Department of Neural and Behavioral Sciences, Penn State College of Medicine, Hershey, Pennsylvania, USA.
Department of Pharmacology, Penn State College of Medicine, Hershey, Pennsylvania, USA.
Cannabis Cannabinoid Res. 2023 Apr;8(2):230-240. doi: 10.1089/can.2022.0130. Epub 2022 Nov 21.
The endocannabinoid (eCB) system plays an important role in homeostatic regulation of anxiety and stress responses; however, the eCB system can be disrupted following traumatic stressors. Additionally, traumatic or chronic stressors that occur during adulthood or early life can cause long-lasting disturbances in the eCB system. These alterations interfere with hypothalamic-pituitary-adrenal axis function and may be involved in lifelong increased fear and anxiety behaviors as well as increased risk for development of post-traumatic stress disorder (PTSD). This review focuses on the implications of trauma and significant stressors on eCB functionality and neural pathways, both in adolescence and into adulthood, as well as the current state of testing for CBD efficacy in treating pediatric and adult patients suffering from stress-induced eCB dysregulation. Articles were searched via Pubmed and included studies examining eCB modulation of stress-related disorders in both clinical settings and preclinical models. Given the potential for lifelong alterations in eCB signaling that can mediate stress responsiveness, consideration of pharmaceutical or nutraceutical agents that impact eCB targets may improve clinical outcomes in stress-related disorders. However, caution may be warranted in utilization of medicinal cannabinoid products that contain delta-9-tetrahydrocannabinol due to pronounced euphorigenic effects and potential to exacerbate stress-related behaviors. Other cannabinoid products, such as cannabidiol (CBD), have shown promise in reducing stress-related behaviors in pre-clinical models. Overall, pre-clinical evidence supports CBD as a potential treatment for stress or anxiety disorders resulting from previously stressful events, particularly by reducing fearful behavior and promoting extinction of contextual fear memories, which are hallmarks of PTSD. However, very limited clinical research has been conducted examining the potential effectiveness of CBD in this regard and should be examined further.
内源性大麻素 (eCB) 系统在调节焦虑和应激反应的体内平衡中发挥着重要作用；然而，创伤后应激源会破坏 eCB 系统。此外，成年期或生命早期发生的创伤性或慢性应激源会导致 eCB 系统长期紊乱。这些改变干扰了下丘脑-垂体-肾上腺轴的功能，可能与终生增加的恐惧和焦虑行为以及创伤后应激障碍 (PTSD) 的发展风险增加有关。
本综述重点介绍了创伤和重大应激源对 eCB 功能和神经通路的影响，包括在青春期和成年期，以及目前测试 CBD 治疗应激引起的 eCB 失调的儿科和成年患者的疗效的现状。通过 Pubmed 搜索了文章，并纳入了研究 eCB 调节临床和临床前模型中与应激相关障碍的研究。
鉴于 eCB 信号的终身改变可能介导应激反应，考虑影响 eCB 靶点的药物或营养保健品可能会改善应激相关疾病的临床结果。然而，由于具有明显的欣快作用和潜在的加剧应激相关行为的作用，在使用含有 delta-9-四氢大麻酚的药用大麻素产品时可能需要谨慎。其他大麻素产品，如大麻二酚 (CBD)，在减少临床前模型中的应激相关行为方面显示出了希望。总体而言，临床前证据支持 CBD 作为治疗由先前应激事件引起的应激或焦虑障碍的潜在药物，特别是通过减少恐惧行为和促进情境恐惧记忆的消退，这是 PTSD 的标志。然而，关于 CBD 在这方面的潜在有效性的临床研究非常有限，应进一步研究。
