Clinical TrialCrossoverHealthy VolunteersPlaceboPsilocybinPlaceboPsilocybinNot yet recruiting

Psilocybin Administration With 5-HT1a Blockade

This early Phase I, randomised, triple-blind, crossover trial (n=18) will evaluate whether 5-HT1A receptor blockade alters the acute subjective effects of psilocybin in healthy volunteers. Participants will receive psilocybin with either pindolol or placebo, with the study focused on subjective survey outcomes, acute electroencephalography (EEG), and the mechanistic basis of the altered state of consciousness induced by psilocybin. In each dosing session, participants will be given a moderate dose of psilocybin trihydrate 18 mg (equivalent to 15 mg psilocybin anhydrate) together with pindolol 30 mg or a microcrystalline cellulose placebo. The study will also examine post-acute sleep and dreaming using sleep EEG, sleep diaries, and dream diaries, collected for 10 days before and 10 days after each drug administration session, alongside at-home sleep EEG recordings for 5 days before and 5 days after each session. The primary outcome is the Mystical Experiences Questionnaire, assessed from the first dosing session to the end of the second dosing session, over approximately 10 days.

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Target Enrollment
18 participants
Study Type
Phase I interventional
Design
Randomized, triple Blind

Detailed Description

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 Arms & Interventions

Psilocybin co-administered with placebo

inactive

Psilocybin will be co-administered with microcrystalline cellulose placebo.

Interventions

  • Placebo
    • single dose
  • Psilocybin18 mg
    • single dose

Psilocybin co-administered with pindolol

experimental

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

Interventions

  • Placebo30 mg
    • single dose

    Unmatched intervention: Pindolol

  • Psilocybin18 mg
    • single dose

Participants

Ages
21 – 60
Sexes
Male & Female

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 Details

Study Team

Sponsors & Collaborators

Investigators

  • SN
    Sandeep Nayak

Locations

Center for Psychedelics and Consciousness Research — Baltimore, Maryland, United States