Rapid Changes in CB1 Receptor Availability in Cannabis Dependent Males after Abstinence from Cannabis

Background: The widespread use of cannabis, the increasing legalization of "medical" cannabis, the increasing potency of cannabis and the growing recreational use of synthetic cannabinoid 1 receptor (CB1R) full agonists underscores the importance of elucidating the effects of cannabinoids on the CB1R system. Exposure to cannabinoids is known to result in CB1R downregulation. However, the precise time course of changes in CB1R availability in cannabis dependent subjects (CDs) following short and intermediate term abstinence has not been determined.

Methods: Using High Resolution Research Tomography (HRRT) and [¹¹C]OMAR, CB1R availability as indexed by the volume of distribution (V_T) [¹¹C]OMAR was measured in male CDs (n=11) and matched healthy controls (HCs) (n=19). CDs were scanned at baseline (while they were neither intoxicated nor in withdrawal), and after 2 days and 28 days of monitored abstinence. HCs were scanned at baseline and a subset (n=4) was rescanned 28 days later.

Results: Compared to HCs, [¹¹C]OMAR V_T was 15% lower in CDs (effect size Cohen's d=-1.11) at baseline in almost all brain regions. However, these group differences in CB1R availability were no longer evident after just 2 days of monitored abstinence from cannabis. There was a robust negative correlation between CB1R availability and withdrawal symptoms after 2 days of abstinence. Finally, there were no significant group differences in CB1R availability in CDs after 28 days of abstinence.

Conclusions: Cannabis dependence is associated with CB1R downregulation, which begins to reverse surprisingly rapidly upon termination of cannabis use and may continue to increase over time.