Department of Psychiatry and Behavioral Sciences, Emory University School of Medicine, Atlanta, GA, USA.
Department of Psychiatry and Behavioral Neurosciences, Wayne State University School of Medicine, Detroit, MI, USA.
J Psychopharmacol. 2022 Mar;36(3):368-377. doi: 10.1177/02698811211069124. Epub 2022 Feb 15.
Fear conditioning and extinction are well-characterized cross-species models of fear-related posttraumatic stress disorder (PTSD) symptoms, and recent animal data suggest that 3,4-methylenedioxymethamphetamine (MDMA) enhances fear extinction retention.
This study investigated the effect of MDMA on fear learning, extinction training, and retention in healthy humans.
The study involved a randomized placebo-controlled, two-group, parallel design trial in a sample of healthy adults, age 21-55 recruited from a major metropolitan area. The experimental paradigm included a fear acquisition session followed by an extinction training session 24 hours later, and 2 hours after study drug administration. Fear extinction retention was measured 48 hours after extinction training. Participants ( = 34; 70.6% male and 29.4% female) were randomly assigned in 1:1 ratio to 100 mg MDMA or placebo. All randomized participants completed the trial and were included in primary analyses. Safety was monitored via adverse events and vital signs. MDMA was well-tolerated with no serious adverse events.
Results indicated a significant main effect of session between extinction training and retention with no significant group differences. Significantly more participants in the MDMA group retained extinction learning compared to the placebo group (χ = 7.29, = 0.007).
Although we did not observe the hypothesized facilitation of extinction retention, the findings from this initial human trial provide compelling rationale to continue to explore the potential for MDMA to impact extinction retention.Clinical Trials Registry Name and Identifier: Evaluation of MDMA on Startle Response (NCT0318176) https://clinicaltrials.gov/ct2/show/NCT03181763?term = MDMA&draw = 2&rank = 9.
恐惧条件反射和消退是具有特征性的跨物种创伤后应激障碍（PTSD）相关恐惧模型，最近的动物数据表明，3,4-亚甲二氧基甲基苯丙胺（MDMA）增强了恐惧消退的保持。
本研究旨在探讨 MDMA 对健康人恐惧学习、消退训练和保持的影响。
这项研究采用了一项随机安慰剂对照、两组成组、平行设计的临床试验，在一个主要大都市区招募的年龄在 21-55 岁的健康成年人样本中进行。实验范式包括恐惧获得阶段，随后在 24 小时后进行消退训练阶段，在研究药物给药后 2 小时进行。在消退训练后 48 小时测量恐惧消退保持。参与者（n=34；70.6%为男性，29.4%为女性）以 1:1 的比例随机分配到 100mg MDMA 或安慰剂组。所有随机分组的参与者均完成了试验，并纳入了主要分析。通过不良事件和生命体征监测安全性。MDMA 耐受性良好，无严重不良事件。
结果表明，在消退训练和保持之间的阶段有显著的主效应，而组间无显著差异。与安慰剂组相比，MDMA 组有更多的参与者保留了消退学习（χ²=7.29，p=0.007）。
尽管我们没有观察到预期的消退保持促进作用，但这项初步的人体试验结果提供了令人信服的理由，继续探索 MDMA 对消退保持的潜在影响。
评估 MDMA 对惊跳反应的影响（NCT0318176）https://clinicaltrials.gov/ct2/show/NCT03181763?term=MDMA&draw=2&rank=9。
