comparison (n=80) Stimulant (n=80) 7 Mean Scores 6 5 4 3 2 1 0 Word Recall** Picture Recall** Longitudinal Memory Performance 25 number correct 20 control baseline 3 mos 6 mos 15 10 5 0 Word Recall Picture Recall Word Recognition test Picture Recognition Control > MA 4 3 2 1 0 MA > Control 5 4 3 2 1 0 DA Receptor Levels and Response to MP 2.5 unpleasant response High Dopamine Transporters 0 Low Dopamine Transporters pleasant response Subjects with low receptor levels found MP pleasant while those with high levels found MP unpleasant How much does the brain heal? PET Scan of Long-Term Meth Brain Damage Partial Recovery of Brain Dopamine Transporters in Methamphetamine (METH) Abuser After Protracted Abstinence 3 0 ml/gm Normal Control METH Abuser (1 month detox) METH Abuser (24 months detox) Source: Volkow, ND et al., Journal of Neuroscience 21, 9414-9418, 2001. Partial Recovery of Brain Metabolism in Methamphetamine (METH) Abuser after Protracted Abstinence 70 0 µmol/100g/min Control Subject (30 y/o, Female) METH Abuser (27 y/o, Female) 3 months detox METH Abuser (27 y/o, Female) 13 months detox Source: Wang, G-J et al., Am J Psychiatry 161:2, February 2004. Medical and Psychosocial Effects of Methamphetamine Organ Toxicity from MA Abuse • • • • • Central nervous system toxicity Cardiovascular toxicity Pulmonary toxicity Renal toxicity Hepatic toxicity Cardiovascular problems • • • • • • ↑ heart rate Palpitations Arrhythmia ↑ blood pressure Chest Pain Valve thickening Neurological problems • • • • • Seizures Stroke Cerebral hemorrhage Cerebral vasculitis Mydriasis Respiratory problems • Dyspnea • Pulmonary hypertension • Pleuritic chest pain Renal / Hepatic Toxicity from MA Abuse • • Renal failure Hepatic failure Other problems • Eye ulcers • Over-heating • Rhabdomyolysis • Obstetric complications • Anorexia / weight loss • Tooth wear, cavities • “Speed bumps” Trauma • Interpersonal trauma • • Assault Gunshot Knife Motor Vehicles Suicide attempts Acute Methamphetamine Intoxication It feels like excitement Methamphetamine Acute Physical Effects Increases Heart rate Blood pressure Pupil size Respiration Sensory acuity Energy Decreases Appetite Sleep Reaction time Methamphetamine Acute Psychological Effects Increases Confidence Alertness Mood Sex drive Energy Talkativeness Decreases Boredom Loneliness Timidity Chronic Methamphetamine Effects It feels like excitement gone bad… Methamphetamine Chronic Psychological Effects Confusion Concentration Hallucinations Fatigue Memory loss Insomnia Irritability Paranoia Panic reactions Depression Anger Psychosis Methamphetamine Chronic Physical Effects Tremor Weakness Dry mouth Weight loss Cough Sinus infection Sweating Burned lips; sore nose Oily skin/complexion Headaches Diarrhea Anorexia 9 years of Meth use… 32 years old 41 years old METH ADDICTED 7-03-94 2-20-93 2-18-94 Faces of Methamphetamine Images courtesy Multnomah County Sheriff’s Office Methamphetamine Chronic Physical Effects Tremor Weakness Dry mouth Weight loss Cough Sinus infection Sweating Burned lips; sore nose Oily skin/complexion Headaches Diarrhea Anorexia Methamphetamine Psychiatric Consequences Paranoid reactions Permanent memory loss Depressive reactions Hallucinations Psychotic reactions Panic disorders Rapid addiction MA Treatment Issues Acute MA Overdose Acute MA Psychosis MA “Withdrawal” Initiating MA Abstinence MA Relapse Prevention Protracted Cognitive Impairment and Symptoms of Paranoia Acute MA Overdose Slowing of Cardiac Conduction Ventricular Irritability Hypertensive Episode Hyperpyrexic Episode CNS Seizures and Anoxia Acute MA Psychosis Extreme Paranoid Ideation Well Formed Delusions Hypersensitivity to Environmental Stimuli Stereotyped Behavior “Tweaking” Panic, Extreme Fearfulness High Potential for Violence Treatment of MA