The main psychedelic component of magic mushrooms is psilocybin, which shows promise as a treatment for depression and other mental disorders. Psychedelic effects are believed to emerge through stimulation of serotonin 2A receptors (5-HT2ARs) by psilocybin's active metabolite, psilocin. We here report for the first time the relationship between intensity of psychedelic effects, cerebral 5-HT2AR occupancy and plasma levels of psilocin in humans. Eight healthy volunteers underwent positron emission tomography (PET) scans with the 5-HT2AR agonist radioligand [11C]Cimbi-36: one at baseline and one or two additional scans on the same day after a single oral intake of psilocybin (3-30 mg). 5-HT2AR occupancy was calculated as the percent change in cerebral 5-HT2AR binding relative to baseline. Subjective psychedelic intensity and plasma psilocin levels were measured during the scans. Relations between subjective intensity, 5-HT2AR occupancy, and plasma psilocin levels were modeled using non-linear regression. Psilocybin intake resulted in dose-related 5-HT2AR occupancies up to 72%; plasma psilocin levels and 5-HT2AR occupancy conformed to a single-site binding model. Subjective intensity was correlated with both 5-HT2AR occupancy and psilocin levels as well as questionnaire scores. We report for the first time that intake of psilocybin leads to significant 5-HT2AR occupancy in the human brain, and that both psilocin plasma levels and 5-HT2AR occupancy are closely associated with subjective intensity ratings, strongly supporting that stimulation of 5-HT2AR is a key determinant for the psychedelic experience. Important for clinical studies, psilocin time-concentration curves varied but psilocin levels were closely associated with psychedelic experience.

中文翻译：

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psilocybin的迷幻效果与血清素2A受体的占有率和血浆psilocin水平相关。

魔术蘑菇的主要迷幻成分是psilocybin，它具有治疗抑郁症和其他精神疾病的潜力。据信迷幻药的作用是通过psilocybin的活性代谢产物psilocin刺激血清素2A受体（5-HT2ARs）出现的。我们在此首次报道了迷幻药作用强度，脑5-HT2AR占用率和人血浆中loclocin水平之间的关系。八名健康志愿者接受了5-HT2AR激动剂放射性配体[11C] Cimbi-36的正电子发射断层扫描（PET）扫描：一次基线摄取，一次口服psilocybin（3-30 mg ）。5-HT2AR占用率计算为大脑5-HT2AR结合相对于基线的变化百分比。在扫描期间测量主观迷幻强度和血浆psilocin水平。使用非线性回归对主观强度，5-HT2AR占用率和血浆psilocin水平之间的关系进行建模。摄入赛洛西宾导致与剂量相关的5-HT2AR占有率高达72％；血浆psilocin水平和5-HT2AR占用符合单位点结合模型。主观强度与5-HT2AR的占有率，psilocin水平以及问卷得分相关。我们首次报告摄入psilocybin会导致人脑中大量5-HT2AR占用，并且psilocin血浆水平和5-HT2AR占用均与主观强度等级密切相关，强烈支持对5-HT2AR的刺激是迷幻体验的关键决定因素。