Abstract：
Background: Cannabidiol (CBD) has been proposed to have a therapeutic potential over a wide range of neuropsychiatric disorders, including substance use disorders. Pre-clinical evidence suggests that CBD can increase anandamide (AEA) plasma concentration, possibly mediating some of its therapeutic properties. Whether CBD exerts such an effect on AEA in individuals with cocaine use disorder (CUD) remains unknown. Aims: To explore the sustained effects of daily CBD administration on AEA plasma concentrations compared with placebo in CUD. Methods: We used data from a randomized, double-blind, placebo-controlled trial evaluating CBD\'s efficacy in CUD. Seventy-eight individuals were randomized to receive a daily oral dose of 800 mg CBD (n = 40) or a placebo (n = 38). Participants stayed in an inpatient detoxification setting for 10 days, after which they were followed in an outpatient setting for 12 weeks. AEA plasma concentration was measured at baseline and at 23-h post CBD ingestion on day 8 and week 4. A generalized estimating equation model was used to assess CBD\'s effects on AEA, and sensitivity analyses were computed using Bayesian linear regressions. Results: Sixty-four participants were included in the analysis. Similar mean AEA plasma concentrations in both treatment groups (p = 0.357) were observed. At day 8, mean AEA plasma concentrations (± standard deviation) were 0.26 (± 0.07) ng/mL in the CBD group and 0.29 (± 0.08) ng/mL in the placebo group (p = 0.832; Bayes factor [BF] = 0.190). At week 4, they were 0.27 (± 0.09) ng/mL in the CBD group and 0.30 (± 0.09) ng/mL in the placebo group (p = 0.181; BF = 0.194). Conclusion: While not excluding any potential acute and short-term effect, daily CBD administration did not exert a sustained impact on AEA plasma concentrations in individuals with CUD compared with placebo. Registration: clinicaltrials.gov (NCT02559167).
摘要：
背景：大麻二酚（CBD）已被提出具有广泛的神经精神疾病的治疗潜力，包括物质使用障碍。临床前证据表明，CBD可以增加anandamide（AEA）血浆浓度，可能调解它的一些治疗特性。CBD是否对可卡因使用障碍（CUD）患者的AEA产生这种影响尚不清楚。目的：探讨与安慰剂相比，每日CBD给药对CUD中AEA血浆浓度的持续影响。方法：我们使用来自随机，双盲,安慰剂对照试验评估CBD在CUD中的疗效。78个个体随机接受每日口服剂量800mgCBD(n=40)或安慰剂(n=38)。参与者在住院戒毒环境中呆了10天，之后，他们在门诊环境中随访12周。在基线和在第8天和第4周摄入CBD后23小时测量AEA血浆浓度。使用广义估计方程模型来评估CBD对AEA的影响，敏感性分析使用贝叶斯线性回归计算。结果：64名参与者被纳入分析。在两个治疗组中观察到相似的平均AEA血浆浓度(p=0.357)。在第8天，CBD组的平均AEA血浆浓度（±标准偏差）为0.26（±0.07）ng/mL，安慰剂组为0.29（±0.08）ng/mL（p=0.832；贝叶斯因子[BF]=0.190）。在第4周，CBD组为0.27（±0.09）ng/mL，安慰剂组为0.30（±0.09）ng/mL（p=0.181；BF=0.194）。结论：虽然不排除任何潜在的急性和短期效应，与安慰剂相比,每日CBD给药对CUD患者的AEA血浆浓度没有持续影响.注册：clinicaltrials.gov(NCT02559167)。