Psychosis • Typical ER Protocol for MA Psychosis Haloperidol - 5mg Clonazepam - 1 mg Cogentin - 1 mg Quiet, Dimly Lit Room Restraints Methamphetamine and Sex Percent Responding "Yes" Q.1: My sexual thoughts, feelings, and behaviors are often associated with … 100 90 80 70 60 50 40 30 20 10 0 73.5 68.4 53.7 52.9 44.4 23.4 22.7 opiates male female 22.2 alcohol cocaine Primary Drug of Abuse meth Percent Responding "Yes" Q.2: My sexual drive is increased by the use of … 100 90 80 70 60 50 40 30 20 10 0 85.3 70.6 55.6 55.3 43.9 male female 18.1 20.5 11.1 opiates alcohol cocaine Primary Drug of Abuse meth Percent Responding "Yes" Q.4: My sexual performance is improved by the use of … 100 90 80 70 60 50 40 30 20 10 0 58.8 61.1 32.4 male female 24.4 19.1 18.4 15.9 11.1 opiates alcohol cocaine Primary Drug of Abuse meth Percent Responding "Yes" Q.10: I am more likely to have sex (e.g., intercourse, oral sex, masturbation, etc.) when using … 100 90 80 70 60 50 40 30 20 10 0 79.4 65.8 61.1 50.0 41.5 male female 27.8 7.4 11.4 opiates alcohol cocaine Primary Drug of Abuse meth Percent Responding "Yes" Q.12: I am more likely to practice “risky” sex under the influence of … (e.g., not use condoms, be less careful about who you choose as a sex partner, etc.) 100 90 80 70 60 50 40 30 20 10 0 57.9 55.6 48.8 52.9 35.3 male female 16.7 4.3 6.8 opiates alcohol cocaine Primary Drug of Abuse meth Methamphetamine and HIV in MSM: Time-to-Response Association? 100 90% Percent HIV+ 80 62% 60 41% 40 20 0 26% 8% Probability Sample* Recreational User** Chronic Non Treatment*** Outpatient Drug-Free**** Residential**** * Deren et al., 1998, Molitor et al., 1998; ** Reback et al., in prep, *** Reback, 1997; **** Shoptaw et al., 2002; ****VNRH, unpublished data www.drugabuse.gov Blood Pressure Investigational Medication for High Blood Pressure Before Tx Tx Tx Removed Treatment Works!!! Symptom Severity Investigational Medication for Asthma Before Tx Tx Tx Removed Treatment Works!!! Level of Use New Behavioral Treatment for Methamphetamine Use Before Tx Tx Tx Removed Treatment Failed!!! 100 90 80 40 30 20 50 to 70% 50 30 to 50% 60 50 to 70% 70 40 to 60% Percent of Patients Who Relapse Relapse Rates Are Similar for Drug Dependence and Other Chronic Illnesses 10 0 Drug Type I Hypertension Asthma Dependence Diabetes Source: McLellan, A.T. et al., JAMA, Vol 284(13), October 4, 2000. Treatment Medical & Behavioral Drugs Sedatives Stimulants Opioids Alcohol Medical Treatment Behavioral Treatment Yes No Yes Yes Yes Yes Yes Yes Methamphetamine Addiction Pharmacotherapies in Clinical Trials Phase I Aripiprazole Atomoxetine Bupropion Carvedilol Clonidine Lobeline Modafinil Perindopril Prazosin Rivastigmine Sertraline Topiramate Phase II Baclofen Bupropion Treatments for Methamphetamine • Cognitive Behavioral Therapies • Contingency Management • MATRIX Model • New Medications (treatment and overdose) are being developed Clinical Challenges for Treatment of Methamphetamine Addiction • • • • • • • Poor treatment engagement rates High dropout rates Severe paranoia High relapse rates Ongoing episodes of psychosis Severe craving Protracted dysphoria Many patients may require medical/psychiatric supervision and need ongoing treatment with antipsychotic medications Manuals in Psychosocial Treatment • • • • • Reduce therapist differences Ensure uniform set of services Can more easily be evaluated Enhance training capabilities Facilitate research to practice Stages of Change Relapse Permanent Exit Maintenance Action Precontemplation Contemplation Determination Prochaska & DiClemente Motivation Interviewing Goals • • • • Increase Motivation Decrease Resistance Increase retention Better outcomes Four Principles of Motivational Interviewing 1. Express empathy 2. Develop discrepancy 3. Avoid argumentation 