Characterising the clinical associations of hallucinogen persisting perception disorder: a retrospective cohort study
Matt Butler, Ellen Moore, James Rucker, Katharine Lynch-kelly, Danish Hafeez, Ed Prideaux, Timothy R. Nicholson, Mark Edwards, Thomas Pollak
Translational Psychiatry April 24, 2026 Peer reviewed DOI: 10.1038/s41398-026-04042-1 via OpenAlex
Summary
Individuals diagnosed with hallucinogen persisting perception disorder (HPPD) showed high rates of comorbidities, including depressive episodes (29.2%), anxiety disorders (26.2%), and chronic pain (15.9%). Compared to psychedelic-using controls, those with HPPD had significantly more anxiety and functional somatic syndromes. Anxiety and post-viral fatigue were identified as predictors for developing HPPD in psychedelic users, with HPPD diagnosis linked to increased risks of further psychiatric disorders and somatic syndromes.
Study at a glance
| Design | retrospective cohort study |
|---|---|
| Sample size | 25,778 |
| Population | individuals diagnosed with hallucinogen persisting perception disorder (HPPD) |
| Key finding | High rates of comorbidities were observed in individuals with HPPD, including a significant association with anxiety and functional somatic syndromes. |
Abstract
Hallucinogen persisting perception disorder (HPPD) is characterised by episodes of altered perception linked to past psychoactive drug use, accompanied by distress and functional impairment. To date, clinical characterisation has been limited in scale. Using TriNetX, a global federated health research network of electronic health records, we conducted a retrospective cohort study comparing clinical associations in individuals with HPPD versus population and psychedelic-using controls. Cumulative incidences of psychiatric and medical disorders were compared. Cox proportional hazards models assessed risk factors for developing HPPD, and odds ratios (ORs) were used to evaluate associated conditions following diagnosis. We identified 25,778 individuals diagnosed with HPPD. Prior to diagnosis, high rates of comorbidities were observed, including depressive episodes (29.2%), anxiety disorders (26.2%), chronic pain (15.9%), headache syndromes (14.7%), post-viral fatigue (12.3%), ADHD (6.6%), and fibromyalgia (6.7%). Anxiety and functional somatic syndromes were significantly more common in the HPPD group than in psychedelic-using controls (p < 0.001). Anxiety (OR 1.5) and post-viral fatigue (OR 1.9) predicted HPPD development in psychedelic users. HPPD diagnosis was associated with increased risk of subsequent functional somatic syndromes (OR 2.0) and psychiatric disorders (OR 1.4) versus psychedelic-using controls. This largest-to-date study of HPPD highlights its psychiatric and somatic complexity, with strong associations with anxiety and functional somatic syndromes. Several methodological limitations are acknowledged. Further research should explore overlapping pathophysiological mechanisms linking HPPD, visual disorders (e.g. visual snow syndrome), anxiety, and functional somatic syndromes.