Clinical Trials of Treatment for Substance Use Disorders (2012-2014)
- Aerobic Exercise to Improve Outcomes of Treatment for Methamphetamine Dependence
- Drum-Assisted Recovery Therapy for Native Americans
- Motivational Interviewing and Culture for Urban Native American Youth (MICUNAY)
- SBIRT for Substance Abuse in Mental Health Treatment Settings
- Sustained-Release Methylphenidate for Management of Methamphetamine Use Disorders
- The National Drug Abuse Clinical Trials Network
- TV-1380: A 12-week, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Once-Weekly Intra-Muscular Injections of TV-1380 (150 mg/week or 300 mg/week) as Treatment for Facilitation of Abstinence in Cocaine-Dependent Subjects
Richard A. Rawson, Ph.D., Principal Investigator (email@example.com)
Christopher Cooper, M.D.; Edythe London, Ph.D., & Larissa Mooney, M.D., Co-Investigators
Joy Chudzynski, Psy.D., Project Director
This 5-year study, funded by NIDA, sought to assess the efficacy of aerobic and resistance exercise for the treatment of methamphetamine dependence in a population of 135 individuals in residential treatment. After signing consent and satisfying all inclusion requirements, participants underwent baseline assessments during approximately 2 weeks of treatment as usual. After randomization, participants entered either the Education condition, consisting of 45- to 50-minute health education sessions 3 times per week for 8 weeks (n = 66), or the Exercise condition, consisting of aerobic and resistance exercise 3 times per week for 8 weeks (n = 69). Most study participants were male (80%), 48% were Latino, and the average age of the sample was 31.7 (SD = 6.9) years old.
The primary goal of the study was 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 135 participants, a subset of voluntary participants took part in a brain imaging sub-study. This sub-study used 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, it sought to investigate whether group participation (exercise or education group) changes the availability of dopamine in the brain.
(Dolezal et al., 2013)
Twenty-nine MA-dependent individuals were randomized to 3 days/week of exercise training (EX, n=15) or health education without training (ED, n=14) over 8 weeks. Aerobic performance (VO2max) was measured by indirect calorimetry, body composition by skinfolds, muscle strength by 1-repetition maximum (1-RM), and endurance at 85% of 1-RM for both the leg press (LP) and chest press (CP).
Results: Baseline characteristics (mean±SD) were balanced between groups: age 31±7 years; height=1.74±0.07 m; weight 82.0±15.0 kg. The EX group significantly improved VO2max by 0.63±0.22 L/min (+21%), LP strength by 24.4±5.6 kg (+40%) and CP strength by 20.6±5.7 kg (+49%). The EX group increased LP and CP endurance by 120% and 96%, respectively and showed significant reductions in body weight of 1.7±2.4 kg (-2%), % body fat of 2.8±1.3% (-15%) and fat weight 2.8±1.8 kg (-18%). All changes were significant (P<0.001) for EX, and no changes were seen for the ED group.
Conclusions: Individuals recovering from methamphetamine dependence showed substantial improvements in aerobic exercise performance, muscle strength and endurance, and body composition with exercise training. These findings demonstrate the feasibility of an exercise training intervention in these participants and also show excellent responsiveness to the exercise stimulus resulting in physiological changes that might enhance recovery from drug dependency.
Heart Rate Variability
(Dolezal et al., 2014)
Healthy, trained individuals exhibit high heart rate variability (HRV) reflecting the ability of the autonomic nervous system (ANS) to adapt quickly to physical challenges. Methamphetamine (MA) dependency causes ANS dysfunction and diminished HRV, but it is unknown whether HRV can be restored with exercise training. We compared participants in the exercise (EX=14) and Education control group (ED=14) with drug-free control participants (DF=22). For all participants, resting heart rate was recorded over 5 min while seated using a monitor affixed to a chest strap. Previously reported time- and frequency-domain parameters of HRV (LFn, HFn, L/F ratio, SDNN, RMSSD and pNN50) were calculated with customized software. An analysis of variance (ANOVA) with Duncan’s post-hoc testing was performed to compare HRV indices between and within groups. Significance was set at P ≤ 0.05. The ED and EX groups, compared with DF, had significantly higher resting heart rate, LF, and LF/HF ratio (P<0.001) as well as lower SDNN, RMSSD, pNN50 and HF (P<0.001), respectively. Before training, there were no significant differences in HRV indices between EX and ED groups. However, after training, the EX group significantly increased SDNN (+14.7±2.0 ms, +34%), RMSSD (+19.6±4.2 ms, +63%), pNN50 (+22.6±2.7%, +173%), HFn (+14.2±1.9%, +60%) and decreased HR (-5.2±1.1 bpm, -7%), LFn (-9.6±1.5, -16%) and LF/HF ratio (-0.7±0.3, -19%). These measures did not change from baseline in the ED group. HRV, based on several conventional indices, was diminished in recently abstinent, MA-dependent individuals. Moreover, physical training yielded a marked increase of HRV, representing increased parasympathetic activity and restored sympathetic-vagal balance.