4. Support selfefficacy BUILDING MOTIVATION OARS •Open-ended questioning •Affirming •Reflective listening •Summarizing MATRIX MODEL TREATMENT Components of Stimulant Addiction Syndrome Behavioral Disruption Cognitive Disruption Emotional Disruption Family/Relationship Disruption STAGES OF RECOVERY STIMULANTS OVERVIEW DAY DAY DAY DAY 0 15 45 120 DAY 180 Stages of Recovery - Stimulants WITHDRAWAL STAGE PROBLEMS ENCOUNTERED DAY DAY 0 15 •Medical Problems •Alcohol Withdrawal •Depression •Difficulty Concentrating •Severe Cravings •Contact with Stimuli •Excessive Sleep MATRIX MODEL TREATMENT Primary Manifestation of Withdrawal Stage Behavioral Cognitive Behavioral Inconsistency Confusion Inability to Concentrate Emotional Relationship Depression/AnxietySelf-Doubt Mutual HostilityFear Matrix Model Treatment Key Concept: Structure •Self-designed structure (scheduling) •Eliminate avoidable triggers •Makes concrete the concept of “One day at a time” •Reduces anxiety •Counters the addict lifestyle •Provides basic foundation for ongoing recovery MATRIX MODEL TREATMENT STRUCTURE Recreational/Leisure Activities Treatment Program Activities 12-Step Meetings Sports Time Scheduling Work School Being with Drug-free Friends Exercise Family-related Events Church/Synagogue Island Building MATRIX MODEL TREATMENT Structure - Pitfalls •Scheduling unrealistically •Neglecting recreation •Being perfectionistic •Therapist imposing schedule •Spouse/parent imposing schedule Adaptations to the Matrix Model Stages of Recovery - Stimulants HONEYMOON STAGE DAY DAY 15 45 •Over-involvement With PROBLEMS Work ENCOUNTERED •Overconfidence •Inability to Initiate Change •Inability to Prioritize •Alcohol Use •Episodic Cravings •Treatment Termination MATRIX MODEL Primary Manifestation of Honeymoon Stage Behavioral High EnergyUnfocused Behavior Emotional Overconfidence/ Feeling Cured Cognitive Inability to Prioritize Relationship Denial of Addiction Disorder MATRIX MODEL TREATMENT INFORMATION MATRIX MODEL TREATMENT Information - What - Substance abuse and the brain - Sex and recovery - Relapse prevention issues - Triggers and cravings - Emotional readjustment - Stages of recovery - Medical effects - Relationships and recovery - Alcohol/marijuana MATRIX MODEL TREATMENT Information - Why •Reduces confusion and guilt •Explains addict behavior •Gives a roadmap for recovery •Clarifies alcohol/marijuana issue •Aids acceptance of addiction •Gives hope/realistic perspective for family MATRIX MODEL TREATMENT Relapse Factors - Honeymoon Stage •Overconfidence •Secondary alcohol or other drug use •Discontinuation of structure •Resistance to behavior change •Return to addict lifestyle •Inability to prioritize •Periodic paranoia Stages of Recovery - Stimulants THE WALL STAGE DAY DAY 45 120 •Return to Old Behaviors •Anhedonia PROBLEMS •Anger ENCOUNTERED •Depression •Emotional Swings •Unclear Thinking •Isolation •Family Problems •Cravings Return •Irritability •Abstinence Violation MATRIX MODEL Primary Manifestation of the Wall Stage Behavioral Cognitive Sluggish Low Energy/Inertia Relapse Justification Emotional Relationship Depression/Anhedonia Irritability/ Mutual Blaming/Impatience Return to Old Behaviors Anhedonia Anger Depression Emotional Swings Unclear Thinking Isolation Family Problems Cravings Return Irritability Abstinence Violation Key Concept: Relapse Justification •Definition •The rational part of the brain attempts to provide a logical explanation for justifying behavior which moves the client closer to his drug of choice •Relapse thoughts gain power when not openly recognized and discussed Associates Use; Justifies Own Use •My wife used so… •I was doing fine until he brought it home… •I went to the beach with my sister and … •My brother came over for dinner and brought some… •I wanted to see my