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

Giammarco di Gregorio, Sophia Basset, Harjot Manmohan, Warren C. Nixon, Amrutha Pogaku, Jing Zhou, David J. Sanderson, Michael L. Lengieza, Marco Bocchio

Research Square March 10, 2026 DOI: 10.21203/rs.3.rs-9022170/v1 via OpenAlex

Summary

AI-generated from the abstract

Depression and anxiety affect one in five adults, with age influencing prevalence. A cross-sectional survey of 1,088 adults aged 18–55+ years examined how lifetime use of classic psychedelics (e.g., psilocybin, LSD), non-classic psychedelics (e.g., MDMA, ketamine), or both relates to mental health. Age significantly moderated these relationships: classic psychedelic use was linked to lower depression and anxiety among younger adults, but these benefits diminished with age and even reversed for anxiety in older participants. These age-related effects persisted regardless of dosage, frequency, or recency of use and were moderated by mystical experiences for depression but not anxiety. Age may be a meaningful moderator of mental health outcomes from psychedelic use, highlighting the need for age-stratified research to optimize psychedelic-assisted interventions.

Study at a glance

Characteristics Cross-sectional survey Peer reviewed
Sample size 1,088
Population Adults aged 18–55+ years
Topics Anxiety
Keywords Mental health Moderation Depression economics Naturalistic observation
Key finding Age significantly moderates the relationship between psychedelic use and mental health: classic psychedelic use was linked to lower depression and anxiety in younger adults, but these effects diminished with age and reversed for anxiety in older participants.

Abstract

Abstract Depression and anxiety affect one in five adults, with age affecting prevalence. While 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 - categorized as classic, non-classic, or mixed - relates to mental health. Using structural equation modeling, we found that age significantly moderates the relationship between psychedelic use and mental health outcomes. Specifically, classic psychedelic use was linked to lower depression and anxiety among younger adults, but these effects diminished with age - even reversing for anxiety in older participants. These age-related effects persisted independently of drug-use parameters - including dosage, frequency, and recency of use - and were moderated by mystical experiences for depression, but not for anxiety. Our 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 optimize the efficacy and safety of psychedelic-assisted interventions, including in aging populations.

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