Clinical TrialTreatment-Resistant Depression (TRD)PsilocybinPsilocybinRecruiting

Psilocybin-Assisted Therapy in Treatment-Resistant Depression

Phase III randomised, parallel-group trial (n≈23) comparing one vs two 25 mg psilocybin-assisted therapy sessions for treatment-resistant depression with preparatory and integration therapy.

Target Enrollment
23 participants
Study Type
Phase III interventional
Design
Randomized, single Blind

Detailed Description

Randomized, parallel-group study comparing a single 25 mg psilocybin session to two 25 mg sessions spaced two weeks apart in adults with treatment-resistant major depressive disorder; all participants receive preparatory and integration psychotherapy.

Outcomes include change in depressive symptoms over 12 months, durability of response, safety and tolerability. Participants undergo screening, preparation visits, dosing sessions, and follow-up assessments over one year.

Study Protocol

Preparation

sessions

Dosing

2 sessions

Integration

sessions

Therapeutic Protocol

Manualized psychotherapy included

Study Arms & Interventions

Single psilocybin

experimental

One 25 mg oral psilocybin session with preparation and integration therapy.

Interventions

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

    25 mg capsule with preparatory and integration therapy

Two psilocybin

active comparator

Two 25 mg oral psilocybin sessions spaced two weeks apart with preparation and integration therapy.

Interventions

  • Psilocybin25 mg
    via Oral• two sessions• 2 doses total

    25 mg capsule per session, sessions spaced two weeks apart

Participants

Ages
18 – 70
Sexes
Male & Female

Inclusion Criteria

  • Provision of signed and dated informed consent form.
  • Willingness to comply with all study procedures and availability for the study.
  • DSM-5 diagnosis of major depressive disorder.
  • Currently experiencing a major depressive episode, lasting at least 3 months.
  • Failure to respond or inability to tolerate at least 2 guideline-concordant pharmacological treatments from different pharmacologic classes during the current major depressive episode.
  • Good health evidenced by medical history and routine lab tests.
  • No central nervous system (CNS) or neurocognitive impairment.
  • Ability to take oral medication and to follow the psilocybin-assisted therapy protocol.
  • Identified support person to accompany patient home after dosing.
  • Use of effective contraception throughout the study by those with child-bearing potential.
  • Use of condoms or other effective contraceptive methods by males with reproductive potential.
  • Fully vaccinated and up to date on COVID-19 vaccination as defined by CDC guidelines.
  • Following lifestyle considerations throughout study (no nicotine-containing products in clinical unit; refrain from operating heavy machinery for the duration of treatment day; no more than two servings 8 hours prior to treatment; no psychoactive drugs 72 hours before treatment; refrain from consuming foods that would interfere with drug absorption; minimise interaction with household immunocompromised contacts).

Exclusion Criteria

  • Family history (first- or second-degree relatives) or diagnosis of bipolar disorder with psychotic features, schizophrenia, schizoaffective disorder, hallucinogen-induced psychosis, antisocial personality disorder, or other psychotic disorder.
  • Borderline personality disorder that in the judgement of the Investigator is likely to complicate assessment or limit compliance.
  • Alcohol or other substance use disorder (except tobacco/nicotine) active within 6 months prior to enrollment.
  • Recent use (within past 4 weeks) of esketamine, ketamine or classic hallucinogens (psilocybin-containing mushrooms or LSD) or use of psychedelics within the past 6 months or more than 10 times in lifetime.
  • Participants with active suicidal ideation or plan with a Columbia Suicide Severity Rating Scale (C-SSRS) score ≥ 4.
  • Current active self-injurious behaviour requiring medical attention or per investigator discretion.
  • Diagnosis of OCD or PTSD.
  • Within 72 hours of psilocybin administration, use of nicotine, alcohol, or other controlled substances.
  • Current delirium, dementia, amnestic disorder, or other cognitive disorders.
  • Any current or past medical or neurological illness that may confound interpretation of assessments.
  • Known allergic reactions to components of psilocybin.
  • Medical instability at screening including hepatic, renal, circulatory, cardiac (arrhythmia, uncontrolled hypertension, systolic BP > 140 mmHg or diastolic BP > 90 mmHg, abnormal QTc), pulmonary or CNS (seizure disorder or treatment with antiepileptic drugs) impairment.
  • Current pregnancy or lactation.
  • Febrile illness in last 3 weeks.
  • Current use or use within 4 weeks of psilocybin administration of MAOIs, alcohol dehydrogenase inhibitors and antipsychotics (concomitant medications allowed per investigator discretion).
  • Current treatment with bupropion > 300 mg/day.
  • Current use of tramadol.
  • Prior participation in psilocybin-assisted therapy trial and/or regular use of hallucinogens.
  • Treatment with another investigational drug or other intervention during study period.

Study Details

Locations

UNC Chapel Hill Medical Center — Chapel Hill, North Carolina, United States

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