friend just once more and he offered me some... I Needed it for a Specific Purpose •I was getting fat again and needed to control my weight •I couldn’t get the energy I needed without it •I can’t have a satisfying sexual experience without it •Life is too boring without… •I can’t be comfortable in social situations without it •I don’t know how to meet people without the “social lubricant”, cocaine magnet, etc. Relapse Factors - The Wall Stage - Increased emotions - Dissolution of structure - Interpersonal conflict - Behavioral drift - Relapse justification - Secondary alcohol or - Anhedonia/loss of motivation - Insomnia/low energy/fatigue other drug use - Resistance to exercise - Paranoia Stages of Recovery - Stimulants ADJUSTMENT AND RESOLUTION STAGES DAY DAY 120 180 •Relationship Problems •Boredom PROBLEMS ENCOUNTERED •Career Dissatisfaction •Lack of Goals • Guilt and Shame • Underlying Psychopathology May Surface or Resurface MATRIX MODEL Primary Manifestation of Adjustment Stage Behavioral Sloppiness Regarding Limits Cognitive Drifting From Commitment to Recovery Emotional Relationship Experiencing Normal Emotions Surfacing of Long-Term Issues Lack of Goals Relationship Problems Guilt and Shame Boredom Career Dissatisfaction Underlying Psychopathology May Surface or Resurface Relapse Factors - Adjustment Stage •Secondary alcohol or other drug use •Relaxation of structure •Struggle over acceptance of addiction •Maintenance of recovery momentum/commitment •Six-month syndrome •Re-emergence of underlying pathology Results from the CADDs Data System (2001) *The statewide data collection system, CADDs has information on the relative usefulness of treatment for MA users, by comparing them to cocaine users. Predictors of Retention in Treatment for more than 90 days 1. Higher rates of retention for men 2. Legal supervision increases treatment retention 3. Injection users were retained more poorly 4. 5. 6. 7. Those with chronic mental illness were retained more poorly Daily users are retained more poorly than those who use less often than daily Those who began use at an older age were retained better than those who started when younger Those who are older at admission were retained better Successful Outpatient Treatment Predictors • • • • • • Durations over 90 days (with continuing care for another 9 months). Techniques and clinic practices that improve treatment retention are critical. Treatment should include 3-5 clinic visits per week for at least 90 days. Employ CBT, CM, Community Reinforcement Approach, Motivational Interviewing, Matrix Model. Family involvement and 12-step program appear to improve outcome. Urine testing (at least weekly is mandatory) Optimal candidates for outpatient treatment include: • • Those who do not inject MA. Those without chronic mental illness and those without significant psychiatric symptoms at admission. • Those who are using MA less than daily at admission. • Those under legal supervision (especially drug court). • Older individuals (over 21)Those who are not disabled. • Those who have a stable living situation (without active drug users). Special treatment consideration should be made for the following groups of individuals: • • • Female MA users (higher rates of depression; very high rates of previous and present sexual and physical abuse; responsibilities for children). Injection MA users (very high rates of psychiatric symptoms; severe withdrawal syndromes; high rates of hepatitis). MA users who take MA daily or in very high doses. Special treatment consideration should be made for the following groups of individuals: • • • Homeless, chronically mentally ill and/or individuals with high levels of psychiatric symptoms at admission. Individuals under the age of 21. Gay men (at very high risk for HIV and hepatitis).