Men With Opioid Use Disorder Had 15% Lower Brain Cannabis Receptor Levels | Research

The takeaway

A brain imaging study found that men with opioid use disorder on stable treatment had 15% lower CB1 receptor availability than healthy controls, particularly in emotion-regulating brain regions.

Addiction neuroscientists, clinicians treating opioid use disorder, endocannabinoid system researchers.

15% lower CB1 receptor availability in the brains of men with opioid use disorder

What the researchers found

Average CB1R availability (measured by volume of distribution) was 15% lower across 13 brain regions in men with OUD compared to healthy controls (p=0.04). Lower CB1R was also observed in several corticolimbic areas. No effects on CB1R were found for treatment medication type, stress levels, antidepressant use, treatment duration, or time since last illicit opioid use.

Why it matters

If confirmed, lower CB1R availability in OUD could provide a rationale for targeting the endocannabinoid system in opioid addiction treatment. Understanding how opioid use alters the brain's cannabinoid system may help explain why some opioid users also develop cannabis use patterns.

The numbers in context

n=10 OUD patients, n=18 healthy controls; 15% lower average CB1R volume of distribution (p=0.04); 13 brain regions assessed; no effect of treatment medication type or duration.

How the study worked

PET brain imaging study using High-Resolution Research Tomography and the CB1R-specific radiotracer [11C]OMAR, comparing 10 males with OUD on stable opioid agonist treatment (methadone or buprenorphine) to 18 healthy male controls. CB1R availability was measured across 13 brain regions.

What this study cannot tell us

Very small sample (n=10 OUD). Males only, limiting generalizability. All OUD participants were on opioid agonist treatment, so findings may reflect treatment effects rather than OUD itself. Cross-sectional design cannot determine whether lower CB1R preceded or resulted from opioid use.

How to read the evidence

Preliminary: Very small sample (n=10 OUD patients) in a pilot PET imaging study; findings require replication in larger, more diverse populations.

When this study was published

Published in 2025 (preprint).

The bigger picture

The endocannabinoid system has been proposed as a target for developing new OUD medications. This is one of the first human brain imaging studies to directly measure CB1R in people with OUD, providing biological evidence for endocannabinoid system involvement in opioid addiction.

Questions still open

Would CB1R differences be similar in women with OUD? Is lower CB1R a cause or consequence of opioid use? Could CB1R availability predict treatment response in OUD?

Common questions

What are CB1 receptors?

CB1 receptors are the main cannabinoid receptors in the brain. They are part of the endocannabinoid system and are involved in mood, reward, pain, and stress regulation. Both cannabis and the body's own endocannabinoids act on these receptors.

How does this relate to cannabis use?

The study did not involve cannabis use, but measured the same brain receptors that cannabis targets. Finding that these receptors are altered in opioid addiction suggests the endocannabinoid system may be involved in multiple types of substance use disorders and could be a treatment target.

Read the original research

A Preliminary Investigation of Brain Cannabinoid Receptor Type 1 (CB1R) Availability in Men with Opioid Use Disorder.

Research square

View on PubMed ↗Publisher’s paper ↗

Citation

Nia, Anahita Bassir; Aghaei, Ardavan Mohammad; Weleff, Jeremy; Shi, Julia; Contreras, Angelina; Griffin, Mackenzie; Jegede, Oluwole; Pittman, Brian; Harpaz-Rotem, Ilan; Hillmer, Ansel; D'Souza, Deepak. (2025). A Preliminary Investigation of Brain Cannabinoid Receptor Type 1 (CB1R) Availability in Men with Opioid Use Disorder.. Research square. https://doi.org/10.21203/rs.3.rs-7715611/v1