Mindfulness-based Psilocybin Therapy for PTSD
Phase II, assessor-blinded, randomised controlled trial (n=30) of a single 25 mg oral synthetic psilocybin dose given with either standard psychological support or psychological support plus MBCT in adults with PTSD.
Detailed Description
This study evaluates whether adding Mindfulness-based Cognitive Therapy (MBCT) to standard psychedelic-assisted therapy (PAT) with a single 25 mg oral psilocybin dose improves PTSD symptoms, neurophysiology and neuroplasticity versus psilocybin with non-directive support.
Design: initial open-label pilot of 10 participants receiving psilocybin + MBCT to refine the intervention, followed by a randomised, assessor-blinded parallel comparison of 20 participants (psilocybin + MBCT vs psilocybin + support). Assessments at baseline, Day 2 and Day 28 include EEG/EMG, fMRI/DWI, CAPS-5, MADRS, C-SSRS and self-report measures.
Safety measures and medication restrictions (e.g., no recent MAOI, specific ECG and lab criteria) are used to reduce risk; contraceptive requirements apply for participants of childbearing potential.
Study Protocol
Preparation
Dosing
Integration
Therapeutic Protocol
Study Arms & Interventions
Psilocybin + MBCT
experimentalSingle 25 mg oral psilocybin with psychological support plus MBCT sessions before, during and after dosing (open-label pilot then randomised phase).
Interventions
- Psilocybin25 mgvia Oral• single dose• 1 doses total
Synthetic psilocybin capsule; paired with MBCT and PAT psychological support.
Psilocybin + support
active comparatorSingle 25 mg oral psilocybin with non-directive PAT psychological support only.
Interventions
- Psilocybin25 mgvia Oral• single dose• 1 doses total
Synthetic psilocybin capsule; paired with standard PAT psychological support.
Participants
Inclusion Criteria
- Inclusion Criteria:
- 1. Participant is assigned female or male at birth.
- 2. Participant is aged between 21 to 65 years, inclusive, at Screening.
- 3. Participant has a BMI of 18 to 35 kg/m2, inclusive, at Screening.
- 4. Participant is ≥60 kg.
- 5. Participant has a diagnosis of PTSD (DSM-5) established through clinician interview including the MINI and CAPS-5.
- 6. PTSD severity moderate to severe based on CAPS score ≥24.
- 7. Depression severity moderate to severe based on MADRS score ≥21.
- 9. Participant has been on a stable dose (no more than 50% change) of antidepressant medication (SSRI) in the last month prior to Screening.
- 10. Participants capable of producing sperm must use a condom during the trial and for 3 months after dosing; partner must use highly effective contraception.
- 11. Participants of childbearing potential must use a highly effective method of contraception and have negative pregnancy test at Screening and Day 1.
- 12. Participants of non-childbearing potential must be postmenopausal or permanently sterile as defined in protocol.
- 13. Provision of written informed consent.
Exclusion Criteria
- Exclusion Criteria:
- 1. Taking buspirone or venlafaxine in past month.
- 2. Current or previous schizophrenia spectrum or other psychotic disorders; current or previous history of bipolar disorder; current personality disorder (per MINI).
- 3. Clinically significant risk of suicidality as determined by psychiatric interview including C-SSRS; C-SSRS suicidal ideation subscale score ≥4 in past 6 months or any lifetime suicidal behaviour is exclusionary.
- 4. History of substance use disorder within 12 months, or intake of >21 units alcohol weekly; inability to refrain from alcohol from 48 hours before Screening until discharge.
- 5. Currently receiving an MAOI, tricyclic, non-SSRI/SNRI antidepressant (e.g., bupropion, mirtazapine), antipsychotic or mood stabiliser.
- 6. Exposure to psilocybin or other psychedelics >10 times in last 10 years, or any psychedelic use within 6 months prior to Screening.
- 7. Use of psychotropic medicines/supplements that interact with psilocybin during 28 days before dosing (stable chronic antidepressant allowed case-by-case).
- 8. Family history of schizophrenia or schizoaffective disorder (first-degree), or bipolar I (first-degree).
- 9. Clinically relevant physical health conditions interfering with study participation.
- 10. History or presence of organic brain disorders associated with seizures.
- 11. Diagnosis of hypertension or arrhythmia.
- 12. Abnormal resting vitals out of range (HR>100 bpm or SBP>140 or DBP>90) at screening.
- 13. Clinically significant ECG abnormalities at Screening.
- 14. QTcF >450 ms at Screening.
- 15. Hypothyroidism or abnormal thyroid function tests not corrected.
- 16. Clinically relevant abnormal labs (hepatic, renal, CBC, chemistry) at Screening.
- 17. Other circumstances or behaviours judged by Investigator to interfere with safe participation.
- 18. Conditions affecting ADME of study drug.
- 19. Any other concomitant disease or condition posing unacceptable risk per Investigator.
- 20. Not fluent in English.
- 21. AST, ALT, GGT or total bilirubin ≥1.5x ULN at Screening.
- 22. Positive urine drug screen or breath alcohol at Screening or Day 1 (cannabinoids may be reviewed case-by-case).
- 23. Excessive caffeine/(methyl)xanthine consumption per Investigator discretion.
- 24. Participation in another clinical study with investigational medication within 3 months prior to dosing.
- 25. Known sensitivity to psilocin or excipients; known fructose intolerance related to vehicle.
- 26. Use of MAO inhibitors within 28 days prior to administration.
- 27. Use of OTC 5-HTP or St John's Wort within 28 days prior to administration.
- 28. Strenuous exercise within 48 hours prior to visits.
- 29. Participants who will not abstain from sperm donation between dosing and 3 months after final dosing.
- 30. Pregnant, breastfeeding or planning conception if of childbearing potential.
Study Details
- StatusNot yet recruiting
- PhasePhase II
- Typeinterventional
- DesignRandomizedsingle Blind
- Target Enrollment30 participants
- TimelineStart: 2025-11-01End: 2029-12-01
- Compounds
- Topic