Fifteen treatment-seeking MA users, enrolled in a 12-week, residential treatment program, were randomized (after 1 week) into 2 conditions for 8 weeks, Exercise (EX, n=9) or Education (ED, n=6). Participants in the EX condition underwent 1 h of supervised endurance and resistance training 3d/wk; those in the ED condition attended health education classes for the same duration and frequency. All participants were tested at baseline and retested after the 8-wk program. D2/3 receptor binding was assessed with positron emission tomography and 18F-fallypride. Striatal BPND was calculated using the simplified reference tissue model. A group of healthy control subjects (n=23), who underwent the same PET procedures, was included for comparison with baseline measures in the MA groups. At baseline, the MA groups did not differ in BPND, and both groups had lower striatal BPND compared to control subjects (p=0.014 ED, 0.021 EX). Participants in the ED condition showed no change in D2/3 BPND after completing the 8-wk program, but those in the EX condition showed an increase in striatal D2/3 BPND from baseline (mean 11.8%; p<.05 for change from baseline). Subjects in the EX condition, but not the ED condition showed normalization of D2/3 BPND to healthy control levels (p’s=0.364 & 0.013, respectively, vs. control). This study is the first to show increases in striatal D2/3 BPND in abstinent MA-dependent subjects. The data suggest adding an exercise regimen to a treatment program may facilitate recovery through actions on DA D2/3 receptors.
(Rawson et al., 2015)
One hundred and thirty-five MA-dependent individuals, newly enrolled in residential treatment were randomly assigned to receive either a thrice-weekly 60-minute structured exercise program for 8 weeks (24 sessions) or an equivalent number of health education sessions. Using linear mixed modeling, we examined changes in mood as measured by weekly Beck depression and Beck anxiety scores over the 8-week study period. Mean age of participants was 31.7 (SD = 6.9); 80% were male, and 48% Latino. Analyses indicate significantly greater reduction in depression and anxiety symptom scores over time (P < 0.001) among exercise intervention participants compared to health education control participants. A significant dose interaction effect between session attendance and exercise intervention was found (P < 0.001) on greater reductions in depression and anxiety symptoms over time compared to the control group. These results support the role of a structured exercise program as an effective intervention for improving dysphoric mood states including those associated with MA abstinence.
(Rawson et al., submitted)
We examined the efficacy of an 8-week exercise intervention on posttreatment methamphetamine (MA) use outcomes among MA-dependent individuals following residential treatment; 135 individuals newly enrolled in residential treatment were randomly assigned to a structured 8-week exercise intervention or health education control group. Approximately 1 week after completion of the intervention, participants were discharged to the community. Interview data and urine samples were collected at 1-, 3-, and 6-months post-residential care. Of the sample, 54.8% were classified as higher severity users (using MA for more than 18 days in the month prior to admission) and 45.2% were classified as lower severity users (using MA for up to 18 days in the month prior to admission). Group differences in MA use outcomes were examined over time using mixed multivariate modeling. While fewer exercise participants returned to MA use compared to education participants at 1- and 3-months post-discharge, differences were not statistically significant. A significant interaction for self-reported MA use (β = 0.46, P = 0.02) and MA urine drug test results (OR = 0.17, P = 0.03) by condition and MA severity was found: lower severity users in the exercise group used MA significantly fewer days at 1- and 3-months post-discharge (0.7 & 1.8 days, respectively) than lower severity users in the education group (3.8 & 7.3 days, respectively). This relationship was not present in the comparison of the higher severity conditions. Results support the value of exercise as a treatment component for individuals who use MA 18 or fewer days/month.
