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

• Published in: Biological psychiatry : cognitive neuroscience and neuroimaging 2016, Vol.1 (1), p.60-67
• Main Authors: D’Souza, Deepak Cyril, Cortes-Briones, Jose A, Ranganathan, Mohini, Thurnauer, Halle, Creatura, Gina, Surti, Toral, Planeta, Beata, Neumeister, Alexander, Pittman, Brian, Normandin, Marc D, Kapinos, Michael, Ropchan, Jim, Huang, Yiyun, Carson, Richard E, Skosnik, Patrick D
• Format: Article
• Language: English
• Subjects: Cannabinoids; Cannabis; CB1R; Dependence; Downregulation; Psychiatry; Recovery; Tolerance; Upregulation; Withdrawal
• ISSN: 2451-9022; 2451-9030
• DOI: 10.1016/j.bpsc.2015.09.008

Abstract 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 (CB1 R) full agonists all underscore the importance of elucidating the effects of cannabinoids on the CB1 R system. Exposure to cannabinoids is known to result in CB1 R downregulation. However, the precise time course of changes in CB1 R 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 [11 C]OMAR, CB1 R availability as indexed by the [11 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, [11 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 CB1 R availability were no longer evident after just 2 days of monitored abstinence from cannabis. There was a robust negative correlation between CB1 R availability and withdrawal symptoms after 2 days of abstinence. There were no significant group differences in CB1 R availability in CD subjects after 28 days of abstinence. Conclusions Cannabis dependence is associated with CB1 R downregulation, which begins to reverse rapidly on termination of cannabis use and may continue to increase over time.