Effects of Randomization to Buprenorphine or Naltrexone for OUD on Cannabis Use Outcomes: A Secondary Analysis of the X:BOT Trial

Overview

Journal Drug Alcohol Depend

Publisher Elsevier

Date 2025 Feb 1

PMID 39892089

Authors

Matisyahu Shulman

Tse-Hwei Choo

Kaitlyn Ohrtman

Martina Pavlicova

John Rotrosen

Edward V Nunes

Affiliations

Soon will be listed here.

Abstract

Aims: Cannabis use is highly prevalent in patients seeking treatment for opioid use disorder. Studies have shown mixed results on the association between cannabis use and opioid use as well as the impact of MOUD on cannabis use. The current study aims to investigate the effects of buprenorphine versus naltrexone on cannabis use outcomes in treatment seeking individuals with Opioid Use Disorder (OUD).

Methods: The current study was based on data from the CTN-0051 X:BOT trial, which compared the time to return to significant opioid use survival outcomes of two treatment seeking groups, one receiving Extended-Release Naltrexone (XR-naltrexone) (N = 283) versus another receiving Buprenorphine-Naloxone (N = 287) for OUD. A mixed-effects logistic regression model including treatment assignment (buprenorphine-naloxone vs XR-naltrexone), time, and a time by treatment interaction was run on the sample with the odds of cannabis use as the outcome, as well as two cross-lagged mediation models to explore the prospective mediation of cannabis use on opioid use outcomes (and opioid use on cannabis use outcomes) by treatment assignment during the trial.

Results: There was a significant effect of buprenorphine treatment on reduced cannabis use. Participants receiving buprenorphine treatment were 39 % less likely to use cannabis than those receiving naltrexone over all the timepoints (p = .0499). No significant mediation was found between treatment assignment and opioid use on cannabis use outcomes or between treatment assignment and cannabis use on opioid use outcomes in this trial.

Conclusion: Participants in this trial receiving buprenorphine treatment for OUD used less cannabis than those receiving naltrexone treatment.

References

Haney M, Ramesh D, Glass A, Pavlicova M, Bedi G, Cooper Z . Naltrexone Maintenance Decreases Cannabis Self-Administration and Subjective Effects in Daily Cannabis Smokers. Neuropsychopharmacology. 2015; 40(11):2489-98. PMC: 4569951. DOI: 10.1038/npp.2015.108. View

Greiner M, Shulman M, Choo T, Scodes J, Pavlicova M, Campbell A . Naturalistic follow-up after a trial of medications for opioid use disorder: Medication status, opioid use, and relapse. J Subst Abuse Treat. 2021; 131:108447. PMC: 8556394. DOI: 10.1016/j.jsat.2021.108447. View

Bunting A, Krawczyk N, Choo T, Pavlicova M, McNeely J, Tofighi B . Polysubstance use before and during treatment with medication for opioid use disorder: Prevalence and association with treatment outcomes. J Subst Abuse Treat. 2022; 143:108830. PMC: 10012431. DOI: 10.1016/j.jsat.2022.108830. View

Wiese B, Wilson-Poe A . Emerging Evidence for Cannabis' Role in Opioid Use Disorder. Cannabis Cannabinoid Res. 2018; 3(1):179-189. PMC: 6135562. DOI: 10.1089/can.2018.0022. View

Navarro M, Carrera M, Fratta W, Valverde O, Cossu G, Fattore L . Functional interaction between opioid and cannabinoid receptors in drug self-administration. J Neurosci. 2001; 21(14):5344-50. PMC: 6762870. View

Castillo F, Hu M, Liu Y, Balise R, Weiss R, Rotrosen J . Risks of returning to opioid use at treatment entry and early in opioid use disorder treatment: Role of non-opioid substances. Drug Alcohol Depend. 2023; 251:110926. PMC: 10712265. DOI: 10.1016/j.drugalcdep.2023.110926. View

