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Buprenorphine Associated with Reduced Cannabis Use Compared to XR-Naltrexone in Patients Receiving Medications for Opioid Use Disorder

published:
February 3, 2025
Author:
Meg Brunner, MLIS
Citation:
Shulman M, et al. Effects of randomization to buprenorphine or naltrexone for OUD on cannabis use outcomes: A secondary analysis of the X:BOT trial. Drug and Alcohol Dependence 2025 (in press).
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What’s the Question?

Cannabis use is common in patients seeking treatment for opioid use disorder (OUD), with about 1 in 4 people in treatment for OUD reporting cannabis use.

Since the opioid receptor is involved not only in the effect of opioids but also other drugs, how medications for OUD interact with cannabis is an important question. It’s also important to know if cannabis use during treatment for OUD has any effects on the outcomes of that treatment.

This study, an analysis of data from the NIDA Clinical Trials Network study CTN-0051 (the X:BOT trial), aimed to determine whether OUD treatment with buprenorphine or long-acting naltrexone (XR-naltrexone) had any impact on cannabis use and whether changes in opioid use led to subsequent changes in cannabis use or vice versa.

How Was This Study Conducted?

The CTN X:BOT trial was a 24-week study comparing the opioid relapse-free survival outcomes of two groups, one receiving XR-naltrexone (N=283) and one receiving buprenorphine-naloxone (N=287) for OUD.

Participants began the study after admission to inpatient withdrawal management units where they were then were randomized to one of the two medications. Patients completed weekly assessments, including a self-reported timeline follow back of illicit opioid, cannabis, and other substance use; urine toxicology screens; opioid craving reports; and documentation of adverse events.

To determine the effect of treatment assignment on cannabis use outcomes, researchers examined treatment assignment, time, and time by treatment, as well as what impact, if any, cannabis use had on opioid use or the reverse.

Who Were the Study Participants?

Five hundred and sixty-nine people participated in the study. Of this sample:

  • 40.6% use cannabis at baseline
    • for the buprenorphine group, it was 42.2%
    • for the naltrexone group, it was 39%
  • 73.3% of participants were male
  • 73.8% were white, 33.3% were Black
  • 67.5% reported IV opioid use at baseline (with similar rates of baseline cannabis use for IV and non-IV users)

What Did Researchers Find Out?

Analysis revealed a significant effect of buprenorphine-naloxone on cannabis use during the trial, with patients on buprenorphine-naloxone having 39% lower odds of cannabis use compared to patients on XR-naltrexone.

There was also a significant effect of time, with odds of cannabis use increasing by 6% on average with each additional week in the study. Additionally, participants who reported using cannabis at the start of the study (“baseline”) had 13.6 times the odds of cannabis use during the trial than those who reported no cannabis use at baseline.

Cannabis use during the trial didn’t appear to affect opioid use, nor did changes in opioid use appear to affect cannabis use.

What Are the Implications for the Workforce?

Though this is just one study, these results suggest that buprenorphine-naloxone might have an advantage over XR-naltrexone for patients who use both opioids and cannabis and want to reduce use of both substances. One possible explanation for this finding is that buprenorphine’s partial agonism of the opioid receptor provides reinforcement and helps address underlying anxiety or mood problems, so patients on buprenorphine might not feel the need to use cannabis. There is also some research that has found that the cannabinoid and opioid pathways in the brain are interconnected, though this interconnectivity is still not clear.

It's also important to note that there was no significant interaction between cannabis use and outcome of treatment for OUD, so clinicians treating patients with opioid use disorder with one of these medications may not need to view continued use of cannabis as a major risk factor for relapse to opioid use.

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