Effect of cannabinol, tetrahydrocannabivarin and cannabidiol on voluntary alcohol consumption.

Three non-psychoactive phytocannabinoids—cannabinol (CBN), tetrahydrocannabivarin (THCV), and cannabidiol (CBD)—all reduced voluntary alcohol consumption in male Wistar rats that had been drinking alcohol long-term. CBN and THCV lowered alcohol intake and preference with mild sedation; CBD had a minor effect on consumption, did not affect preference, reduced activity, and lowered positive emotional states. None caused discomfort or distress. CBN and THCV may be promising for treating alcohol use disorder.

Study at a glance

Abstract

Previous studies have demonstrated that the endocannabinoid system plays a significant role in the development of alcohol use disorder (AUD), and CB1 receptor antagonists/inverse agonists show promise as a novel AUD pharmacotherapy. However, these compounds failed in clinical trials due to the severe psychiatric side effects. Non-psychoactive phytocannabinoids may have a better safety profile and could be used as an alternative approach to treat AUD. The aim of this study was to test the potential of three phytocannabinoids in reducing alcohol consumption: CB1 receptor partial agonist cannabinol (CBN), neutral antagonist tetrahydrocannabivarin (THCV) and negative allosteric modulator cannabidiol (CBD). Male Wistar rats were subjected to a long-term voluntary alcohol drinking procedure that lasted for several months. Thereafter, rats were given three once daily administrations of CBN, THCV, or CBD. Their side-effect profile was examined by recording changes in water consumption, body weight and locomotor activity. Ultrasonic vocalisations were recorded in alcohol-naïve group-housed rats to monitor if treatment induced discomfort, distress, or other changes in emotional states. Our data demonstrated that all phytocannabinoids reduced voluntary alcohol consumption; however, the compounds differed in their effectiveness and side-effect profile. Treatment with CBN and THCV reduced alcohol intake and alcohol preference and had a mild sedative effect. CBD had a minor effect on alcohol consumption, did not affect alcohol preference, reduced the locomotor activity and lowered the positive emotional states of rats. None of the compounds caused discomfort or distress. We conclude that CBN and THCV may have potential in treating AUD.