Format

Send to

Choose Destination
Biol Psychiatry Cogn Neurosci Neuroimaging. 2016 Jan;1(1):60-67. doi: 10.1016/j.bpsc.2015.09.008. Epub 2015 Oct 22.

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

Author information

1
Schizophrenia and Neuropharmacology Research Group, Department of Veterans Affairs Connecticut Healthcare System, West Haven; Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, Connecticut; Departments of Psychiatry and Radiology, Yale School of Medicine, New Haven, Connecticut. Electronic address: deepak.dsouza@yale.edu.
2
Schizophrenia and Neuropharmacology Research Group, Department of Veterans Affairs Connecticut Healthcare System, West Haven; Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, Connecticut; Departments of Psychiatry and Radiology, Yale School of Medicine, New Haven, Connecticut.
3
Departments of Psychiatry and Radiology, Yale School of Medicine, New Haven, Connecticut.
4
Molecular Imaging Program for Mood and Anxiety Disorders, New York University Langone Medical Center, New York, New York.
5
Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, Connecticut; Departments of Psychiatry and Radiology, Yale School of Medicine, New Haven, Connecticut.
6
Massachusetts General Hospital), Harvard Medical School, Boston, Massachusetts.
7
Schizophrenia and Neuropharmacology Research Group, Department of Veterans Affairs Connecticut Healthcare System, West Haven; Abraham Ribicoff Research Facilities, Connecticut Mental Health Center, New Haven, Connecticut.

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 (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.

METHODS:

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.

RESULTS:

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.

CONCLUSIONS:

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

KEYWORDS:

CB(1)R; Cannabinoids; Cannabis; Dependence; Downregulation; Recovery; Tolerance; Upregulation; Withdrawal

PMID:
29560896
DOI:
10.1016/j.bpsc.2015.09.008

Supplemental Content

Loading ...
Support Center