Shulman M, Choo T, Scodes J, Pavlicova M, Wai J, Haenlein P . Association between methadone or buprenorphine use during medically supervised opioid withdrawal and extended-release injectable naltrexone induction failure. J Subst Abuse Treat. 2021; 124:108292. PMC: 8004552. DOI: 10.1016/j.jsat.2021.108292. View

Williams A . Cannabis as a Gateway Drug for Opioid Use Disorder. J Law Med Ethics. 2020; 48(2):268-274. PMC: 7359408. DOI: 10.1177/1073110520935338. View

Powell D, Pacula R, Jacobson M . Do medical marijuana laws reduce addictions and deaths related to pain killers?. J Health Econ. 2018; 58:29-42. PMC: 7867411. DOI: 10.1016/j.jhealeco.2017.12.007. View

10.

Cooper Z, Haney M . Opioid antagonism enhances marijuana's effects in heavy marijuana smokers. Psychopharmacology (Berl). 2010; 211(2):141-8. PMC: 2923559. DOI: 10.1007/s00213-010-1875-y. View

11.

Hill K, Bennett H, Griffin M, Connery H, Fitzmaurice G, Subramaniam G . Association of cannabis use with opioid outcomes among opioid-dependent youth. Drug Alcohol Depend. 2013; 132(1-2):342-5. PMC: 3724203. DOI: 10.1016/j.drugalcdep.2013.02.030. View

12.

Flexon J, Stolzenberg L, DAlessio S . The effect of cannabis laws on opioid use. Int J Drug Policy. 2019; 74:152-159. DOI: 10.1016/j.drugpo.2019.09.013. View

13.

Foot C, Korthuis P, Tsui J, Luo S, Chan B, Cook R . Associations between stimulant use and return to illicit opioid use following initiation onto medication for opioid use disorder. Addiction. 2023; 119(1):149-157. PMC: 11139042. DOI: 10.1111/add.16334. View

14.

Trivedi M, Walker R, Ling W, Dela Cruz A, Sharma G, Carmody T . Bupropion and Naltrexone in Methamphetamine Use Disorder. N Engl J Med. 2021; 384(2):140-153. PMC: 8111570. DOI: 10.1056/NEJMoa2020214. View

15.

Rosner S, Hackl-Herrwerth A, Leucht S, Vecchi S, Srisurapanont M, Soyka M . Opioid antagonists for alcohol dependence. Cochrane Database Syst Rev. 2010; (12):CD001867. DOI: 10.1002/14651858.CD001867.pub3. View

16.

Lee J, Nunes Jr E, Novo P, Bachrach K, Bailey G, Bhatt S . Comparative effectiveness of extended-release naltrexone versus buprenorphine-naloxone for opioid relapse prevention (X:BOT): a multicentre, open-label, randomised controlled trial. Lancet. 2017; 391(10118):309-318. PMC: 5806119. DOI: 10.1016/S0140-6736(17)32812-X. View

17.

Bawor M, Dennis B, Varenbut M, Daiter J, Marsh D, Plater C . Sex differences in substance use, health, and social functioning among opioid users receiving methadone treatment: a multicenter cohort study. Biol Sex Differ. 2015; 6:21. PMC: 4640383. DOI: 10.1186/s13293-015-0038-6. View

18.

Bleyer A, Barnes B, Finn K . United States marijuana legalization and opioid mortality epidemic during 2010-2020 and pandemic implications. J Natl Med Assoc. 2022; 114(4):412-425. DOI: 10.1016/j.jnma.2022.03.004. View

19.

Haney M, Bisaga A, Foltin R . Interaction between naltrexone and oral THC in heavy marijuana smokers. Psychopharmacology (Berl). 2002; 166(1):77-85. DOI: 10.1007/s00213-002-1279-8. View

20.

Budney A, Bickel W, Amass L . Marijuana use and treatment outcome among opioid-dependent patients. Addiction. 1998; 93(4):493-503. DOI: 10.1046/j.1360-0443.1998.9344935.x. View