Naltrexone Restored Brain Connectivity Disrupted by Cannabis Use Disorder in Opioid Users

What the researchers found

At baseline, people with opioid use disorder plus co-occurring cannabis use disorder showed distinct brain connectivity alterations compared to those with OUD alone, primarily involving the default mode network. Two weeks after naltrexone administration, these connectivity differences globally diminished in the cannabis group. Similar but more limited restoration occurred in co-occurring alcohol use disorder, while no change occurred in co-occurring cocaine use disorder.

Why it matters

No medication is currently approved for cannabis use disorder. This study provides neuroimaging evidence that naltrexone, already approved for opioid and alcohol use disorders, may address the brain connectivity disruptions specific to cannabis use disorder, potentially offering a treatment pathway.

The numbers in context

Brain connectivity differences between co-occurring CanUD and OUD-only diminished globally after naltrexone; default mode network primarily affected at baseline; parietal, subcortical, sensory, and cerebellar restoration in AUD group; no change in CocUD group; younger participants showed larger baseline differences; effects controlled for opioid use

How the study worked

Retrospective secondary analysis of fMRI data from individuals with primary opioid use disorder and co-occurring cannabis, alcohol, or cocaine use disorder. All received long-acting intramuscular naltrexone (Vivitrol) and were imaged before and 2 weeks after treatment.

What this study cannot tell us

Retrospective secondary analysis not designed to study CUD, small subgroup sizes, cannot separate CUD-specific effects from general opioid recovery effects, no behavioral cannabis use outcomes measured, participants had co-occurring OUD complicating interpretation

How to read the evidence

Retrospective secondary analysis of neuroimaging data; generates a compelling hypothesis but was not designed or powered to study CUD specifically

When this study was published

Published 2025

The bigger picture

The lack of approved medications for cannabis use disorder is a major treatment gap. This secondary analysis suggests naltrexone deserves prospective investigation as a CUD treatment, especially since it is already widely available and well-characterized in clinical practice.

Questions still open

• Would naltrexone reduce cannabis use in people with CUD who do not have co-occurring OUD? Is the connectivity restoration associated with reduced cannabis craving or use? What is the optimal naltrexone dose and duration for CUD specifically?

Common questions

Read the original research

Long-acting naltrexone restores network connectivity in subjects with co-morbid cannabis and opioid use disorder.

bioRxiv : the preprint server for biology

Citation

Brier, Lindsey M; Langleben, Daniel D; Wiers, Corinde E; Shi, Zhenhao. (2025). Long-acting naltrexone restores network connectivity in subjects with co-morbid cannabis and opioid use disorder.. bioRxiv : the preprint server for biology. https://doi.org/10.1101/2025.09.18.676931

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