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NIH grant 1K23AG093106-01A1: Safety and Mechanisms of Psilocybin Therapy in Older Adults
Institute: {'code': 'AG', 'abbreviation': 'NIA', 'name': 'National Institute on Aging', 'admin_org_id': '12500002', 'admin_funding_url': ''}. PI: ALI JOHN ZARRABI. Award: $175189.
Start: 2026-09-11T00:00:00.
PROJECT SUMMARY/ABSTRACT
Psilocybin Therapy (PT) has demonstrated safety and preliminary efficacy for difficult-to-treat conditions such
as chronic pain and depression which are prevalent in older adults (OAs). PT couples psilocybin (a serotonin
receptor agonist) with psychotherapeutic support. PT stands to potentially benefit millions of older adults (OAs)
with pain, mental illness, and loneliness. Population-based studies of community psilocybin use reveal >6% of
adults report persisting adverse events (AEs). OAs metabolize medicines differently compared to younger
adults and may have differing prevalence, severity, and types of PT-related AEs; however, this has never been
described. The lack of any safety data puts OAs in danger of harm and necessitates safety trials and
observational studies to safety apply PT the meet the unique needs of OAs. To address this knowledge gap, I
led a proof-of-concept pilot study of PT in palliative care patients (N=10, three OAs) which demonstrated
safety, feasibility, and acceptability. The three OAs in my study, however, had 23 adverse events (AEs), many
of which were likely attributable to psilocybin (e.g. nausea, anxiety, headache). Given the frequency and variety
of AEs among OAs in my pilot trial, as well as favorable outcomes in my pilot, my next critical step to advance
the safe and effective delivery of PT in OAs is to focus specifically on OAs. As a physician-investigator with
clinical training in palliative medicine and experience conducting PT trials, I am ideally positioned to conduct
this research. Yet, I lack essential skills and expertise to become a leader in the science of medication-assisted
therapies in OAs, including: (1) clinical trials with a focus on phase 1 trials and PK/PD, (2) quantitative methods
relevant to PT trials and mixed methods, (3) geriatric medicine to understand the unique care needs of OAs,
(4) practitioner training in PT, and (5) scientific leadership and grant writing. Following a robust training plan
supported by a nationally renowned team of experts and responding to NIA research priorities, I will pursue
three Specific Aims. In Aim 1, I will evaluate the safety of psilocybin in OA in a phase 1 clinical trial in which I
will evaluate acute PK/PD and cardiovascular effects and physical and psychological AEs over six months
(N=30, age-stratified healthy OAs: 65-75, 76-80, >80). In Aim 2, I will use mixed methods to identify barriers,
facilitators, and care preferences for PT in OAs. In Aim 3, I will conduct a longitudinal observational study to
evaluate the safety and mechanisms of psilocybin use in OAs outside of clinical trials. Bolstered by newly
acquired skills, if I identify a safe dose range of psilocybin on OAs, I will develop R-level phase 2 trials targeting
pain and depression in OAs. The proposed project is the essential next step toward my long-term career goal
of advancing the science of medication-assisted therapies in older and seriously ill adults.document fetched 2026-09-20 02:42