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
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.
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.
Biol Psychiatry Cogn Neurosci Neuroimaging. 2016 Jan;1(1):60-67. doi: 10.1016/j.bpsc.2015.09.008. Epub 2015 Oct 22.
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.
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.
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.
Cannabis dependence is associated with CBR downregulation, which begins to reverse rapidly on termination of cannabis use and may continue to increase over time.
大麻的广泛使用、“医用”大麻日益合法化、大麻效力的增强以及合成大麻素1型受体（CBR）完全激动剂娱乐性使用的增加，都凸显了阐明大麻素对CBR系统影响的重要性。已知接触大麻素会导致CBR下调。然而，大麻依赖（CD）受试者在短期和中期禁欲后CBR可用性变化的精确时间进程尚未确定。
使用高分辨率研究断层扫描和可逆配体[C]OMAR，在男性CD受试者（n = 11）和匹配的健康对照（HC）受试者（n = 19）中测量以[C]OMAR分布体积为指标的CBR可用性。CD受试者在基线（既未中毒也未戒断时）以及在监测禁欲2天和28天后进行扫描。HC受试者在基线进行扫描，其中一个子集（n = 4）在28天后再次扫描。
与HC受试者相比，几乎所有脑区中CD受试者在基线时的[C]OMAR分布体积低15%（效应量Cohen's d = -1.11）。然而，在监测停止使用大麻仅2天后，这些CBR可用性的组间差异就不再明显。禁欲2天后，CBR可用性与戒断症状之间存在强烈的负相关。禁欲28天后，CD受试者的CBR可用性没有显著的组间差异。
大麻依赖与CBR下调有关，在停止使用大麻后CBR下调开始迅速逆转，并且可能会随着时间的推移持续增加。
