A Pilot Mechanistic RCT of Psilocybin With Mindfulness-based Therapy vs Support for Posttraumatic Stress Disorder (PTSD)
The goal of this study is to learn how psilocybin delivered with mindfulness-based therapy may help symptoms of posttraumatic stress disorder (PTSD). This is an assessor-blinded, randomized, controlled study in participants with PTSD. The study will investigate the changes in brain activity, connectivity, and microstructural neuroplasticity assessed using EEG/EMG and multimodal MRI measures after administration of one oral dose of psilocybin, accompanied either with standard psychological support only; or with standard support plus Mindfulness-based Cognitive Therapy (MBCT).
⁃ Participants meeting the following criteria will be included in the study:
• Participant is assigned female or male at birth.
• Participant is aged between 21 to 65 years, inclusive, at Screening. This is to reduce variability in brain function and connectivity in this small pilot study that may be related to age / developmental factors in persons under 21 and over 65.
• Participant has a BMI of 18 to 30 kg/m2, inclusive, at Screening.
• Participant has a diagnosis of PTSD (as defined in the Diagnostic and Statistical Manual of Mental Disorders, 5th edition \[DSM-5\] established through a clinician interview that includes the Mini-International Neuropsychiatric Interview \[MINI\]) and the Clinician Administered PTSD Scale for DSM-5 (CAPS-5).
• PTSD severity moderate to severe based on CAPS-5 score ≥25, and with moderate depression MADRS ≥20.
• Participants capable of producing sperm must use a condom during the trial and for 3 months after their dose of trial medication, if their partner is a person of childbearing potential. In addition, their partner of childbearing potential must also use a highly effective method of contraception (i.e., failure rate less than 1% when used consistently and correctly) from dosing until 3 months following dosing. Condoms alone and abstinence are not considered highly effective methods of contraception.
• Participants of childbearing potential must agree to use a highly effective method of contraception (i.e., failure rate less than 1% when used consistently and correctly) in combination with use of a condom by a partner who is capable of producing sperm, during the trial and for 3 months after dosing. Condoms alone and abstinence are not considered highly effective methods of contraception. Such participants must have a negative pregnancy test at Screening and Day 1.
• Participants of non-childbearing potential who are or were capable of producing eggs (ova) must be postmenopausal or permanently sterile following hysterectomy, bilateral salpingectomy or bilateral oophorectomy. Postmenopausal is defined as spontaneous amenorrhea for at least 12 months, and a serum follicle stimulating hormone (FSH) level in the menopausal range, unless the participant is taking hormone replacement therapy or is using hormonal contraception.
• Provision of giving written informed consent, which includes compliance with the requirements and restrictions listed in the consent form.
⁃ If appropriate, describe why certain populations may be excluded (e.g., non-English speaking individuals for studies involving informed consent).