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The UCLA Integrated Substance Abuse Programs (ISAP) conducts research, provides research training and clinical training, and arranges treatment for substance abuse disorders in coordination with the UCLA Department of Psychiatry and Biobehavioral Sciences and in affiliation with other community-based treatment providers. ISAP efforts span the spectrum of scientific and clinical activities pertinent to the investigation and amelioration of substance abuse and related consequences. ISAP work ranges from epidemiological and policy studies to basic science and human laboratory programs to clinical trials of treatments involving innovative behavioral and pharmacological approaches.

Past UCLA ISAP Methamphetamine Studies



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Aerobic Exercise to Improve Outcomes of Treatment
for Methamphetamine Dependence
Richard A. Rawson, Ph.D., Principal Investigator (rrawson@mednet.ucla.edu)
Christopher Cooper, MD;  Edythe London, PhD, & Larissa Mooney, MD, Co-Investigators
Joy Chudzynski, Psy.D., Project Director (joychud@ucla.edu)

This five-year study, funded by NIDA, seeks to assess the efficacy of aerobic and resistance exercise for the treatment of methamphetamine dependence in a population of 150 individuals in residential treatment. After signing consent and satisfying all inclusion requirements, participants undergo baseline assessments during approximately two weeks of treatment as usual. After randomization, participants enter either the Education condition, consisting of 45- to 50-minute health education sessions three times per week for 8 weeks (n=75), or the Exercise condition, consisting of aerobic and resistance exercise three times per week for 8 weeks (n=75).

The primary goal of the study is to determine whether inclusion of aerobic and resistance exercise within a residential program improves treatment outcomes in terms of reduced methamphetamine use during the first 12 weeks after discharge and at a 26-week follow-up, as well as to characterize effects of exercise on health, psychiatric symptoms and cognition compared to the control (education) group at pre/post intervention.

Of the 150 participants, a subset of voluntary participants will take part in a brain imaging sub-study. This sub-study will use Positron Emission Tomography (PET) and Magnetic Resonance Imaging (MRI) scans to see if cells in the brain change after therapy and treatment for methamphetamine dependence. Specifically, we will see if group participation (exercise or education group) changes the availability of dopamine in the brain.

Aerobic Exercise to Improve Outcomes of Treatment for Methamphetamine Dependence was funded by the National Institute on Drug Abuse, grant 1R01DA027633-01 (September 2009 to August 2014).

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A Phase 2, Double-Blind, Placebo-Controlled Trial of
Bupropion for Methamphetamine Dependence
Walter Ling, M.D., Principal Investigator (lwalter@ucla.edu)
Richard Rawson, Ph.D., Site Principal Investigator
Valerie Pearce, M.P.H., Project Director

This project is a multi-site double-blind, placebo-controlled, parallel-group design study targeting methamphetamine users in which, participants are randomly assigned to  receive either placebo or bupropion daily for 12 weeks. Participants also receive group Cognitive Behavioral Therapy (CBT) three times weekly along with weekly assessments to collect information on status and functioning. Additional follow-up assessments occur weekly for 4 weeks after completion of study interventions.   Eligibility criteria includes methamphetamine use on 29 or fewer days (non-daily use) during the 30 days prior to signing consent.

The primary goal of this study is to assess the efficacy of bupropion in reducing methamphetamine use in participants using methamphetamine use on 29 or fewer days during the 30 days prior to signing consent. It is hypothesized that bupropion, compared to placebo, will be associated with an increase in the proportion of subjects who achieve abstinence (confirmed by at least two methamphetamine negative urines) each week during the last two weeks (Weeks 11 and 12) for non-daily users as the primary outcome.

A Phase2, Double-Blind, Placebo-Controlled Trial of Bupropion for Methamphetamine Dependence was funded by the National Institute on Drug Abuse, grant number N01 DA-3-8824, from September 2007 to December 2010.

