Rapid Changes in Cannabinoid 1 Receptor Availability in Cannabis-Dependent Male Subjects 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 (CBR) full agonists all underscore the importance of elucidating the effects of cannabinoids on the CBR system. Exposure to cannabinoids is known to result in CBR downregulation. However, the precise time course of changes in CBR availability in cannabis-dependent (CD) subjects after short-term and intermediate-term abstinence has not been determined.

METHODS

Using high-resolution research tomography and the reversible ligand [C]OMAR, CBR availability as indexed by the [C]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.

RESULTS

Compared with HC subjects, [C]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 CBR availability were no longer evident after just 2 days of monitored abstinence from cannabis. There was a robust negative correlation between CBR availability and withdrawal symptoms after 2 days of abstinence. There were no significant group differences in CBR availability in CD subjects after 28 days of abstinence.

CONCLUSIONS

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