Safety and Tolerability Trial of Psilocybin in Healthy Older Adults (Psil-Pk)

A Multicenter Phase 1 Safety and Tolerability Trial of Psilocybin in Healthy Older Adults

This study plans to learn more about the safety and tolerability of psychedelic administration (psilocybin) in healthy older adults ages 65-85.

Study Overview

• Status: Recruiting
• Conditions: Healthy Volunteer; Older Adults (65-85 Years)
• Intervention / Treatment: Drug: Psilocybin (Usona Institute)

Detailed Description

The purpose of this study is to learn whether psilocybin, a psychedelic compound, can be given safely to older adults. We want to understand how psilocybin affects the body and mind, including blood pressure, heart rhythm, and mood. We also want to see how the body processes psilocybin (how quickly it is absorbed and cleared) and whether it affects thinking, memory, or wellbeing.

• Primary Objective: Evaluate the safety and tolerability of psychedelic administration in two cohorts of healthy older adults.

  • Cohort 1a Psilocybin Moderate Dose: 2 doses of oral psilocybin (10mg and then 25mg) 30 days apart.
  • Cohort 1b Psilocybin High Dose: 2 doses of oral psilocybin (15mg and then 30mg) 30 days apart.
• Secondary Objectives: Evaluate the pharmacokinetics of Psilocybin for each Cohort of healthy older adults.
• Exploratory Objectives: Evaluate patient-reported outcomes related to Psilocybin administration (e.g., psychedelic experience and well-being) in each Cohort.

Assess the relationships between the pharmacokinetic profile, safety endpoints, and patient-reported outcomes in each Cohort.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Mary P Mancuso, MA (dual degrees); Phone Number: 3037245729; Email: inspire@cuanschutz.edu
• Study Contact Backup: Name: Lila Harris, BS; Email: lila.m.harris@cuanschutz.edu

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94158
      • Recruiting
      • University of California San Francisco (UCSF) Department of Neurology
      • Principal Investigator: Jennifer Mitchell, PhD
      • Contact: Jennifer Mitchell, PhD; Phone Number: 510-985-3522; Email: psy.elder@ucsf.edu
  • Colorado
    • Aurora, Colorado, United States, 80045
      • Recruiting
      • University of Colorado Anschutz Medical Campus
      • Principal Investigator: Stacy Fischer, MD
      • Contact: Mary Mancuso, MS; Phone Number: 3037245729; Email: inspire@cuanschutz.edu
      • Contact: Lila Harris, BA
  • Georgia
    • Atlanta, Georgia, United States, 30329
      • Not yet recruiting
      • Emory University Brain Health Center
      • Contact: Tanja Mletzko, MA; Phone Number: 404-778-6663; Email: study@emory.edu
      • Contact: Joyelle Van Eron, MPH; Phone Number: 404-727-8966; Email: jvanero@emory.edu
      • Principal Investigator: Ali John Zarrabi, MD
  • Massachusetts
    • Boston, Massachusetts, United States, 02215
      • Not yet recruiting
      • Dana-Farber Cancer Institute
      • Principal Investigator: Yvan Beaussant, MD
      • Contact: Gabriel Najarian; Email: patresearch@dfci.harvard.edu
  • Nebraska
    • Omaha, Nebraska, United States, 68105
      • Not yet recruiting
      • University of Nebraska Medical Center
      • Principal Investigator: Lou Lukas, MD
      • Contact: Jennifer Wettschreck, MS; Phone Number: 402.559.3342; Email: jemurray@unmc.edu
  • New York
    • New York, New York, United States, 10016
      • Not yet recruiting
      • New York University Langone Health, Center for Psychedelic Medicine
      • Principal Investigator: Stephen Ross, MD
      • Contact: Denise Balili, MS; Phone Number: 646-501-2623; Email: denise.balili@nyulangone.org

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Older Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Aged 65-85 years & be male, female, or non-binary
• Generally healthy
• Have an identified support person
• Capacity to Consent

Exclusion Criteria:

• Unstable medical condition
• Risk for hypertensive crisis (screening blood pressure >140/90 mmHg)
• Significant central nervous system (CNS) pathology
• Primary psychotic or affective psychotic disorders
• Family history of psychotic or serious bipolar spectrum illnesses
• High risk of adverse emotional or behavioral reaction
• Active substance use disorders (SUDs)
• Extensive use of serotonergic hallucinogens
• High risk of completed suicide
• History of hallucinogen persisting perception disorder (HPPD)
• Concurrent Medications: centrally-acting serotonergic agents; antipsychotics; certain mood stabilizers, aldehyde dehydrogenase inhibitors; significant inhibitors of UGT 1A9 or UGT 1A10
• Certain psychiatric conditions
• Presence of relevant finding (psychological, physical symptom, medication) prior to dosing that would make a participant unsuitable for the study

