Treatment of Methamphetamine Dependence: A brief overview Richard A. Rawson, Ph.D, Professor Semel Institute for Neuroscience and Human Behavior David Geffen School of Medicine University of California at Los Angeles Supported by: National Institute on Drug Abuse (NIDA) National Institute on Drug Abuse (NIDA) Pacific Southwest Technology Transfer Center (SAMHSA) Pacific Southwest Technology Transfer Center (SAMHSA) International Network of Treatment and Rehabilitation Resource Centres (UNODC)

Anhydrous Ammonia Tank Tips Officers to Possible Meth Lab 5/4/04 Omaha, Neb. – A large anhydrous ammonia tank helped Sarpy County Sheriff’s deputies bust a suspected methamphetamine lab Tuesday. SOURCE: TheOmahaChannel.com

Medical and Psychiatric Treatment Issues

Long-term effects of stimulants  Strokes, seizures, and headaches  Irritability, restlessness  Depression, anxiety, irritability, anger  Memory loss, confusion, attention problems  Insomnia  Paranoia, auditory hallucinations, panic reactions  Suicidal ideation  Sinus infection  Loss of sense of smell, nosebleeds, chronic runny nose, hoarseness  Dry mouth, burned lips  Worn teeth (due to grinding during intoxication)  Problems swallowing  Chest pain, cough, respiratory failure  Disturbances in heart rhythm and heart attack  Gastrointestinal complications (abdominal pain and nausea)  Loss of libido  Malnourishment, weight loss, anorexia  Weakness, fatigue  Tremors  Sweating  Oily skin, complexion

Cardiac Disorders and MA Use Coronary Syndromes ArrhythmiaCardiomyopathyHypertension Valvular Disease

Neurologic Disorders and MA Use HeadacheSeizureCerebrovascular –Ischemic stroke –Cerebral hemorrhage –Cerebral vasculitis Cerebral edema

Respiratory Disorders and MA Use Pulmonary edema Bronchitis Pulmonary hypertension COPD

Source: The New York Times, June 11, “ METH Mouth ” METH Use Leads to Severe Tooth Decay

–33 year old man, high on methamphetamine admitted to emergency room complaining of severe headache in Portland Oregon. –X-ray revealed 12, 2 inch nails (6 on each side) in his head, administered with aq nail gun. –The man at first claimed it was an accident, but he later admitted that it was a suicide attempt. The nails were removed, and the man survived without any serious permanent damage. –He was eventually transferred to psychiatric care; he stayed for almost one month under court order but then left against doctors’ orders MSNBC-TV

Methamphetamine Psychiatric Consequences Paranoid reactions Long term memory loss Depressive reactions Hallucinations Psychotic reactions Panic disorders Rapid addiction

My Sexual Pleasure is Enhanced by the use of: (Rawson et al., 2002)

My Sexual Performance is Improved by the use of: (Rawson et al., 2002)

BSI Psychiatric Symptoms by Route P<.05 Positive Symptom Total (PST)

Hepatitis C by Route P<.05

MA Treatment Issues Acute MA Overdose Acute MA Psychosis MA “Withdrawal” Initiating MA Abstinence MA Relapse Prevention Protracted Cognitive Impairment and Symptoms of Paranoia

MA “Withdrawal” - Depression- Paranoia - Fatigue- Cognitive Impairment - Anxiety- Agitation - Anergia- Confusion Duration: 2 days – 10 days

Clinical Challenges Clinical Challenges Poor treatment engagement rates High drop out rates Severe paranoia High relapse rates Ongoing episodes of psychosis Severe craving Protracted dysphoria Anhedonia

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. 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).

Medications Currently, there are no medications that can quickly and safely reverse life threatening MA overdose. There are no medications that can reliably reduce paranoia and psychotic symptoms, that contribute to episodes of dangerous and violent behavior associated with MA use.

Promising Pharmacotherapies? Newton, T. et al (Biological Psychiatry, Dec, 2005) Bupropion reduces craving and reinforcing effects of methamphetamine in a laboratory self-administration study. Elkashef, A. et al (recently completed; reported at the ACNP methamphetamine satelite meeting in Kona, Hawaii) Bupropion reduces meth use in an outpatient trial, with particularly strong effect with less severe users. Tiihonen, J. et al (recently completed; reported at the ACNP methamphetamine satelite meeting in Kona, Hawaii) Methylphenidate SR (sustained release) has shown promise in a recent Finnish study with very heavy amphetamine injectors.

