Post-traumatic stress disorder (PTSD) is a complex disorder that involves dysregulation of multiple neurobiological systems. The traumatic stressor plays a causal role in producing psychological dysfunction and the pattern of findings suggests that the hypothalamic-pituitary-adrenal (HPA) axis, which is instrumental for stress adaptation, is critically dysfunctional in PTSD. Given the lack of understanding of the basic mechanisms and underlying pathways that cause the disorder and its heterogeneity, PTSD poses challenges for treatment. Targeting the endocannabinoid (ECB) system to treat mental disorders, and PTSD in particular, has been the focus of research and interest in recent years. The ECB system modulates multiple functions, and drugs enhancing ECB signaling have shown promise as potential therapeutic agents in stress effects and other psychiatric and medical conditions. In this review, we focus on the interaction between the ECB-HPA systems in animal models for PTSD and in patients with PTSD. We summarize evidence supporting the use of cannabinoids in preventing and treating PTSD in preclinical and clinical studies. As the HPA system plays a key role in the mediation of the stress response and the pathophysiology of PTSD, we describe preclinical studies suggesting that enhancing ECB signaling is consistent with decreasing PTSD symptoms and dysfunction of the HPA axis. Overall, we suggest that a pharmacological treatment targeted at one system (e.g., HPA) may not be very effective because of the heterogeneity of the disorder. There are abnormalities across different neurotransmitter systems in the pathophysiology of PTSD and none of these systems function uniformly among all patients with PTSD. Hence, conceptually, enhancing ECB signaling may be a more effective avenue for pharmacological treatment.

中文翻译：

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大麻素作为PTSD的疗法。

创伤后应激障碍（PTSD）是一种复杂的疾病，涉及多种神经生物学系统的失调。创伤性应激源在产生心理功能障碍中起因果作用，研究结果的模式表明，下丘脑-垂体-肾上腺（HPA）轴（在压力适应中起重要作用）在PTSD中严重功能障碍。鉴于对导致疾病及其异质性的基本机制和潜在途径缺乏了解，PTSD对治疗提出了挑战。靶向内源性大麻素（ECB）系统以治疗精神疾病，尤其是PTSD，已成为近年来研究和关注的焦点。ECB系统可调节多种功能，增强ECB信号的药物已显示出有望成为缓解压力以及其他精神病和医学疾病的潜在治疗剂。在这篇综述中，我们着重于PTSD动物模型和PTSD患者的ECB-HPA系统之间的相互作用。我们在临床前和临床研究中总结了支持使用大麻素预防和治疗PTSD的证据。由于HPA系统在应激反应和PTSD的病理生理调节中起着关键作用，因此我们描述的临床前研究表明增强ECB信号与减少PTSD症状和HPA轴功能障碍一致。总的来说，由于该疾病的异质性，我们建议针对一种系统的药物治疗（例如HPA）可能不是很有效。在PTSD的病理生理中，不同的神经递质系统之间存在异常，并且在所有PTSD患者中，这些系统均无法正常发挥作用。因此，从概念上讲，增强ECB信号传导可能是药物治疗的更有效途径。