Clinical TrialDepressive DisordersPsilocybinRecruiting

Open-Label Psilocybin

This open-label, Phase Ib clinical trial (n=50) will investigate the safety, feasibility, and tolerability of a single dose of oral psilocybin (25 mg) in individuals with functional impairment due to psychiatric symptoms, including mood, anxiety, trauma, or addiction.

Target Enrollment
50 participants
Study Type
Phase I interventional
Design
Non-randomized

Detailed Description

Phase 1b, open-label, single-arm trial assessing safety, feasibility and tolerability of a single oral 25 mg dose of psilocybin in people with psychiatric symptom-related functional impairment; DSM-5 diagnosis is not required and comorbidity is permitted to mirror real-world complexity.

All participants receive one dosing session with non-directive psychological support before, during, and after administration; follow-up assessments occur at 1, 4, and 6 weeks, with optional long-term follow-up at 3, 6, and 12 months.

Safety evaluations include C-SSRS, vitals, ECG, laboratory tests, and adverse event monitoring at acute and follow-up visits; descriptive analyses will summarise safety and feasibility outcomes, screening failure and dropout rates.

Study Protocol

Preparation

sessions

Dosing

1 sessions

Integration

sessions

Study Arms & Interventions

Open-label

experimental

Single treatment arm: one oral dose of psilocybin 25 mg with non-directive support before, during, and after dosing.

Interventions

  • Psilocybin25 mg
    via Oral• single dose• 1 doses total

    Opaque size 2 gelatin capsule administered with ~180 ml water at dosing visit.

Participants

Ages
18 – 70
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 1. At least one psychiatric symptom causing functional impairment over the past 30 days as established by a trained rater on the DIAMOND (at least "mild" impairment) and/or the WHODAS-2.0 12-item (a raw score of >16) - assessment instruments indexing health and disability.
  • 2. English fluency - able to understand the process of consent and the risks and benefits associated with the study, and able to provide written (signed and dated) informed consent form.
  • 3. Agree to set up safe transportation after leaving the site following the dosing session (friend/family escort or study-arranged private transport).
  • 4. Must be able to identify a physician/treater who can be contacted and agree to sign a medical release for investigator communication to confirm treatment and medical history.
  • 5. Ability to orally ingest pills for psilocybin dosing visit.
  • 6. Must provide an adult contact willing and able to be reached by study personnel in the event of an emergency and who can comment on changes in mood or behaviour after psilocybin administration.
  • 7. Be medically stable as determined by screening (medical history, physical exam, ECG, routine labs and urinalysis) and demonstrate decisional capacity to consent.
  • 8. Psychologically stable: concurrent psychotherapy allowed if type and frequency stable for at least one month prior to screening and expected to remain stable through 4 weeks post-dosing.
  • 9. Childbearing potential participants must agree to use adequate birth control and have a negative urine pregnancy test at screening and prior to dosing; avoid pregnancy and egg donation from 1 month before dosing to 1 week after final follow-up.

Exclusion Criteria

  • Exclusion Criteria:
  • Psychiatric Exclusion Criteria:
  • 1. Personal history of a primary psychotic disorder (e.g., schizophrenia, delusional disorder, schizoaffective disorder) or Bipolar I disorder, or at least one first-degree relative with a diagnosis of primary psychotic disorder or Bipolar I disorder.
  • 2. Active suicidal intent or suicidal or non-suicidal self-injurious behaviours, as defined by a "yes" response to question 4 on the C-SSRS within the past 6 months at screening or prior to dosing (Active Suicidal Ideation with Some Intent to Act, with or without Specific Plan).
  • 3. Use of a classic psychedelic (LSD, psilocybin, DMT, mescaline) within 3 months prior to enrollment (not including microdosing).
  • 4. Use of ketamine within the past month at screening.
  • 5. History of regular and frequent use of a classic psychedelic (>10 times per year in structured settings over past 10 years).
  • 6. History of Other Hallucinogen Use Disorder.
  • 7. History of intolerance to drugs known to significantly alter perception (psilocybin, LSD, salvinorin A, mescaline).
  • 8. Patients taking 5-hydroxytryptophan or St. John's Wort.
  • 9. A positive breathalyzer test.
  • 10. A positive urine toxicology screen for the standard panel (marijuana, cocaine, opioids/opiates, amphetamines, PCP), benzodiazepines, or MDMA; exceptions for prescribed opioids and benzodiazepines; cannabis permitted but must be abstinent day before, day of, and day after dosing.
  • 11. Changes to psychotropic medication or dosages within the past 3 months.
  • 12. Current or recent (within 2 weeks) prescription of MAOI, lithium, and/or methadone.
  • 13. Psychiatric condition that precludes establishment of therapeutic rapport (eg, long-term unstable relationships, significant stress-related paranoia, identity disturbance).
  • 14. Use of any other investigational drug within 30 days prior to screening.
  • 15. Allergy to gelatin.
  • General Medical/Laboratory Exclusion Criteria:
  • 1. Hypertension at screening: systolic >140 mmHg or diastolic >90 mmHg on the lowest of three measurements.
  • 2. History of cardiovascular disease (eg, coronary artery disease, cardiac hypertrophy, ischemia, heart failure, myocardial infarction, angina, coronary bypass, artificial heart valve, stroke, TIA, clinically significant arrhythmia).
  • 3. Clinically significant abnormal ECG (ischemia/infarct signs, complete bundle branch block, atrial fibrillation, symptomatic arrhythmias, predominantly non-sinus rhythm).
  • 4. Resting QTcF ≥450 msec (male) or ≥470 msec (female) at screening, or inability to determine QTcF.
  • 5. Presence of risk factors for torsades de pointes (long QT syndrome, uncontrolled hypokalaemia/hypomagnesaemia, history of cardiac failure, clinically significant bradycardia, family history of sudden death or congenital long QT, concomitant torsadogenic medication).
  • 6. Moderate-to-severe hepatic impairment (Child-Pugh ≥5, ALT/AST >2x ULN, bilirubin >1.5x ULN) unless due to Gilbert's syndrome.
  • 7. Use of vasoconstrictive medications (eg, sumatriptan, pseudoephedrine, midodrine) within 5 half-lives of test days, or recent steroids/immunomodulators in past 2 weeks.
  • 8. Moderate-to-severe renal impairment (eGFR <50 mL/min/1.73 m2).
  • 9. Uncontrolled diabetes with HbA1c >8.
  • 10. Significant uncontrolled thyroid disease as specified in protocol.
  • Any other condition or finding that in the investigator's opinion would adversely impact participant safety or ability to complete study procedures.

Study Details

  • Status
    Recruiting
  • Phase
    Phase I
  • Type
    interventional
  • Design
    Non-randomized
  • Target Enrollment50 participants
  • Timeline
    Start: 2024-07-01
    End: 2027-07-31
  • Compound
    Psilocybin
  • Topic
    Depressive Disorders

Locations

Connecticut Mental Health Center - Yale School of Medicine — New Haven, Connecticut, United States

Your Library