Department of Psychological and Brain Sciences, Indiana University, 1101 E 10th St, Bloomington, IN, 47405, USA.
Program in Neuroscience, Indiana University, Bloomington, IN, USA.
Psychopharmacology (Berl). 2023 Aug;240(8):1805-1821. doi: 10.1007/s00213-023-06400-z. Epub 2023 Jun 27.
Cannabis is the most widely used illicit substance in the USA and is often reportedly used for stress reduction. Indeed, cannabinoids modulate signaling of the hypothalamic-pituitary-adrenal axis and sympathetic nervous system. However, the role of biological sex in this interaction between cannabis use and stress is poorly understood, despite sex differences in neurobiological stress responsivity, endocannabinoid signaling, and clinical correlates of cannabis use.
The study aims to examine the role of biological sex in multisystem stress responsivity in cannabis users.
Frequent cannabis users (> 3 times/week, n = 48, 52% male) and non-users (n = 41, 49% male) participated in an acute psychosocial stress paradigm. Saliva was collected at eight timepoints and analyzed for hypothalamic-pituitary-adrenal (cortisol) and sympathetic (alpha-amylase) indices of stress responsivity, and basal estradiol. Subjective ratings of negative affect, including distress, were collected at three timepoints.
Cannabis users showed blunted pre-to-post-stress cortisol reactivity. Female cannabis users demonstrated greater blunted cortisol reactivity than their male counterparts. Sex moderated the effect of cannabis use on alpha-amylase responsivity over time, wherein female cannabis users showed flattened alpha-amylase responses across the stressor compared to male cannabis users and both non-user groups. Qualitatively, female cannabis users demonstrated the greatest pre-to-post-stress change in subjective distress. Differences in stress responding were not explained by estradiol or distress intolerance.
Biological sex impacts multisystem stress responding in cannabis users. Paradoxically, female cannabis users showed the least physiological, but greatest subjective, responses to the stressor. Further research into sex differences in the effects of cannabis use is warranted to better understand mechanisms and clinical implications.
大麻是美国使用最广泛的非法物质，常被报道用于减轻压力。事实上，大麻素调节下丘脑-垂体-肾上腺轴和交感神经系统的信号。然而，尽管大麻使用与压力之间存在神经生物学应激反应、内源性大麻素信号和临床相关性方面的性别差异，但大麻使用与压力之间的这种相互作用中生物性别所起的作用仍知之甚少。
本研究旨在探讨生物性别在大麻使用者多系统应激反应中的作用。
频繁使用大麻者（>3 次/周，男性占 52%，n=48）和非使用者（n=41，男性占 49%）参与了急性心理社会应激范式。在八个时间点采集唾液，并分析下丘脑-垂体-肾上腺（皮质醇）和交感（α-淀粉酶）应激反应指标以及基础雌二醇。在三个时间点采集主观负面情绪（包括痛苦）评分。
大麻使用者的应激前后皮质醇反应迟钝。女性大麻使用者的皮质醇反应迟钝程度大于男性。性别调节了大麻使用对随时间变化的α-淀粉酶反应的影响，女性大麻使用者在整个应激过程中α-淀粉酶反应呈平坦趋势，而男性大麻使用者和两组非使用者均呈上升趋势。定性分析显示，女性大麻使用者在应激前后的主观痛苦变化最大。应激反应的差异不能用雌二醇或痛苦耐受力来解释。
生物性别影响大麻使用者的多系统应激反应。矛盾的是，女性大麻使用者对压力源表现出最小的生理反应，但最大的主观反应。需要进一步研究大麻使用对性别差异的影响，以更好地了解其机制和临床意义。
