Clinical Trials and Medication Development Projects


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 18 or fewer days 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 18 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 participants who achieve abstinence, confirmed by at least two methamphetamine-negative urines,  each week during the final two weeks of treatment.

A Phase2, Double-Blind, Placebo-Controlledl Trial of Bupropion for Methamphetamine Dependence was funded by the National Institute on Drug Abuse, grant number N01 DA-3-8824, from April 2008 to September 2009.


A Randomized, Double-Blind, Cross-Over Trial Comparing the Analgesic Potency and
Side Effects of Buprenorphine+Ultra-Low-Dose Naloxone to Buprenorphine Alone

Walter Ling, M.D., Principal Investigator (lwalter@ucla.edu)
Jessica Jenkins, M.S., Project Director

The objective of this randomized, double-blind, crossover study is to determine whether treatment with IV buprenorphine in conjenction with ultra-low-dose naloxone results in increased analgesic potency, fewer side effects, and reduced opioid tolerance compared to treatment with IV buprenorphine alone.  Twelve participants with lingering pain (rated as 4-7 on a 0-10 likert pain scale) will be randomly assigned to a treatment order such that they will undergo treatment with one study drug for 5 days followed by a 7-day inter-trial interval, and finally treatment with the other drug for another 5 days.

A Randomized, Double-Blind, Cross-Over Trial Comparing the Analgesic Potency and Side Effects of Buprenorphine+Ultra-Low-Dose Naloxone to Buprenorphine Alone  was funded by the Reckitt-Benckiser, contract 20080605 number (April 2008 to March 2009).

Top of Page


Double-Blind, Placebo-Controlled Trial of Modafinil
for the Treatment of Methamphetamine Dependence

Richard A. Rawson, Ph.D., Principal Investigator (rrawson@mednet.ucla.edu)
Donnie W. Watson, Ph.D., & Mark Hrymoc, M.D., Co-Investigators
Valerie Pearce, B.A., Project Director

This double-blind, multicenter, placebo-controlled, randomized, parallel group design study on methamphetamine-dependent outpatients is coordinated through the Department of Veterans Affairs and the Cooperative Studies Program Coordinating Center. Subjects (N = 210) with DSM-IV criteria for methamphetamine (MA) dependence will be randomized to one of three treatment arms. Subjects will receive 200 mg modafinil, 400 mg modafinil or matched placebo daily for 12 weeks, with a follow-up assessment 4 weeks after treatment completion/termination.  All subjects will receive standardized manual-guided cognitive behavioral therapy (CBT) three times a week during the 12-week study drug administration period. Randomization to treatment groups will be done by stratifying by clinical site then using an adaptive randomization procedure  based on ADHD, gender, and frequency of historical self-report of MA use in the 30 days prior to informed consent (£ 18 vs. >18).

The modafinil protocol will be conducted by investigators associated with eight organizations: UCLA/Friends Research Institute, Torrance, California; Matrix Institute on Addictions, Tarzana, California; South Bay Treatment Center, San Diego, California; University of Colorado Health Sciences Center, Denver; Iowa Health Systems (Office of Research, Lutheran Hospital), Des Moines; Salt Lake City Health Care System, Utah; START Research & Treatment, Kansas City, Missouri; and University of Hawaii (Queens Hospital) Honolulu. This study is a preliminary assessment to evaluate the efficacy and safety of modafinil in reducing MA use in subjects with MA dependence. It is hypothesized that modafinil, compared to placebo, will be associated with an increase in the number of MA non-use weeks over time as measured by quantitative urine analysis for MA.

Double-Blind, Placebo-Controlled Trial of Modafinil for the Treatment of Methamphetamine Dependence was funded by the National Institute on Drug Abuse, Grant NIDA-CSP-1026 (October 2006 to June 2008).


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 assesses 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 includes random assignment to pharmacotherapy condition, and both participants and study personnel are blinded to assigned condition. Screening verifies participant eligibility and collects demographic, drug use, psychiatric, and neuropsychological information before participants are randomly assigned to either the PROMETAÔ pharmacotherapy condition (n = 60) or to the placebo condition (n = 60). Pharmacotherapy includes 2 infusion phases (starting at Day 0, and again at Day 21) in addition to 40 days of oral medications. Participants are also provided with weekly cognitive behavioral therapy for the duration of the study. Weekly assessments collect information to evaluate medical and psychological status throughout the study (15 weeks). Drug use outcomes are measured using self-report, verified by biological markers of abstinence (urine tested for metabolites of MA, cocaine, heroin, marijuana, and benzodiazepines). Individuals assigned to receive the PROMETAÔ pharmacotherapy, compared to placebo, are expected to demonstrate significantly fewer and less intense withdrawal symptoms, more days of abstinence from MA use, and fewer relapses to MA use. (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).

