Age moderates the relationship between psychedelic use and mental health in naturalistic settings

Abstract Depression and anxiety affect one in five adults and vary across the lifespan; while prevalence generally declines with age until midlife, later life is marked by a re-emergence of symptoms. Although clinical trials suggest classic psychedelics (e.g., psilocybin, LSD) and non-classic psychedelics (e.g., MDMA, ketamine) may alleviate these symptoms, it remains unclear how these relationships function in naturalistic settings or how they vary across the lifespan. We conducted a cross-sectional survey of 1,088 adults (18–55 + years) to assess how lifetime psychedelic use – categorised as classic, non-classic, or mixed – relates to mental health. We found that age significantly moderates the relationship between lifetime history of psychedelic use and mental health measures. Specifically, classic psychedelic use was linked to lower depression and anxiety among younger adults, but these effects diminished with age. These associations persisted independently of drug-use parameters, including dosage, frequency, and recency of use. Moderated-mediation analyses indicated that mystical-type experiences accounted for the associations with both depression and anxiety among younger adults, but not among older adults, where a residual association with anxiety remained independent of mystical experience. These findings suggest that age may be a meaningful moderator of mental health outcomes from psychedelic use. This underscores the potential value of age-stratified research to optimise the efficacy and safety of psychedelic-assisted interventions.