Psilocybin and Methylenedioxymethamphetamine (MDMA) for Post-traumatic Stress Disorder (PTSD)

Incidence of Adverse Events

Participants will be asked how the participant has been feeling since the last visit and will be asked about incidence of any adverse events (AEs) since the last visit. In addition to monitoring any spontaneously reported AEs at each study visit, participants will also be queried specifically if the participant has experienced any return of drug-like (i.e., MDMA or psilocybin) effects or other AEs the participant suspects to be drug-related at all meetings occurring after the first dosing session. A serious adverse event (SAE) will be defined as either: a death or a life-threatening occurrence, including hospitalization; incarceration; new onset of a significant medical disorder; or significant exacerbation of an existing medical disorder. All AEs and SAEs will be monitored closely by the study team to guide appropriate follow-up and all AEs and SAEs will be documented and followed to resolution.

The Columbia Suicide Severity Rating Scale (C-SSRS)

The Columbia Suicide Severity Rating Scale (C-SSRS) will be used to assess severity of suicide ideation during every study visit. Suicidal Ideation Intensity scale (0-25 score range summed from five items, with higher scores indicating more severe suicidal ideation).

Clinician-Administered PTSD Scale for Diagnostic and Statistical Manual-5 (CAPS-5)

The CAPS-5 assessment consists of 30 items that are designed to measure the frequency and intensity of PTSD symptoms, covering all 20 Diagnostic and Statistical Manual-5 (DSM-5) PTSD symptoms. Each item is scored on a 5-point scale (0, absent - 4, extreme/incapacitating). Score ranges from 0 to 80 with higher scores indicating higher symptom severity.

PTSD Checklist (PCL-5)

The PTSD Checklist for DSM-5 is a self-report psychometric instrument widely employed in both clinical and research settings to assess the presence and severity of PTSD symptoms as outlined in the DSM-5. The PCL-5's 20 items correspond to the DSM-5 symptom criteria for PTSD. This version of the PCL-5 will assess symptoms within the preceding week. PCL-5 questionnaires will be administered to participants via email (not clinician-administered). It is scored by summing the responses to 20 items, each rated on a 5-point scale (0-4), resulting in a total score ranging from 0 to 80. A higher score indicates greater severity of PTSD symptoms.

Clinical Global Impression (CGI-I) Scale

The CGI-I scale ranges from 1 to 7 (1=very much improved; 2=much improved, 3=minimally Improved, 4=no change, 5=minimally worse, 6= much worse, and 7=very much worse).

Patient global impression of improvement (PGI-I)

The PGI-I was developed for use in National Institute of Mental Health sponsored clinical trials in order to broadly define participant progress/improvement. The PGI-I scale is a 7-point scale used to assess a patient's perception of condition's change, typically after a treatment or intervention. The scale ranges from 1 to 7, with 1 representing "very much improved" and 7 representing "very much worse."

The Sheehan Disability (SDS) Scale

The Sheehan Disability (SDS) Scale will be used to assess functional impairment in three domains of disability that can be impaired during depression: work/school, social, and family life. It uses a Likert scale from 0 to 10, with higher scores indicating greater functional impairment. The total SDS score ranges from 0 to 30.