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Other
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Psilocybin; Two escalating doses of psilocybin 30 days apart	Drug: Psilocybin (Usona Institute); Evaluate the safety and tolerability of psychedelic administration in two cohorts of healthy older adults.; Cohort 1a Psilocybin Moderate Dose: 2 doses of oral psilocybin (10mg and then 25mg) 30 days apart.; Cohort 1b Psilocybin High Dose: 2 doses of oral psilocybin (15mg and then 30mg) 30 days apart.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Adverse Events	Frequency and severity of adverse events; Proportion of participants who complete the intervention, do not advance to the second dose, and who withdraw early from the trial	up to 14 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Total drug exposure (Area Under the Curve, AUC)	Total drug exposure measured with blood samples - Pharmacokinetics	Two separate medication administration days 30 days apart (Week 2 & Week 6 of study participation)
Elimination Half-life	Elimination Half-life measured with blood samples - Pharmacokinetics	Two separate medication administration days 30 days apart (Week 2 & Week 6 of study participation)
Maximum concentration (Cmax)	Maximum plasma concentration (Cmax) measured with blood samples - Pharmacokinetics	Two separate medication administration days 30 days apart (Week 2 & Week 6 of study participation)
Minimum concentration (Cmin)	Minimum plasma concentration (Cmin) measured with blood samples - Pharmacokinetics	Two separate medication administration days 30 days apart (Week 2 & Week 6 of study participation)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Psychedelic Experience (Exploratory)	Psychedelic Experience: Mystical Experience Questionnaire 4-item (Range: 0-20 (4 items × 0-5 each; higher score predicts greater improvement in clinical outcomes); Persisting Effects Questionnaire-4 (Range: 0-32 (4 items × 0-8 each; drug experience measuring meaningfulness, spiritual significance, psychologically challenges, & personal psychological insights gained); Challenging Experience Questionnaire 7-item (Range: 0-42 (7 items × 0-5 each; higher score indicates more challenging experiences related to psychedelic administration); Emotional Breakthrough Inventory (Range: 0-100, 6 items, higher score indicates emotional breakthroughs in psychedelic experiences & predicts post-psychedelic changes in well-being); Awe Experience Scale (Range: 30-210, 30 items × 1-7 each, six factors: vastness, need for accommodation, altered time perception, self-diminishment, connectedness, physical sensation; Stanford Expectations of Treatment Scale Range: 0-24, positive & negative expectations	Enrollment/Baseline study visit, Week 2, and Week 6 of study participation
Well-being & Participant Feedback (Exploratory)	Brief Inventory of Thriving (Brief Inventory of Thriving, Range: 10-50 (10 items × 1-5 each, strongly disagree → strongly agree; Higher scores = greater overall psychological well-being / "thriving" & Participant Feedback Questionnaire, 6 questions, strongly disagree → strongly agree, higher score indicates more positive experience with the study	Enrollment/Baseline study visit, Week 2, Week 6, Week 10, and Week 14 of study participation
Pain (Exploratory, optional)	Pain intensity and tolerance in response to acute noxious stimuli both intensity and the unpleasantness of the sensation. Pin prick task involves the dorsum of the hand to be pricked twice, followed by 2 trains of 10 pricks, 1/second, and 0-100 pain ratings will be collected from 0-10. Cold pressor tasks involves participants submerging their hand in cold water up to 3 minutes and rating pain intensity and unpleasantness every 30 seconds on a 0-100 scale.	Enrollment/Baseline study visit, Week 2, and Week 6 of study participation

Collaborators and Investigators

• Sponsor: University of Colorado, Denver
• Collaborators: Dana-Farber Cancer Institute; NYU Langone Health; Emory University; National Institute on Aging (NIA); University of California, San Francisco; University of Nebraska

Study record dates

Study Major Dates

• Study Start (Actual): April 1, 2026
• Primary Completion (Estimated): March 1, 2028
• Study Completion (Estimated): March 1, 2028

Study Registration Dates

• First Submitted: March 17, 2026
• First Submitted That Met QC Criteria: April 6, 2026
• First Posted (Actual): April 8, 2026

Study Record Updates

• Last Update Posted (Actual): May 11, 2026
• Last Update Submitted That Met QC Criteria: May 7, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: healthy older adults ages 65-85; psilocybin safety; psilocybin tolerability
• Additional Relevant MeSH Terms: Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Indoles; Indole Alkaloids; Indolizidines; Indolizines; Tryptamines; Psilocybin
• Other Study ID Numbers: 25-2070; UG3AG094957 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No