Abstract

Background: Current drug policy debates often center on whether hallucinogen-related hospital admissions indicate a causal relationship with psychosis. This study examines the extent to which observed associations between hallucinogen use and psychosis are mediated by preexisting psychiatric conditions, providing important evidence for psychedelic policy formulation.

Methods: We conducted a retrospective analysis using MarketScan Medicaid and commercial claims databases from 2015–2019. The population-based sample included individuals receiving substance use disorder treatment with documented substance-related emergency admissions or hospitalizations. We compared psychosis-related admissions occurring 30 days to 6 months postindex event between individuals with hallucinogen-related admissions versus those with nonhallucinogen substance-related admissions. Cox regression models adjusted for demographics and clinical characteristics to determine whether prior psychiatric history explained observed associations.

Results: Among 273,466 individuals with substance-related admissions, psychosis diagnoses were more prevalent following hallucinogen-related admissions (16.4%) compared to nonhallucinogen substance admissions (6.6%, P<.001). While unadjusted models showed increased psychosis risk for hallucinogen-related admissions (hazard ratio [HR]=1.22, 95% CI=1.19–1.25), this association became nonsignificant after adjusting for clinical characteristics (HR=0.97, 95% CI=0.95–1.00).

Conclusions: Apparent associations between hallucinogen use and psychosis appear largely attributable to baseline psychiatric comorbidities rather than direct causal effects. These findings carry implications for evidence-based policy development, suggesting that observed epidemiologic associations may reflect underlying vulnerability factors rather than hallucinogen-induced psychosis. Policymakers should consider these results when interpreting population-level data regarding hallucinogen safety profiles and regulatory frameworks.

J Clin Psychiatry 2026;87(3):25m16034

Author affiliations are listed at the end of this article.

Members Only Content

This full article is available exclusively to Professional tier members. Subscribe now to unlock the HTML version and gain unlimited access to our entire library plus all PDFs. If you're already a subscriber, please log in below to continue reading.

