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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\u2009&lt;\u20090.001). 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.<\/jats:p>","DOI":"10.1038\/s41398-026-04042-1","type":"journal-article","created":{"date-parts":[[2026,4,24]],"date-time":"2026-04-24T13:45:35Z","timestamp":1777038335000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Characterising the clinical associations of hallucinogen persisting perception disorder: a retrospective cohort study"],"prefix":"10.1038","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9734-6539","authenticated-orcid":false,"given":"Matt","family":"Butler","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5321-0575","authenticated-orcid":false,"given":"Ellen","family":"Moore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4647-8088","authenticated-orcid":false,"given":"James J.","family":"Rucker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1920-3986","authenticated-orcid":false,"given":"Katharine","family":"Lynch-Kelly","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3712-136X","authenticated-orcid":false,"given":"Danish","family":"Hafeez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ed","family":"Prideaux","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy R.","family":"Nicholson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Edwards","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6171-0810","authenticated-orcid":false,"given":"Thomas A.","family":"Pollak","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,24]]},"reference":[{"key":"4042_CR1","unstructured":"World Health Organization. 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JR has undertaken paid advisory boards for Clerkenwell Health (Past), Beckley PsyTech (Past), Delica Therapeutics (Past), and paid articles for Janssen. JR has received assistance for attendance at conferences from Compass Pathways (past) and Janssen. JR has been awarded grant funding (received and managed by King\u2019s College London) from Compass Pathways, Beckley PsyTech, Multidisciplinary Association for Psychedelic Studies, Transcend Therapeutics, National Institute for Health Research, Wellcome Trust, Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust. TAP has received consultancy fees from Arialys Therapeutics.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"This study used de-identified aggregate information via the TriNetX platform, which does not require additional informed consent.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent"}}],"article-number":"308"}}