Mooney LJ, Cooper CB, London ED, Chudzynski J, Rawson, RA. (2015). Exercise for Substance Use Disorders. In: El-Guebaly, N., Carra, G., Galanter, M., Eds. Textbook of Addiction Treatment: International Perspectives. P.973-986, Springer, New York
Mooney, L.J., Cooper, C.B., London, E., Chudzynski, J., Dolezal, B.A., Dickerson, D., Brecht, M., Penate, J., & Rawson, R. (2014). Exercise for methamphetamine dependence: Rationale, design, and methodology. Contemporary Clinical Trials, Jan;37(1):139-47. doi: 10.1016/j.cct.2013.11.010
Dolezal, B.A., Chudzynski, J., Dickerson, D., Mooney, L., Rawson, R., Garfinkel, A., & Cooper, C.B. (2014). Exercise training improves heart rate variability in methamphetamine-dependent individuals. Med Sci Sports Exercise, Jun;46(6):1057-66.
Haglund, M., Ang, A., Mooney, L., Gonzales, R., Chudzynski, J., Cooper, CB., Dolezal, B., Gitlin, M., Rawson, R. (2014). Predictors of depression outcomes among abstinent methamphetamine-dependent individuals exposed to an exercise intervention. American Journal on Addictions,24(3), 246-251. doi: 10.1111/j.1521-0391.2014.12175.x. [Epub ahead of print]
Dolezal, B.A., Chudzynski, J., Storer, T.W., Abrazado, M., Penate, J., Dickerson, D., Mooney, L., Rawson, R., & Cooper, C.B. (2013). Eight weeks of exercise training improves fitness measures in methamphetamine-dependent individuals in residential treatment. Journal of Addiction Medicine, 7(2):122-8.
Rawson, R.A., Chudzynski, J., Gonzales, R., Mooney, L., Dickerson, D., Ang, A., Dolezal, B., & Cooper, C.B. (2015). The impact of exercise on depression and anxiety symptoms among abstinent methamphetamine-dependent individuals in a residential treatment setting. Journal of Substance Abuse Treatment. [Epub ahead of print] doi:10.1016/j.jsat.2015.04.007. NIHMS ID 681246
Rawson, R.A., Chudzynski, J., Mooney, L., Gonzales, R., Ang, A., Dickerson, D., Penate, J., Salem, B.A., Dolezal, B., & Cooper, C.B. (in submission). Impact of an exercise intervention on methamphetamine use outcomes post-residential treatment care. Drug and Alcohol DependenceAerobic Exercise to Improve Outcomes of Treatment for Methamphetamine Dependence was funded by the National Institute on Drug Abuse, grant 1R01DA027633-01, from September 2009 to August 2014.
Daniel Dickerson, D.O, M.P.H., Principal Investigator (firstname.lastname@example.org)
Yih-Ing Hser, Ph.D., Co-Investigator
Cheryl Teruya, Ph.D., Project Director
American Indians/Alaska Natives have the highest rates of alcohol and drug use disorders compared to other racial/ethnic groups in the United States. However, very few culturally tailored substance abuse treatment strategies have been empirically tested. Drumming is recognized as a viable healing tool for American Indians/Alaska Natives. Evidence suggests that drumming enhances substance abuse recovery as revealed in studies on physical and psychological effects. Drum-Assisted Recovery Therapy for Native Americans (DARTNA) is a culturally tailored drum therapy model for American Indians/Alaska Natives with substance abuse disorders. The purpose of this grant is to develop this treatment protocol and to develop strategies to conduct a follow-up clinical trial. To meet these goals, the primary goals of this research project are to (1) develop and pretest a culturally tailored treatment strategy, DARTNA, for American Indians/Alaska Natives with alcohol and drug use disorders, and (2) obtain community-based input to assist in a follow-up clinical trial. Our findings will assist us in gathering data needed to develop a follow-up study to formally test the efficacy of DARTNA among American Indians/Alaska Natives with alcohol and drug use disorders.Drum-Assisted Recovery Therapy for Native Americans was funded by the National Center for Alternative and Complementary Medicine, grant 1 R21 AT005360, from September 2010 to August 2013.
