Korem Nachshon, Bassir Nia Anahita, Hillmer Ansel T, D'Souza Deepak, Nabulsi Nabeel, Ropchan Jim, Huang Yiyun, Cosgrove Kelly, Levy Ifat, Pietrzak Robert H, Harpaz-Rotem Ilan
Department of Psychiatry, Yale University School of Medicine, New Haven, CT, USA.
U.S. Department of Veterans Affairs National Center for Posttraumatic Stress Disorder, VA Connecticut Healthcare System, West Haven, CT, USA.
Transl Psychiatry. 2025 Aug 22;15(1):310. doi: 10.1038/s41398-025-03519-9.
The endocannabinoid system (ECS) plays a critical role in fear learning and maintenance and may, therefore, be implicated in the pathophysiology of posttraumatic stress disorder (PTSD). The exact role of cannabinoid receptor 1 (CB1R), a key component of the ECS, remains unclear. Although preclinical studies largely suggest CB1R downregulation in PTSD, the only prior study of CB1R availability in individuals with PTSD reported higher levels than in controls. In this study, we investigated the relationship between CB1R availability and PTSD diagnosis and symptoms. Using positron emission tomography (PET) with the CB1R-specific radiotracer [C]OMAR, scans from 62 individuals, including 46 trauma-exposed participants (19 with current PTSD) and 16 healthy controls, were analyzed. Our findings revealed no differences in CB1R availability between groups in either the whole brain or regions of interest. However, emotional numbing symptoms of PTSD were significantly linked to CB1R availability. These results suggest that the ECS role in the maintenance of PTSD is more nuanced than previously suggested. The ECS was linked to specific PTSD symptom expression, highlighting the potential for treatments targeting the ECS in mitigating these specific symptoms of this multi-faceted disorder.
内源性大麻素系统(ECS)在恐惧学习和维持过程中发挥着关键作用,因此可能与创伤后应激障碍(PTSD)的病理生理学有关。大麻素受体1(CB1R)作为ECS的关键组成部分,其确切作用仍不清楚。尽管临床前研究大多表明PTSD患者中CB1R下调,但之前唯一一项关于PTSD患者CB1R可用性的研究报告称其水平高于对照组。在本研究中,我们调查了CB1R可用性与PTSD诊断及症状之间的关系。使用正电子发射断层扫描(PET)和CB1R特异性放射性示踪剂[C]OMAR,对62名个体的扫描结果进行了分析,其中包括46名有创伤经历的参与者(19名患有当前PTSD)和16名健康对照。我们的研究结果显示,无论是在全脑还是感兴趣区域,各组之间CB1R可用性均无差异。然而,PTSD的情感麻木症状与CB1R可用性显著相关。这些结果表明,ECS在PTSD维持中的作用比之前认为的更为细微。ECS与PTSD的特定症状表达有关,这突出了针对ECS的治疗在减轻这种多方面疾病的这些特定症状方面的潜力。