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Double-Blind, Placebo-Controlled Trial of Prometa Pharmacotherapy for the
Treatment of Methamphetamine Abuse
Walter Ling, M.D., Principal Investigator (lwalter@ucla.edu)
Maureen Hillhouse, Ph.D., Project Director

This study assessed the efficacy of the PROMETAÔ pharmacotherapy compared to placebo for initiating abstinence and for preventing relapse to methamphetamine (MA) use in treatment-seeking individuals meeting criteria for MA abuse in multiple treatment locations. The study design included random assignment to pharmacotherapy condition, and both participants and study personnel were blinded to assigned condition. Screening verified participant eligibility and collected demographic, drug use, psychiatric, and neuropsychological information before participants were randomly assigned to either the PROMETA pharmacotherapy condition or to the placebo condition. Pharmacotherapy included 2 infusion phases (starting at Day 0, and again at Day 21) in addition to 40 days of oral medications. Participants were also provided with weekly cognitive behavioral therapy for the duration of the study. Weekly assessments collected information to evaluate medical and psychological status throughout the 15-week study. Drug use outcomes were measured using self-report, verified by biological markers of abstinence (urine tested for metabolites of MA, cocaine, heroin, marijuana, and benzodiazepines).  Analyses of  participants who received at least one day of medication dosing are underway, and included 55 participants who received the  PROMETA pharmacotherapy and 56 participants who received matching placebo. (Additional information is available at www.hythiam.com.)

Double-Blind, Placebo-Controlled Trial of Prometa Pharmacotherapy for the Treatment of Methamphetamine was funded by Hythiam, Inc., Clinical Trial 05072347 (March 2005 through December 2008).

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Duloxetine for Depressed Substance Abusers
Suzette Glasner-Edwards, Ph.D., Principal Investigator (sglasner@ucla.edu)
Richard A Rawson, Ph.D., and Walter Ling, M.D., Co-Investigators

This pilot study examines the efficacy of duloxetine combined with group psychotherapy for individuals with stimulant dependence and comorbid major depressive disorder. Although the past decade has seen new pharmacological and psychological interventions producing improvement in substance use outcomes, few studies have systematically explored the efficacy of these approaches in combination in patients with substance use disorders and comorbid mental health disorders. This open-label trial will include 20 dually diagnosed individuals with stimulant dependence and Major Depressive Disorder. We will examine the efficacy of 12 weeks of treatment with duloxetine and group psychotherapy on outcomes for depression and substance use. The primary hypothesis is that duloxetine in conjunction with psychotherapy will produce reductions in depressive symptoms and stimulant use. This is an open-label, prospective pilot study without an active comparator or placebo arm. The preliminary data gathered in this investigation will inform the potential significance and feasibility of a subsequent randomized, controlled trial for treatment of depressed adults with concomitant substance use disorders.

Duloxetine For Depressed Substance Abusers was funded by the Eli Lilly Corporate Center, Contract number: F1J-US-X046 (October 2007 to September 2009).

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Four Models of Telephone Support
for Stimulant Recovery
David Farabee, Ph.D., Principal Investigator (dfarabee@ucla.edu)
Richard Rawson, Ph.D., & Mitchell Karno, Ph.D, Co-Investigators
Valerie Pearce, MPH, Project Director
Sarah Cousins, B.S., B.A., Project Coordinator

The purpose of this study is to develop and compare the efficacy of four low-cost, telephone support protocols for patients who have completed the intensive phase of a structured, outpatient stimulant abuse treatment protocol. Patients (N = 300) who have successfully completed a Primary Outpatient model of stimulant abuse treatment are randomly assigned to one of five aftercare counseling conditions: (1) unstructured/non-directive, (2) unstructured/directive, (3) structured/non-directive, (4) structured/directive, or (5) standard referral to aftercare without telephone counseling (control). The two structured conditions are based on the behavioral “prompts” identified by Farabee et al. (2002) as being associated with drug avoidance. In the non-directive conditions, patients state their own goals and how they intend to achieve them. In the directive conditions, the coaches provide specific recommendations for the adoption of as many drug-avoidance activities as possible. Certain patient personality traits or styles are also assessed for their possible interaction with the telephone counseling dimensions. Outcomes will be tracked at 3 and 12 months following completion of primary treatment and will include measurement of participation in drug-avoidance activities (including aftercare participation), as well as self-reported and objective measures of substance use and associated prosocial behavior change.

Four Models of Telephone Support for Stimulant Recovery was funded by the National Institute on Drug Abuse, Grant 1 R01 DA018208 (August 2005 through July 2010).

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Medication Development for
Stimulant Dependence (MDS)
Walter Ling, M.D., Principal Investigator (lwalter@ucla.edu)

Outstanding facilities and appropriately trained staff experienced in the conduct of clinical trials provides UCLA ISAP with a superior reputation in the area of medication development for stimulant dependence. UCLA ISAP serves as one of only a few medication development groups across the nation contracted with the National Institute on Drug Abuse to investigate the effectiveness of new medications for stimulant dependence in Phase I and Phase II research. Each umbrella contract includes a mechanism whereby proposed investigations are offered through a task order to a MDS group for clinical trial research. The specific study is funded according to the pertinent aims, scope, and design of the protocol, and includes a study team led by a principal investigator named by Dr. Ling. Individual studies are typically administered in conjunction with investigators affiliated with the UCLA Department of Family Medicine and the UCLA Department of Psychiatry and Biobehavioral Sciences.

