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)
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 |