Rapid Changes in Cannabinoid 1 Receptor Availability in Cannabis-Dependent Male Subjects After Abstinence From...

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 all underscore 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 (CD) subjects after short-term and intermediate-term abstinence has not been determined.

Using high-resolution research tomography and the reversible ligand [¹¹C]OMAR, CB₁R availability as indexed by the [¹¹C]OMAR volume of distribution was measured in male CD subjects (n = 11) and matched healthy control (HC) subjects (n = 19). The CD subjects were scanned at baseline (while they were neither intoxicated nor in withdrawal) and after 2 days and 28 days of monitored abstinence. The HC subjects were scanned at baseline, and a subset (n = 4) was scanned again 28 days later.

Compared with HC subjects, [¹¹C]OMAR volume of distribution was 15% lower in CD subjects (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. There were no significant group differences in CB₁R availability in CD subjects after 28 days of abstinence.

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