Medicine Combination With the Potential to Beat Methamphetamine Use Disorder


In an ADAPT-2 study, a combination of injectable naltrexone and oral bupropion showed promise for methamphetamine users.


The Accelerated Development of Additive Pharmacotherapy Treatment for Methamphetamine Use Disorder study, or ADAPT-2 study, discovered that a combination of injectable naltrexone and oral bupropion was safe and effective for treating adults with moderate to severe methamphetamine use disorder. This combination therapy may be a potential treatment addition for those struggling to overcome addiction to methamphetamine.

“The opioid crisis and resulting overdose deaths in the United States are now well known, but what is less recognized is that there is a growing crisis of overdose deaths involving methamphetamine and other stimulants. However, unlike for opioids, there are currently no approved medications for treating methamphetamine use disorder,” National Institute on Drug Abuse (NIDA) Director Nora D. Volkow, MD, said to the press. “This advance demonstrates that medical treatment for methamphetamine use disorder can help improve patient outcomes.”1

The research was conducted from 2017 to 2019 at multiple sites within the NIDA Clinical Trials Network (NIDA CTN). The study enrolled 403 adult participants aged 18 to 65 years with moderate to severe methamphetamine use disorder for stage 1, and 225 participants in stage 2. All of these participants wanted to reduce or cease use of the drug.

The study was broken down into 2 stages, 6 weeks each. Participants in the treatment group were given an injection of extended-release naltrexone every 3 weeks and extended-release tablets of bupropion daily. Participants in the control group were given injectable and oral placebos over the same time periods. Adverse events within the naltrexone–bupropion treatment group included gastrointestinal disorders, tremor, malaise, hyperhidrosis, and anorexia. Serious adverse events occurred in 8 of 223 participants who received naltrexone–bupropion during the trial.2

At the end of each stage of the trial, researchers gave 4 urine drug screens. If at least 3 of the 4 urine screens were negative, the participant was considered to have responded to treatment.

Over a 12-week period, responses among participants who received extended-release injectable naltrexone plus oral extended-release bupropion was low; however, it was higher than that of the participants who received placebo.

“Long-term methamphetamine misuse has been shown to cause diffuse changes to the brain, which can contribute to severe health consequences beyond addiction itself,” trial leader Madhukar H. Trivedi, MD, of the University of Texas Southwestern Medical Center, Dallas, said to the press. “The good news is that some of the structural and neurochemical brain changes are reversed in people who recover, underscoring the importance of identifying new and more effective treatment strategies.”1


1. National Institutes of Health. Combination treatment for methamphetamine use disorder shows promise in NIH study. News release. January 13, 2021.

2. Trivedi MH, Walker R, Ling W, dela Cruz A, et al. Bupropion and naltrexone in methamphetamine use disorder. N Engl J Med. 2021;384:140-153.

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