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

In this preprint the study aimed to examine:

• How psychedelic use relates to mental health outcomes (depression and anxiety)

• Whether this relationship differs by age

It used a naturalistic, cross-sectional survey (not a clinical trial). Of key interest it found the relationship between psychedelic use and mental health varies across the lifespan. Notably, psychedelic use was associated with reduced depression and anxiety in younger adults, but with increasing age, these benefits diminished, and anxiety was positively associated with psychedelic use in older individuals.

“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.”

Giammarco Di Gregorio, Sophia Basset, Harjot Manmohan et al. Age moderates the relationship between psychedelics use and mental health in naturalistic settings, 10 March 2026, PREPRINT (Version 1) available at Research Square Read Paper

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