Characterising the clinical associations of hallucinogen persisting perception disorder: a retrospective cohort study

This large retrospective cohort study of 25,778 people with hallucinogen persisting perception disorder (HPPD) found that the condition is strongly associated not only with visual disturbances but also with broader psychiatric and functional somatic symptoms.

Individuals with HPPD had high rates of anxiety, depression, chronic pain, headache syndromes, post-viral fatigue, ADHD, and fibromyalgia before diagnosis, and anxiety disorders and functional somatic syndromes were significantly more common than in psychedelic-using control groups. Among psychedelic users, anxiety and post-viral fatigue predicted later development of HPPD, while an HPPD diagnosis was linked to increased risk of subsequent psychiatric disorders and somatic syndromes. The authors conclude that HPPD may involve overlapping mechanisms with anxiety disorders, visual snow syndrome, and functional neurological/somatic conditions, challenging the idea that it is solely a visual side effect of psychedelic use. The study was the largest HPPD cohort study to date and used electronic health records from the TriNetX global database.

“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.”

Butler, M., Moore, E., Rucker, J.J. et al. Characterising the clinical associations of hallucinogen persisting perception disorder: a retrospective cohort study. Transl Psychiatry (2026). Read Paper

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