Can Methamphetamine Users be Successfully Treated? Successful treatment of methamphetamine (MA) users employs many elements in common with treatment strategies for other groups of drug users. There is no evidence that MA users have poorer outcomes than other groups of drug users. However, with attention to some specific clinical issues and application of some specific clinical strategies, treatment outcomes can be substantially improved.

Clinical Challenges with Methamphetamine Dependent Individuals Limited Understanding of Addiction Cognitive Impairment Anhedonia Sexual Reactivity and Meth Craving Elevated Potential for Violence Persisting “Flashbacks”of Meth Paranoia Sleep Disorders Poor Retention in Outpatient Treatment Elevated Rates of Psychiatric Co-morbidity

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. 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).

Behavioral/Cognitive Behavioral Treatments Cognitive/Behavioral Therapy-CBT Motivational Interviewing-MI Contingency Management-CM 12 Step Facilitation Therapy Community Reinforcement Approach-CRA Matrix Model of Outpatient Treatment

Clinical Strategies to Enhance Treatment Outcomes with Methamphetamine Users Educate clients about the reality of MA addiction including: –biology impacted by MA; –conditioning factors that create craving; –common relapse scenarios (eg. drug using friends, alcohol, extended periods of unstructured time); –how MA impacts families; –potential benefits of mental health care; –relationship between participation in aftercare/community care and relapse/recidivism.

Clinical Strategies to Enhance Treatment Outcomes with Methamphetamine Users Employ varied adult learning formats to increase comprehension and retention of knowledge in view of cognitive deficiencies (especially verbal memory problems). Incorporate presentations by recovering MA users to reinforce treatment messages. Provide “workbooks” and learning aids on relapse prevention for clients to take with them into continuing care.

Clinical Strategies to Enhance Treatment Outcomes with Methamphetamine Users Strategies to reduce anhedonia and negative mood states, episodic paranoia, sleep problems (aerobic exercise, Yoga, Tai Chi, meditation) Anger management strategies (to cope with possible serotonergic dysregulation-induced irritability). Groups to address extensive maladaptive sexual behaviors and expectations. Whenever possible, educate family members about ways they can promote recovery.

Clinical Strategies to Enhance Treatment Outcomes with Methamphetamine Users During pre-release period (30 days?) emphasize relapse prevention tools, including time planning, identifying triggers and high risk situations, practice craving prevention/reduction strategies and behavioral strategies for saying “no”. To the extent possible make residential treatment and community aftercare as congruent and complimentary as possible. Coordinate treatment content, language, philosophy and recovery “message” between residential care and community aftercare.

Clinical Strategies to Enhance Treatment Outcomes with Methamphetamine Users The single most important factor for positive treatment outcome will be the degree to which clients are retained in post-residential treatment. –Use community care organizations with a continuum of care that can decrease and increase intensity of care when clinically indicated. –Create treatment plans that maximize compliance –Employ positive reinforcement (vouchers-contingency management) methods to promote retention and prosocial alternative behaviors. –Coordinate parole monitoring and treatment participation in community care. –Make mental health care available. –Involve family in community care services.

Treatments for Stimulant-use Disorders with Empirical Support Cognitive-Behavioral Therapy (CBT) Community Reinforcement Approach Contingency Management 12 Step Facilitation All have demonstrated efficacy for the treatment of cocaine dependence

Methamphetamine Treatment: Controlled Clinical Trials Brief Cognitive Behavioral Therapy Extended Cognitive Behavioral Therapy Contingency Management Matrix Model

Brief cognitive behavioural interventions for regular amphetamine users: a step in the right direction Design: RTC Intervention: 2 session vs 4 session CBT Findings The main finding of this study was that there was a significant increase in the likelihood of abstinence from amphetamines among those receiving two or more treatment sessions. In addition, the number of treatment sessions attended had a significant short-term beneficial effect on level of depression. There was a marked reduction in amphetamine use among this sample over time and, apart from abstinence rates and short-term effects on depression level, this was not differential by treatment group. Reduction in amphetamine use was accompanied by significant improvements in stage of change, benzodiazepine use, tobacco smoking, polydrug use, injecting risk-taking behaviour, criminal activity level, and psychiatric distress and depression level. Baker, et al; Addiction: Vol 100, March 2005

