How Psychedelics Modulate Multiple Memory Mechanisms in Posttraumatic Stress Disorder.

IF 13 1区 医学 Q1 PHARMACOLOGY & PHARMACY Drugs Pub Date : 2024-10-26 DOI:10.1007/s40265-024-02106-4
Manoj K Doss, AnnaMarie DeMarco, Joseph E Dunsmoor, Josh M Cisler, Gregory A Fonzo, Charles B Nemeroff
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Abstract

Posttraumatic stress disorder (PTSD) is a psychiatric disorder with defining abnormalities in memory, and psychedelics may be promising candidates for the treatment of PTSD given their effects on multiple memory systems. Most PTSD and psychedelic research has investigated memory with fear conditioning and extinction. While fruitful, conditioning and extinction provide a limited model of the complexity of PTSD and phenomenology of psychedelics, thereby limiting the refinement of therapies. In this review, we discuss abnormalities in fear conditioning and extinction in PTSD and review 25 studies testing psychedelics on these forms of memory. Perhaps the most reliable effect is that the acute effects of psychedelics can enhance extinction learning, which is impaired in PTSD. However, the post-acute effects may also enhance extinction learning, and the acute effects can also enhance fear conditioning. We then discuss abnormalities in episodic and semantic memory in PTSD and review current knowledge on how psychedelics impact these memory systems. Although PTSD and psychedelics acutely impair the formation of hippocampal-dependent episodic memories, psychedelics may acutely enhance cortical-dependent learning of semantic memories that could facilitate the integration of trauma memories and disrupt maladaptive beliefs. More research is needed on the acute effects of psychedelics on episodic memory consolidation, retrieval, and reconsolidation and post-acute effects of psychedelics on all phases of episodic memory. We conclude by discussing how targeting multiple memory mechanisms could improve upon the current psychedelic therapy paradigm for PTSD, thereby necessitating a greater emphasis on assessing diverse measures of memory in translational PTSD and psychedelic research.

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迷幻剂如何调节创伤后应激障碍的多种记忆机制?
创伤后应激障碍(PTSD)是一种具有明显记忆异常的精神疾病,鉴于迷幻药对多种记忆系统的影响,迷幻药可能是治疗创伤后应激障碍的有前途的候选药物。大多数创伤后应激障碍和迷幻药研究都是通过恐惧条件反射和消退来研究记忆的。尽管取得了丰硕成果,但条件反射和消退法对创伤后应激障碍的复杂性和迷幻药的现象学提供了一个有限的模型,从而限制了疗法的完善。在这篇综述中,我们讨论了创伤后应激障碍中恐惧条件反射和消退的异常现象,并回顾了25项测试迷幻药对这些记忆形式的影响的研究。也许最可靠的效果是,迷幻药的急性效应可以增强消退学习,而这在创伤后应激障碍中是受损的。不过,急性期后的作用也可以增强消减学习,而急性期的作用也可以增强恐惧条件反射。然后,我们将讨论创伤后应激障碍患者的外显记忆和语义记忆异常,并回顾目前关于迷幻药如何影响这些记忆系统的知识。虽然创伤后应激障碍和迷幻药会急性损害依赖海马的表观记忆的形成,但迷幻药可能会急性增强依赖大脑皮层的语义记忆学习,从而促进创伤记忆的整合并破坏不良信念。关于迷幻药对外显记忆巩固、检索和再巩固的急性效应,以及迷幻药对外显记忆所有阶段的急性后效应,还需要进行更多的研究。最后,我们讨论了针对多种记忆机制如何改善目前治疗创伤后应激障碍的迷幻药疗法范例,因此有必要在创伤后应激障碍和迷幻药的转化研究中更加重视评估记忆的各种措施。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
Drugs
Drugs 医学-毒理学
CiteScore
22.70
自引率
0.90%
发文量
134
审稿时长
3-8 weeks
期刊介绍: Drugs is a journal that aims to enhance pharmacotherapy by publishing review and original research articles on key aspects of clinical pharmacology and therapeutics. The journal includes: Leading/current opinion articles providing an overview of contentious or emerging issues. Definitive reviews of drugs and drug classes, and their place in disease management. Therapy in Practice articles including recommendations for specific clinical situations. High-quality, well designed, original clinical research. Adis Drug Evaluations reviewing the properties and place in therapy of both newer and established drugs. AdisInsight Reports summarising development at first global approval. Moreover, the journal offers additional digital features such as animated abstracts, video abstracts, instructional videos, and podcasts to increase visibility and educational value. Plain language summaries accompany articles to assist readers with some knowledge of the field in understanding important medical advances.
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