The MDS contract focuses on medication development for stimulant abuse by evaluating medications in the context of carefully metered doses of specific behavioral therapies, by advancing measurement and analysis strategies, and by increasing the efficiency of the clinical trials processes. From extensive research experience conducting medication trials for pharmacological and behavioral treatments for drug dependence, the MDS project contributes to the knowledge base regarding treatments for stimulant abuse. Innovative work is also possible through collaborative efforts with the UCLA ISAP Center grant for research addressing pharmaceutical treatment for stimulant abuse (see “UCLA Medication Development Unit for Stimulant Abuse”). Until recently, the MDS also served as the umbrella contract for the Methamphetamine Clinical Trials Group (MCTG), tasked with investigating medications specifically for methamphetamine-dependent individuals.

Medication Development for Stimulant Dependence (MDS) was funded by the National Institute on Drug Abuse, Grant N01DA-3-8824 (January 2003 through February 2010).

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Methamphetamine Abuse: Long-Term Trajectories, Correlates, Treatment Effects
Mary-Lynn Brecht, Ph.D., Principal Investigator (lbrecht@ucla.edu)
Diane Herbeck, MA, Project Director

 The project is a follow-up of 596 previously studied methamphetamine (meth) users, half recruited from drug treatment participation in Los Angeles County and half with no prior meth treatment at recruitment. The project uses the Natural History Interview to collect detailed histories of substance use, treatment, and criminal careers; these new data combined with previously collected data will produce life course trajectories averaging at least 28 years in duration, covering teen and adult periods. Additional data will come from administrative records from several state agencies. The sample is 35% female/65% male, 33% Hispanic/38% non-Hispanic White/17% African-American/12% other ethnicity, and will be 28-74 years of age (average 42) at beginning of the follow-up study. Analyses will describe the current status and extended patterns of meth and other substance use including escalation, deceleration, and possible cessation and recovery; examine drug treatment utilization patterns and relationship to meth use patterns; describe health morbidity and mortality; assess long-term outcomes (14 or more years) of a previously identified drug treatment episode (for the subsample recruited from treatment); and estimate cumulative social costs of meth abuse for the sample in terms of criminal activity, incarceration, and drug treatment, health, and mental health services utilization. Analysis methods will include growth models and growth mixture models.

Methamphetamine Abuse: Long-Term Trajectories, Correlates, Treatment Effects was funded by the National Institute on Drug Abuse, grant 1 R01 DA025113-01A1, from July 2009 to May 2013.

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METH INSIDE OUT Video Series
Thomas Freese, Ph.D., Principal Investigator (tefreese@ix.netcom.com)

METH INSIDE OUT is a groundbreaking video-based treatment curriculum on methamphetamine addiction and recovery. The series is designed to equip meth users, their families and the professionals who assist them with a solid understanding of the neurological basis of addiction, effective tools for recovery, and, most importantly, hope for the future. Presented by UCLA, the world leaders in methamphetamine research, and Eyes of the World Media Group, this research-based series presents the most up-to-date information in a compelling and easy-to-understand format. METH INSIDE OUT emphasizes the human impact of addiction by sharing personal stories of users and their families. Shot in high definition with state-of-the-art graphics, the series goes beyond presenting information by engaging and inspiring viewers. Created for maximum flexibility, the curriculum is designed to meet the needs of treatment centers, jails/prisons, community centers, social service agencies and universities. The series is comprised of five episodes, which can be used individually or as a set. Companion Leader’s Guides allow counselors to maximize the educational potential of each episode. After an initial overview episode (The Human Impact), two subsequent episodes focus on the brain and behavior (Brain & Behavior), and treatment (Windows to Recovery).

Methamphetamine Video Series was funded by the State of California Alcohol and Drug Programs, Contract 06-00169 (June 2007 to June 2009).

