Post-traumatic stress disorder (PTSD), characterized by abnormally persistent and distressing memories, is a chronic debilitating condition in need of new treatment options. Current treatment guidelines recommend psychotherapy as first line management with only two drugs, sertraline and paroxetine, approved by U.S. Food and Drug Administration (FDA) for treatment of PTSD. These drugs have limited efficacy as they only reduce symptoms related to depression and anxiety without producing permanent remission. PTSD remains a significant public health problem with high morbidity and mortality requiring major advances in therapeutics. Early evidence has emerged for the beneficial effects of psychedelics particularly in combination with psychotherapy for management of PTSD, including psilocybin, MDMA, LSD, cannabinoids, ayahuasca and ketamine. MDMA and psilocybin reduce barrier to therapy by increasing trust between therapist and patient, thus allowing for modification of trauma related memories. Furthermore, research into the memory reconsolidation mechanisms has allowed for identification of various pharmacological targets to disrupt abnormally persistent memories. A number of pre-clinical and clinical studies have investigated novel and re-purposed pharmacological agents to disrupt fear memory in PTSD. Novel therapeutic approaches like neuropeptide Y, oxytocin, cannabinoids and neuroactive steroids have also shown potential for PTSD treatment. Here, we focus on the role of fear memory in the pathophysiology of PTSD and propose that many of these new therapeutic strategies produce benefits through the effect on fear memory. Evaluation of recent research findings suggests that while a number of drugs have shown promising results in preclinical studies and pilot clinical trials, the evidence from large scale clinical trials would be needed for these drugs to be incorporated in clinical practice.

创伤后应激障碍 (PTSD) 以异常持久和令人痛苦的记忆为特征，是一种慢性衰弱性疾病，需要新的治疗方案。目前的治疗指南建议将心理治疗作为一线治疗，仅使用美国食品和药物管理局 (FDA) 批准用于治疗 PTSD 的两种药物舍曲林和帕罗西汀。这些药物的疗效有限，因为它们只能减轻与抑郁和焦虑相关的症状，而不会产生永久缓解。PTSD 仍然是一个重要的公共卫生问题，其发病率和死亡率都很高，需要在治疗方面取得重大进展。早期证据表明迷幻剂的有益作用，特别是与心理治疗相结合用于管理 PTSD，包括裸盖菇碱、摇头丸、LSD、大麻素、死藤水和氯胺酮。MDMA 和裸盖菇素通过增加治疗师和患者之间的信任来减少治疗障碍，从而允许修改与创伤相关的记忆。此外，对记忆再巩固机制的研究已经允许识别各种药理学目标来破坏异常持久的记忆。许多临床前和临床研究已经调查了新的和重新使用的药物制剂，以破坏 PTSD 中的恐惧记忆。神经肽 Y、催产素、大麻素和神经活性类固醇等新型治疗方法也显示出治疗 PTSD 的潜力。在这里，我们关注恐惧记忆在 PTSD 病理生理学中的作用，并提出许多这些新的治疗策略通过对恐惧记忆的影响而产生益处。