Shinozuka Kenneth, Jerotic Katarina, Mediano Pedro, Zhao Alex T, Preller Katrin H, Carhart-Harris Robin, Kringelbach Morten L
Centre for Eudaimonia and Human Flourishing, Linacre College, University of Oxford, Oxford, UK.
Department of Psychiatry, University of Oxford, Oxford, UK.
Transl Psychiatry. 2024 Dec 4;14(1):485. doi: 10.1038/s41398-024-03187-1.
Serotonergic psychedelics induce altered states of consciousness and have shown potential for treating a variety of neuropsychiatric disorders, including depression and addiction. Yet their modes of action are not fully understood. Here, we provide a novel, synergistic understanding of psychedelics arising from systematic reviews and meta-analyses of three hierarchical levels of analysis: (1) subjective experience (phenomenology), (2) neuroimaging and (3) molecular pharmacology. Phenomenologically, medium and high doses of LSD yield significantly higher ratings of visionary restructuralisation than psilocybin on the 5-dimensional Altered States of Consciousness Scale. Our neuroimaging results reveal that, in general, psychedelics significantly strengthen between-network functional connectivity (FC) while significantly diminishing within-network FC. Pharmacologically, LSD induces significantly more inositol phosphate formation at the 5-HT receptor than DMT and psilocin, yet there are no significant between-drug differences in the selectivity of psychedelics for the 5-HT, 5-HT, or D receptors, relative to the 5-HT receptor. Our meta-analyses link DMT, LSD, and psilocybin to specific neural fingerprints at each level of analysis. The results show a highly non-linear relationship between these fingerprints. Overall, our analysis highlighted the high heterogeneity and risk of bias in the literature. This suggests an urgent need for standardising experimental procedures and analysis techniques, as well as for more research on the emergence between different levels of psychedelic effects.
血清素能致幻剂会引发意识状态的改变，并已显示出治疗多种神经精神疾病（包括抑郁症和成瘾症）的潜力。然而，它们的作用方式尚未完全被理解。在此，我们通过对三个层次分析的系统综述和荟萃分析，对致幻剂提出了一种全新的、协同的理解：（1）主观体验（现象学）、（2）神经影像学和（3）分子药理学。从现象学角度来看，在五维意识状态量表上，中高剂量的麦角酸二乙酰胺（LSD）产生的幻觉重构评分显著高于裸盖菇素。我们的神经影像学结果显示，一般来说，致幻剂会显著增强网络间功能连接（FC），同时显著减弱网络内FC。在药理学方面，相对于5-羟色胺（5-HT）受体，LSD在5-HT受体处诱导产生的肌醇磷酸形成量比二甲基色胺（DMT）和脱磷酸裸盖菇素显著更多，但致幻剂对5-HT、5-HT或D受体的选择性在药物之间没有显著差异。我们的荟萃分析将DMT、LSD和裸盖菇素与每个分析层次上的特定神经特征联系起来。结果显示这些特征之间存在高度非线性关系。总体而言，我们的分析突出了文献中高度的异质性和偏倚风险。这表明迫切需要规范实验程序和分析技术，以及对不同层次致幻效果之间的关联性进行更多研究。
