Investigating the Persisting Effects of a Single Dose of Psilocybin on Structural Plasticity in Healthy Older Adults

NCT06367738 | Recruiting Phase 1 FDA Drug

• 1 other identifier: 2024-11-14799
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 1

Brief Summary

Participants in this study will undergo a series of non-invasive tests and activities designed to understand how a single dose of psilocybin might influence cognition and emotional well-being in healthy older adults. After providing written informed consent, eligible participants, aged between 60 and 85, will be randomly assigned to receive a dose of psilocybin ranging from a microdose to a moderate-to-high dose. Anatomical magnetic resonance imaging (MRI) and diffusion weighted imaging (DWI) will be used to assess changes in brain structure, while functional magnetic resonance imaging (fMRI) will be used to quantify changes in functional brain activity.

Conditions

Aging

Outcome Measures

Primary Outcomes (1)

• MRI measurements of brain structure

  Diffusion-weighted MRI will be used to measure mean diffusivity in prefrontal cortex and hippocampus.

  Baseline, week 1, and week 4

Secondary Outcomes (33)

• Amplitude and pattern of fMRI cortical responses

  Baseline, week 1, and week 4

• Vagus nerve reactivity

  Baseline, week 1, and week 4

• Perceptual measurements

  Baseline, week 1, and week 4

• Penn Conditional Exclusion Test (PCET)

  Baseline, week 1, and week 4

• California Verbal Learning Test, Second Ed. (CVLT-II)

  Baseline, week 1, and week 4

Study Arms (3)

Psilocybin Level 1

EXPERIMENTAL

The effects of different doses of psilocybin (1 - 10 mg) will be compared.

Drug: Psilocybin

Psilocybin Level 2

EXPERIMENTAL

Psilocybin (11 - 20 mg) will be administered.

Drug: Psilocybin

Psilocybin Level 3

EXPERIMENTAL

Psilocybin (21 - 30 mg) will be administered.

Drug: Psilocybin

Interventions

Psilocybin DRUG

Psilocybin 1-30 mg

Psilocybin Level 1; Psilocybin Level 2; Psilocybin Level 3

Eligibility Criteria

• Age: 60 Years - 85 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Are 60-85 years of age at time of Informed Consent Form signing. Are able and willing to adhere to study requirements, including attending all study visits, preparatory and follow-up sessions, and completing all study evaluations.
• Are able to swallow capsules. Women of childbearing potential (WOCBP) must agree to practice an effective means of birth control throughout the duration of the study.
• Have normal or corrected-to-normal vision as determined by the study staff. Written informed consent obtained from and ability for subject to comply with the requirements of the study.
• Have an identified support person and agree to be accompanied home (or to an otherwise safe destination) by the support person, or another responsible party, following dosing.
• Agree to inform the investigators within 48 hours of any new or changed medical conditions during the course of their study participation.
• Have access to a quiet space and a computer to perform online assessments.

You may not qualify if:

• Breastfeeding, have a positive pregnancy test at screening or at any point during the course of the study, or unwilling to practice birth control during participation in the study.
• Have a current psychiatric disorder, general medical condition, or other problem or abnormality that, in the opinion of the study clinician or PI, could compromise safety, render them unsuitable for the study, or would make them unable to comply with study activities.
• Have MRI contraindications (e.g., metal implants, pacemakers, claustrophobia etc.) as determined by an MRI contraindications questionnaire.
• Have a history of recent, clinically significant suicidal ideation or behavior.
• Have a history of a psychotic disorder, bipolar disorder (type I or II), or a dissociative disorder (determined by history).
• History of Hallucinogen Persisting Perception Disorder (HPPD). History of a seizure disorder in adulthood, central nervous system (CNS) metastases or current symptomatic CNS infection.
• History of intracerebral hemorrhage, embolic stroke, transient ischemic attack (TIA), or history of any aneurysmal vascular disease (including thoracic and abdominal aorta, intracranial and peripheral arterial vessels) or arteriovenous malformation.
• History of valvulopathy or pulmonary hypertension. Uncontrolled hypertension (Systolic BP\>139mmHG or Diastolic BP\>89mmHG) or tachycardia (average HR\>90bpm) averaged over at least two measurements.
• Clinically significant cardiovascular disease (e.g., history of myocardial infarction or congestive heart failure); or baseline QT/QTc\>500msec; or baseline QT/QTc 451-500msec with repeat QT/QTc \>500msec.
• Poorly controlled diabetes mellitus (e.g., history of an episode of severe hypoglycemia or hospitalization for hyperglycemia on the current diabetes regimen).
• Inadequate hepatic function as determined by total bilirubin or alkaline phosphatase \>3x institutional upper limit of normal; or AST or ALT \>6x institutional upper limit of normal. However, participants with Gilbert syndrome are allowed to enroll.
• Inadequate renal function as determined by eGFR \< 30 mL/min/1.73 m2 (based on the MDRD equation) or CrCl \< 30 mL/min (based on the C-G equation).
• The regular use of psychotropic medications, such as antidepressants (i.e., SSRIs, tricyclic antidepressants, and monoamine oxidase inhibitors), antipsychotics, and mood stabilizers.
• The use of Prohibited Medications:
• Serotonin Reuptake Inhibitors (SSRIs and SNRIs) Tricyclic Antidepressants (TCAs) Monoamine Oxidase Inhibitors (MAOIs) Atypical antidepressants (e.g., mirtazapine, trazodone, buspar) Antipsychotics/Neuroleptics (typical and atypical) Anti-epileptics or mood stabilizers (e.g., lithium, valproate) (does not include gabapentin used for non-epilepsy conditions) Efavirenz (Sustiva, in Atripla) Lorcaserin Over-the-counter supplements intended to affect mood or anxiety (e.g., 5HT-P, SAMe or St. John's Wort).

Sponsors & Collaborators

• University of California, Berkeley: lead

Study Sites (1)

University of California, Berkeley

Berkeley, California, 94720, United States

RECRUITING

MeSH Terms

Interventions

Psilocybin

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Central Study Contacts

BCSP Research Staff

CONTACT

(669) 244-2436; bcspresearchsubjects@berkeley.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 11, 2024
• First Posted: April 16, 2024
• Study Start: November 1, 2025
• Primary Completion (Estimated): December 30, 2026
• Study Completion (Estimated): December 30, 2027
• Last Updated: October 21, 2025

Record last verified: 2025-10

Locations

US (1)