Clinical TrialPTSDPsilocybinPsilocybinActive not recruiting

A Study of Psilocybin for PTSD (PSI-3PO)

Randomized, parallel-group pilot (n=20) testing psilocybin therapy (25 mg initial; second dose conditional up to 40 mg) for adults with chronic PTSD on an SSRI, comparing trauma-focused psychotherapy versus standard psychological support.

Target Enrollment
20 participants
Study Type
Phase I interventional
Design
Randomized

Detailed Description

This randomized, parallel-group study at Johns Hopkins CPCR will evaluate feasibility, safety, and preliminary efficacy of psilocybin-assisted therapy in adults with chronic PTSD who remain on an SSRI.

Participants receive about 8 hours of preparatory meetings, two oral psilocybin sessions approximately two weeks apart (initial 25 mg; second session may remain 25 mg or be escalated to 40 mg based on MEQ30 score, clinician judgement, and participant preference), and multiple integration contacts after each session.

Outcomes include clinician- and participant-rated PTSD and mood measures, safety monitoring (vitals, ECG, labs, AEs), and measures of wellbeing and integration; trial compares trauma-focused psychotherapy plus psilocybin versus psilocybin with standard psychological support.

Study Protocol

Preparation

sessions
480 min each

Dosing

2 sessions
360 min each

Integration

sessions

Therapeutic Protocol

cbtsupport

Study Arms & Interventions

Trauma-focused + psilocybin

experimental

Psilocybin (25 mg initial; second dose conditional up to 40 mg) plus trauma-focused psychotherapy beginning after first psilocybin session.

Interventions

  • Psilocybin25 - 40 mg
    via Oral• two sessions• 2 doses total

    Second session dose escalated to 40 mg if MEQ30 score <60% or by clinical judgement; participant may decline escalation.

  • Compound
    via Other• throughout study

    Trauma-focused psychotherapy (includes Cognitive Processing Therapy and in vivo exposure) begins after first psilocybin session.

  • Compound
    via Other• throughout study

    Standard psychological support (empathic support and session integration) provided to all participants.

Standard support + psilocybin

active comparator

Psilocybin (same dosing schedule) with standard psychological support only.

Interventions

  • Psilocybin25 - 40 mg
    via Oral• two sessions• 2 doses total

    Second session dose escalated to 40 mg if MEQ30 score <60% or by clinical judgement; participant may decline escalation.

  • Compound
    via Other• throughout study

    Standard psychological support (integration and emotional support) provided to participants.

Participants

Ages
21 – 75
Sexes
Male & Female

Inclusion Criteria

  • Be at least 21 years old
  • Have given written informed consent
  • Have a confirmed DSM-5 diagnosis of Post-Traumatic Stress Disorder with symptom duration >= 6 months
  • Have a baseline CAPS-5 score of >=35
  • Currently taking a serotonin reuptake inhibitor (SSRI or SNRI) at a stable dose for at least 3 months
  • Be judged by study team clinicians to be at low acute risk for suicidality
  • Be medically stable as determined by screening (medical interview, questionnaire, physical exam, ECG, routine labs)
  • Agree to consume approximately the same amount of caffeine on session mornings as usual (or abstain if not a routine consumer)
  • Agree to refrain from alcohol, anxiolytics, stimulants, sedatives/hypnotics, opioids, dissociatives, cannabinoids, or other unapproved substances within 24 hours of psilocybin administration (caffeine and nicotine exceptions)
  • Agree not to take PRN medications on mornings of drug sessions
  • Agree to stop taking 5HT2A antagonist medications at least 5 half-lives before dosing
  • Agree not to take sildenafil, tadalafil, or similar within 72 hours of dosing
  • Have no classic psychedelic use in the past five years
  • Have at least a high school level of education or equivalent
  • Weigh at least 40 kg
  • (For female participants) Agree to use highly effective birth control within two weeks before and after dosing
  • (For male participants) Agree to use contraception and refrain from sperm donation two weeks before and after dosing

Exclusion Criteria

  • General medical exclusion criteria:
  • Women who are pregnant or nursing; women of child-bearing potential not using effective birth control
  • Cardiovascular conditions: coronary artery disease, stroke, angina, hypertension with resting BP systolic >139 or diastolic >89, clinically significant ECG abnormality, prolonged QTc (>450 msec), artificial heart valve, or TIA in past year
  • Family history of Torsades de Pointes and sudden cardiac death
  • Epilepsy with history of seizures
  • Insulin-dependent diabetes; if on oral hypoglycemics, then no history of hypoglycaemia
  • Currently taking a Monoamine Oxidase Inhibitor
  • Psychiatric Exclusion Criteria:
  • Current or past history of schizophrenia spectrum or other psychotic disorders, or Bipolar I or II Disorder
  • Current or history within one year of severe alcohol, tobacco, or other drug use disorder (excluding caffeine)
  • Current or history within one year of Borderline Personality Disorder
  • First-degree relative with schizophrenia spectrum or other psychotic disorders or Bipolar I
  • Psychiatric condition judged incompatible with rapport or safe exposure to psilocybin
  • History of a medically significant suicide attempt
  • Unwilling or unable to pause concurrent psychotherapy during the study
  • Determined to be at risk for re-exposure to the index trauma or other significant trauma in daily life

Study Details

  • Status
    Active not recruiting
  • Phase
    Phase I
  • Type
    interventional
  • Design
    Randomized
  • Target Enrollment20 participants
  • Timeline
    Start: 2024-05-01
    End: 2027-05-31
  • Compounds
    PsilocybinPsilocybin
  • Topic
    PTSD

Locations

Johns Hopkins Center for Psychedelic and Consciousness Research — Baltimore, Maryland, United States

Your Library