Top of Page


Double-Blind, Placebo-Controlled Trial of Topiramate
for the Treatment of Methamphetamine Dependence

Richard A. Rawson, Ph.D., Principal Investigator (rrawson@mednet.ucla.edu)
Donnie Watson, Ph.D., & Mark Hrymoc, M.D., Co-Investigators
Valerie Pearce, B.A., Project Director

This is a double-blind, multicenter, placebo-controlled, randomized, parallel group design study on methamphetamine-dependent outpatients. This protocol is coordinated through the Department of Veterans Affairs and the Cooperative Studies Program Coordinating Center. Subjects (N = 140) with DSM-IV criteria for methamphetamine (MA) dependence will be randomized in a 1:1 ratio to daily dosing with the investigational products, topiramate or matched placebo. Once during baseline and once per week during the 12-week treatment phase, all subjects will receive Brief Behavioral Compliance Enhancement Treatment (BBCET), a manual-driven, low-intensity supportive program to foster, maintain, and promote compliance with investigational product use and to promote continuation in the study. A final follow-up assessment will be conducted approximately 28 days after completion of treatment.

The topiramate protocol will be conducted by investigators associated with eight organizations: UCLA/Friends Research Institute, Torrance, California; Matrix Institute on Addictions, Costa Mesa, California; South Bay Treatment Center, San Diego, California; Iowa Health Systems (Office of Research, Lutheran Hospital), Des Moines; University of Virginia Health System, Charlottesville; Salt Lake City Health Care System, Utah; START Research & Treatment, Kansas City, Missouri; and University of Hawaii (Queens Hospital) Honolulu. This study is a preliminary assessment of the efficacy and safety of topiramate in reducing MA use in subjects with MA dependence. It is hypothesized that topiramate treatment, compared to placebo, will be associated with fewer days of MA use as measured by quantitative urine analysis for MA.

Double-Blind, Placebo-Controlled Trial of Topiramate for the Treatment of Methamphetamine Dependence was funded by the National Institute on Drug Abuse, Contract NIDA-CSP-1025 (October 2005 through March 2007).


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
Anne Bellows, M.S.W., Project Director

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 2008).


HIV/STD Risk Behaviors in Methamphetamine User Networks
Walter Ling, M.D., Principal Investigator (lwalter@ucla.edu)

Similar to the parent project and in concert with ongoing research in Thailand, the design of this supplement project includes interviews, neurocognitive assessments, and HIV testing of the entire follow-up sample (n = 500).  A subsample who have experienced intermittent psychosis symptoms (n=100) will be randomized to medication or placebo condition to assess effectiveness of the medication compared to placebo in reducing MAP; 50 subjects will receive resperidone and 50 subjects will receive matched placebo. A second subsample will include subjects with chronic psychosis (n=50) who will be assessed and provided with Treatment-As-Usual, which may include use of medications to varying amounts, for a period of one year. The supplement work will be completed in two years. The applicant team consists of UCLA-based researchers and highly experienced investigators in Thailand who have all worked together on previous similar research.

HIV/STD Risk Behaviors in Methamphetamine User Networks was funded by a NIDA supplemental grant 5 U01 DA017394 (July 2007 to June 2009).

Top of Page


Hyperalgesia in Methadone-Maintained Patients: Can It be Treated?

Walter Ling, M.D., Principal Investigator (lwalter@ucla.edu)
Peggy Compton, Ph.D., Co-Investigator
Albert Hasson, M.S.W., Project Director

Addressing the undertreatment of clinical pain has sparked increasing efforts aimed at identifying effective interventions for subgroups of patients most at risk for suffering unrelieved pain. Novel data accumulated by our investigative group has shown that methadone-maintained (MM) patients for the treatment of addiction have significantly diminished tolerance for pain, or hyperalgesia. This, in addition to contextual prohibitions associated with providing opiate analgesics to known opioid addicts, makes this a population uniquely vulnerable to the undertreatment of their pain. Unfortunately, little is known about how best to manage pain suffered by over 120,000 methadone-maintained (MM) patients in this country, in part because hyperalgesia appears to be akin to opioid-induced and neuropathic pain.