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Mindfulness-Based Relapse Prevention for Stimulant Users
Suzette Glasner-Edwards, Ph.D., Principal Investigator (sglasner@ucla.edu)
Richard Rawson, Ph.D., Larissa Mooney, M.D., Co-Investigators

The objective of the current research is to improve treatment for stimulant dependence by augmenting traditional relapse prevention therapy with innovative meditation-based strategies to promote affect regulation skills. Based on Mindfulness-Based Cognitive Therapy for depression (Segal, Teasdale, & Williams, 2002), Marlatt and colleagues recently developed a manualized intervention for the treatment of substance-using populations: Mindfulness Based Relapse Prevention (MBRP). The specific aims of this research are (1) To conduct a pilot randomized clinical trial comparing MBRP relative to a health education (ED) control group in stimulant users receiving contingency management (CM). (2) To test the impact of MBRP compared to ED on negative affect, stimulant use, and healthcare outcomes. (3) To evaluate the differential effects of MBRP versus ED on HIV-risk behavior of participants, and (4) To examine potential mechanisms of action of MBRP, including reductions in stress reactivity and biological indicators of arousal (e.g., blood pressure and heart rate).  We hypothesize that MBRP will be more efficacious than ED in reducing negative affect and stimulant use. Further, we expect that MBRP will produce greater reductions in HIV-risk behaviors, stress reactivity, and arousal, and these changes will be associated with substance use outcomes. By providing coping skills to address affect regulation and stress reactivity, two important factors in stimulant relapse, MBRP may provide a promising augmenting strategy for the treatment of stimulant users.

Mindfulness-Based Relapse Prevention for Stimulant Users was funded by the National Institute on Drug Abuse, grant 1 R21 DA029255, from April 2010 to March 2012.

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Motivational Therapy for Substance Users with Depression
Suzette Glasner-Edwards, Ph.D., Principal Investigator (sglasner@ucla.edu)
Anne Bellows, Project Director

This study examines the incremental efficacy of an aftercare  psychosocial treatment program of a motivational intervention combined with cognitive behavioral therapy (CBT), relative to standard care or treatment as usual (TAU) for individuals with alcohol or drug dependence and comorbid major depressive disorder. Although the past decade has seen new cognitive and motivational interventions producing improvement in substance use outcomes, few studies have systematically explored the efficacy of these approaches in combination in patients with substance use disorders and comorbid mental health disorders. This randomized psychosocial clinical trial will include 80 dually diagnosed individuals with alcohol or drug dependence and a substance-independent diagnosis of Major Depressive Disorder. Among patients receiving pharmacotherapy for depression, we will compare 12 weeks of CBT combined with motivational therapy (CBT-MT) to 12 weeks of treatment-as-usual (TAU) on 6, 12, and 24 week outcomes for depression, substance use, HIV-risk behaviors, and other healthcare outcomes. The primary hypothesis is that CBT-MT will produce better outcomes than TAU. We will also examine predictors of early attrition and treatment retention and examine neuropsychological predictors of treatment retention and outcome. The results of this study might provide a dual-diagnosis specific, cognitive- motivational alternative to traditional aftercare programs for the treatment of stimulant users with depression.   

Motivational Therapy for Stimulant Users with Depression was funded by the National Institute on Drug Abuse, Grant 1 K23 DA020085 (September 2007 to August 2012).

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Prenatal Methamphetamine Exposure
and School Age Outcome
Barry Lester, M.D., Brown University, Principal Investigator
Richard A. Rawson, Ph.D., Co-Investigator (rrawson@mednet.ucla.edu)
Jeffrey Annon, M.A., Project Director

The rapidly escalating abuse of methamphetamine (METH) in the United States, places a sense of urgency on understanding the consequences of METH use during pregnancy for the developing child. To our knowledge, IDEAL (Infant Development Environment and Lifestyle) is the only prospective longitudinal NIH study of prenatal METH exposure and child outcome. This is the continuation of a multi-site, longitudinal study that includes 4 diverse data collection sites, where METH use is prevalent (Iowa, Oklahoma, California, and Hawaii) and 3 data coordinating centers (Brown Center for the Study of Children at Risk- Core, the Data Management Center at UCLA and the Center for Substance Abuse Research (CESAR).  The responsibilities of the 3 data coordinating centers include study development and oversight, data management, communication and documentation. The children were enrolled at birth and assessed at multiple age points until 36 months old during Phase I of this study (IDEAL I). The cohort is now being followed during Phase II which spans the age range from 5 years old through 7.5 years old (IDEAL II).

We have followed 204 METH exposed and 208 Comparison children since birth. We are currently at an important age range when executive function neural networks develop and children make the critical transition to school. We are studying a relatively narrow band of executive function domain outcomes supported by the published preclinical and clinical literature and our own preliminary findings. We also plan to study how these executive function domains affect school related academic skills.

