Cannabis use during methadone maintenance treatment for opioid use disorder: a systematic review and meta-analysis

We read with interest the recent publication by McBrien and colleagues systematically reviewing the impacts of cannabis use on outcomes from methadone-based opioid agonist treatment (OAT). Given the well-known benefits of retention in OAT on reducing the risk of mortality,1 we were particularly interested in their examination of the relationship between cannabis use and retention in methadone-based OAT.

In their systematic review, the authors analyzed eleven studies and found inconclusive evidence on the effect of cannabis use on retention in methadone. This is not surprising given high heterogeneity across studies arising from differences in operational definitions of cannabis use, including frequency of use, frequency of measurement, and temporal relationship with the outcome assessed. What is notable, however, is the difference found in their sub-group analysis by country, with studies conducted in the United States (U.S.) generally showing a negative association between cannabis use and retention in methadone-based OAT and those from Israel generally showing the opposite.

Unfortunately, our recently-published longitudinal study of individuals initiating OAT (>99% methadone)2 was not included in McBrien and colleagues' review. In our analysis, published in Addiction, we found that among 820 individuals initiating methadone or buprenorphine- based OAT, at least daily cannabis use was associated with higher likelihood of being retained in treatment for at least six months (adjusted odds ratio [AOR] = 1.21, 95% Confidence Interval [CI] = 1.04- 1.41). In light of McBrien et al. review, we decided to re-analyze our data restricting the study sample to the 806 individuals who started methadone-based OAT; and the results were essentially unchanged (AOR = 1.22, 95% CI = 1.03-1.44).

Taken together, these results raise the question as to whether characteristics of treatment programs in different jurisdiction may have played a role. For instance, strict regulations of many opioid treatment programs (OTPs) (e.g., discharging patient from methadone-based OAT if continued evidence of use of other illicit substance is documented)3 as well as the implementation context (e.g., restriction of methadone-based OAT to OTPs) in the U.S. may partially explain divergent findings between countries. These considerations aside, as McBrien et al. point out, conclusions from their review are limited due to the observational nature, as well as small sample size, of the studies. In our view, their failure to find a beneficial impact of cannabis use among this collection of preliminary studies is not evidence that cannabis is ineffective in improving opioid use disorder (OUD) treatment outcomes but rather underlines the need for experimental studies to determine the possible risks and benefits of cannabis among people on OAT.

Over 4,000 Canadians died of an opioid-related overdose in 2018.4 Retention in OAT is effective in reducing illicit opioid use and mortality.1,5 However, attrition rates are high,6,7 underscoring the need for innovative strategies to support people in OAT. Therefore, we add our voices to the call of many others8,9 for urgently needed experimental research to investigate the potential of cannabis as adjunct therapy for OAT.

References

1. Sordo L, Barrio G, Bravo MJ, et al. Mortality risk during and after opioid substitution treatment: systematic review and meta-analysis of cohort studies. BMJ. 2017;357:j1550.

2. Socias ME, Wood E, Lake S, et al. High-intensity cannabis use is associated with retention in opioid agonist treatment: a longitudinal analysis. Addiction. 2018;113(12):2250-2258.

3. Drug Testing: a White Paper of the American Society of Addiction Medicine. 2013. https://www.asam.org/docs/default-source/public-policy- statements/drug-testing-a-white-paper-by-asam.pdf. Accessed November 29, 2019.

4. Special Advisory Committee on the Epidemic of Opioid Overdoses. National report: Apparent opioid-related deaths in Canada (January 2016 to March 2019). Web Based Report. September 2019; https://health- infobase.canada.ca/datalab/national-surveillance-opioid-mortality.html. Accessed September 26, 2019.

5. Mattick RP, Breen C, Kimber J, Davoli M. Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence. Cochrane Database Syst Rev. 2014;2:CD002207.

6. Socias ME, Wood E, Kerr T, et al. Trends in engagement in the cascade of care for opioid use disorder, Vancouver, Canada, 2006-2016. Drug Alcohol Depend. 2018;189:90-95.

7. Timko C, Schultz NR, Cucciare MA, Vittorio L, Garrison-Diehn C. Retention in medication-assisted treatment for opiate dependence: A systematic review. J Addict Dis. 2016;35(1):22-35.

8. Hurd YL. Cannabidiol: Swinging the Marijuana Pendulum From 'Weed' to Medication to Treat the Opioid Epidemic. Trends Neurosci. 2017;40(3):124-127.

9. Lucas P. Rationale for cannabis-based interventions in the opioid overdose crisis. Harm Reduct J. 2017;14(1):58.

Conflict of Interest:

M-JM is the Canopy Growth professor of cannabis science at the University of British Columbia, a position created by unstructured gifts to the university from Canopy Growth, a licensed producer of cannabis, and the Government of British Columbia's Ministry of Mental Health and Addictions. The University of British Columbia has also received unstructured funding from NG Biomed, Ltd. to support M-JM. All other authors declare no competing interests.