Clinical TrialPTSDPsilocybinPsilocybinPsilocybinPsilocybinPsilocybinWithdrawn

Safety and Tolerability of Psilocybin in Post-Traumatic Stress Disorder

Phase I, non-randomised, sequential 3-session psilocybin-assisted psychotherapy study (n=30) using 3+3 dose-escalation sequences (doses 15→45 mg) to evaluate safety, tolerability, and preliminary efficacy for PTSD.

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

Detailed Description

This Phase I, non-randomised sequential trial will enrol up to 30 participants with PTSD to receive psilocybin-assisted psychotherapy across three dosing sessions approximately two weeks apart. A 3+3 dose-escalation framework evaluates predefined dose sequences ranging from 15 mg to 45 mg.

Safety and tolerability will be assessed after each session and at 1-month, 3-month, and 6-month follow-ups; efficacy endpoints include change in PTSD symptom severity measured by clinician- and self-report instruments.

Key exclusions include current suicidality, psychotic or bipolar I disorder, significant cardiovascular or neurologic illness, and recent or extensive hallucinogen use.

Study Protocol

Preparation

sessions

Dosing

3 sessions

Integration

sessions

Therapeutic Protocol

Manualized psychotherapy included

Study Arms & Interventions

Dose Sequence 1 (15, 20, 25)

experimental

Psilocybin dose sequence: Session 1: 15 mg; Session 2: 20 mg; Session 3: 25 mg.

Interventions

  • Psilocybin15 - 25 mg
    via Oral• three sessions• 3 doses total

    Sessions ~2 weeks apart

Dose Sequence 2 (20, 25, 30)

experimental

Psilocybin dose sequence: Session 1: 20 mg; Session 2: 25 mg; Session 3: 30 mg.

Interventions

  • Psilocybin20 - 30 mg
    via Oral• three sessions• 3 doses total

    Sessions ~2 weeks apart

Dose Sequence 3 (25, 30, 35)

experimental

Psilocybin dose sequence: Session 1: 25 mg; Session 2: 30 mg; Session 3: 35 mg.

Interventions

  • Psilocybin25 - 35 mg
    via Oral• three sessions• 3 doses total

    Sessions ~2 weeks apart

Dose Sequence 4 (30, 35, 40)

experimental

Psilocybin dose sequence: Session 1: 30 mg; Session 2: 35 mg; Session 3: 40 mg.

Interventions

  • Psilocybin30 - 40 mg
    via Oral• three sessions• 3 doses total

    Sessions ~2 weeks apart

Dose Sequence 5 (35, 40, 45)

experimental

Psilocybin dose sequence: Session 1: 35 mg; Session 2: 40 mg; Session 3: 45 mg.

Interventions

  • Psilocybin35 - 45 mg
    via Oral• three sessions• 3 doses total

    Sessions ~2 weeks apart

Participants

Ages
18 – 80
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 18 to 80 years old. Participants up to 80 years old who otherwise meet safety criteria will be included.
  • Have given written informed consent
  • Read, write, and speak English
  • At Screening, meet DSM-5 criteria for current PTSD with a symptom duration of 6 months or longer according to the CAPS-5
  • Able to complete the study measures
  • Previously sought treatment for PTSD (e.g., prolonged exposure therapy, cognitive processing therapy, sertraline, paroxetine)
  • Be otherwise medically stable as determined by screening (medical interview, questionnaire, physical exam, ECG, routine labs).

Exclusion Criteria

  • Exclusion Criteria:
  • Current physical dependence (other than caffeine or nicotine)
  • Seizure disorder
  • Receiving current treatment for PTSD
  • Cardiovascular conditions: angina, clinically significant ECG abnormality (e.g., atrial fibrillation or QTc >450 ms), TIA in last 6 months, stroke, or uncontrolled hypertension (resting BP systolic >150 or diastolic >95)
  • Recent (<1 year) intracranial or subarachnoid hemorrhage, ischemic stroke, TIA
  • Pulmonary disease: COPD, active asthma (inhaler use in last 6 months)
  • Diabetes mellitus treated with insulin or oral hypoglycemics
  • Current suicidal ideation or suicidality
  • Current engagement in evidence-based PTSD therapy/treatment (prior to psilocybin session)
  • Women: pregnancy (pregnancy tests will be conducted during screen and prior to sessions)
  • Current or past history of DSM-5 Schizophrenia, Psychotic Disorder (unless substance-induced/medical), or Bipolar I Disorder
  • Currently taking efavirenz or serotonin-acting dietary supplements (e.g., 5-HTP, St John's wort)
  • Currently taking antidepressants of any class, antipsychotics, or MAOIs
  • Recent (within 12 months) or extensive history of hallucinogen use (>20 lifetime uses)
  • Moderate or severe DSM-5 Substance Use Disorder in past five years (excluding tobacco and caffeine)
  • Family (1st-degree) history of Schizophrenia, Psychotic Disorder (unless substance-induced/medical)
  • For the final (5th) dose sequence (35, 40, 45 mg) participants that weigh less than 50 kg

Study Details

Locations

United States

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