Cognitive Behavioral Therapy and Contingency Management for Stimulant Dependence Design Randomized clinical trial. Participants Stimulant-dependent individuals (n = 171). Intervention CM, CBT, or combined CM and CBT, 16-week treatment conditions. CM condition participants received vouchers for stimulant-free urine samples. CBT condition participants attended three 90-minute group sessions each week. CM procedures produced better retention and lower rates of stimulant use during the study period. Results Self-reported stimulant use was reduced from baseline levels at all follow-up points for all groups and urinalysis data did not differ between groups at follow-up. While CM produced robust evidence of efficacy during treatment application, CBT produced comparable longer-term outcomes. There was no evidence of an additive effect when the two treatments were combined. The response of cocaine and methamphetamine users appeared comparable. Conclusions: This study suggests that CM is an efficacious treatment for reducing stimulant use and is superior during treatment to a CBT approach. CM is useful in engaging substance abusers, retaining them in treatment, and helping them achieve abstinence from stimulant use. CBT also reduces drug use from baseline levels and produces comparable outcomes on all measures at follow-up. Rawson, RA et al. Addiction, Jan 2006

Contingency Management for treatment of methamphetamine dependence Design: RTC Method: 113 patients diagnosed with methamphetamine abuse or dependence were randomly assigned to receive either treatment as usual (TAU) or TAU plus contingency management. Results indicate that both groups were retained in treatment for equivalent times but those in the combined group accrued more abstinence and were abstinent for a longer period of time. These results suggest that contingency management has promise as a component in methamphetamine use disorder treatment strategies. Contingency Management for the Treatment of Methamphetamine Use Disorders. Roll, JM et al, Archives of General Psychiatry, (In Press)

Contingency Management A technique employing the systematic delivery of positive reinforcement for desired behaviors. In the treatment of methamphetamine dependence, vouchers or prizes can be “earned” for submission of methamphetamine-free urine samples.

12-Step Facilitation Therapy “ The therapist acts as a resource and advocate of the 12- Step approach to recovery”: – Explains the AA view of alcoholism, analyzes slips and resistance to AA in terms of disease of alcoholism and denial. – Introduces AA-Steps and concepts by applying these to patient history – Advocates Reliance on fellowship of AA and its role in ongoing recovery – 12 sessions 1:1

12-Step Facilitation Therapy 12-step Facilitation Manual can be downloaded from the NIAAA web site Book: 12-Step Facilitation Handbook, by Nowitzki and Baker

Matrix Model in Treatment of Methamphetamine Dependence Design: The study was conducted as an eight-site randomized clinical trial. Method: 978 treatment-seeking, MA-dependent persons were randomly assigned to receive either TAU at each site, or a manualized 16-week treatment (Matrix Model) for their MA dependence. Results: Analyses of study data indicate that in the overall sample, and in the majority of sites, those who were assigned to Matrix treatment attended more clinical sessions, stayed in treatment longer, provided more MA-free urine samples during the treatment period, and had longer periods of MA abstinence than those assigned to receive TAU. Measures of drug use and functioning collected at treatment discharge and 6 months post-admission indicate significant improvement by participants in all sites and conditions when compared to baseline levels, but the superiority of the Matrix approach did not persist at these two time points. Conclusions: Study results demonstrate a significant initial step in documenting the efficacy of the Matrix approach. Although the superiority of the Matrix approach over TAU was not maintained at the posttreatment time points, the in-treatment benefit is an important demonstration of empirical support for this psychosocial treatment approach. Rawson, R et al Addiction vol 99, 2004

Matrix Model Is a manualized, 16-week, non-residential, psychosocial approach used for the treatment of drug dependence. Designed to integrate several interventions into a comprehensive approach. Elements include : –Individual counseling –Cognitive behavioral therapy –Motivational interviewing –Family education groups –Urine testing –Participation in 12-step programs

Days of Methamphetamine Use in Past 30 (ASI) Possible is 0-30; t paired =20.90; p-value<0.000 (highly sig.)

