The Cannabis-Dependent Relationship Between Methadone Treatment Dose and Illicit Opioid Use in a Community-Based Cohort of People Who Use Drugs

Cannabis Cannabinoid Res. 2023 Feb;8(1):155-165. doi: 10.1089/can.2021.0080. Epub 2021 Nov 22.


Background: Methadone maintenance treatment (MMT) is an effective treatment for opioid use disorder. However, subtherapeutic dosing may lead to continued opioid use by failing to suppress opioid withdrawal and craving. Preclinical and pilot experimental research suggests that cannabinoids may reduce opioid withdrawal and craving. We sought to test whether the association between low methadone dose and illicit opioid use differs according to concurrent cannabis use patterns. Methods: Data for this study were derived from two community-recruited cohorts of people (≥18 years old) who use illicit drugs in Vancouver, Canada. We used generalized estimating equations to estimate the adjusted association between lower daily MMT dose (<90 mg/day) and daily illicit opioid use, testing for interaction between dose and daily cannabis use. Results: Between December 2005 and December 2018, 1389 participants reported MMT enrolment and were included in the study. We observed a significant interaction (p<0.01) between daily cannabis and lower MMT dose on concurrent daily illicit opioid use: lower MMT doses increased the odds of daily illicit opioid use by 86% (adjusted odds ratio [AOR]=1.86, 95% confidence interval [CI]=1.61-2.16) during periods of no or low-frequency cannabis use and by 30% during periods of daily cannabis use (AOR=1.30, 95% CI=1.01-1.67). Discussion: This study provides preliminary observational evidence that cannabis may mitigate some of the negative effects of subtherapeutic MMT dosing, guiding future clinical investigations into the safety and efficacy of cannabis and cannabinoids as adjunct treatment for MMT.

Keywords: cannabis; cohort study; methadone; opioid agonist treatment; opioid use disorder; opioids.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Adolescent
  • Analgesics, Opioid
  • Cannabinoid Receptor Agonists / therapeutic use
  • Cannabinoids* / therapeutic use
  • Cannabis*
  • Hallucinogens*
  • Humans
  • Methadone / therapeutic use
  • Narcotics / therapeutic use
  • Opiate Substitution Treatment
  • Opioid-Related Disorders* / drug therapy
  • Opioid-Related Disorders* / rehabilitation
  • Substance Withdrawal Syndrome* / drug therapy


  • Methadone
  • Analgesics, Opioid
  • Narcotics
  • Hallucinogens
  • Cannabinoid Receptor Agonists
  • Cannabinoids