Associations between stimulant use and return to illicit opioid use following initiation onto medication for opioid use disorder

Addiction. 2024 Jan;119(1):149-157. doi: 10.1111/add.16334. Epub 2023 Sep 15.


Aim: The aim of this study was to estimate how ongoing stimulant use affects return to illicit opioid use after initiation onto medication for opioid use disorder (MOUD).

Design: This was a secondary analysis of pooled data from two clinical trials comparing buprenorphine (BUP-NX) and extended-release naltrexone (XR-NTX).

Setting: Thirteen opioid treatment programs and HIV clinics across 10 states in the United States from 2014 to 2019 took part in this study.

Participants: A total of 528 participants who initiated MOUD as part of trial participation were included. Nearly half (49%) were between 30 and 49 years of age, 69% were male and 66% were non-Hispanic White.

Measurements: The primary outcome was first self-reported day of non-prescribed opioid use following MOUD initiation, and the exposure of interest was daily stimulant use (methamphetamine, amphetamines or cocaine). Both were defined using time-line follow-back. Among participants reporting at least 1 day of illicit opioid use, we also examined relapse to ongoing use, defined as (1) 7 days of continuous opioid use or (2) 4 consecutive weeks with self-reported opioid use, one or more positive urine drug screens (UDS) for opioids or one or more missing UDS.

Findings: Forty-seven per cent of participants reported stimulant use following MOUD initiation, 58% returned to illicit opioid use and 66% of those relapsed to ongoing use. Stimulant use was strongly associated with increased risk of misusing opioids after MOUD initiation when measured daily [adjusted hazard ratio (aHR) = 9.23, 95% confidence interval (CI) = 6.80-12.50, P < 0.001] and over a 7-day period (aHR = 1.27 for each additional day, CI = 1.18-1.37, P < 0.001). Using stimulants weekly or more often was associated with increased likelihood of relapse to ongoing opioid use compared with less than weekly or no stimulant use (adjusted odds ratio = 2.30, CI = 1.05-5.39, P = 0.044).

Conclusions: People initiated on medication for opioid use disorder who subsequently use stimulants appear to be more likely to return to and continue using non-prescribed opioids compared with those without stimulant use. The association appears to be stronger among patients who initiate buprenorphine compared with those who initiate extended-release naltrexone.

Keywords: Buprenorphine; extended-release naltrexone; medications for opioid use disorder; opioids; relapse; stimulants.

MeSH terms

  • Adult
  • Analgesics, Opioid / adverse effects
  • Buprenorphine / therapeutic use
  • Central Nervous System Stimulants* / adverse effects
  • Clinical Trials as Topic
  • Delayed-Action Preparations / therapeutic use
  • Female
  • Humans
  • Male
  • Middle Aged
  • Naltrexone / therapeutic use
  • Opioid-Related Disorders* / drug therapy
  • Opioid-Related Disorders* / epidemiology
  • Recurrence
  • United States / epidemiology


  • Analgesics, Opioid
  • Buprenorphine
  • Central Nervous System Stimulants
  • Delayed-Action Preparations
  • Naltrexone