Craving, Impulsivity, and Subsequent Methamphetamine Use With Naltrexone-Bupropion Versus Placebo: Findings From a Randomized Clinical Trial

J Addict Med. 2026 Mar-Apr;20(2):214-222. doi: 10.1097/ADM.0000000000001538. Epub 2025 Jul 7.

Abstract

Objectives: The accelerated development of additive pharmacotherapy treatment (ADAPT-2) for methamphetamine use disorder (MUD) trial demonstrated the efficacy of extended-release injectable naltrexone (NTX) and oral bupropion (BUP). In this secondary analysis, we determined whether craving and impulsivity levels could predict subsequent use of methamphetamine.

Methods: Participants (N = 357) of the ADAPT-2 trial with at least one transition point [transition from positive-to-negative urine drug screen (UDS) or vice versa] during stage 1 (baseline through week-6) were included in this secondary analysis. Craving was assessed using the Visual Analog Scale (VAS). Impulsivity was assessed using the 2-item impulsivity factor of the Concise Health Risk Tracking (CHRT) Scale.

Results: A significant treatment by craving by time interaction was noted ( P = 0.018), where higher craving levels were consistently associated with a lower likelihood positive-to-negative UDS transition at the next visit in both NTX-BUP and placebo groups. However, no such effect was present by week 6 of treatment in the placebo group. CHRT Impulsivity also had a significant effect on the probability of a positive-to-negative UDS transition ( P = 0.019) in addition to the 3-way interaction of VAS, week, and treatment group. Individuals with lower craving levels but higher impulsivity exhibited a lower probability of transitioning to negative UDS at the next visit. Higher craving, but not impulsivity, was associated with a higher likelihood of negative-to-positive UDS transition at the next visit in both treatment groups.

Conclusions: Further investigations are necessary to optimize NTX-BUP treatment, focusing on the impact of craving and impulsivity on outcomes.

Trial registration: ClinicalTrials.gov NCT03078075.

Keywords: ADAPT-2; craving; impulsivity; methamphetamine use disorder; treatment outcome.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adult
  • Amphetamine-Related Disorders* / drug therapy
  • Bupropion* / administration & dosage
  • Bupropion* / pharmacology
  • Bupropion* / therapeutic use
  • Craving* / drug effects
  • Drug Therapy, Combination
  • Female
  • Humans
  • Impulsive Behavior* / drug effects
  • Male
  • Methamphetamine* / adverse effects
  • Middle Aged
  • Naltrexone* / administration & dosage
  • Naltrexone* / pharmacology
  • Naltrexone* / therapeutic use
  • Narcotic Antagonists* / administration & dosage
  • Narcotic Antagonists* / pharmacology
  • Young Adult

Substances

  • Naltrexone
  • Bupropion
  • Methamphetamine
  • Narcotic Antagonists

Associated data

  • ClinicalTrials.gov/NCT03078075