Psilocybin Administration With 5-HT1a Blockade (PsilBlock1)

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: Not yet recruiting
• Conditions: Psychedelic Effects in Healthy Volunteers
• Intervention / Treatment: Drug: Placebo; Drug: Psilocybin; Drug: Pindolol

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: Interventional
• Enrollment (Estimated): 18
• Phase: Early Phase 1

Contacts and Locations

• Study Contact: Name: Zarmeen Zahid, PhD; Phone Number: 667-208-8099; Email: zzahid2@jh.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21224-5010
      • Center for Psychedelics and Consciousness Research
      • Principal Investigator: Sandeep M Nayak, MD
      • Contact: Zarmeen Zahid, PhD; Phone Number: 667-208-8099; Email: zzahid2@jh.edu
      • Sub-Investigator: Zarmeen Zahid, PhD

Participation Criteria

Eligibility Criteria

• 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

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
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

Outcome Measure	Measure Description	Time Frame
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 Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in alpha power (Spectral Power)	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

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Sandeep M Nayak, MD, Center for Psychedelics and Consciousness Research

Publications and helpful links

General Publications

• 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.

Study record dates

Study Major Dates

• Study Start (Estimated): June 15, 2026
• Primary Completion (Estimated): June 15, 2028
• Study Completion (Estimated): June 15, 2028

Study Registration Dates

• First Submitted: April 27, 2026
• First Submitted That Met QC Criteria: April 27, 2026
• First Posted (Actual): May 4, 2026

Study Record Updates

• Last Update Posted (Actual): May 5, 2026
• Last Update Submitted That Met QC Criteria: May 1, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Keywords: Sleep; EEG; Psilocybin; Psychedelic; Subjective experience; Dreaming; 5-HT1A; Antagonism; Altered state of consciousness; Serotonin receptor
• Additional Relevant MeSH Terms: Organic Chemicals; Heterocyclic Compounds; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Alkaloids; Amines; Indoles; Alcohols; Indole Alkaloids; Indolizidines; Indolizines; Phenoxypropanolamines; Propanolamines; Amino Alcohols; Propanols; Tryptamines; Psilocybin; Pindolol
• Other Study ID 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