Mindfulness-based Psilocybin Therapy for PTSD

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.

Participants

Ages

21 – 65

Sexes

Male & Female

BMI

18 - 35

Psychosis History

Excluded

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.

Company

Product

Legal

Detailed Description

Study Protocol

Preparation

Dosing

Integration

Therapeutic Protocol

Study Arms & Interventions

Psilocybin + MBCT

Interventions

Psilocybin + support

Interventions

Participants

Inclusion Criteria

Exclusion Criteria

Study Details