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

The endocannabinoid (eCB) system has been proposed as a potential target for developing new medications for opioid use disorder (OUD). However, the status of the eCB system, specifically brain cannabinoid receptor type 1 (CB1R) in OUD, is unknown. In this study, CB1R availability was measured in males with OUD on stable opioid agonist treatment (OAT) (n = 10) versus healthy controls (HC) (n = 18), using High-Resolution Research Tomography (HRRT) and the CB1R-specific radiotracer, [¹¹C]OMAR. The average volume of distribution (V _T ) across 13 regions was compared between the OUD and HC groups. Average V _T was 15% lower in OUD vs. HC subjects (p = 0.04). Lower V _T in OUD compared to HC was also observed in several corticolimbic areas. Within OUD no effects on CB1R availability were observed for treatment medication (methadone vs. buprenorphine), current stress levels, or antidepressant medication. No associations between the average V _T and duration of OAT treatment or time since the last illicit opioid use were observed. This preliminary study suggests lower CB1R availability in men with OUD. Larger studies are necessary to replicate these findings. Future research should also draw from a more heterogeneous population, particularly by incorporating females, to better assess the potential confounding and moderating clinical factors. If confirmed, the observed alterations in CB1R availability in OUD may provide a rationale for targeting the eCB system in the treatment of OUD.