Subscribe Now

Already a member? Log in

  1. Haikazian S, Chen-Li DCJ, Johnson DE, et al. Psilocybin-assisted therapy for depression: a systematic review and meta-analysis. Psychiatry Res. 2023;329:115531. CrossRef
  2. Yao Y, Guo D, Lu TS, et al. Efficacy and safety of psychedelics for the treatment of mental disorders: a systematic review and meta-analysis. Psychiatry Res. 2024;335:115886. CrossRef
  3. Schimmers N, Breeksema JJ, Smith-Apeldoorn SY, et al. Psychedelics for the treatment of depression, anxiety, and existential distress in patients with a terminal illness: a systematic review. Psychopharmacology. 2022;239(1):15–33. PubMed CrossRef
  4. Barrett FS, Griffiths RR. Classic hallucinogens and mystical experiences: phenomenology and neural correlates. Curr Top Behav Neurosci. 2018;36:393–430. PubMed CrossRef
  5. Luoma JB, Hoffman K, Wilson-Poe AR, et al. Oregon’s emerging psilocybin services workforce: a survey of the first legal psilocybin facilitators and their training programs. J Psychoact Drugs. 2025:1–11. PubMed CrossRef
  6. Chwyl C, Wilson-Poe AR, Hoffman KA, et al. Building standards of psychedelic care: qualitative examination of expert perspectives on safety, inclusion, and accountability. Int J Drug Pol. 2026;147:104938. PubMed CrossRef
  7. Korthuis PT, Wilson-Poe AR, Black JC, et al. Expanded psychedelic access requires new safety monitoring systems. Addiction. 2024;119(9):1572–1574. PubMed CrossRef
  8. Simonsson O, Johnson MW, Hendricks PS. Psychedelic and MDMA-related adverse effects—a call for action. JAMA Health Forum. 2024;5(11):e243630. PubMed CrossRef
  9. Ehrenkranz R, Agrawal M, Sandeep MN, et al. Adverse events should not be surprising in psychedelic research. Psychedelic Med. 2024 Sept:4. Ahead of Print.
  10. Simonsson O, Goldberg SB, Hendricks PS. Into the wild frontier: mapping the terrain of adverse events in psychedelic-assisted therapies. J Psychopharmacol. 2024:02698811241292944.
  11. Schlag AK, Aday J, Salam I, et al. Adverse effects of psychedelics: from anecdotes and misinformation to systematic science. J Psychopharmacol. 2022;36(3):258–272. PubMed CrossRef
  12. Nutt DJ, King LA, Phillips LD, et al. Drug harms in the UK: a multicriteria decision analysis. Lancet. 2010;376(9752):1558–1565. PubMed CrossRef
  13. Nutt D, King LA, Saulsbury W, et al. Development of a rational scale to assess the harm of drugs of potential misuse. Lancet. 2007;369(9566):1047–1053. PubMed CrossRef
  14. Hendricks PS, Thorne CB, Clark CB, et al. Classic psychedelic use is associated with reduced psychological distress and suicidality in the United States adult population. J Psychopharmacol. 2015;29(3):280–288. PubMed CrossRef
  15. Johansen PØ, Krebs TS. Psychedelics not linked to mental health problems or suicidal behavior: a population study. J Psychopharmacol. 2015;29(3):270–279. PubMed CrossRef
  16. Hjorthøj C, Madsen T, Starzer M, et al. Mortality in substance-induced psychosis: a register-based national cohort study. Addiction. 2021;116(12):3515–3524. PubMed CrossRef
  17. Fiorentini A, Cantù F, Crisanti C, et al. Substance-induced psychoses: an updated literature review. Front Psychiatry. 2021;12:694863. PubMed CrossRef
  18. Myran DT, Pugliese M, Xiao J, et al. Emergency department visits involving hallucinogen use and risk of Schizophrenia spectrum disorder. JAMA Psychiatry. 2025;82(2):142–150. PubMed CrossRef
  19. Rognli EB, Heiberg IH, Jacobsen BK, et al. Transition from substance-induced psychosis to schizophrenia spectrum disorder or bipolar disorder. Am J Psychiatry. 2023;180(6):437–444. CrossRef
  20. Starzer MSK, Nordentoft M, Hjorthøj C. Rates and predictors of conversion to schizophrenia or bipolar disorder following substance-induced psychosis. Am J Psychiatry. 2018;175(4):343–350. CrossRef
  21. Steinle JT, Gong L, Buss JL, et al. Trends in hallucinogen-related emergency department and hospital admissions, 2016 to 2023. JAMA Netw Open. 2025;8(11):e2543453. PubMed CrossRef
  22. Siegel JS, Daily JE, Perry DA, et al. Psychedelic drug legislative reform and legalization in the US. JAMA Psychiatry. 2023;80(1):77–83. PubMed CrossRef
  23. Humphreys K, Korthuis PT, Stjepanović D, et al. Therapeutic potential of psychedelic drugs: navigating high hopes, strong claims, weak evidence, and big money. Annu Rev Psychol. 2025;76(1):143–165. PubMed CrossRef
  24. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders. 5th ed., text rev. American Psychiatric Association; 2022.
  25. Kumar D, Klefsjö B. Proportional hazards model: a review. Reliab Eng Syst Saf. 1994;44(2):177–188. CrossRef
  26. Hsieh FY, Lavori PW, Cohen HJ, et al. An overview of variance inflation factors for sample-size calculation. Eval Health Prof. 2003;26(3):239–257. PubMed CrossRef
  27. Schoenfeld D. Partial residuals for the proportional hazards regression model. Biometrika. 1982;69(1):239–241. CrossRef
  28. Miettunen J, Immonen J, McGrath JJ, et al. The age of onset of schizophrenia spectrum disorders. In: de Girolamo G, McGorry PD, Sartorius N, eds. Age of Onset of Mental Disorders: Etiopathogenetic and Treatment Implications. Springer International Publishing; 2019:55–73. CrossRef
