Research Imaging Centre, Centre for Addiction and Mental Health, Toronto, Ontario, Canada.
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada.
JAMA Psychiatry. 2019 Dec 1;76(12):1305-1313. doi: 10.1001/jamapsychiatry.2019.2516.
Cannabis is the most commonly used illicit drug in the world. Cannabinoids have been shown to modulate immune responses; however, the association of cannabis with neuroimmune function has never been investigated in vivo in the human brain.
To investigate neuroimmune activation or 18-kDa translocator protein (TSPO) levels in long-term cannabis users, and to evaluate the association of brain TSPO levels with behavioral measures and inflammatory blood biomarkers.
DESIGN, SETTING, AND PARTICIPANTS: This cross-sectional study based in Toronto, Ontario, recruited individuals from January 1, 2015, to October 30, 2018. Participants included long-term cannabis users (n = 24) and non-cannabis-using controls (n = 27). Cannabis users were included if they had a positive urine drug screen for only cannabis and if they used cannabis at least 4 times per week for the past 12 months and/or met the criteria for cannabis use disorder. All participants underwent a positron emission tomography scan with [18F]FEPPA, or fluorine F 18-labeled N-(2-(2-fluoroethoxy)benzyl)-N-(4-phenoxypyridin-3-yl)acetamide.
Total distribution volume was quantified across regions of interest. Stress and anxiety as well as peripheral measures of inflammatory cytokines and C-reactive protein levels were also measured.
In total, 24 long-term cannabis users (mean [SD] age, 23.1 [3.8] years; 15 men [63%]) and 27 non-cannabis-using controls (mean [SD] age, 23.6 [4.2] years; 18 women [67%]) were included and completed all study procedures. Compared with the controls, cannabis users had higher [18F]FEPPA total distribution volume (main group effect: F1,48 = 6.5 [P = .01]; ROI effect: F1,200 = 28.4 [P < .001]; Cohen d = 0.6; 23.3% higher), with a more prominent implication for the cannabis use disorder subgroup (n = 15; main group effect: F1,39 = 8.5 [P = .006]; ROI effect: F1,164 = 19.3 [P < .001]; Cohen d = 0.8; 31.5% higher). Greater TSPO levels in the brain were associated with stress and anxiety and with higher circulating C-reactive protein levels in cannabis users.
The results of this study suggest that TSPO levels in cannabis users, particularly in those with cannabis use disorder, are higher than those in non-cannabis-using controls. The findings emphasize the need for more complementary preclinical systems for a better understanding of the role of cannabinoids and TSPO in neuroimmune signaling.
大麻是世界上使用最广泛的非法药物。大麻素已被证明可以调节免疫反应；然而，大麻与神经免疫功能的关联在人类大脑中从未在体内进行过研究。
研究长期大麻使用者的神经免疫激活或 18-kDa 转位蛋白（TSPO）水平，并评估大脑 TSPO 水平与行为测量和炎症血液生物标志物的相关性。
设计、地点和参与者：这项基于安大略省多伦多的横断面研究于 2015 年 1 月 1 日至 2018 年 10 月 30 日招募参与者。参与者包括长期大麻使用者（n=24）和非大麻使用者对照（n=27）。如果尿液药物检测仅呈大麻阳性，且过去 12 个月每周至少使用大麻 4 次，或符合大麻使用障碍标准，则将大麻使用者纳入研究。所有参与者均接受[18F]FEPPA 正电子发射断层扫描，即氟 F 18 标记的 N-（2-（2-氟乙氧基）苄基）-N-（4-苯氧基吡啶-3-基）乙酰胺。
在感兴趣的区域内定量了总分布体积。还测量了压力和焦虑以及外周炎症细胞因子和 C 反应蛋白水平。
共有 24 名长期大麻使用者（平均[标准差]年龄 23.1[3.8]岁；15 名男性[63%]）和 27 名非大麻使用者对照（平均[标准差]年龄 23.6[4.2]岁；18 名女性[67%]）完成了所有研究程序。与对照组相比，大麻使用者的[18F]FEPPA 总分布体积更高（主要组效应：F1,48=6.5[P=0.01]；ROI 效应：F1,200=28.4[P<0.001]；Cohen d=0.6；高 23.3%），大麻使用障碍亚组更为明显（n=15；主要组效应：F1,39=8.5[P=0.006]；ROI 效应：F1,164=19.3[P<0.001]；Cohen d=0.8；高 31.5%）。大脑中更高的 TSPO 水平与压力和焦虑以及大麻使用者的循环 C 反应蛋白水平升高有关。
这项研究的结果表明，大麻使用者的 TSPO 水平，尤其是那些患有大麻使用障碍的人，高于非大麻使用者。这些发现强调需要更多的补充临床前系统，以更好地理解大麻素和 TSPO 在神经免疫信号中的作用。
