Kearney-Ramos Tonisha, Herrmann Evan S, Belluomo Ilaria, Matias Isabel, Vallée Monique, Monlezun Stéphanie, Piazza Pier Vincenzo, Haney Margaret
Division on Substance Use Disorders, New York State Psychiatric Institute, Columbia University Irving Medical Center, New York, New York, USA.
Division of Therapeutics and Medical Consequences, National Institute on Drug Abuse, Bethesda, Maryland, USA.
Cannabis Cannabinoid Res. 2023 Dec;8(6):1069-1078. doi: 10.1089/can.2021.0185. Epub 2022 Apr 29.
The endogenous cannabinoid system (ECS), including the endocannabinoids (eCBs), anandamide (AEA), and 2-arachidonoylglycerol (2-AG), plays an integral role in psychophysiological functions. Although frequent cannabis use is associated with adaptations in the ECS, the impact of acute smoked cannabis administration on circulating eCBs, and the relationship between cannabis effects and circulating eCBs are poorly understood. This study measured the plasma levels of AEA, 2-AG, and Δ-9-tetrahydrocannabinol (THC), subjective drug-effects ratings, and cardiovascular measures at baseline and 15-180 min after cannabis users (=26) smoked 70% of a cannabis cigarette (5.6% THC). Cannabis administration increased the ratings of intoxication, heart rate, and plasma THC levels relative to baseline. Although cannabis administration did not affect eCB levels relative to baseline, there was a significant positive correlation between baseline AEA levels and peak ratings of "High" and "Good Drug Effect." Further, baseline 2-AG levels negatively correlated with frequency of cannabis use (mean days/week) and with baseline THC metabolite levels. In a subset of heavy cannabis smokers: (1) more frequent cannabis use was associated with lower baseline 2-AG, and (2) those with lower AEA got less intoxicated after smoking cannabis. These findings contribute to a sparse literature on the interaction between endo- and phyto-cannabinoids. Future studies in participants with varied cannabis use patterns are needed to clarify the association between circulating eCBs and the abuse-related effects of cannabis, and to test whether baseline eCBs predict the intoxicating effects of cannabis and are a potential biomarker of cannabis tolerance.
内源性大麻素系统（ECS），包括内源性大麻素（eCBs）、花生四烯乙醇胺（AEA）和2-花生四烯酸甘油酯（2-AG），在心理生理功能中发挥着不可或缺的作用。尽管频繁使用大麻与ECS的适应性变化有关，但急性吸食大麻对循环eCBs的影响以及大麻效应与循环eCBs之间的关系仍知之甚少。本研究测量了26名大麻使用者在基线时以及吸食含5.6%四氢大麻酚（THC）的大麻香烟70%后15 - 180分钟时血浆中AEA、2-AG和Δ-9-四氢大麻酚（THC）的水平、主观药物效应评分以及心血管指标。与基线相比，吸食大麻后中毒评分、心率和血浆THC水平升高。尽管吸食大麻相对于基线并未影响eCB水平，但基线AEA水平与“兴奋”和“良好药物效应”的峰值评分之间存在显著正相关。此外，基线2-AG水平与大麻使用频率（平均每周天数）以及基线THC代谢物水平呈负相关。在一部分重度大麻吸烟者中：（1）更频繁的大麻使用与更低的基线2-AG相关，（2）AEA水平较低的人吸食大麻后中毒程度较轻。这些发现为关于内源性大麻素和植物性大麻素之间相互作用的稀少文献增添了内容。未来需要对具有不同大麻使用模式的参与者进行研究，以阐明循环eCBs与大麻滥用相关效应之间的关联，并测试基线eCBs是否能预测大麻的中毒效应以及是否是大麻耐受性的潜在生物标志物。
