Psilocybin Administration With 5-HT1a Blockade

NCT07565493 | Not Yet Recruiting Early Phase 1 FDA Drug

• 1 other identifier: IRB00478908
• Study Type: interventional
• Target: 18
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to assess the effects of 5-HT1A receptor blockade on the acute subjective effects of psilocybin, as measured through subjective survey measures and acute electroencephalography (EEG). Further, the investigators will assess the effects of psilocybin on post-acute sleep and dreaming through the use of sleep EEG and sleep and dream diaries.

Conditions

Psychedelic Effects in Healthy Volunteers

Keywords

Psilocybin; Sleep; Dreaming; EEG; 5-HT1A; Antagonism; Altered state of consciousness; Subjective experience; Serotonin receptor; Psychedelic

Outcome Measures

Primary Outcomes (1)

• Mystical Experiences Questionnaire

  Assess changes in intensity of the subjective effects induced by psilocybin with co-administration of a 5-HT1A antagonist, pindolol as measured through the mystical experience questionnaire. Scores can range from 0-150 with a higher score indicating a more intense mystical-type experience.

  From the first dosing session to the end of the second dosing session, approximately 10 days

Secondary Outcomes (1)

• Change in alpha power (Spectral Power)

  From the first dosing session to the end of the second dosing session, approximately 10 days

Study Arms (2)

Psilocybin co-administered with placebo

PLACEBO COMPARATOR

Psilocybin will be co-administered with microcrystalline cellulose placebo.

Drug: Placebo; Drug: Psilocybin

Psilocybin co-administered with pindolol

EXPERIMENTAL

Psilocybin will be co-administered with 5-HT1A antagonist pindolol.

Drug: Pindolol; Drug: Psilocybin

Interventions

Pindolol DRUG

Pindolol is a 5-HT1A antagonist drug that will be used as a pharmacological probe for the mechanism of acute subjective effects in the altered state of consciousness induced by psilocybin.

Psilocybin co-administered with pindolol

Placebo DRUG

Microcrystalline cellulose capsules, identical in appearance to the active treatment, containing no pharmacologically active ingredients, will be administered as an inert placebo comparator.

Also known as: Microcrystalline cellulose placebo

Psilocybin co-administered with placebo

Psilocybin DRUG

Psilocybin is a tryptamine psychedelic with 5-HT2A agonist activity. The psilocybin-induced altered state of consciousness is characterized by changes in sensory perception, cognition, and induction of mystical-type experiences. These subjective effects will be assessed in each dosing session.

Psilocybin co-administered with pindolol; Psilocybin co-administered with placebo

Eligibility Criteria

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

You may qualify if:

• years old
• Must give written or electronic informed consent
• Must have at least a high-school level of education or equivalent (e.g. GED) and are fluent in English
• Must 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
• Must agree not to take any as needed (PRN) medications on the mornings of drug sessions
• Must agree not to take sildenafil (Viagra®), tadalafil, or similar medications within 72 hours of each drug administration.
• Must agree to refrain from using all psychoactive substances within 24 hours or 5 elimination half-lives (whichever is greater) before psilocybin administration. Caffeine is the exception.
• Must have a negative urine toxicology report on the same day as drug dosing.
• Who are female and of child-bearing potential and are sexually active, must agree to use highly effective means of birth control (i.e. implants, injectables, combined oral contraceptives, progestin-containing intrauterine device (IUD) or vasectomized partner) for the duration of this study.
• Who are male and sexually active, must agree to use contraception and refrain from sperm donation within 90 days of completing dosing sessions. Effective methods of contraception are barrier, hormonal, and sterilization methods.

You may not qualify if:

• Are currently taking a medication with any significant pharmacokinetic or pharmacodynamic interactions with pindolol (e.g. beta-blockers or other anti-hypertensive medications).
• Have a history of orthostatic hypotension or low blood-pressure.
• Have elevated transaminases (2x the upper limit of normal)
• Have a Child-Pugh score that falls within classes B or C.
• Are pregnant (as indicated by a positive urine pregnancy test assessed at intake and before each drug session) or nursing.
• Have 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, symptomatic valvopathy, history of pulmonary hypertension or transient ischemic attack (TIA) in the past year; systolic blood pressure \> 139, diastolic blood pressure \> 89
• Have epilepsy or a history of seizures
• Have insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
• Are 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.
• Have a current diagnosis of schizophrenia spectrum disorders
• Have a current diagnosis of bipolar spectrum disorders
• Have a current diagnosis of major depressive disorder or Generalized Anxiety Disorder
• Have a current diagnosis or history of substance induced psychotic disorder
• Have a current DSM-5 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.

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Center for Psychedelics and Consciousness Research

Baltimore, Maryland, 21224-5010, United States

Location

Related Publications (1)

• Strassman RJ. Human psychopharmacology of N,N-dimethyltryptamine. Behav Brain Res. 1996;73(1-2):121-4. doi: 10.1016/0166-4328(96)00081-2.

  PMID: 8788488 BACKGROUND

MeSH Terms

Interventions

Pindolol; Psilocybin

Intervention Hierarchy (Ancestors)

Phenoxypropanolamines; Propanolamines; Amino Alcohols; Alcohols; Organic Chemicals; Propanols; Amines; Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Sandeep M Nayak, MD

  Center for Psychedelics and Consciousness Research

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Zarmeen Zahid, PhD

CONTACT

667-208-8099; zzahid2@jh.edu

Study Design

• Study Type: interventional
• Phase: early phase 1
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Within subjects crossover design with 2 conditions: Psilocybin co-administered with placebo, and psilocybin co-administered with pindolol.

Study Record Dates

• First Submitted: April 27, 2026
• First Posted: May 4, 2026
• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): June 15, 2028
• Study Completion (Estimated): June 15, 2028
• Last Updated: May 5, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: ANALYTIC CODE

Locations

US (1)