Psilocybin Administration With 5-HT1a Blockade (PsilBlock1)

September 11, 2026 updated by: Johns Hopkins University
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

This double-blind, randomized, cross-over study (N = 18) will administer a moderate dose of psilocybin trihydrate (18 mg, equivalent to 15 mg psilocybin anhydrate), with pindolol (30 mg), or placebo to assess the effects of 5-HT1A receptor blockade on the acute subjective effects and the acute neurophysiological effects of psilocybin through the use of self-report measures and acute EEG. Participants will also complete sleep and dream diaries 10 days prior to and 10 days following each drug administration session as well as wear an at-home sleep EEG device for 5 days prior to and 5 days following each drug session. This study aims to understand the mechanistic basis of the perceptual changes in the altered state of consciousness induced by psilocybin as well as its effects on post-acute sleep and dreaming.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
18

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Early Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • Maryland
      • Baltimore, Maryland, United States, 21224-5010
        • Recruiting
        • Center for Psychedelics and Consciousness Research
        • Principal Investigator:
          • Sandeep M Nayak, MD
        • Sub-Investigator:
          • Zarmeen Zahid, PhD
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult

Accepts Healthy Volunteers

Yes

Description

Inclusion criteria:

  • 21 - 60 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.

Exclusion Criteria:

  • 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.
  • Have a psychiatric condition judged to be incompatible with establishment of safe exposure to psilocybin.
  • Have a BMI ≥ 40
  • Report a known history of sleep apnea, symptoms indicative of sleep apnea, or have an Apnea-Hypopnea Index (AHI) > 15, or STOP BANG >5
  • Taking prescribed hypnotics or other medications known to alter sleep physiology: i.e., Z-drugs, Benzodiazepines, Orexin Agonists or Antagonist, Beta Blockers.
  • Regularly taking over-the-counter sleep aids (inc. melatonin and diphenhydramine) and unwilling to abstain during the study.
  • Insomnia Severity Index ≥ 10

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: Psilocybin co-administered with placebo
Psilocybin will be co-administered with microcrystalline cellulose placebo.
Drug: Placebo
Microcrystalline cellulose capsules, identical in appearance to the active treatment, containing no pharmacologically active ingredients, will be administered as an inert placebo comparator.
Other Names:
  • Microcrystalline cellulose placebo
Drug: Psilocybin
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.
Experimental: Psilocybin co-administered with pindolol
Psilocybin will be co-administered with 5-HT1A antagonist pindolol.
Drug: Psilocybin
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.
Drug: Pindolol
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mystical Experiences Questionnaire
Time Frame: From the first dosing session to the end of the second dosing session, approximately 10 days
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 Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
Change in alpha power (Spectral Power)
Time Frame: From the first dosing session to the end of the second dosing session, approximately 10 days
Assess changes in neural measures of drug intensity acutely using EEG, specifically global change in alpha power.
From the first dosing session to the end of the second dosing session, approximately 10 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Johns Hopkins University

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Sandeep M Nayak, MD, Center for Psychedelics and Consciousness Research

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
August 12, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
June 15, 2028

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
June 15, 2028

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 27, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 27, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
May 4, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
September 14, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 11, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
September 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • IRB00478908

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

YES

IPD Plan Description

De-identified data with no participant information will be shared on an open science platform to allow for independent analysis by other researchers. Subjective survey data, acute EEG, and sleep EEG data will be shared.

IPD Sharing Supporting Information Type

  • ANALYTIC_CODE

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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