Daniel Dickerson, D.O., M.P.H., Co-Principal Investigator (email@example.com)
Co-Principal Investigator: Elizabeth D’Amico, Ph.D. (RAND Corporation)
Co-Investigator, Ryan Brown, Ph.D. (RAND Corporation)
Co-Investigator, Jeremy Miles, Ph.D.
Jennifer Parker, Survey Administrator (RAND Corporation)
Kirsten Becker, Survey Administrator (RAND Corporation)
Motivational Interviewing and Culture for Urban Native American Youth (MICUNAY) is an R-01 study, funded by NIAAA with supplemental funding from NIDA, focusing on developing, adapting, and testing the effectiveness of a new substance use prevention program for urban Native American youth. MICUNAY comprises 3 workshops that integrate motivational interviewing (MI) and Native American cultural activities. The first year of this grant involved the completion of MICUNAY and manual development. Focus groups were conducted among Native American youth, parents, providers, and the MICUNAY community advisory board. From years 2-5, a randomized trial will be completed to compare AI/AN youth who only receive the existing Community Wellness Gatherings (CWG; n=100) to AI/AN youth who receive the CWG plus our integrated group intervention, MICUNAY (n=100) across two urban sites (Los Angeles and Oakland). This grant is currently (2015) in its second year. Outcomes at 3- and 6-month follow-ups are currently be collected to (a) determine whether clinically significant changes in AOD expectancies, perceived prevalence of peer AOD use, alcohol consumption, marijuana and other drug use, and related consequences occur; (b) determine whether clinically significant changes in physical, social, emotional, and functional well-being, as well as spirituality and cultural identification occur, and (c) if reductions occur, to estimate effect sizes for the CWG group and the CWG plus MICUNAY group.Motivational Interviewing and Culture for Urban Native American Youth was funded by the RAND Corporation, grant R01AA022066, from July 2013 to June 2018.
Principal Investigators: Mitchell Karno, Ph.D., firstname.lastname@example.org; Suzette Glasner Edwards, Ph.D. (email@example.com), and Richard Rawson, Ph.D. (firstname.lastname@example.org)
Co-Investigators: Christine Grella, Ph.D., Richard Saitz, M.D., and Larissa Mooney, M.D.
Project Director: Blanca Dominguez, M.P.H.
The proposed study uses a randomized controlled trial to examine the extent to which the World Health Organization’s SBIRT model and the ASSIST (Alcohol, Smoking, and Substance Involvement Screening Test) and its associated brief behavioral intervention lead to reductions in substances prevalent in mental health settings: alcohol, cannabis, and stimulants (i.e., cocaine and methamphetamine). The study will also examine the effect of SBIRT on improvement in psychiatric symptoms, improved quality of life, and for those whose level of substance misuse indicates a need for treatment, initiation and engagement into SUD treatment services. Eligible participants will be mental health patients who report any past year use of cannabis or stimulants or at least one heavy drinking day in the past year. Mental health patients (n = 1,080) who meet eligibility criteria will be enrolled and randomly assigned to either the SBIRT intervention condition or to a health education attention control condition. Participants will be assessed at baseline on substance use, psychiatric symptoms, and quality of life. Each participant will be assessed at 3-, 6- and 12-month follow-up points for alcohol and drug use, involvement in SUD treatment services, severity of psychiatric symptoms, and quality of life. If successful, this study will yield valuable new knowledge about the effectiveness of SBIRT in mental health treatment settings and will promote improved well being of mental health patients.
SBIRT for Substance Abuse in Mental Health Treatment Settings was funded by the National Institute on Drug Abuse, grant 5 R01 DA032733, from September 2012 through August 2017.
