A widely held dogma in the preclinical addiction field is that females are more vulnerable than males to drug craving and relapse. Here, we first review clinical studies on sex differences in psychostimulant and opioid craving and relapse. Next, we review preclinical studies on sex differences in psychostimulant and opioid reinstatement of drug seeking after extinction of drug self-administration, and incubation of drug craving (time-dependent increase in drug seeking during abstinence). We also discuss ovarian hormones’ role in relapse and craving in humans and animal models and speculate on brain mechanisms underlying their role in cocaine craving and relapse in rodent models. Finally, we discuss imaging studies on brain responses to cocaine cues and stress in men and women.The results of the clinical studies reviewed do not appear to support the notion that women are more vulnerable to psychostimulant and opioid craving and relapse. However, this conclusion is tentative because most of the studies reviewed were correlational, not sufficiently powered, and not a priori designed to detect sex differences. Additionally, imaging studies suggest sex differences in brain responses to cocaine cues and stress. The results of the preclinical studies reviewed provide evidence for sex differences in stress-induced reinstatement and incubation of cocaine craving but not cue- or cocaine-induced reinstatement of cocaine seeking. These sex differences are modulated in part by ovarian hormones. In contrast, the available data do not support the notion of sex differences in craving and relapse/reinstatement for methamphetamine or opioids in rodent models.

中文翻译：

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阿片类药物和精神兴奋剂渴望和复发的性别差异：一项批判性评论

临床前成瘾领域普遍持有的教条是，女性比男性更容易产生毒瘾和复吸。在这里，我们首先回顾了关于精神兴奋剂和阿片类药物渴望和复发的性别差异的临床研究。接下来，我们回顾了关于在药物自我管理消失后寻求药物的精神兴奋剂和阿片类药物恢复以及药物渴望的孵化（禁欲期间药物寻求的时间依赖性增加）的性别差异的临床前研究。我们还讨论了卵巢激素在人类和动物模型中对可卡因渴望和复发的作用，并推测了它们在啮齿动物模型中对可卡因渴望和复发的作用背后的大脑机制。最后，我们讨论了男性和女性大脑对可卡因线索和压力反应的影像学研究。审查的临床研究结果似乎并不支持女性更容易对精神兴奋剂和阿片类药物产生渴望和复发的观点。然而，这个结论是暂时的，因为大多数审查的研究都是相关的，没有足够的力量，并且不是先验设计来检测性别差异。此外，影像学研究表明大脑对可卡因线索和压力的反应存在性别差异。审查的临床前研究结果提供了证据，证明压力诱导的可卡因渴望恢复和潜伏期存在性别差异，但线索或可卡因诱导的可卡因寻求恢复没有。这些性别差异部分受卵巢激素的调节。相比之下，