Mean Number of Weeks in Treatment

Mean Number of UA’s that were MA-free during treatment

Urinalysis Results Results of Ua Tests at Discharge, 6 months and 12 Months post admission ** Matrix GroupTAU Group D/C: 66% MA-free 65% MA-free 6 Ms: 69% MA-free 67% MA-free 12 Ms: 59% MA-free 55% MA-free **Over 80% follow up rate in both groups at all points

Predictors of In-treatment Performance and Post- Treatment Outcomes in a Methamphetamine-Dependent Adults

Analyses In-Treatment: Immediate Drop Out (within 2 wks) Drop Out (within 30 days) Retention (weeks) Retention (stayed for 90+ days) Abstinence during Treatment Continued abstinence (3 consecutive clean UAs) Treatment Completion Post-Treatment: Methamphetamine Use/Abstinence

Predictors of Long-Term Abstinence Predictors of no MA use at treatment discharge, and at the 6- and 12-mos follow-ups includes: MA use of < 15 days at baseline, Lifetime MA use of < 2 years No previous drug abuse treatment Providing 3 consecutive MA-free UAs during treatment

Drug Courts and Methamphetamine Users Recently the marketing material for an experimental methamphetamine procedure costing $15,000 (Prometa/Hythiam) has reported what they considered extraordinarily high rates (98%+) of drug-free urine specimens in 2 pilot trials in drug court programs in Michigan and Washington State. An examination was conducted of the urinalysis data from 2 California drug court programs using more traditional treatments. –In one program treating meth users in Rancho Cucamonga Calif, over a 6 year period and over 40,000 urine samples, the rate of drug free samples was 96.5% –In a second drug court program in Hayward, California, over a 2 year period, with exclusively a meth population, the rate of drug free urine samples was 97.2%.

MSM-specific cognitive behavioral therapy and contingency management for the treatment of MSMs Design: Randomized clinical trial Methods: 162 MSM randomly assigned to one of 4 conditions; CM, CBT, CBT plus CM, MSM-specific CBT. Results: All conditions showed significant reductions in meth use by self-report and urinalysis, with CM and CM plus CBT showing significantly better reductions. Gay specific intervention also showed promise. Shoptaw et al Drug and Alcohol Dependence, 79, 2005

Sex Risks Reduced with Treatment: UARI Past 30 Days  2 (3) =6.75, p<.01

Low Threshold Treatment for Services MSM Methamphetamine Users Street outreach and field workers in clubs and bath houses Needle exchange Drop in centers for food, medical services “Safe House” Housing for homeless methamphetamine users HIV risk reduction groups employing peer and professional counseling. No empirical evidence at this point

Summary Methamphetamine is a significant public health problem in the US and in the world It produces significant damage to the body and the brain Recovery from methamphetamine dependence is possible and most brain changes are reversible. There are effective treatments for methamphetamine dependence.

Matrix Early Recovery Groups

Early Recovery Groups Scheduling and Calendars Triggers Questionnaires and Chart 12 Step Introduction Alcohol Issues Thoughts Emotions and Behaviors KISS (and other 12-step slogans)

Early Recovery Issues Engaging and Retaining TRIGGERS

Triggers and Cravings I.P. Pavlov ( )

Triggers and Cravings Pavlov’s Dog: UCR

Triggers and Cravings Pavlov’s Dog: CR

Early Recovery Issues Engaging and Retaining TriggerThoughtCravingUse

Trigger Thought Craving Use Early Recovery Issues Engaging and Retaining

MATRIX MODEL TREATMENT Triggers - Places Drug dealer’s home Bars and clubs Drug use neighborhoods Freeway offramps Worksite Street corners

MATRIX MODEL TREATMENT Triggers - Things Paraphernalia Sexually explicit magazines/movies Money/bank machines Music Movies/TV shows about alcohol and other drugs Secondary alcohol or other drug use

MATRIX MODEL TREATMENT Triggers - Times Periods of idle time Periods of extended stress After work Payday/AFDC payment day Holidays Friday/Saturday night Birthdays/Anniversaries

MATRIX MODEL TREATMENT Triggers - Emotional States  Anxiety  Fatigue  Anger  Boredom  Frustration  Adrenalized states  Sexual arousal  Sexual deprivation  Gradually building emotional states with no expected relief

THOUGHT STOPPING Prevents the thought from developing into an overpowering craving Requires practice TriggerThought Thought Stopping Continued ThoughtsUseCravings

MOTIVATIONAL INTERVIEWING Increase Motivation Decrease Resistance Increase retention Better outcomes

MATRIX MODEL TREATMENT STRUCTURE Treatment Program Activities Recreational/Leisure Activities 12-Step Meetings School SportsBeing with Drug-free Friends Time SchedulingExercise WorkFamily-related Events Church/SynagogueIsland Building

MATRIX MODEL TREATMENT INFORMATION

MATRIX MODEL TREATMENT Information - What - Substance abuse- Sex and recovery and the brain- 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

