Prediction of hallucinogen persisting perception disorder and thought disturbance symptoms following psychedelic use.
Katie Zhou, David de Wied, Robin Carhart-Harris, Hannes Kettner
PNAS Nexus April 1, 2025 DOI: 10.1093/pnasnexus/pgae560 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Prospective cohort study Peer reviewed |
|---|---|
| Sample size | 654 |
| Population | Self-selected naturalistic sample of individuals planning a psychedelic experience |
| Intervention | psychedelic experience |
| Duration | One week before to four weeks after a planned psychedelic experience |
| Keywords | Hppd Adverse effects Delusional ideation Magical thinking Psychedelics Mental health effects Adverse reactions |
| Citations | 9 |
| Key findings | Delusional ideation was reduced one month after psychedelic use, while HPPD-type effects occurred in over 30% of participants but were rarely distressing. |
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.