Investigation to Understand and Optimize Psilocybin

Montgomery-Åsberg Depression Rating Scale (MADRS) score

The MADRS is a 10-item depression rating scale that includes questions on the following symptoms: 1. Reported sadness, 2. Apparent sadness, 3. Inner tension, 4. Reduced sleep, 5. Reduced appetite, 6. Concentration difficulties, 7. Lassitude, 8. Inability to feel, 9. Pessimistic thoughts, and 10. Suicidal thoughts. Items are scored via a blinded clinical interview and rated to capture the patient's clinical state over the prior week. Each item yields a score of 0 to 6, and higher scores indicate more severe depression. The overall score ranges from 0 to 60. For this study, the structured MADRS interview will be used.

PROMIS Ability to Participate in Social Roles and Activities - Short Form 8a

An 8-item validated measure assessing an individual's perceived ability to engage in social roles and activities, such as work, family responsibilities, and leisure. Participants rate each item on a 5-point Likert scale. Total score can range from 8 to 40 with higher scores indicating greater functional ability and social participation.

Quality of Life Enjoyment and Satisfaction Questionnaire Short-Form (Q-LES-Q) score

The Short Form version (Q-LES-Q-SF) will be used in this trial. The measure contains 16 items that assess quality of life. A total score is derived from summing the first 14 items on the scale, with the last 2 items serving as stand-alone queries. Total score can range from 14 to 70 with higher scores indicating better quality of life.

Electronically Activated Recorder (EAR)

The EAR is a naturalistic observation method that uses an audio recording app worn by subjects to silently and unobtrusively record short samples of ambient sounds while subjects go about their daily lives. These recordings can then be transcribed for subjects' natural daily speech, as well as coded for a wide range of aspects of subjects' objectively assessed locations, activities, conversations, social environments, and other behaviors. In the present study, the EAR allows us to measure how subjects' daily behaviors, activities and social interactions change over the course of the study.

Voicediary

Voicediaries will be collected via the Fabla Voicediary App. The app will collect brief speech samples from subjects' talking about (a) the events of their days and (b) retrospective reflections on their experience of psilocybin (after dosing).

Ecological Momentary Assessment (EMA)

EMA will be conducted via the Fabla Voicediary app. The app will send notifications to subjects' smartphones for assessments three times per day. Each item on the assessments will include 2 slider-type items assessing valence and arousal, 3 free response items assessing current context, 2 items assessing connectedness, 1 item assessing sense of meaning, and 2 collaboratively developed items that are personalized to the subject. In addition, one end-of-day assessment will also include 1 item about hours of sleep the previous night, 1 item about substance use in the past 24 hours, and 1 item asking whether subjects have had conversations about their upcoming (during pre-dosing) or past (during post-dosing) psilocybin experiences, and with whom.

Challenging Experiences Questionnaire (CEQ) score

The CEQ is a 26-item questionnaire that consists of seven factors of challenging experience with psilocybin mushrooms: fear, grief, feeling of losing your sanity (insanity), feel as though you are dying (death), feelings of isolation, physiological distress, and paranoia. The CEQ uses a 6-point response scale \[0: None/not at all, 1: So slight cannot decide, 2: Slight, 3: Moderate, 4: Strong; 5: Extreme (more than ever before in my life)\] to indicate the degree to which a participant experiences each of a series of subjective effects during their psilocybin session. Total CEQ score is expressed as the percentage of the total possible ratings on the scale. Total score can range from 0-100% with higher scores indicating a greater challenging experience.