Centres for Neuropsychopharmacology & Psychedelic Research, Division of Psychiatry, Department of Brain Sciences, Imperial College London, London, UK.
Psychedelics Division, Neuroscape, University of California San Francisco, San Francisco, CA, USA.
Curr Top Behav Neurosci. 2024;66:149-174. doi: 10.1007/7854_2023_451.
Psychedelic drugs such as psilocybin and ketamine are returning to clinical research and intervention across several disorders including the treatment of depression. This chapter focusses on psychedelics that specifically target the 5-HT receptor such as psilocybin and DMT. These produce plasma-concentration related psychological effects such as hallucinations and out of body experiences, insightful and emotional breakthroughs as well as mystical-type experiences. When coupled with psychological support, effects can produce a rapid improvement in mood among people with depression that can last for months. In this chapter, we summarise the scientific studies to date that explore the use of psychedelics in depressed individuals, highlighting key clinical, psychological and neuroimaging features of psychedelics that may account for their therapeutic effects. These include alterations in brain entropy that disrupt fixed negative ruminations, a period of post-treatment increased cognitive flexibility, and changes in self-referential psychological processes. Finally, we propose that the brain mechanisms underlying the therapeutic effect of serotonergic psychedelics might be distinct from those underlying classical serotonin reuptake-blocking antidepressants.
致幻剂如裸盖菇素和氯胺酮等正在重新回到多种障碍的临床研究和干预中，包括抑郁症的治疗。本章专注于专门针对 5-HT 受体的致幻剂，如裸盖菇素和 DMT。这些药物会产生与血浆浓度相关的心理效应，如幻觉和出体体验、深刻的情感突破以及神秘体验。当与心理支持相结合时，这些效果可以在抑郁症患者中迅速改善情绪，并持续数月。在本章中，我们总结了迄今为止探索使用致幻剂治疗抑郁症患者的科学研究，强调了致幻剂可能解释其治疗效果的关键临床、心理和神经影像学特征。这些特征包括改变大脑熵，打破固定的消极沉思；治疗后认知灵活性增加的时期；以及自我参照心理过程的变化。最后，我们提出，血清素能致幻剂治疗效果的大脑机制可能与经典的血清素再摄取抑制剂抗抑郁药的机制不同。
