Safety for Home Administration of Microdose Psilocybin Use

NCT06450210 | Recruiting Phase 1 FDA Drug

• 1 other identifier: IRB00422973
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this laboratory study is to establish whether and which microdoses of psilocybin are safe to administer at home to healthy participants. Eligible participants will be given ascending doses of psilocybin trihydrate and a single, interspersed, randomized placebo on separate days in double-blind fashion. The participants will be asked to complete questionnaires and undergo safety assessments.

Conditions

Psychedelic Experiences

Outcome Measures

Primary Outcomes (4)

• Systolic and Diastolic Blood pressure (mmHg)

  Blood pressure will be measured at 60, 120, 180, and 240 minutes. A dose will be deemed safe for home dosing if participants do not have elevations in blood pressure beyond threshold values; systolic blood pressure \> 150 mmHg, diastolic blood pressure \> 90mmHg) at any timepoint.

  Baseline, 1-4 hours post dose

• Heart rate in beats per minute (bpm)

  Heart rate will be measured at 60, 120, 180, and 240 minutes. A dose will be deemed safe for home dosing if participants do not have elevations in heart rate beyond threshold value of \> 110 bpm

  Baseline; 1-4 hours post dose

• Field sobriety testing

  The standardized battery of field sobriety tests includes: The Walk-and-Turn (W\&T), One-Leg Stand (OLS), Horizontal Gaze Nystagmus (HGN). A dose will be deemed safe for home dosing if participants pass field sobriety testing at time of expected peak psilocybin effects. The cumulative amount of clues observed across these tasks (out of a possible 22 clues) will be reported.

  Baseline; 90 minutes post dose

• Number of participants with normal or abnormal psychological status as assessed by a psychiatric mental status exam

  The Psychiatric Mental Status Exam will be a clinical interview identical to that performed by psychiatrists in daily clinical practice and will assess and document the participant's mood, affect, thought process (including the presence of formal thought disorder), paranoia, delusions, hallucinations, other perceptual alterations, speech (including rate, volume, prosody, whether or not speech is pressured), suicidal thoughts, and orientation to person, place and time. A dose will be deemed safe for home dosing if there is no evidence of abnormal psychological status on a psychiatric mental status exam performed by a blinded study psychiatrist. There is no formal scoring rubric for this outcome. A psychiatrist will use their clinical judgment to evaluate whether a participant has normal or abnormal psychological status based on a clinical interview.

  120 minutes post dose

Secondary Outcomes (1)

• Driving Performance as assessed by The Systems Technology, Inc. Simulation (STISIM) Drive® M4000-R Console

  Baseline; 60 minutes post dose

Study Arms (5)

1.2 mg psilocybin trihydrate microdose

EXPERIMENTAL

Participants will receive a single microdose of 1.2 mg psilocybin trihydrate via oral capsule in the laboratory in double-blind fashion.

Drug: psilocybin trihydrate

2.0 mg psilocybin trihydrate microdose

EXPERIMENTAL

Participants will receive a single microdose of 2.0 mg psilocybin trihydrate via oral capsule in the laboratory in double-blind fashion.

Drug: psilocybin trihydrate

3.0 mg psilocybin trihydrate microdose

EXPERIMENTAL

Participants will receive a single microdose of 3.0 mg psilocybin trihydrate via oral capsule in the laboratory in double-blind fashion.

Drug: psilocybin trihydrate

4.2 mg psilocybin trihydrate microdose

EXPERIMENTAL

Participants will receive a single microdose of 4.2 mg psilocybin trihydrate via oral capsule in the laboratory in double-blind fashion.

Drug: psilocybin trihydrate

Placebo

PLACEBO COMPARATOR

Participants will receive a single placebo oral capsule in the laboratory in double-blind fashion.

Drug: Placebo

Interventions

psilocybin trihydrate DRUG

Microdoses of psilocybin trihydrate will be administered to participants (1.2 mg, 2.0 mg, 3.0 mg, and 4.2 mg).

1.2 mg psilocybin trihydrate microdose; 2.0 mg psilocybin trihydrate microdose; 3.0 mg psilocybin trihydrate microdose; 4.2 mg psilocybin trihydrate microdose

Placebo DRUG

Participants will receive a capsule identical in appearance to the active drug that contains an inactive substance.

Placebo

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• to 60 years old
• Have given written informed consent
• Have at least a high-school level of education or equivalent (e.g. GED) and be fluent in English
• Be healthy and psychologically stable as determined by screening for medical and psychiatric problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests
• Agree to refrain from using any psychoactive drugs, including alcoholic beverages and nicotine, within 24 hours of each drug administration. The exception is caffeine.
• Agree not to take any as needed (PRN) medications on the mornings of drug sessions
• Agree not to take sildenafil (Viagra®), tadalafil, or similar medications within 72 hours of each drug administration.
• Agree that for one week before each drug session, he/she will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except when approved by the study investigators. Exceptions will be evaluated by the study investigators and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals.
• Licensed to drive (for driving simulator test).

You may not qualify if:

• Women who are pregnant (as indicated by a positive urine pregnancy test assessed at intake and before each drug session) or nursing; women who are of child-bearing potential and sexually active who are not practicing an effective means of birth control.
• Cardiovascular conditions: coronary artery disease, stroke, angina, uncontrolled hypertension, a clinically significant ECG abnormality (e.g. atrial fibrillation, corrected QT interval (QTc) \> 450 msec), artificial heart valve, or transient ischemic attack (TIA) in the past year
• Epilepsy
• Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
• Currently taking psychoactive drugs (prescribed or not) on a daily basis. This includes nicotine but excepts caffeine.
• Currently taking on a regular (e.g. daily) basis any medications having a centrally-acting serotonergic effect, including monoamine oxidase inhibitors (MAOIs). For individuals who have intermittent or PRN use of such medications, psilocybin sessions will not be conducted until at least five half-lives of the agent have elapsed after the last dose.
• More than 20% outside the upper or lower range of ideal body weight according to Metropolitan Life height and weight table
• History of schizophrenia spectrum disorder
• History of bipolar I disorder
• History of substance induced psychotic disorder
• Current history of meeting Diagnostic and Statistical Manual (DSM)-5 criteria for a moderate or severe alcohol or drug use disorder (excluding caffeine and nicotine)
• Have a first degree relative with bipolar I disorder, or schizophrenia spectrum disorder.
• Cardiovascular screening: To qualify for the study, blood pressure at screening will be less than 130 mmHg systolic, 80 mmHg diastolic, and 90 beats per minute; mean heart rate must also be no less than 40 beats per minute. Blood pressure will be taken while subjects are at rest and have been seated or supine for at least 5 minutes.

Sponsors & Collaborators

• Johns Hopkins University: lead
• Private Philanthropic Funds: collaborator

Study Sites (1)

5510 Nathan Shock Drive

Baltimore, Maryland, 21224, United States

RECRUITING

Study Officials

• Sandeep M. Nayak, MD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Matthew Nielsen Dick

CONTACT

410-999-8066; microdose@jh.edu

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: This is a double-blind study. Participants will be told they will receive a range of psilocybin doses (maximum 4.2 mg) and "at least one" dose of placebo. This will control for expectancy effects on cognitive testing and questionnaires.
• Purpose: OTHER
• Intervention Model: SEQUENTIAL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 4, 2024
• First Posted: June 10, 2024
• Study Start: December 6, 2024
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): July 1, 2027
• Last Updated: February 23, 2026

Record last verified: 2026-02

Locations

US (1)