Accelerated Development of Additive Pharmacotherapy Treatment (ADAPT-2) for Methamphetamine Use Disorder

Summary

This is a double-blind, placebo-controlled, randomized clinical trial evaluating the efficacy of extended-release naltrexone plus bupropion as a combination pharmacotherapy for methamphetamine use disorder. Participants will be randomly assigned to the active medication combination (AMC) group or matching placebo group and will receive medications over the course of 12 weeks. Follow-ups will occur in weeks 13 and 16.

Timeline

Start

2017-05-05

Primary completion

2019-07-03

Completion

2019-07-25

Outcome

Met primary endpoint

paper The weighted average response across the two stages was 13.6% with naltrexone-bupropion and 2.5% with placebo PMID 33497547 ↗

paper for an overall treatment effect of 11.1 percentage points (Wald z-test statistic, 4.53; P<0.001). PMID 33497547 ↗

Publications

• Mojtabai R, Susukida R, Farokhnia M, Nguyen TQ, Leggio L, Bergeria C, Prasad S, Dunn KE, Amin-Esmaeili M. Mediators of Treatment Response in Clinical Trial of Naltrexone and Bupropion for Methamphetamine Use Disorder: A Longitudinal Mediation Analysis. medRxiv [Preprint]. 2026 May 13:2026.05.09.26352807. doi: 10.64898/2026.05.09.26352807.
• Jha MK, Ghitza UE, Shoptaw S, Minhajuddin A, Kuruvila S, Wakhlu S, Nunes EV, Schmitz J, Coffin PO, Bart G, Carmody T, Trivedi MH. Early Change in Depressive Symptom Severity With Naltrexone-Bupropion Combination and Its Association With Reduction in Methamphetamine Use in ADAPT-2 Trial. J Clin Psychiatry. 2025 Jul 30;86(3):25m15825. doi: 10.4088/JCP.25m15825.
• Jha MK, Ghitza UE, Carmody T, Kuruvila S, Shoptaw S, Minhajuddin A, Wakhlu S, Schmitz JM, Coffin PO, Bart G, Nunes EV, Kenny P, Trivedi MH. Craving, Impulsivity, and Subsequent Methamphetamine Use With Naltrexone-Bupropion Versus Placebo: Findings From a Randomized Clinical Trial. J Addict Med. 2026 Mar-Apr 01;20(2):214-222. doi: 10.1097/ADM.0000000000001538. Epub 2025 Jul 7.
• Li MJ, Chau B, Belin T, Carmody T, Jha MK, Marino EN, Trivedi M, Shoptaw SJ. Extended observation of reduced methamphetamine use with combined naltrexone plus bupropion in the ADAPT-2 trial. Addiction. 2024 Oct;119(10):1840-1845. doi: 10.1111/add.16529. Epub 2024 Jun 10.
• Okafor CN, Carmody T, Stotts AL, Bart G, Mayes TL, Karns-Wright T, Trivedi M, Shoptaw S, Potter JS. Sociodemographic and patient reported outcomes by racial and ethnicity status among participants in a randomized controlled trial for methamphetamine use disorder. Drug Alcohol Depend Rep. 2024 Apr 6;11:100230. doi: 10.1016/j.dadr.2024.100230. eCollection 2024 Jun.
• Trombello JM, Kulikova A, Mayes TL, Nandy K, Carmody T, Bart G, Nunes EV, Schmitz J, Kalmin M, Shoptaw S, Trivedi MH. Psychometrics of the Concise Health Risk Tracking Self-Report (CHRT-SR16) Assessment of Suicidality in a Sample of Adults with Moderate to Severe Methamphetamine Use Disorder: Findings from the ADAPT-2 Randomized Trial. Neuropsychiatr Dis Treat. 2023 Jun 22;19:1443-1454. doi: 10.2147/NDT.S406909. eCollection 2023.
• Vo HT, Kulikova A, Mayes TL, Carmody T, Shoptaw S, Ling W, Trombello JM, Trivedi MH. Psychometric properties of the Treatment Effectiveness Assessment in methamphetamine use disorder. J Subst Use Addict Treat. 2023 Aug;151:209085. doi: 10.1016/j.josat.2023.209085. Epub 2023 May 26.
• Trivedi MH, Walker R, Ling W, Dela Cruz A, Sharma G, Carmody T, Ghitza UE, Wahle A, Kim M, Shores-Wilson K, Sparenborg S, Coffin P, Schmitz J, Wiest K, Bart G, Sonne SC, Wakhlu S, Rush AJ, Nunes EV, Shoptaw S. Bupropion and Naltrexone in Methamphetamine Use Disorder. N Engl J Med. 2021 Jan 14;384(2):140-153. doi: 10.1056/NEJMoa2020214.

Drugs

Evaluation	Drug	Modality	Dose	Route
Subject	Bupropion	Small molecule	450 mg	Oral
Subject	Naltrexone	Small molecule	380 mg	Intramuscular

Indications