Our preliminary findings show effects of prenatal METH exposure on fetal growth, and on behavior between birth and 3 years on arousal-regulation, attention, and inhibitory control, with some effects due to heavy METH exposure. These effects suggest that motor development and precursors of executive function may be affected by prenatal METH exposure. We also found effects of psychosocial risk factors including low SES, family conflict, maternal psychiatric status and abuse potential, and out of home placement. We are in the process of studying the effects of prenatal METH exposure on emerging executive function domains including higher order motivation, attention, memory, inhibitory control, visual motor integration, and motor control, and how the effects of prenatal METH exposure are affected by psychosocial risk factors and by postnatal passive drug exposure (e.g., smoke).

Prenatal Methamphetamine Exposure and School Age Outcome was funded by the National Institute on Drug Abuse to Women & Infants Hospital with collaboration by UCLA ISAP (September 2007 through May 2012).

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Sustained-Release Methylphenidate for Management of
Methamphetamine Use Disorders
Walter Ling, M.D., Principal Investigator (lwalter@ucla.edu)
Maureen Hillhouse, Ph.D., Richard Rawson, Ph.D., Co-Investigators
Shannon Schroeder, B.A., Project Director

This study will evaluate the ability of sustained-release methylphenidate (MPH) to reduce stimulant abuse and increase treatment retention among a 90 individuals seeking treatment for methamphetamine dependence. Thefour-year double-blind, placebo-controlled study includes individuals seeking treatment for methamphetamine dependence, assessed using DSM-IV criteria. Eligible participants are enrolled for an initial two weeks to establish compliance and provide compensation for clinic attendance. After satisfactory adherence to clinic attendance requirements (at least 2 of 4 scheduled days during weeks 1-2), participants are randomized to placebo (n = 45) or MPH (n = 45). Active medication participants receive 18mg MPH/daily for week 3, 36mg/daily for week 4, and 54mg/daily for weeks 5-10. Placebo participants are given placebo prepared to appear identical to active medication. During the active medication phase, all participants will be provided with weekly group sessions of cognitive behavioral therapy (CBT), and motivational incentives (MI) provided for methamphetamine-negative urine test results. After the active medication phase, participants receive placebo (single blind) for the final four study weeks (weeks 11-14), and continue CBT and MI. 

Sustained-Release Methylphenidate for Management of Methamphetamine Use Disorders was funded by the National Institute on Drug Abuse, grant 1 R01 DA025084, from February 2009 to December 2012.

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The Oral and Dental Consequences of Methamphetamine Use
Debra A. Murphy, Ph.D., Principal Investigator (dmurphy@mednet.ucla.edu)
Vivek Shetty, DDS, Dr Med Dent, Co-Investigator
Rachel Fintzy, M.A., Project Director

The primary objectives of this study are:  to validate that the rates and patterns of dental caries and oral disease are substantially different in methamphetamine (MA) users than non-MA users; to characterize the relationship between dental consequences, patterns of MA-use and other individual characteristics; and to investigate the extent to which negative self-image among MA-users is associated with a willingness to seek treatment.

The Oral and Dental Consequences of Methamphetamine Use was funded by the NIH, Grant 1 R01 DA025680 to the UCLA Department of Dentistry (April 2010 to January 2014).

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Women, Methamphetamine, and Sex
Alison Hamilton, Ph.D., M.P.H. Principal Investigator (alisonh@ucla.edu)

This 5-year project focuses on the relationship between methamphetamine (MA) and sex among women MA users. Thirty women in residential treatment participated in in-depth interviews. They were asked about their history of using MA and other substances, their life experiences (including any trauma or abuse they may have experienced), and their perspectives on how MA has affected their lives, specifically, their intimate relationships and sexual behaviors. Now in the follow-up phase, these participants are being interviewed about their experiences since the first interview. Recovery, relapse, intimate relationships, and several other topics are being explored. As a career development award, the project also involved training for the principal investigator (PI) in public health and community health sciences. This study will add to the body of literature on the impact of substance abuse on life experiences. Considering that women who abuse substances such as MA typically have multiple factors placing them at risk for poor sexual decision-making (e.g., histories of violence and abuse), a more in-depth understanding of how women MA users conceptualize their sexual behaviors and experiences could assist in developing interventions for them. The PI’s co-mentors on the project are Drs. Richard Rawson (UCLA ISAP), Yih-Ing Hser (UCLA ISAP), and Vivian Brown (PROTOTYPES).

Women, Methamphetamine and Sex was funded by the National Institute on Drug Abuse, Grant 1 K01 DA017647 (April 2006 through March 2011).

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