A Study of Psychedelics in Healthy Older Adults With Low Well-being

NCT07386730 | Not Yet Recruiting Phase 1 FDA Drug

• 2 other identifiers: 25-45261A146672
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief Summary

This study is being conducted to understand changes in brain activity following administration of two different drugs (Psilocybin and Dextromethorphan) in older adults with low well-being. The main questions it aims to answer are, does psilocybin:

• A low-to-moderate dose of Psilocybin (5-10 mg)
• A moderate-to-high dose of Psilocybin (25-30 mg)
• A low-to-moderate dose of Dextromethorphan (30-60 mg)
• A moderate-to-high dose of Dextromethorphan (80-90 mg)

Conditions

Anhedonia in Healthy Volunteers; Older Adults (50-90 Years)

Keywords

Psilocybin; Dextromethorphan; older adults; well-being; EEG; MRI; neuroinflammation; Alzheimer's disease plasma markers; wearables

Outcome Measures

Primary Outcomes (1)

• Acute changes in EEG-based ESBA

  Compare acute changes in EEG-based Lempel Ziv complexity (pre- to post-dose, arbitrary unit) between the four study arms, with the presence of biomarkers of AD pathology used in the statistical analyses as a moderator. Lempel-Ziv complexity in EEG is a non-linear analysis tool that quantifies the amount of entropy of spontaneous brain activity (ESBA).

  Pre- to post-dose two hours later

Secondary Outcomes (1)

• Changes in TNF-alpha

  Screening to three weeks post dosing

Study Arms (4)

A low-to-moderate dose of Psilocybin (5-10 mg)

EXPERIMENTAL

A single low-to-moderate dose of Psilocybin (5-10 mg)

Drug: Psilocybin (drug)

A moderate-to-high dose of Psilocybin (25-30 mg)

EXPERIMENTAL

A single moderate-to-high dose of Psilocybin (25-30 mg)

Drug: Psilocybin (drug)

A low-to-moderate dose of Dextromethorphan (30-60 mg)

EXPERIMENTAL

A single low-to-moderate dose of Dextromethorphan (30-60 mg)

Drug: Dextromethorphan (DXM)

A moderate-to-high dose of Dextromethorphan (80-90 mg)

EXPERIMENTAL

A single moderate-to-high dose of Dextromethorphan (80-90 mg)

Drug: Dextromethorphan (DXM)

Interventions

Dextromethorphan (DXM) DRUG

Participants will receive either Psilocybin or Dextromethorphan in this clinical trial

A low-to-moderate dose of Dextromethorphan (30-60 mg); A moderate-to-high dose of Dextromethorphan (80-90 mg)

Psilocybin (drug) DRUG

Participants will receive either Psilocybin or Dextromethorphan in this clinical trial

A low-to-moderate dose of Psilocybin (5-10 mg); A moderate-to-high dose of Psilocybin (25-30 mg)

Eligibility Criteria

• Age: 50 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are between 50-85 years inclusive at time of consent signing
• Have below-average well-being, defined by the World Health Organization Well-Being Index (WHO-5)
• Have no cognitive impairments, indicated by a Mini-Mental State Examination (MMSE) score \>24
• Have an identified willing contact person with at least weekly contact with the participant to be able to provide meaningful information about the participant's daily function and able to pick up the study participant at the end of the Dosing Visit
• Participants assigned female sex at birth must be non-lactating, and post-menopausal, defined as a period of over 12 months since the last menstrual period, or otherwise physically unable to become pregnant
• Participants assigned male sex at birth must 1) refrain from sperm donation for 3 months after the Dosing Visit, and 2) if engaging in sexual activities that may result in pregnancy, must use a condom, plus their partner of childbearing potential must use a second, highly effective form of contraception for 3 months after the Dosing Visit
• Be proficient in English
• Are able and willing to provide consent as assessed by comprehension questions in informed consent process
• Stated willingness to comply with all study procedures and availability for the duration of the study
• Ability to swallow oral medications (capsules)

You may not qualify if:

• General:
• Have a known allergic or severe reaction to Psilocybin, Dextromethorphan, or any of the non-active components of the IMP capsules
• Insufficient ability to report on symptoms to make a valid assessment on any required instrument
• Have a condition or presence of clinical feature which, in the opinion of the investigators might interfere with or prevent appropriate study participation or interfere with data interpretation
• Any implanted object or device that poses a safety risk or could interfere with MRI scanning (e.g. aneurysm clips, cardiac pacemakers, defibrillators, neurostimulators, cochlear implants, spinal cord stimulators, insulin or infusion pumps, metallic prostheses or fragments, heart valves, vascular stents, or shunts. surgical staples, clips, or joint replacements, radiation seeds, medication patches containing metal, or any other metallic or electronic implants)
• History of metallic injury to the eyes or body, or those with tattoos containing metallic ink, permanent makeup, or body piercings that cannot be removed.
• Any condition that poses a safety risk or could interfere with MRI scanning (e.g. severe claustrophobia or motion disorders or breathing problems, etc)
• Psychiatric:
• History of hallucinogen persisting perception disorder (HPPD) (as per DSM-5 criteria)
• Cardiovascular:
• Clinically significant cardiovascular conditions e.g., clinically significant EKG abnormalities, transient ischemic attack in the last 6 months, history of hemorrhagic stroke, history of myocardial infarction within 1 year of signing informed consent form (ICF)
• Baseline (heart rate \< 60 bpm or \> 90 bpm at screening or pre-dose
• Baseline hypertension (≥140 SBP or ≥90 DBP), after repeated measurements
• QTc Interval \> 450msec on 12-lead EKG. Note: If QT-prolonging medications are started or increased in dose after enrollment and prior to dosing visit, a repeat EKG must be done \>12-hours after this change to assure continued safe enrollment in the trial
• Clinically significant arrhythmia (e.g., uncontrolled atrial fibrillation, or untreated supraventricular tachycardia)

Sponsors & Collaborators

• Jennifer Mitchell: lead

Study Sites (1)

University of California San Francisco, Sandler Neuroscience Building

San Francisco, California, 94158, United States

Location

MeSH Terms

Conditions

Neuroinflammatory Diseases

Interventions

Psilocybin; Pharmaceutical Preparations; Dextromethorphan

Condition Hierarchy (Ancestors)

Nervous System Diseases; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Morphinans; Opiate Alkaloids; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Phenanthrenes; Polycyclic Aromatic Hydrocarbons; Polycyclic Compounds

Study Officials

• Lorenzo Pasquini, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

• Jennifer Mitchell, PhD

  University of California, San Francisco

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Gabriella Mace

CONTACT

415-707-5399; agingandpsychedelics@ucsf.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Professor

Study Record Dates

• First Submitted: January 20, 2026
• First Posted: February 4, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): February 1, 2030
• Study Completion (Estimated): February 1, 2030
• Last Updated: May 4, 2026

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)