Lewis Candace R, Preller Katrin H, Braden B Blair, Riecken Cory, Vollenweider Franz X
Translational Genomics Research Institute, Neurogenomics Division, Phoenix, AZ 85004, USA.
Neuropsychopharamacology and Brain Imaging, Department of Psychiatry, Psychotherapy and Psychosomatics, University Hospital for Psychiatry, Zurich 8032, Switzerland.
Biomedicines. 2020 Feb 18;8(2):34. doi: 10.3390/biomedicines8020034.
Psilocybin is the psychoactive compound of mushrooms in the species. Psilocybin directly affects a number of serotonin receptors, with highest affinity for the serotonin 2A receptor (5HT-2Ar). Generally, the effects of psilocybin, and its active metabolite psilocin, are well established and include a range of cognitive, emotional, and perceptual perturbations. Despite the generality of these effects, there is a high degree of inter-individual variability in subjective psilocybin experiences that are not well understood. Others have shown brain morphology metrics derived from magnetic resonance imaging (MRI) can predict individual drug response. Due to high expression of serotonin 2A receptors (5HT-2Ar) in the cingulate cortex, and its prior associations with psilocybin, we investigate if cortical thickness of this structure predicts the psilocybin experience in healthy adults. We hypothesized that greater cingulate thickness would predict higher subjective ratings in sub-scales of the Five-Dimensional Altered State of Consciousness (5D-ASC) with high emotionality in healthy participants ( = 55) who received oral psilocybin (either low dose: 0.160 mg/kg or high dose: 0.215 mg/kg). After controlling for sex, age, and using false discovery rate (FDR) correction, we found the rostral anterior cingulate predicted all four emotional sub-scales, whereas the caudal and posterior cingulate did not. How classic psychedelic compounds induce such large inter-individual variability in subjective states has been a long-standing question in serotonergic research. These results extend the traditional set and setting hypothesis of the psychedelic experience to include brain structure metrics.
裸盖菇素是该物种蘑菇中的精神活性化合物。裸盖菇素直接影响多种血清素受体，对血清素2A受体（5HT-2Ar）具有最高亲和力。一般来说，裸盖菇素及其活性代谢物脱磷酸裸盖菇素的作用已得到充分证实，包括一系列认知、情绪和感知方面的扰动。尽管有这些普遍的作用，但个体在裸盖菇素主观体验上存在高度的个体差异，对此人们还了解得不够。其他人已经表明，源自磁共振成像（MRI） 的脑形态学指标可以预测个体对药物的反应。由于扣带回皮质中血清素2A受体（5HT-2Ar）的高表达，以及其与裸盖菇素的先前关联，我们研究了该结构的皮质厚度是否能预测健康成年人的裸盖菇素体验。我们假设，在接受口服裸盖菇素（低剂量：0.160 mg/kg或高剂量：0.215 mg/kg）的健康参与者（n = 55）中，更大的扣带回厚度将预测在具有高情绪性的五维意识改变状态（5D-ASC）子量表中的更高主观评分。在控制了性别、年龄并使用错误发现率（FDR）校正后，我们发现喙部前扣带回预测了所有四个情绪子量表，而尾部和后部扣带回则没有。经典的迷幻化合物如何在主观状态中引起如此大的个体差异，一直是血清素能研究中的一个长期问题。这些结果将迷幻体验的传统环境和情境假设扩展到包括脑结构指标。
