Zhou Katie, de Wied David, Carhart-Harris Robin L, Kettner Hannes
Centre for Psychedelic Research, Department of Brain Sciences, Imperial College London, London SW7 2AZ, United Kingdom.
Department of Neurology, University of California, San Francisco, San Francisco, CA 94158, USA.
PNAS Nexus. 2025 Apr 22;4(4):pgae560. doi: 10.1093/pnasnexus/pgae560. eCollection 2025 Apr.
Interest in using psychedelic drugs to treat psychiatric disorders is growing rapidly. While modern controlled clinical trials show a favorable safety and efficacy profile, it remains unclear if the risk of side effects would increase with broader use in more heterogeneous populations. To address this, we investigated the frequency and baseline predictors of delusional ideation, magical thinking, and "hallucinogen persisting perception disorder" (HPPD)-related symptoms following psychedelic use in a self-selected naturalistic sample. Using a prospective cohort study, symptoms were assessed in ( ) participants at one week before a planned psychedelic experience, and at two and four weeks afterward. Across the sample, delusional ideation was found to be reduced one month after psychedelic use ( ) with no changes detected in magical thinking. These findings were in seeming opposition to positive correlations between lifetime psychedelic use at baseline with magical thinking ( , ) and delusional ideation ( , ), suggesting that schizotypal traits, instead of being caused by, may merely correlate with psychedelic use. Importantly, over 30% of the sample reported HPPD-type effects at the 4-week endpoint, although rarely perceived as distressing (< 1% of the population). Younger age, female gender, history of a psychiatric diagnosis and baseline trait absorption predicted the occurrence of HPPD-like effects. This is in line with prior studies showing a high prevalence of HPPD-like symptoms in psychedelic users, which, however, appear to remain at a subclinical severity in most cases, explaining the comparatively lower prevalence of HPPD diagnoses.
使用迷幻药物治疗精神疾病的兴趣正在迅速增长。虽然现代对照临床试验显示出良好的安全性和有效性,但在更多样化的人群中更广泛地使用时,副作用风险是否会增加仍不清楚。为了解决这个问题,我们在一个自我选择的自然主义样本中,调查了迷幻药物使用后妄想观念、奇幻思维和“致幻剂持续性感知障碍”(HPPD)相关症状的发生频率和基线预测因素。采用前瞻性队列研究,在计划进行迷幻体验前一周、之后两周和四周,对( )名参与者的症状进行评估。在整个样本中,发现迷幻药物使用后一个月妄想观念减少( ),奇幻思维未发现变化。这些发现似乎与基线时终生迷幻药物使用与奇幻思维( , )和妄想观念( , )之间的正相关相反,表明分裂型特质可能只是与迷幻药物使用相关,而非由其引起。重要的是,超过30%的样本在4周终点报告了HPPD类型的效应,尽管很少有人认为痛苦(<1%的人群)。年轻、女性、精神科诊断史和基线特质吸收可预测HPPD样效应的发生。这与先前的研究一致,先前研究表明迷幻药物使用者中HPPD样症状的患病率很高,然而,在大多数情况下这些症状似乎仍处于亚临床严重程度,这解释了HPPD诊断相对较低的患病率。