National Research Council of Italy, Institute of Neuroscience-Cagliari, Cagliari, Italy.
Sezione Farmacologia, Dipt. Diagnostica e Sanità Pubblica, Università degli Studi di Verona, Policlinico Borgo Roma, P.le Scuro 10, 37134, Verona, Italy.
Psychopharmacology (Berl). 2018 Feb;235(2):433-445. doi: 10.1007/s00213-017-4793-4. Epub 2017 Nov 25.
Clinical data with 3,4-methylenedioxymethamphetamine (MDMA) in post-traumatic stress disorder (PTSD) patients recently stimulated interest on the potential therapeutic use of psychedelics in disorders characterized by maladaptive memories, including substance use disorders (SUD). The rationale for the use of MDMA in PTSD and SUD is being extended to a broader beneficial "psychedelic effect," which is supporting further clinical investigations, in spite of the lack of mechanistic hypothesis. Considering that the retrieval of emotional memories reactivates specific brain mechanisms vulnerable to inhibition, interference, or strengthening (i.e., the reconsolidation process), it was proposed that the ability to retrieve and change these maladaptive memories might be a novel intervention for PTSD and SUD. The mechanisms underlying MDMA effects indicate memory reconsolidation modulation as a hypothetical process underlying its efficacy.
Mechanistic and clinical studies with other two classes of psychedelic substances, namely cannabinoids and ketamine, are providing data in support of a potential use in PTSD and SUD based on the modulation of traumatic and appetitive memory reconsolidation, respectively. Here, we review preclinical and clinical data on cannabinoids and ketamine effects on biobehavioral processes related to the reconsolidation of maladaptive memories.
We report the findings supporting (or not) the working hypothesis linking the potential therapeutic effect of these substances to the underlying reconsolidation process. We also proposed possible approaches for testing the use of these two classes of drugs within the current paradigm of reconsolidation memory inhibition.
Metaplasticity may be the process in common between cannabinoids and ketamine/ketamine-like substance effects on the mediation and potential manipulation of maladaptive memories.
最近，创伤后应激障碍（PTSD）患者使用 3,4-亚甲二氧基甲基苯丙胺（MDMA）的临床数据激发了人们对致幻剂在包括物质使用障碍（SUD）在内的以适应不良记忆为特征的疾病中潜在治疗用途的兴趣。在 PTSD 和 SUD 中使用 MDMA 的基本原理正在扩展到更广泛的有益“致幻效应”，这支持了进一步的临床研究，尽管缺乏机制假设。鉴于情绪记忆的检索会重新激活特定的大脑机制，这些机制容易受到抑制、干扰或增强（即再巩固过程），因此有人提出，检索和改变这些适应不良记忆的能力可能是 PTSD 和 SUD 的一种新干预措施。MDMA 作用的机制表明，记忆再巩固调节是其疗效的一个假设过程。
其他两类致幻物质，即大麻素和氯胺酮的机制和临床研究提供的数据支持了它们在 PTSD 和 SUD 中的潜在用途，分别基于对创伤和食欲记忆再巩固的调节。在这里，我们回顾了大麻素和氯胺酮对与适应不良记忆再巩固相关的生物行为过程的影响的临床前和临床数据。
我们报告了支持（或不支持）将这些物质的潜在治疗效果与潜在的再巩固过程联系起来的工作假设的发现。我们还提出了在再巩固记忆抑制的当前范式内测试这两类药物使用的可能方法。
可能的共同过程是大麻素和氯胺酮/类似氯胺酮物质对调节和潜在操纵适应不良记忆的影响之间的类质同晶性。
