Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels
Psychedelic effects of psilocybin correlate with serotonin 2A receptor occupancy and plasma psilocin levels
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DOI：
10.1038/s41386-019-0324-9
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发表时间：
2019-06-01
影响因子：
7.6
通讯作者：
Knudsen, Gitte M.
中科院分区：
文献类型：
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作者：
Madsen, Martin K.;Fisher, Patrick M.;Knudsen, Gitte M.
迷幻蘑菇的主要迷幻成分是裸盖菇素，有望用于治疗抑郁症和其他精神障碍。迷幻效应被认为是通过裸盖菇素的活性代谢物裸盖菇素刺激5-羟色胺2A受体（5-HT2ARs）而产生的。我们在此首次报道了迷幻作用强度、大脑5-HT2AR占用率和人类血浆psilocin水平之间的关系。8名健康志愿者接受了5-HT2AR激动剂放射配体[C-11] Cimbi-36的正电子发射断层扫描（PET）扫描：在基线时进行一次扫描，在单次口服裸盖头素（3- 30mg）后的同一天进行一次或两次额外扫描。5-HT2AR占用率计算为大脑5-HT2AR结合相对于基线的百分比变化。在扫描过程中测量主观迷幻强度和血浆裸裸素水平。主观强度、5-HT2AR占用率与血浆psilocin水平之间的关系采用非线性回归模型。裸盖菇素摄入导致与剂量相关的5-HT2AR占用量高达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占用率、psilocin水平及问卷得分均相关。我们首次报道了裸盖菇素的摄入导致人脑中5-HT2AR的显著占用，并且裸盖菇素血浆水平和5-HT2AR占用都与主观强度评级密切相关，这有力地支持了5-HT2AR的刺激是迷幻体验的关键决定因素。对临床研究很重要的是，裸裸素时间-浓度曲线变化，但裸裸素水平与迷幻体验密切相关。
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 [C-11] 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.