Beijing Key Laboratory of Neuropsychopharmacology, State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, 27th Taiping Road, Beijing, 100850, China.
Shanxi Medical University School and Hospital of Stomatology, Taiyuan, 030001, China.
Psychopharmacology (Berl). 2022 May;239(5):1605-1620. doi: 10.1007/s00213-022-06132-6. Epub 2022 Apr 9.
Post-traumatic stress disorder (PTSD) is characterized by poor adaptation to a traumatic experience and disturbances in fear memory regulation, and currently lacks effective medication. Cannabidiol is a main constituent of Cannabis sativa; it has no psychotomimetic effects and has been implicated in modulating fear learning in mammals. Using a mouse PTSD model, we investigated the effects of CBD on PTSD-like behaviors and the modulation of trauma-related fear memory, a crucial process leading to core symptoms of PTSD.
We applied the modified pre-shock model to evaluated PTSD-like behaviors from days 3 to 26. The measures included the freezing time to the conditioned context, open field test, elevated plus maze test, and social interaction test. CBD and sertraline were administered at different stages of fear memory.
CBD (10 mg/kg, i.p.) administration alleviated main PTSD-like symptoms in the mouse pre-shock model by attenuating trauma-related fear memory and anxiety-like behavior, and increasing social interaction behavior. The effects of CBD were apparent irrespective of whether it was administered before, during, or after re-exposure to the aversive context. However, sertraline (15 mg/kg, p.o.) was only effective when administered before the behavioral test. CBD also reduced the consolidation, retrieval, and reconsolidation of trauma-related fear memory, whereas sertraline only reduced fear-memory retrieval.
CBD produced anti-PTSD-like actions in mice and disrupted trauma-related fear memory by interfering with multiple aspects of fear memory processing. These findings indicate that CBD may be a promising candidate for treating PTSD.
创伤后应激障碍（PTSD）的特征是对创伤经历适应不良和恐惧记忆调节紊乱，目前缺乏有效的药物治疗。大麻二酚（CBD）是大麻的主要成分之一；它没有致幻作用，并且被认为可以调节哺乳动物的恐惧学习。使用 PTSD 样鼠模型，我们研究了 CBD 对 PTSD 样行为和创伤相关恐惧记忆调节的影响，这是导致 PTSD 核心症状的关键过程。
我们应用改良的预电击模型评估了 PTSD 样行为，从第 3 天到第 26 天。测量包括对条件化环境的冻结时间、旷场试验、高架十字迷宫试验和社交互动试验。CBD 和舍曲林在恐惧记忆的不同阶段给药。
CBD（10mg/kg，腹腔注射）通过减轻与创伤相关的恐惧记忆和焦虑样行为，并增加社交互动行为，缓解了小鼠预电击模型中的主要 PTSD 样症状。CBD 的作用在再次暴露于厌恶环境之前、期间或之后给药时均明显。然而，舍曲林（15mg/kg，口服）仅在行为测试前给药时有效。CBD 还减少了与创伤相关的恐惧记忆的巩固、提取和再巩固，而舍曲林仅减少了恐惧记忆的提取。
CBD 对小鼠产生了抗 PTSD 样作用，并通过干扰恐惧记忆处理的多个方面破坏了与创伤相关的恐惧记忆。这些发现表明 CBD 可能是治疗 PTSD 的有前途的候选药物。
