Biological sex differences in Cannabis Use Disorder (CUD) progression, cannabis withdrawal severity, and pharmacotherapy response have been reported, suggesting that CUD mechanisms may differ by sex. Drug cue reactivity is an established predictor of drug use behavior, but the literature on sex differences in drug cue reactivity is mixed, including in CUD. One possible moderator of sex differences in drug cue reactivity is hormonal contraceptive (HC) use. The aim of the present study was to test whether sex differences in neural cannabis cue reactivity and craving varied by female HC use in a CUD sample. As part of a larger study, 152 adults reporting frequent cannabis use completed a drug cue reactivity task during electrocenphalogram recording. Late positive potential (LPP) amplitude modulation by cannabis cues was used to measure neural cue reactivity. Craving after the cue reactivity task was also assessed. Males (n = 74) and naturally-cycling females (n = 26), who did not differ from each other, showed significantly greater LPP enhancement to cannabis vs. neutral cues compared to HC-using females (n = 52), an effect mostly driven by neutral cues. Craving was significantly higher in naturally-cycling but not HC-using females compared to males, but only in covariate-unadjusted analyses. Exploratory analyses of HC and menstrual phase characteristics indicate a progesterone-related mechanism may underlie HC effects on cannabis cue reactivity. The present study's results suggest that mixed findings on drug cue reactivity sex differences may be due to variability in HC use, which has implications for sex-specific models of CUD progression and treatment.

中文翻译：

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生物性别和激素避孕药与大麻使用障碍药物提示反应性的关系

大麻使用障碍 (CUD) 进展、大麻戒断严重程度和药物治疗反应方面的生物性别差异已有报道，表明 CUD 机制可能因性别而异。药物提示反应性是药物使用行为的既定预测因子，但关于药物提示反应性性别差异的文献是混杂的，包括在 CUD 中。药物提示反应性性别差异的一种可能调节因素是激素避孕药 (HC) 的使用。本研究的目的是测试 CUD 样本中女性大麻提示反应性和渴望的性别差异是否因女性 HC 使用情况而变化。作为一项更大规模研究的一部分，152 名经常使用大麻的成年人在脑电图记录期间完成了药物提示反应任务。大麻线索的晚正电位（LPP）振幅调制用于测量神经线索反应性。还评估了提示反应任务后的渴望。与使用 HC 的女性 (n = 52) 相比，男性 (n = 74) 和自然循环的女性 (n = 26) 彼此没有差异，与中性线索相比，大麻对 LPP 的增强显着更大，这是一种效果主要由中性线索驱动。与男性相比，自然循环但使用 HC 的女性的渴望明显更高，但仅在协变量未经调整的分析中出现。对 HC 和月经阶段特征的探索性分析表明，黄体酮相关机制可能是 HC 对大麻提示反应性影响的基础。本研究的结果表明，药物提示反应性性别差异的混合结果可能是由于 HC 使用的差异造成的，这对 CUD 进展和治疗的性别特异性模型具有影响。