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Psilocybin in late-life mental health: Addressing depression, loneliness, and existential anxiety

Gerasimos Konstantinou, Joshua D. Rosenblat, Sarah Hales, Muhammad Ishrat Husain, Daniel M. Blumberger

General Hospital Psychiatry December 9, 2025 DOI: 10.1016/j.genhosppsych.2025.12.005 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Review Peer reviewed
Topics Anxiety Psilocybin Depression
Keywords Psychological intervention Mental health Tolerability Cognition Antidepressant Clinical psychology Psychotherapist Informed consent Clinical trial Medline
Citations 4
Key findings Psilocybin-assisted therapy may offer distinct therapeutic benefits for late-life mental health, but dedicated geriatric studies with rigorous safety assessments are needed.

Abstract

The global demographic shift toward aging populations has intensified the need for innovative therapeutic interventions targeting late-life mental health conditions, notably depression, loneliness, and existential distress. Traditional pharmacological treatments often exhibit limited efficacy and poor tolerability in older patients, primarily due to age-related physiological changes and the challenges associated with polypharmacy. Recently, psychedelic-assisted therapy, particularly psilocybin, has gained attention for its potential antidepressant and psychological benefits. This comprehensive review critically evaluates the current evidence supporting psilocybin's effectiveness in older populations and elucidates its neurobiological mechanisms, including serotonergic modulation, enhanced neuroplasticity, and the disruption of maladaptive default mode network activity. Clinical trials in general adult samples demonstrate sustained improvements in depressive symptoms, existential anxiety, and social connectedness following psilocybin administration, suggesting its distinct therapeutic potential beyond conventional treatments. However, geriatric populations are underrepresented in psychedelic research, creating significant knowledge gaps regarding dosing, safety profiles, and long-term outcomes. Pharmacokinetic complexities, cardiovascular risks, and drug interactions necessitate age-specific therapeutic protocols. Ethical considerations, including the complexities of informed consent in cases of cognitive impairment, further underscore the importance of tailored approaches. Future directions must prioritize dedicated geriatric studies that incorporate rigorous safety assessments and integrate findings into existing geriatric care frameworks to fully assess the potential of psilocybin for enhancing late-life mental health and quality of life.

Comparable studies

Other narrative reviews on psilocybin for anxiety, most cited first.

Study Year Design Participants
Psychedelics as anti-inflammatory agents Animal models and cellular studies 2018 Review
Ayahuasca: Pharmacology, neuroscience and therapeutic potential 2016 Review
Psychedelic Drugs in Biomedicine 2017 Review
A review of emerging therapeutic potential of psychedelic drugs in the treatment of psychiatric illnesses 2020 Review
Psychedelics and health behaviour change 2021 Review

Citations in the library

Cited by 4

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Anxiety Psilocybin Depression Default mode network End-of-life distress Neuroplasticity Psychedelic-assisted therapy Serotonin

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