  29. Larson MK, Walker EF, Compton MT. Early signs, diagnosis and therapeutics of the prodromal phase of schizophrenia and related psychotic disorders. Expert Rev Neurother. 2010;10(8):1347–1359. PubMed CrossRef
  30. Khokhar JY, Dwiel L, Henricks A, et al. The link between schizophrenia and substance use disorder: a unifying hypothesis. Schizophr Res. 2018;194:78–85. PubMed CrossRef
  31. Kendler KS, Ohlsson H, Sundquist J, et al. Prediction of onset of substance-induced psychotic disorder and its progression to schizophrenia in a Swedish national sample. Am J Psychiatr. 2019;176(9):711–719. PubMed CrossRef
  32. Baker MR, O’Shea CI. Drug-induced psychosis following use of ayahuasca: a presentation to forensic psychiatric services. BMJ Case Rep. 2024;17(8):e260648. PubMed CrossRef
  33. Barber G, Nemeroff CB, Siegel S. A case of prolonged mania, psychosis, and severe depression after psilocybin use: implications of increased psychedelic drug availability. Am J Psychiatry. 2022;179(12):892–896. https://doi.org/10.1176/appi.ajp.22010073 PubMedCrossRef
  34. Barbic D, Fernandes J, Eberdt C, et al. N-Dimethyltryptamine: DMT-induced psychosis. Am J Emerg Med. 2020;38(9):1961.e1–1961.e2. PubMed
  35. Cohen S. Lysergic acid diethylamide: side effects and complications. J Nerv Ment Dis. 1960;130(1):30–40. PubMed CrossRef
  36. Jauhar S, Johnstone M, McKenna PJ. Schizophrenia. Lancet. 2022;399(10323):473–486. PubMed CrossRef
  37. Tandon R, Nasrallah H, Akbarian S, et al. The schizophrenia syndrome, circa 2024: what we know and how that informs its nature. Schizophrenia Res. 2024;264:1–28. PubMed CrossRef
  38. Bukovsky D, Amaev A, Song J, et al. Adverse event reporting and management in psilocybin therapy clinical trials: a systematic review to guide clinical and research protocol development. Prog Neuro Psychopharmacol Biol Psychiatr. 2025;143:111541. PubMed CrossRef
  39. Hughes M. Toward Greater Diversity in Psychedelic Science. Psychiatr Serv. 2026;77(4):367–370. PubMed CrossRef
  40. Adams DR, Xu KY, Cabassa LJ. Psychedelic-Assisted Therapy: Breakthrough for Whom? Psychiatr Serv. 2026;77(4):289. PubMed CrossRef
  41. Gilman JM. Association of cannabis legalization with prevalence of schizophrenia—challenges of attributing biological causality to Policy change. JAMA Netw Open. 2025;8(2):e2457876. PubMed CrossRef
  42. Joshi S, Snyder KM, Thurstone C, et al. Changes in psychosis-related emergency department and hospitalization rates among youth following cannabis legalization in Colorado. Drug Alcohol Depend. 2025;273:112719. PubMed CrossRef
  43. Elser H, Humphreys K, Kiang MV, et al. State cannabis legalization and psychosis-related health care utilization. JAMA Netw Open. 2023;6(1):e2252689. PubMed CrossRef
  44. Wang GS, Buttorff C, Wilks A, et al. Impact of cannabis legalization on healthcare utilization for psychosis and schizophrenia in Colorado. Int J Drug Pol. 2022;104:103685. PubMed CrossRef
  45. Myran DT, Pugliese M, Harrison LD, et al. Changes in incident schizophrenia diagnoses associated with cannabis use disorder after cannabis legalization. JAMA Netw Open. 2025;8(2):e2457868. PubMed CrossRef
  46. Barrett SP, Darredeau C, Pihl RO. Patterns of simultaneous polysubstance use in drug using university students. Hum Psychopharmacol Clin Exp. 2006 June;21(4):255–263. PubMed CrossRef
  47. Licht CL, Christoffersen M, Okholm M, et al. Simultaneous polysubstance use among Danish 3,4-methylenedioxymethamphetamine and hallucinogen users: combination patterns and proposed biological bases. Hum Psychopharmacol Clin Exp. 2012;27(4):352–363. PubMed CrossRef
  48. Connor JP, Leung J, Chan GCK, et al. Seeking order in patterns of polysubstance use. Curr Opin Psychiatr. 2023;36(4):263–268. PubMed CrossRef
  49. Zhu H, Wu LT. Multiple drug use disorder diagnoses among drug-involved hospitalizations in the United States: results from the 2016 National Inpatient Sample. Drug Alcohol Depend. 2020;213:108113. PubMed CrossRef
  50. Kruse AO, Bustillo JR. Glutamatergic dysfunction in schizophrenia. Transl Psychiatry. 2022;12(1):500. CrossRef
  51. Garey RE. PCP (phencyclidine): an update. J Psychedelic Drugs. 1979;11(4):265–275. PubMed CrossRef
  52. Key substance use and mental health indicators in the United States: Results from the 2024 National Survey on Drug Use and Health. Center for Behavioral Health Statistics and Quality, Substance Abuse and Mental Health Services Administration: Substance Abuse and Mental Health Services Administration. 2025. Accessed January 22, 2026. https://www.samhsa.gov/data/data-we-collect/nsduh-national-surveydrug-use-and-health/national-releases.
  53. Powers ARIII, Addington J, Perkins DO, et al. Duration of the psychosis prodrome. Schizophrenia Res. 2019;216:443–449. PubMed CrossRef
  54. Livne O, Shmulewitz D, Walsh C, et al. Adolescent and adult time trends in US hallucinogen use, 2002–19: any use, and use of ecstasy, LSD and PCP. Addiction [Abingdon, Engl. 2022;117(12):3099–3109. CrossRef
Buy PDF for $40

Please sign in or purchase this PDF for $40.