Prediction of hallucinogen persisting perception disorder and thought disturbance symptoms following psychedelic use

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 ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>N</mml:mi> <mml:mo>=</mml:mo> <mml:mn>654</mml:mn></mml:math> ) 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 ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>P</mml:mi> <mml:mo><</mml:mo> <mml:mn>0.001</mml:mn></mml:math> ) 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 ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>r</mml:mi> <mml:mi>s</mml:mi></mml:msub> <mml:mo>=</mml:mo> <mml:mn>0.12</mml:mn></mml:math> , <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>P</mml:mi> <mml:mo>=</mml:mo> <mml:mn>0.003</mml:mn></mml:math> ) and delusional ideation ( <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:msub><mml:mi>r</mml:mi> <mml:mi>s</mml:mi></mml:msub> <mml:mo>=</mml:mo> <mml:mn>0.11</mml:mn></mml:math> , <mml:math xmlns:mml="http://www.w3.org/1998/Math/MathML"><mml:mi>P</mml:mi> <mml:mo>=</mml:mo> <mml:mn>0.01</mml:mn></mml:math> ), 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.