Prediction of hallucinogen persisting perception disorder and thought disturbance symptoms following psychedelic use
This prospective cohort study (n=654 start, n=212 end) investigated delusional ideation, magical thinking, and HPPD symptoms in participants before and after planned psychedelic use. Results showed reduced delusional ideation after one month, no changes in magical thinking, and HPPD-like effects in 30% of participants (though rarely distressing at <1%), with younger age, female gender, psychiatric history, and baseline trait absorption predicting HPPD-like effects.
Authors
- Robin Carhart-Harris
- Hannes Kettner
Published
Abstract
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 ( N = 654 ) 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 ( P < 0.001 ) 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 ( r s = 0.12 , P = 0.003 ) and delusional ideation ( r s = 0.11 , P = 0.01 ), 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.
Research Summary of 'Prediction of hallucinogen persisting perception disorder and thought disturbance symptoms following psychedelic use'
Introduction
After a long hiatus, research into classic serotonergic psychedelics (for example psilocybin, LSD, mescaline, and DMT) has expanded rapidly because these compounds induce profound alterations in perception, mood and cognition and show therapeutic promise for several psychiatric conditions. Despite generally favourable safety profiles in controlled trials, case reports and naturalistic surveys have raised concerns about rare but potentially persistent adverse outcomes, notably prolonged psychotic reactions or increased schizotypal traits, and enduring visuoperceptual disturbances clinically recognised as hallucinogen persisting perception disorder (HPPD). HPPD is commonly described in two subtypes: transient “flashbacks” (type 1) and chronic visuoperceptual aberrations (type 2), such as motion trails, halos and intensified colours. Observational studies of naturalistic psychedelic use are particularly important because clinical trials typically exclude individuals considered at-risk, leaving uncertainty about frequency and predictors of iatrogenic effects in broader populations. Zhou and colleagues designed a prospective, naturalistic study to examine changes in delusional ideation and magical thinking surrounding a planned psychedelic experience, and to estimate the prevalence and baseline predictors of HPPD-type visual symptoms. The investigators hypothesised that baseline delusional ideation and magical thinking would correlate positively with lifetime psychedelic use and performed exploratory regression analyses to test whether demographics, trait absorption, psychiatric history, aspects of drug use or features of the acute experience predicted HPPD-type effects or shifts in schizotypal measures over a four-week follow-up period.
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Study Details
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- APA Citation
Zhou, K., de Wied, D., Carhart-Harris, R. L., & Kettner, H. (2025). Prediction of hallucinogen persisting perception disorder and thought disturbance symptoms following psychedelic use. PNAS Nexus, 4(4). https://doi.org/10.1093/pnasnexus/pgae560
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