Breaking Free From Meth: UCLA’s Dual Drug Therapy Proves Effective in Clinical Trials

White Crystals Bag Methamphetamine

A UCLA-led study on a two-drug therapy combining injectable naltrexone and extended-release bupropion showed significant reductions in methamphetamine use among participants up to 12 weeks into treatment.

Research from UCLA demonstrated that a combination therapy of naltrexone and bupropion effectively reduced methamphetamine use in trial participants over 12 weeks, suggesting the potential of pharmacological interventions in addressing rising overdose rates.

A clinical trial on a two-drug therapy for methamphetamine use disorder reduced use of the highly addictive drug for up to 12 weeks after initiation of treatment, according to the results of UCLA-led research.

Participants in the ADAPT-2 clinical trial who received a combination of injectable naltrexone plus extended-release oral bupropion (NTX+BUPN) had a 27% increase in methamphetamine-negative urine tests, indicating reduced usage. By contrast, the placebo group had an 11% increase in negative tests.

The study will be published in the peer-reviewed journal Addiction.

“These findings have important implications for pharmacological treatment for methamphetamine use disorder. There is no FDA-approved medication for it, yet methamphetamine-involved overdoses have greatly increased over the past decade,” said Dr. Michael Li, assistant professor-in-residence of family medicine at the David Geffen School of Medicine at UCLA and the study’s lead author.

Methamphetamine use has continued growing over the years around the world, increasing from 33 million people in 2010 to 34 million in 2020. Overdose deaths from the drug have jumped fivefold in the US from 2012 to 2018, and are followed by Canada and Australia in increases.

To curb the ongoing crisis, the National Institute on Drug Abuse (NIDA) Clinical Trials Network has supported various trials, including the ADAPT-2 trial, to test the effects of different pharmacological treatments for methamphetamine use disorder. ADAPT-2 was carried out from May 23, 2017, to July 25, 2019, across the eight trial sites that included UCLA. It included 403 participants, with 109 assigned to the drug combo group and the rest to the placebo group in the first stage.

The latest findings are the second stage of the multi-site trial. The earlier stage had demonstrated that the two-drug combination worked at six weeks, but the unanswered question was whether the intervention remained efficacious over a longer period.

In the second stage, the researchers conducted urine tests on the participants at weeks seven and 12, and again post-treatment at weeks 13 and 16 comparing the group on NTX+BUPN with the placebo group.

There is a need for further research to determine whether the drug treatment effect lasts longer than 12 weeks and yields further methamphetamine use reductions, the researchers write.

“Prior stimulant use disorder treatment trials suggest that change in use is gradual (consistent with our findings), unlikely to result in sustained abstinence in a typical 12-week trial, and dependent on treatment duration,” they write. “This warrants future clinical trials to quantify changes in MA use beyond 12 weeks and to identify the optimal duration of treatment with this medication.”

Reference: “Extended observation of reduced methamphetamine use with combined naltrexone plus bupropion in the ADAPT-2 trial” by Michael J. Li, Brendon Chau, Thomas Belin, Thomas Carmody, Manish K. Jha, Elise N. Marino, Madhukar Trivedi and Steven J. Shoptaw, 10 June 2024, Addiction.
DOI: 10.1111/add.16529

Study co-authors are Brendon Chau, Thomas Belin, and Steven Shoptaw of UCLA, and Thomas Carmody, Manish Jha, Elise Marino, and Dr. Madhukar Trivedi of the University of Texas.

The study was funded by awards from the National Institute on Drug Abuse of the U.S. National Institutes of Health (UG1DA020024, K01DA051329, UG1DA013035, UG1DA040316, UG1DA013727, and UG1DA015815), the U.S. Department of Health and Human Services under contract numbers HHSN271201500065C (Clinical Coordinating Center, the Emmes Company) and HHSN271201400028C (Data and Statistics Center, the Emmes Company), the U.S. National Institute of Mental Health (K23MH126202) and the O’Donnell Clinical Neuroscience Scholar Award from the University of Texas, Southwestern Medical Center.

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