BACKGROUND The mental health benefits of cannabidiol (CBD) are promising but can be inconsistent, in part due to challenges in defining an individual's effective dosage. In schizophrenia, alterations in anandamide (AEA) concentrations, an endocannabinoid (eCB) agonist of the eCB system, reflect positively on treatment with CBD. Here, we expanded this assessment to include eCBs alongside AEA congeners, comparing phytocannabinoids and dosage in a clinical setting. METHODS Liquid chromatography-tandem mass spectrometry quantified changes in serum levels of AEA, 2-arachidonoylglycerol (2-AG), alongside AEA-related compounds oleoylethanolamide (OEA) and palmitoylethanolamide (PEA), which were attained from two independent, parallel-designed, clinical trials investigating single, oral CBD (600 or 800 mg), delta-9-tetrahydrocannabinol (Δ9-THC, 10 or 20 mg) and combination administration (CBD|800 mg+Δ9-THC|20 mg) in healthy volunteers (HVs, n=75). Concentrations were measured at baseline (t=0), 65 and 160 min post administration. RESULTS CBD-led increases in AEA (1.6-fold), OEA and PEA (1.4-fold) were observed following a single 800 mg (pcorr<0.05) but not 600 mg dosage. Declining AEA was observed with Δ9-THC at 10 mg (-1.3-fold) and 20 mg (-1.4-fold) but restored to baseline levels by 160 min. CBD+Δ9-THC yielded the highest increases in AEA (2.1-fold), OEA (1.9-fold) and PEA (1.8-fold) without reaching a maximal response. CONCLUSION CBD-administered effects towards AEA, OEA and PEA are consistent with phase II trials reporting clinical improvement for acute schizophrenia (CBD≥800 mg). Including Δ9-THC appears to enhance the CBD-induced response towards AEA and its congeners. Our results warrant further investigations into the potential of these lipid-derived mediators as metabolic measures for CBD dose prescription and co-cannabinoid administration.

中文翻译：

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口服大麻二酚和 delta-9-四氢大麻酚对健康志愿者血清 anandamide 和相关 N-酰基乙醇胺的剂量依赖性影响。


背景技术大麻二酚（CBD）对心理健康的益处是有希望的，但可能不一致，部分原因是在确定个人有效剂量方面存在挑战。在精神分裂症中，eCB 系统的内源性大麻素 (eCB) 激动剂 anandamide (AEA) 浓度的变化对 CBD 治疗产生积极影响。在这里，我们将评估范围扩大到包括 eCB 和 AEA 同系物，比较临床环境中的植物大麻素和剂量。方法 液相色谱-串联质谱法定量了 AEA、2-花生四烯酰甘油 (2-AG) 以及 AEA 相关化合物油酰乙醇酰胺 (OEA) 和棕榈酰乙醇酰胺 (PEA) 的血清水平变化，这些化合物是从两个独立、平行设计的、在健康志愿者 (HV) 中调查单一口服 CBD（600 或 800 毫克）、δ-9-四氢大麻酚（Δ9-THC，10 或 20 毫克）和联合给药（CBD|800 毫克+Δ9-THC|20 毫克）的临床试验，n=75)。在基线 (t=0)、给药后 65 和 160 分钟测量浓度。结果 在单次 800 mg (pcorr<0.05) 而非 600 mg 剂量后观察到 CBD 导致 AEA（1.6 倍）、OEA 和 PEA（1.4 倍）增加。使用 10 mg（-1.3 倍）和 20 mg（-1.4 倍）的 Δ9-THC 观察到 AEA 下降，但在 160 分钟后恢复到基线水平。 CBD+Δ9-THC 使 AEA（2.1 倍）、OEA（1.9 倍）和 PEA（1.8 倍）增加最高，但未达到最大响应。结论 CBD 对 AEA、OEA 和 PEA 的作用与报告急性精神分裂症临床改善（CBD≥800 mg）的 II 期试验一致。包含 Δ9-THC 似乎可以增强 CBD 诱导的对 AEA 及其同系物的反应。 我们的结果值得进一步研究这些脂质衍生介质作为 CBD 剂量处方和联合大麻素管理的代谢指标的潜力。