Department of Neuroscience, Medical University of South Carolina, Charleston, South Carolina, USA.
Department of Public Health Sciences, Medical University of South Carolina, Charleston, South Carolina, USA.
Addict Biol. 2023 Oct;28(10):e13337. doi: 10.1111/adb.13337.
Cannabis use disorder (CUD) presents differently in men and women, particularly in symptoms of cannabis withdrawal. Novel pharmacotherapeutic interventions for CUD, such as those that target the endocannabinoid (eCB) system, must be developed in a manner consistent with these sex differences. The present pilot study sought to prospectively assess sex differences in cannabis withdrawal in a small sample of adults with moderate-to-severe CUD and to determine if withdrawal was associated with peripheral eCB and eCB congener tone. Men and women (n = 5/sex) completed 2 weeks of study participation separated by 1 month; in the latter week, participants abstained from cannabis use. Each week, participants attended in-person laboratory visits during which blood was drawn repeatedly to assess plasma eCB and eCB congener tone. Participants also completed multiple daily ambulatory assessments to assess cannabis use and withdrawal symptoms. As anticipated, women reported a greater increase in withdrawal symptoms during the abstinent week [Δ = 9.4 (SE = 1.1); p < 0.001] than men [Δ = 1.2 (SE = 1.2); p = 0.35]. Sex differences in levels of the eCB N-arachidonoylethanolamide (AEA), as well as the eCB congeners stearoylethanolamide (SEA) and linoleylethanolamide (LEA), were evident during abstinence at the morning time point only (p's < 0.05). LEA was associated with withdrawal symptom expression in both sexes [β = 0.16 (SE = 0.09)] and palmitoylethanolamide (PEA) [β = 0.22 (SE = 0.13)] and 2-arachidonoylglycerol (2-AG) [β = 0.32 (SE = 0.15)] were associated with withdrawal symptoms in women only. Pharmacotherapeutic development for CUD should consider evident sex differences in eCB and eCB congener tone during abstinence and their associations with cannabis withdrawal, as eCB-based interventions may produce differential effects by sex.
大麻使用障碍 (CUD) 在男性和女性中的表现不同，特别是在大麻戒断症状方面。新型的大麻使用障碍治疗药物干预措施，如针对内源性大麻素 (eCB) 系统的治疗药物，必须以符合这些性别差异的方式进行开发。本初步研究旨在前瞻性评估中等至重度 CUD 成人中大麻戒断的性别差异，并确定戒断是否与外周 eCB 和 eCB 同系物的音高有关。男性和女性 (n=5/性别) 在 1 个月的间隔内完成了 2 周的研究参与；在后者的一周中，参与者戒断大麻。每周，参与者都会在实验室进行多次现场访问，在此期间反复抽取血液以评估血浆 eCB 和 eCB 同系物的音高。参与者还完成了多次日常动态评估，以评估大麻使用和戒断症状。正如预期的那样，女性在戒断周报告的戒断症状增加更多[Δ=9.4(SE=1.1)；p<0.001]，而男性[Δ=1.2(SE=1.2)；p=0.35]。只有在上午时间点，才会出现内源性大麻素 N-花生四烯酸乙醇酰胺 (AEA) 以及内源性大麻素同系物硬脂酰乙醇酰胺 (SEA) 和亚油酸乙醇酰胺 (LEA) 水平的性别差异在禁欲期间出现(p<0.05)。LEA 与两种性别的戒断症状表达相关[β=0.16(SE=0.09)]，棕榈酰乙醇酰胺 (PEA)[β=0.22(SE=0.13)]和 2-花生四烯酸甘油 (2-AG)[β=0.32(SE=0.15)]仅与女性的戒断症状相关。大麻使用障碍的药物治疗开发应考虑到戒断期间明显的性别差异以及内源性大麻素和内源性大麻素同系物音高与其与大麻戒断的关联，因为基于内源性大麻素的干预措施可能会因性别而异产生不同的效果。