Walter Ling, M.D., Principal Investigator (email@example.com)
Maureen Hillhouse, Ph.D., & Richard Rawson, Ph.D.,
Jessica Jenkins, M.S., Project Director
This completed study investigated the effectiveness of sustained-release methylphenidate (MPH) for the treatment of methamphetamine (MA) use disorders in 110 participants at two treatment sites (UCLA, University of Hawaii). The4-year double-blind, placebo-controlled study included MA-dependent individuals assessed using DSM-IV criteria. Eligible participants were randomized to placebo (n = 55) or MPH (n = 55) for 10 weeks in the active medication phase. Active medication participants received 18mg MPH/daily for Week 1, 36mg/daily for Week 2, and 54mg/daily for Weeks 3-10. Placebo participants were given a matched placebo. During the final 4 study weeks (Weeks 11-14) all participants received a single-blind placebo. Across the entire study, participants were offered weekly group cognitive behavioral therapy, and motivational incentives were provided for MA-negative urine test results. Study results show no difference between treatment groups in self-reported days of MA use during the last 30 days of the active medication phase (p=0.22). In planned secondary outcomes analyses, however, the active medication group had fewer self-reported MA use days from baseline through the active phase compared to the placebo group (p=0.05). The active medication group also had lower craving scores and fewer marijuana-positive urine drug tests than the placebo group in the last 30 days of the active medication phase. The two groups had similar retention, other drug use, adverse events, and treatment satisfaction.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.
Walter Ling, M.D., Principal Investigator (firstname.lastname@example.org)
Richard A. Rawson, Ph.D., Larissa Mooney, M.D., Maureen Hillhouse, Ph.D., & Steven Shoptaw, Ph.D., Co-Investigators
Albert L. Hasson, M.S.W., Project Director
As one of 13 Regional Research Training Centers, ISAP has completed its 16th year as the Pacific Region Node of NIDA’s Clinical Trials Network (CTN) and continues to collaborate with academic centers and local community treatment programs in an effort to make substance abuse research more relevant to the treatment community. The Pacific Region Node includes a collaboration with Dr. Linda Chang at the University of Hawaii, Queens Medical Center. ISAP continues its longstanding relationship with community treatment programs: The Betty Ford Center, Bay Area Addiction Research and Treatment, Inc., Matrix Institute on Addictions, Hina Mauka Treatment Programs, Tarzana Treatment Center, and the Harbor-UCLA Division of HIV Medicine.
Data collection for Accelerated Development of Additive Pharmacotherapy Treatment (ADAPT)- Methamphetamine Dependence was completed in the first quarter of 2015. ADAPT-MD was a three-site, two-stage, open-label trial designed to investigate a combination medication, extended-release depot naltrexone plus extended release bupropion as a potential pharmacotherapy for methamphetamine use disorders. ADAPT was led by Drs. Walter Ling and Larissa Mooney, and included an ISAP site. Using a novel stepped design to determine a signal of success in a first stage that included 20 participants, meeting the pre-determined number of “responders” led to a second stage with 29 participants. Analyses of the total sample shows that 11 participants met “responder” criteria (responders were defined as submitting 6 of 8 urine drug tests in the last 4 weeks of the medication phase), which exceeds the number of responders (9) identified as the criteria for a positive study. Efforts to develop a large, randomized follow-up trial is underway.
Soon to be launched is a follow-up study to the CTN 0049 study, Hospital Visit as Opportunity for Prevention and Engagement for HIV-Infected Drug Users (HOPE). Follow-up interviews with study participants will assess status and functioning about 18 months after study completion. The study site at Harbor-UCLA will contact all those who participated in the parent study.
In the recently completed CTN 0048, Cocaine Use Reduction with Buprenorphine, CURB, led by Drs. Ling, Saxon, and Mooney at 10 sites nationwide, including the ISAP Outpatient Clinical Research Center, recruitment was completed 7 months in advance of the projected recruitment timeline. This study randomized participants to buprenorphine condition (daily 4mg or 16 mg buprenorphine, or placebo) given on a platform of extended-release naltrexone, for the treatment of cocaine use disorders. The CURB “methods” paper has been published by the journal Contemporary Clinical Trials. Pre-planned analyses that combined self-reported cocaine use and urine drug screens (UDS) indicate no difference in treatment outcome between the buprenorphine and placebo groups. Secondary analyses of only the UDS data show that the 16mg buprenorphine group had significantly fewer cocaine use days during the evaluation period compared to the placebo group. These findings will be discussed in the main outcome paper, currently in preparation.