Triggers and Cravings Human Brain

Cognitive Process During Addiction Relief From Depression Anxiety Loneliness Insomnia Euphoria Increased Status Increased Energy Increased Sexual/Social Confidence Increased Work Output Increased Thinking Ability AOD Introductory Phase May Be Illegal May Be Expensive Hangover/Feeling Ill May Miss Work

Conditioning Process During Addiction Introductory Phase Triggers Parties Special Occasions Responses Pleasant Thoughts about AOD No Physiological Response Infrequent Use Strength of Conditioned Connection Mild

Development of Obsessive Thinking Introductory Phase Sports Food School TV Girlfriend Hobbies Job AOD Family Exercise Parties

Development of Craving Response Introductory Phase Entering Using Site Use of AODs AOD Effects  Heart/Pulse Rate  Respiration  Adrenaline  Energy  Taste

Cognitive Process During Addiction Maintenance Phase Depression Relief Confidence Boost Boredom Relief Sexual Enhancement Social Lubricant Vocational Disruption Relationship Concerns Financial Problems Beginnings of Physiological Dependence

Conditioning Process During Addiction Maintenance Phase Strength of Conditioned Connection Triggers Parties Friday Nights Friends Concerts Alcohol “Good Times” Sexual Situations Responses Thoughts of AOD Eager Anticipation of AOD Use Mild Physiological Arousal Cravings Occur as Use Approaches Occasional Use Moderate

Development of Obsessive Thinking Maintenance Phase AOD Food School TV Girlfriend Hobbies Job AOD Family Exercise Parties

Development of Craving Response Maintenance Phase Entering Using Site Physiological Response Use of AODs AOD Effects  Heart  Blood Pressure  Energy  Heart  Breathing  Adrenaline Effects  Energy Taste

Cognitive Process During Addiction Disenchantment Phase Social Currency Occasional Euphoria Relief From Lethargy Relief From Stress Nose Bleeds Infections Relationship Disruption Family Distress Impending Job Loss

Conditioning Process During Addiction Disenchantment Phase Strength of Conditioned Connection Triggers Weekends All Friends Stress Boredom Anxiety After Work Loneliness Responses Continual Thoughts of AOD Strong Physiological Arousal Psychological Dependency Strong Cravings Frequent Use STRONG

Development of Obsessive Thinking Disenchantment Phase AOD Food AOD TV Girlfriend AOD Job AOD Family AOD Parties AOD

Development of Craving Response Disenchantment Phase Thinking of Using Mild Physiological Response Entering Using Site  Heart Rate  Breathing Rate  Energy  Adrenaline Effects Powerful Physiological Response Use of AODsAOD Effects  Heart Rate  Breathing Rate  Energy  Adrenaline Effects  Heart  Blood Pressure  Energy

Cognitive Process During Addiction Disaster Phase Relief From Fatigue Relief From Stress Relief From Depression Weight Loss Paranoia Loss of Family Seizures Severe Depression Unemployment Bankruptcy

Conditioning Process During Addiction Disaster Phase Strength of Conditioned Connection Triggers Any Emotion Day Night Work Non-Work Responses Obsessive Thoughts About AOD Powerful Autonomic Response Powerful Physiological Dependence Automatic Use OVERPOWERING

Development of Obsessive Thinking Disaster Phase AOD

Development of Craving Response Disaster Phase Thoughts of AOD Using Place Powerful Physiological Response  Heart Rate  Breathing Rate  Energy  Adrenaline Effects

Outpatient Treatment Strategies Scheduling Treatment Programs Recreational/Leisure Activities 12-Step MeetingsSchool Sports Being with Drug-Free Friends Time Scheduling Exercise WorkFamily-related Events Church/SynagogueIsland Building

Matrix Relapse Prevention Groups

Matrix Relapse Prevention Group Topics (Sample) Alcohol -The Legal Drug Boredom Avoiding Relapse Drift/Mooring Lines Guilt and Shame Motivation for Recovery Truthfulness Work and Recovery Staying Busy Relapse Prevention Dealing with Feelings

Roadmap for Recovery Withdrawal Early Abstinence/Honeymoon Protracted Abstinence or The Wall Adjustment/Resolution

Roadmap for Recovery The Wall Return to Old Behaviors Anhedonia Anger Depression Emotional Swings Unclear Thinking Isolation Family Problems Cravings Return Irritability Abstinence Violation Protracted Abstinence

Other Components of the Matrix Model

Components Of The Matrix Model Family Education Lectures Conjoint Sessions Urine Testing Relapse Analysis Self help Initiation MATRIX

Thank you

Thank you