Abstract
BACKGROUND: Although clinical trials involving psychedelic-assisted psychotherapy have not observed short-term increases in the risk of death, limited data exist on mortality associated with hallucinogen use outside of controlled trial settings. We sought to determine whether people with an emergency department visit or hospital admission involving hallucinogen use were at increased risk of all-cause death compared with the general population and with people with acute care presentations involving other substances. METHODS: We conducted a retrospective cohort study using linked health administrative data on all people aged 15 years and older living in Ontario, Canada, from 2006 to 2022. We compared overall and cause-specific mortality between members of the general population and people with incident acute care (an emergency department visit or hospital admission) involving hallucinogens and other substances. RESULTS: We included 11 415 713 people; 7953 (0.07%) had incident acute care involving hallucinogens. In a matched analysis with 77 101 people with a median follow-up of 7 (interquartile range 3-11) years, acute care involving hallucinogens was associated with a 2.6-fold (hazard ratio [HR] 2.57, 95% confidence interval [CI] 2.09-3.15) increased all-cause mortality within 5 years (n = 482, absolute risk 6.1%) relative to the general population (n = 460, absolute risk 0.6%). Analyses excluding people with comorbid mental or substance use disorders showed similar elevations in mortality risk for acute care involving hallucinogens relative to the general population (HR 3.25, 95% CI 2.27-4.63). People with acute care involving hallucinogens were at a significantly elevated risk of death by unintentional drug poisoning (HR 2.03, 95% CI 1.02-4.05), suicide (HR 5.23, 95% CI 1.38-19.74), respiratory disease (HR 2.46, 95% CI 1.18-5.11), and cancer (HR 2.88, 95% CI 1.61-5.14) relative to the general population. INTERPRETATION: Requiring hospital-based care for hallucinogen use was associated with increases in risk of death relative to the general population, particularly from suicide. These findings should be considered in clinical and policy decision-making, given the increasing use of hallucinogens and associated problematic use.