Following the completion of the 9-site trial comparing the impact of Suboxone and methadone on liver function in treatment-seeking opioid-dependent individuals, Starting Treatment with Agonist Replacement Therapies (START), Maureen Hillhouse, Ph.D., led several working groups in the development and publication of the study results. The START main outcome results were published in the August 2012 Journal of Drug and Alcohol Dependence, and six secondary papers have been published that address genetic analyses, HIV risk behaviors, retention, facets of opioid use, and study staff perspectives on treatment. Additional manuscripts have been submitted for publication or are in the development phase. A long-term START follow-up study is currently surveying participants at three time-points on their status and functioning.
Currently in the recruitment phase, The CTN0054, Achieving Cannabis Cessation-Evaluating N-Acetylcysteine Treatment (ACCENT) study is investigating N-acetylcysteine (NAC) versus matched placebo (PBO) added to contingency management (CM) for the treatment of cannabis use disorders among treatment-seeking cannabis-dependent adults. This is a Phase 3, 12-week, intent-to-treat, two-group, double-blind, randomized, placebo-controlled trial with one follow-up visit approximately 4 weeks posttreatment. The ISAP site will recruit 50 participants. This study is expected to complete recruitment in the first quarter of 2015.
The randomized clinical trial of medication for opioid use disorders, CTN0051, Extended-Release Naltrexone vs. Buprenorphine for Opioid Treatment (X:BOT), will compare the effectiveness of extended-release naltrexone (XR-NTX, Vivitrol®) to buprenorphine/naloxone (BUP-NX, Suboxone®) to prevent relapse to opioid use and addiction over 24 weeks of treatment. About 500 participants will be randomly assigned to the two conditions. This study is currently recruiting at the Tarzana Treatment Center.
Investigating the process of HIV testing, the CTN0056 Testing and Linkage to HIV Care in China: A Cluster Randomized Trial, compared the One4all HIV testing procedure with standard testing in 16 hospitals in the Guangxi Autonomous Region randomized to testing procedure. Recruitment and testing of over 400 participants was completed in the first quarter of 2015. A follow-up study is being developed to collect information from study participants approximately a year after initial testing. The follow-up study will include HIV testing and psychosocial assessments. This follow-up is expected to begin in the last quarter of 2015.
(Additional information is available at www.uclaisap.org/ctn/index.html.)
TV-1380: A 12-week, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group Study to Evaluate the Efficacy and Safety of Once-Weekly Intra-Muscular Injections of TV-1380 (150 mg/week or 300 mg/week) as Treatment for Facilitation of Abstinence in Cocaine-Dependent Subjects
Walter Ling, M.D., Principal Investigator (email@example.com)
Larissa Mooney, M.D., Co-Investigator
Sandy MacNicoll, M.B.A., Project Director
This was a Phase II, multicenter, double-blind, 3-arm, randomized, parallel-group, placebo-controlled trial to assess efficacy and safety of once-weekly TV-1380 of 150 mg and 300 mg IM injections every week for a total of 12 weeks for the facilitation of cocaine abstinence. There were approximately 20 centers in North America and Europe with approximately 210 subjects (males and females) aged 18-60 years old, inclusive, with cocaine dependence, and seeking treatment. This study consisted of a screening period of up to 3 weeks , a 12-week, double-blind treatment period and an end-of-study visit that will occur 4 weeks after completion of the treatment phase. The primary objective of this study is to assess the efficacy and safety of TV-1380 in facilitating abstinence in cocaine-dependent subjects. The secondary objective of the study is to assess the efficacy of TV-1380 in reducing measures of cocaine use compared to placebo treatment. The other objectives of the study are to assess the effect of TV-1380 on cocaine craving; to assess the effect of TV-1380 on the change in global assessment of disease severity; to assess the effect of TV-1380 on physical, emotional, and social functioning; to assess the safety of TV-1380 in subjects with cocaine dependence; and to assess the pharmacokinetics of TV-1380 in subjects with cocaine dependence.TV-1380: A 12-week, Multicenter, Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Study to Evaluate the Efficacy and Safety of Once-Weekly Intra-Muscular Injections of TV-1380 (150 mg/week or 300 mg/week) as Treatment for Facilitation of Abstinence in Cocaine-Dependent Subjects was funded by the National Institute on Drug Abuse, grant TV-1380-COA-201, from June 2013 through May 2015.