In this study, we build upon our previous research to explore the underlying mechanism from a pharmacological perspective. Utilizing a double-blind, placebo-controlled design, we are evaluating the ability of several drugs typically used to treat pain (e.g., dextromethorphan and gabapentin) to diminish or reverse the opioid-induced hyperalgesia complicating the pain states in MM patients. As such, medication that may interfere with the development of opioid-induced hyperalgesia will be evaluated for its ability to ameliorate or diminish hyperalgesia in MM patients, as reflected by changes in pain threshold and tolerance to both cold-pressor and electrical pain. The results of this work will provide pharmacologic insight into the mechanisms underlying poor pain tolerance in this at-risk population, as well as direction for the medical management of pain complicated by opioid-induced hyperalgesia.

Hyperalgesia in Methadone-Maintained Patients: Can It be Treated? was funded by the National Institute on Drug Abuse, Grant 5 R01 DA015463 to UCLA School of Nursing, with collaboration by UCLA ISAP (September 2002 through May 2007).


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 January 2008).

Top of Page


Motivational Therapy for Stimulant 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 stimulant 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. The proposed randomized trial will include 80 dually diagnosed individuals with stimulant dependence and a substance-independent diagnosis of Major Depressive Disorder. In patients receiving pharmacotherapy for depression, we will compare 12 weeks of CBT combined with motivational therapy (CBT-MT) to 12 weeks of TAU on 6, 12, 24, and 36 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 TSF. 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).


Optimizing Outcomes Using Suboxone for Opiate Dependence

Walter Ling, M.D., Principal Investigator (lwalter@ucla.edu)
Maureen Hillhouse, Ph.D, & Richard Rawson, Ph.D., Co-Investigators
Jackie Fahey, B.A., Project Director

This study is a randomized controlled trial that will test the comparative efficacy of several approaches combining psychosocial treatment with pharmacotherapy for treatment of opioid dependence. In conjunction with buprenorphine pharmacotherapy, psychosocial treatment conditions will include a Cognitive Behavioral Therapy (CBT) condition with medical management (MM), a Contingency Management condition (CM) with MM, a combined CBT+CM condition with MM, and a standard MM condition with neither CBT nor CM, which approximates what physicians do in general when prescribing buprenorphine in their office practice to patients with opioid dependence. Eligible participants will be stabilized on the study drug for a period of 2 weeks and will then be randomly assigned to one of the four conditions for 16 weeks. This first period will be followed by a second 16-week period during which all participants will continue to receive buprenorphine treatment but will not engage in any psychosocial treatment as part of continued study participation. Medical management of the participants will be identical to that delivered during the first treatment phase. At the end of this second 16-week buprenorphine-only treatment period, participants will be tapered off buprenorphine within a maximum of 6 weeks, or will receive referral for continued treatment if unable to successfully complete the taper. Participants will again be assessed at 40-weeks and 52-weeks post-entry into the study. Participants will be 240 opioid-dependent males and non-pregnant, non-lactating females of all racial/ethnic groups who are at least 15 years of age.

Optimizing Outcomes Using Suboxone for Opiate Dependence was funded by the National Institute on Drug Abuse, Grant 1 R01 DA020210 (September 2006 to May 2011).


PRO 807: An Open Label, Multi-Center Extension Study of
Probuphine in Patients with Opioid Dependence

Walter Ling, M.D., Principal Investigator (lwalter@ix.netcom.com)
Catherine Domier, M.A., Project Coordinator

This study provides an opportunity to evaluate participants who have received 24 weeks of investigational treatment for opioid dependence with Probuphine® for an additional 6 mos trial. Probuphine® is a product that is inserted into the inner side of the upper arm. Each Probuphine® implant is about the size of a matchstick and contains buprenorphine HCL and ethylene vinyl acetate (EVA [a type of plastic]). Probuphine® is designed to release buprenorphine, a medication already approved by the FDA for the treatment of opioid dependence, into the body continuously for up to 6 months.

Study participants will initially receive four implants with active study medication, and may also receive supplemental Suboxone If clinically indicated.  Safety, pharmacokinetics, and efficacy measures will be collected over the 24 week period, and participants will be seen a minimum of 12 times. At the end of the treatment period, participants will have implants removed, and will return for a follow-up visit 2 weeks later.  (Additional information is available at http://theaddictionstudy.com/locations.php.)

PRO 805: A Randomized, Double-Blind, Placebo-controlled, Multi-Center Study of Probuphine in Patients with Opioid Dependence was funded by Titan Pharmaceuticals, Inc., Contract 20054064 (January 2007 to December 2007).

