Psychiatry and Mental Health Department, North Lisbon Hospital Centre, Lisbon, Portugal.
Psychiatry and Medical Psychology Department, School of Medicine, University of Lisbon, Lisbon, Portugal.
Curr Top Med Chem. 2022;22(15):1250-1260. doi: 10.2174/1568026621666211201145800.
The therapeutic options for neurobehavioral disorders are still limited, and in many cases, they lack a satisfactory balance between efficacy and side effects.
This work aims to review current evidence regarding the potential contribution of psychedelics and hallucinogens to the discovery of new drugs for treating different psychiatric disorders.
Ayahuasca/N,N-dimethyltryptamine (DMT), lysergic acid diethylamide (LSD), and psilocybin have evidence supporting their use in depression, and psilocybin and ayahuasca have also shown good results in treatment-resistant depression. In randomized controlled trials (RCTs) conducted with anxious patients, there were symptomatic improvements with psilocybin and LSD. Psilocybin diminished Yale-Brown Obsessive Compulsive Scale (Y-BOCS) scores in a small obsessive- compulsive disorder (OCD) sample. The evidence is less robust regarding substance use disorders, but it suggests a possible role for LSD and psilocybin in alcohol use disorders and for psilocybin in tobacco addiction. In a clinical setting, these substances seem to be safe and well-tolerated. Their mechanisms of action are not fully elucidated, but there seems to be a preponderant role of 5-hydroxytryptamine (5HT) 2A agonism, as well as connectivity changes within the default mode network (DMN) and amygdala and some other molecular modifications.
The studies underlying the conclusions have small samples and are heterogeneous in their methods. However, the results suggest that the use of psychedelics and hallucinogens could be considered in some disorders. More studies are needed to reinforce their evidence as potential new drugs.
神经行为障碍的治疗选择仍然有限，在许多情况下，它们在疗效和副作用之间缺乏令人满意的平衡。
本工作旨在综述关于迷幻剂和致幻剂在发现治疗不同精神障碍的新药方面的潜在贡献的现有证据。
安非他命/N,N-二甲基色胺（DMT）、麦角酸二乙酰胺（LSD）和裸盖菇素在抑郁症的治疗中已有证据支持，而裸盖菇素和安非他命在治疗抵抗性抑郁症中也显示出良好的效果。在对焦虑患者进行的随机对照试验（RCT）中，裸盖菇素和 LSD 可改善症状。在一项小型强迫症（OCD）样本中，裸盖菇素降低了耶鲁-布朗强迫量表（Y-BOCS）的评分。在物质使用障碍方面，证据不那么确凿，但 LSD 和裸盖菇素在酒精使用障碍中以及裸盖菇素在烟草成瘾中可能具有一定作用。在临床环境中，这些物质似乎是安全且耐受良好的。其作用机制尚未完全阐明，但似乎存在 5-羟色胺（5HT）2A 激动作用以及默认模式网络（DMN）和杏仁核内连接变化和其他一些分子修饰的主导作用。
支持这些结论的研究样本量小，方法存在异质性。然而，结果表明，在某些疾病中可以考虑使用迷幻剂和致幻剂。需要更多的研究来加强它们作为潜在新药的证据。
