Craving reduction explains half the drug’s effect on meth use
STUDY: Mojtabai R et al, medRxiv 2026
STUDY TYPE: Secondary mediation analysis of a randomized controlled trial
FUNDING: National Institute on Drug Abuse, Louisiana Board of Regents
Background
Naltrexone-bupropion combination is one of the best studied options for methamphetamine use disorder, but does it work by reducing cravings, depression, or impulsivity?
The Study
- 403 adults with methamphetamine use disorder from the ADAPT-2 trial, randomized to injectable naltrexone plus oral bupropion versus placebo.
- Researchers tracked craving, depression (PHQ-9), and impulsivity (CHRT) weekly for six weeks.
- They used structural equation modeling to see which of these three factors explained the drug’s effect on methamphetamine use, measured by self-report and urine drug screens.
Craving was the strongest predictor of response. It explained 56% of the treatment’s effect on self-reported use and 45% of its effect on urine-confirmed use.
Depression and impulsivity didn’t reach significance.
Limitations
Secondary analysis. The models could only test one mediator at a time, even though craving, depression, and impulsivity likely overlap.
Practice Implications
- Look for reductions in cravings when using bupropion-naltrexone combination for meth use, and favor this combo when cravings are a clear part of the problem.
—Chris Aiken, MD
Director, Psych Partners
Editor in Chief, Carlat Psychiatry Report
