Recruiting
Early Phase 1

Psilocybin

Sponsor:

Johns Hopkins University

Code:

NCT07565493

Conditions

Psychedelic Effects in Healthy Volunteers

Eligibility Criteria

Sex: All

Age: 21 - 60

Healthy Volunteers: Accepted

Interventions

Pindolol

Placebo

Psilocybin

Study Details

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

Study ID

NCT07565493

Start date

Aug 12, 2026

Status verified date

Aug, 2026

Completion date

Jun 15, 2028

Anticipated

Primary completion date

Jun 15, 2028

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 21 - 60

Healthy Volunteers: Accepted

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 Design

Enrollment

18 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

placebo comparator: Psilocybin co-administered with placebo

Psilocybin will be co-administered with microcrystalline cellulose placebo.

experimental: Psilocybin co-administered with pindolol

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

Interventions

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.

Placebo

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

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.

Primary outcome measure

  • Mystical Experiences Questionnaire [ Time Frame: From the first dosing session to the end of the second dosing session, approximately 10 days ]

Central Contacts and Locations

Central contacts

Zarmeen Zahid, PhD

667-208-8099psilblock1@jh.edu

Locations

Center for Psychedelics and Consciousness Research

Recruiting

Baltimore, Maryland, United States, 21224-5010

Contacts

Zarmeen Zahid, PhD

667-208-8099psilblock1@jh.edu

Principal Investigator:

Sandeep M Nayak, MD

More Information

Sponsor

Johns Hopkins University

Last update posted

Aug 14, 2026

Last verified

Aug, 2026

Keywords

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

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Johns Hopkins University on 2026-08-14.