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Neural Mechanisms and Psychology of Psychedelic Ego Dissolution
Pharmacological Reviews ( IF 19.3 ) Pub Date : 2022-10-01 , DOI: 10.1124/pharmrev.121.000508
Devon Stoliker 1 , Gary F Egan 1 , Karl J Friston 1 , Adeel Razi 2
Affiliation  

Neuroimaging studies of psychedelics have advanced our understanding of hierarchical brain organization and the mechanisms underlying their subjective and therapeutic effects. The primary mechanism of action of classic psychedelics is binding to serotonergic 5-HT2A receptors. Agonist activity at these receptors leads to neuromodulatory changes in synaptic efficacy that can have a profound effect on hierarchical message-passing in the brain. Here, we review the cognitive and neuroimaging evidence for the effects of psychedelics: in particular, their influence on selfhood and subject-object boundaries—known as ego dissolution—surmised to underwrite their subjective and therapeutic effects. Agonism of 5-HT2A receptors, located at the apex of the cortical hierarchy, may have a particularly powerful effect on sentience and consciousness. These effects can endure well after the pharmacological half-life, suggesting that psychedelics may have effects on neural plasticity that may play a role in their therapeutic efficacy. Psychologically, this may be accompanied by a disarming of ego resistance that increases the repertoire of perceptual hypotheses and affords alternate pathways for thought and behavior, including those that undergird selfhood. We consider the interaction between serotonergic neuromodulation and sentience through the lens of hierarchical predictive coding, which speaks to the value of psychedelics in understanding how we make sense of the world and specific predictions about effective connectivity in cortical hierarchies that can be tested using functional neuroimaging.

中文翻译:

迷幻自我消解的神经机制和心理学

迷幻药的神经影像学研究加深了我们对大脑层次结构及其主观和治疗效果潜在机制的理解。经典迷幻药的主要作用机制是与血清素能 5-HT2A 受体结合。这些受体的激动剂活性导致突触功效的神经调节变化,这可能对大脑中的分级信息传递产生深远影响。在这里,我们回顾了迷幻剂影响的认知和神经影像学证据:特别是它们对自我和主体-客体边界的影响——称为自我消解-推测可以证明它们的主观和治疗效果。位于皮质层级顶端的 5-HT2A 受体的激动作用可能对知觉和意识具有特别强大的影响。这些影响在药理半衰期后仍能很好地持续,表明迷幻药可能对神经可塑性产生影响,而神经可塑性可能在其治疗效果中发挥作用。在心理上,这可能伴随着自我抵抗的解除这增加了感知假设的全部内容,并为思想和行为提供了替代途径,包括那些巩固自我的途径。我们通过分层预测编码的镜头考虑血清素能神经调节和感知之间的相互作用,这说明了迷幻药在理解我们如何理解世界以及对皮质层级中有效连接的具体预测方面的价值,这些可以使用功能神经成像进行测试。
更新日期:2022-09-30
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