Clinical TrialMajor Depressive Disorder (MDD)PsilocybinPlaceboUnknown status

Evaluation of Psilocybin-Assisted Psychotherapy in Treating Severe Depression in Patients With PTSD

This randomized, double-blind, placebo-controlled study (n=160) aims to evaluate the safety, tolerability, and efficacy of Psilocybin-Assisted Psychotherapy (APEX-002-A02) in treating severe depression among adults with Post-Traumatic Stress Disorder (PTSD).

Target Enrollment
160 participants
Study Type
Phase II interventional
Design
Randomized, quadruple Blind

Detailed Description

Randomized, quadruple-blind, parallel-group trial (n=160) comparing a single active psilocybin formulation (APEX-002-A02) versus matched placebo, administered with psychotherapeutic support to adults with PTSD and severe depression.

Rationale: psilocybin has demonstrated preliminary efficacy and an acceptable safety profile for depressive symptoms across prior studies; this trial evaluates its effect on severe depression in the context of chronic PTSD.

Key eligibility: adults 18–65 with DSM-5 PTSD ≥6 months, CAPS-5 ≥35, and BDI-II ≥30; exclusions include psychosis/bipolar history, first-degree relatives with schizophrenia/bipolar, unstable medical illness, and recent suicidal behaviour per C-SSRS.

Study Protocol

Preparation

sessions

Dosing

sessions

Integration

sessions

Therapeutic Protocol

Manualized psychotherapy included

Study Arms & Interventions

APEX-002-A02

experimental

APEX-002-A02 (psilocybin)

Interventions

  • Psilocybin

    APEX-002-A02 (psilocybin); dose not specified in registry fragment.

Placebo

inactive

matched placebo

Interventions

  • Placebo

    matched placebo

Participants

Ages
18 – 65
Sexes
Male & Female

Inclusion Criteria

  • Inclusion Criteria:
  • 1. Individuals between 18 and 65 years of age, inclusive, at the time of consent.
  • 2. Individuals who are fluent in the language of the study site, specifically English or French.
  • 3. Meet DSM-5 criteria for current PTSD with presence of symptoms for at least 6 months at screening.
  • 4. Participant must have at least moderate PTSD, as scored as ≥35 on the CAPS-5 scale at screening.
  • 5. Participant must have severe depression, as scored as ≥30 on the BDI-II scale at screening.
  • 6. If individuals are on psychotropic medications, they must be on stable doses (no dosing adjustments/changes for ≥4 weeks) prior to beginning of the study and for the duration of the study.
  • 7. If individuals are users of psychoactive substances, including alcoholic beverages, tobacco, and cannabis, they must remain on stable doses for the duration of the study.
  • 8. For individuals of childbearing potential involved in any sexual intercourse that could lead to pregnancy: willing to use adequate birth control to prevent pregnancy (in participant or partner) for the entire duration of the study.
  • 9. Capable of providing ongoing, signed informed consent.
  • 10. Available for the duration of the study, and able and willing to comply with all study procedures, including completion of questionnaires.
  • 11. Agree to identify a local contact person to the research team, that is available over the entire course of the subject's participation in the study to act as an emergency contact.

Exclusion Criteria

  • Exclusion Criteria:
  • 1. Female subject that is pregnant, is planning or suspected to become pregnant, or is lactating.
  • 2. Known or suspected hypersensitivity or contraindication to psilocybin or any constituents or excipients of the study drug.
  • 3. Abnormal and clinically significant results on the physical examination, vital signs, ECG or laboratory tests at screening.
  • 4. Presence of any unstable medical condition or neurological illness, in the opinion of the Investigator.
  • 5. History of clinically significant cardiovascular disease including but not limited to stroke, myocardial infarction or clinically significant arrhythmia (in the past 1 year).
  • 6. Indication of inadequately treated current hypertension (resting systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg) at screening.
  • 7. If a subject is being treated with inhibitor(s) of UGT1A9, UGT1A10, monoamine oxidase (MAO), aldehyde dehydrogenase (ALDH), or alcohol dehydrogenase (ADH) they should be discontinued at least five half lives prior to administration of study drug.
  • 8. Lifetime history of psychosis-related disorder or bipolar disorder (I or II).
  • 9. Subject has 1st degree relative(s) with schizophrenia or bipolar disorder.
  • 10. At the time of screening, any condition other than PTSD judged to be the primary presenting psychiatric diagnosis, in the opinion of the Investigator.
  • 11. Clinical diagnosis of dementia or any physical, cognitive, or language impairment of such severity as to adversely affect the validity of the data derived from the patient reported outcomes.
  • 12. History of any other clinically significant pulmonary, gastrointestinal, hepatic, renal or any other major concurrent illness that, in the opinion of the investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if he/she takes part in the study.
  • 13. Individuals who present a current risk to themselves or others, as assessed by the Investigator. This includes, but is not limited to:
  • 1. Active suicidal ideation with specific plan and intent in the past 1 month, as assessed with the C-SSRS at screening.
  • 2. History of suicidal behavior (actual attempt, interrupted attempt, aborted or self-interrupted attempt, preparatory acts or behavior) in the past 3 months, as assessed with the C-SSRS at screening.
  • 3. Any prior suicidal ideation/behavior that, per the Investigator's judgment, makes the participant unsuitable for the study.
  • 14. Current active Substance Use Disorder or Alcohol Use Disorder, as assessed by the Investigator via medical screening.
  • 15. Individuals with other personal circumstances and behaviour judged to impact safety (risk and not be able to adhere to the protocol requirements).
  • 16. Individuals with significant prior exposure to psilocybin, defined as:
  • 1. Chronic use (>10 exposures) of psilocybin in any form and at any dose in the past year; OR
  • 2. Any use of psilocybin within 4 weeks prior to screening; OR
  • 3. Any previous use of psilocybin for PTSD or related symptoms, including depression, that was discontinued due to lack of effect, as judged by the individual or their treating physician.
  • 17. Self reported use within 12 weeks prior to screening of (i) classical psychedelics other than psilocybin (LSD, mescaline, dimethyltryptamine); (ii) MDMA; (iii) ketamine, and; (iv) dextromethorphan.
  • 18. Actively participating in other interventional clinical trial(s).

Study Details

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