Top of Page


The National Drug Abuse
Clinical Trials Network

Walter Ling, M.D., Principal Investigator (lwalter@ucla.edu)
Richard A. Rawson, Ph.D., M. Douglas Anglin, Ph.D., & Steven Shoptaw, Ph.D., Co-Investigators
Albert L. Hasson, M.S.W., Project Director

As one of 17 Regional Research Training Centers, ISAP is in its eighth year as the Pacific Region Node of NIDA’s Clinical Trials Network (CTN), and continues to collaborate with local community treatment programs in an effort to make substance abuse research more relevant to the treatment community. The Betty Ford Center, Bay Area Addiction Research and Treatment, Inc., Matrix Institute on Addictions, Hina Mauka Treatment  Programs, Phoenix House, Tarzana Treatment Center, and the Van Ness Recovery Center are participants within the Pacific Region Node helping to guide the CTN research portfolio.

The Pacific Region Node continues to take an active role in the Clinical Trials Network. In addition to leading a 9-site trial comparing the impact of Suboxone and methadone on liver function in treatment-seeking opioid-dependent individuals, “Starting Treatment with Agonist Replacement Therapy” (START), ISAP is the co-lead on a project evaluating Suboxone with and without enhanced medical management in the detoxification of prescription opioid users. “Prescription Opioid Addition Treatment” (POAT) is currently being piloted in two sites including ISAP, with eight more sites nationwide set to begin recruitment in 2007. A third project launched in the fall of 2008, “Twelve Step Facilitation: Evaluation of an Intervention to Increase 12-Step Involvement and Improve Substance Abuse Treatment Outcomes” will evaluate the degree to which a group-based 12-Step Facilitation (TSF) intervention, integrated into treatment as usual (TAU), improves substance-related outcomes. (Additional information is available at www.uclaisap.org/ctn/index.html.)

The National Drug Abuse Clinical Trials Network was funded by the National Institute on Drug Abuse, Grant 2 U10 DA13045 (September 2005 through August 2010).


UCLA Medication Development Unit
for Stimulant Abuse

Steven Shoptaw, Ph.D., Principal Investigator (sshoptaw@mednet.ucla.edu)
Keith Heinzerling, M.D., M.P.H., Co-Investigator

ISAP’s P50-funded Center “Medication Development Unit for Stimulant Dependence” (MDU; DA 12755, Principal Investigator (PI) Walter Ling, M.D.) conducted medication development trials for stimulant abuse and dependence beginning in 1999. Continuation of the P50 funding replaces and extends that original effort with the “Medication Development Unit for Stimulant Abuse” (MDUSA; PI Steven Shoptaw). The MDUSA Center continues to involve the substantial expertise in clinical drug abuse research of ISAP faculty, and the scope of the Center is broadened by integrating P50 activities with research conducted by investigators of the UCLA Department of Psychiatry and Biobehavioral Sciences and Department of Family Medicine.

Like past P50 efforts, the continuation Center 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. The Center reflects significant strengths of proven multidisciplinary collaborations that have helped guide medication development through early safety experiences to single-site pilot studies to multisite clinical trials. The Center has outstanding facilities and  staff members who are trained and experienced in the conduct of clinical trials. Moreover, the local environment has diverse populations of stimulant abusers (particularly methamphetamine abusers) in sufficient numbers to enable successful conduct of the proposed research.

The thematic emphasis that unifies the Center research is the development of pharmacological treatments for stimulant abuse through comprehensive and efficient methodologies applied by a multidisciplinary team. The Center team’s decades of experience in conducting medication trials for pharmacological and behavioral treatments for drug dependence are the basis for the Center’s integrative approach. The Center will increase the knowledge base on treatments for stimulant abuse by means of an ever greater linkage of Phase I with Phase II work, a stronger effort to apply advanced biostatistical methods to isolate potential medication effects in subgroups, a more concerted effort to identify biomarkers that discriminate meaningful differences between subgroups of stimulant abusers, and a more focused approach to the evaluation of medications within the context of carefully specified and timed behavioral interventions, ultimately seeking to improve clinical practice and to address emerging problems in the field. 

UCLA Medication Development Unit for Stimulant Abuse was funded by the National Institute on Drug Abuse, Grant 5 P50 DA018185 (September 2004 through February 2010).

Last Updated:  03/30/2009

Top of Page

2016 ISAP Publications
2015 ISAP Publications