Addiction and Mental Health Group (AIM), Department of Psychology, University of Bath, Bath, UK.
Clinical Psychopharmacology Unit, UCL, London, UK.
Transl Psychiatry. 2023 Apr 21;13(1):131. doi: 10.1038/s41398-023-02410-9.
Cannabidiol (CBD) has shown promise in treating psychiatric disorders, including cannabis use disorder - a major public health burden with no approved pharmacotherapies. However, the mechanisms through which CBD acts are poorly understood. One potential mechanism of CBD is increasing levels of anandamide, which has been implicated in psychiatric disorders including depression and cannabis use disorder. However, there is a lack of placebo-controlled human trials investigating this in psychiatric disorders. We therefore assessed whether CBD affects plasma anandamide levels compared to placebo, within a randomised clinical trial of CBD for the treatment of cannabis use disorder. Individuals meeting criteria for cannabis use disorder and attempting cannabis cessation were randomised to 28-day administration with placebo (n = 23), 400 mg CBD/day (n = 24) or 800 mg CBD/day (n = 23). We estimated the effects of each CBD dose compared to placebo on anandamide levels from baseline to day 28. Analyses were conducted both unadjusted and adjusted for cannabis use during the trial to account for effects of cannabis on the endocannabinoid system. We also investigated whether changes in plasma anandamide levels were associated with clinical outcomes relevant for cannabis use disorder (cannabis use, withdrawal, anxiety, depression). There was an effect of 800 mg CBD compared to placebo on anandamide levels from baseline to day 28 after adjusting for cannabis use. Pairwise comparisons indicated that anandamide levels unexpectedly reduced from baseline to day 28 in the placebo group (-0.048, 95% CI [-0.089, -0.007]), but did not change in the 800 mg CBD group (0.005, 95% CI [-0.036, 0.047]). There was no evidence for an effect of 400 mg CBD compared to placebo. Changes in anandamide levels were not associated with clinical outcomes. In conclusion, this study found preliminary evidence that 28-day treatment with CBD modulates anandamide levels in individuals with cannabis use disorder at doses of 800 mg/day but not 400 mg/day compared to placebo.
大麻二酚（CBD）在治疗精神疾病方面显示出前景，包括大麻使用障碍-一种没有批准的药物治疗方法的主要公共卫生负担。然而，CBD 作用的机制还了解甚少。CBD 的一个潜在机制是增加花生四烯酸乙醇胺的水平，花生四烯酸乙醇胺已被牵连到包括抑郁症和大麻使用障碍在内的精神疾病中。然而，在精神疾病中，缺乏安慰剂对照的人体试验来对此进行研究。因此，我们评估了与安慰剂相比，CBD 是否会影响治疗大麻使用障碍的随机临床试验中血浆花生四烯酸乙醇胺的水平。符合大麻使用障碍标准并试图停止使用大麻的个体被随机分配接受 28 天的安慰剂（n=23）、400mg CBD/天（n=24）或 800mg CBD/天（n=23）治疗。我们从基线到第 28 天估计了每种 CBD 剂量与安慰剂相比对花生四烯酸乙醇胺水平的影响。分析未调整和调整了试验期间的大麻使用情况，以解释大麻对内源性大麻素系统的影响。我们还研究了血浆花生四烯酸乙醇胺水平的变化是否与大麻使用障碍的相关临床结局（大麻使用、戒断、焦虑、抑郁）相关。调整大麻使用情况后，与安慰剂相比，800mg CBD 在从基线到第 28 天的花生四烯酸乙醇胺水平上有影响。两两比较表明，安慰剂组的花生四烯酸乙醇胺水平从基线到第 28 天意外下降（-0.048，95%CI[-0.089，-0.007]），但在 800mg CBD 组中没有变化（0.005，95%CI[-0.036，0.047]）。400mg CBD 与安慰剂相比没有证据表明有影响。花生四烯酸乙醇胺水平的变化与临床结局无关。总之，这项研究初步发现，与安慰剂相比，28 天的 CBD 治疗可调节大麻使用障碍个体的花生四烯酸乙醇胺水平，800mg/天剂量有效，但 400mg/天剂量无效。
