31% Of Participants In Stimulant Use Disorder Trials Reduced Use; 13% Achieved Abstinence

June 15, 2026

Among 2,000 adults enrolled in pharmacotherapy trials for cocaine or methamphetamine use disorder, 31.2% achieved reduced stimulant use and 13.3% achieved abstinence by the end of their respective trials, according to a recent study. All participants received cognitive behavioral therapy, and outcomes were measured across both active medication and placebo groups. Among those receiving active medication, 32.5% achieved reduced use compared with 29.3% of those receiving placebo, while abstinence rates were 13.6% and 12.7%, respectively.

The study pooled harmonized, individual-level data from 12 multisite randomized controlled trials (RCTs) sponsored by the U.S. National Institute on Drug Abuse (NIDA) and conducted between 2001 and 2011. The trials evaluated pharmacological interventions among people seeking treatment for cocaine dependence (1,134 participants) or methamphetamine dependence (866 participants). All participants received cognitive behavioral therapy regardless of whether they were assigned to an active medication or placebo.

“Reduced use” was defined as a transition from high-frequency use (five or more days per month) to low-frequency use (one to four days per month), or a transition to abstinence. Abstinence was verified by urine toxicology and required both self-reported no drug use and a negative urine test during the final treatment month.

Reduced use outcomes were more common in methamphetamine trials, where 35.0% of participants achieved reduced use, compared with 28.2% in cocaine trials. Abstinence rates followed the same pattern, with 21.1% of methamphetamine trial participants achieving abstinence compared with 7.1% of cocaine trial participants.

When individual medications were examined separately, cabergoline stood out in cocaine use disorder trials. Among participants receiving cabergoline, 44.2% achieved reduced cocaine use compared with 27.6% of those receiving placebo. Cabergoline did not, however, demonstrate superiority over placebo for achieving abstinence.

Among methamphetamine trials, topiramate showed a positive but not statistically significant effect on reduced use compared with placebo, with a confidence interval ranging from negative 0.052 to 0.605.

These findings were presented in Evaluating Reduced Use and Abstinence as Outcomes in Pharmacotherapy Trials for Stimulant Use Disorder, by Masoumeh Amin-Esmaeili, M.D., MPH; Mehdi Farokhnia, M.D., MPH; Ramin Mojtabai, M.D., MPH, Ph.D.; and colleagues. The goal was to determine whether pharmacotherapies for stimulant use disorder show evidence of benefit when reduced use is evaluated as an outcome.

The pharmacotherapies tested across the trials included topiramate, bupropion, modafinil, ondansetron, tiagabine, cabergoline, reserpine, selegiline, and baclofen, each compared with placebo in double-blind trials. Among methamphetamine trials specifically, the medications studied were topiramate, bupropion, modafinil, and ondansetron. Among cocaine trials, the medications studied were ondansetron, modafinil, tiagabine, cabergoline, reserpine, selegiline, and baclofen.

The full text of Evaluating Reduced Use and Abstinence as Outcomes in Pharmacotherapy Trials for Stimulant Use Disorder was published on June 3, 2026, by JAMA Psychiatry. A free abstract is available (accessed June 10, 2026).

For more information, contact: Masoumeh Amin-Esmaeili, M.D., MPH, Associate Scientist, Department of Mental Health, Johns Hopkins Bloomberg School of Public Health, 550 Broadway, 2nd Floor, Room 213H, Baltimore, Maryland 21205; Email: mamines1@jh.edu; Website: https://publichealth.jhu.edu/faculty/4542/masoumeh-amin-esmaeili