This study will examine the effects of a single dose of psilocybin, administered with psychological support, on symptoms of depression. It will also assess whether different post-dosing interventions, including a non-invasive technique called transcutaneous auricular Vagus Nerve Stimulation (taVNS), influence various psychological and behavioral outcomes. In addition, the study will explore objective measures of real-world social behavior and identify early behavioral responses that may be associated with long-term treatment outcomes.
One hundred forty-one adults ages 18 to 70 experiencing a major depressive episode of at least 60 days duration of moderate or greater severity at screening will be enrolled to obtain evaluable data on approximately 120 participants. All participants will receive a single 25 mg dose of psilocybin using a "set and setting" therapeutic approach that will include 1) several hours of preparatory sessions prior to dosing and 2) the presence of two facilitators throughout the dosing session; and 3) several post dosing integration sessions with a facilitator. Following the psilocybin dosing session, participants will be randomized to 1) taVNS (7 days of twice daily taVNS), 2) sham taVNS (7 days of twice daily sham taVNS), or 3) no taVNS. Both taVNS and sham sessions will include guided prompts encouraging participants to reflect on key aspects of their psychedelic experience, accompanied by music previously used during the psilocybin dosing session. Participants will complete assessments at multiple time points to evaluate depression, anxiety, well-being, functional disability, quality of life, social behavior, suicidal ideation, and adverse events before and after psilocybin dosing.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
QUADRUPLE
Enrollment
141
The psilocybin used in this study is synthesized under Good Manufacturing Practice (GMP) guidelines and is provided in a capsule containing 25 mg of synthetic psilocybin.
Participants will be provided with a taVNS device and trained on its use. The device delivers gentle stimulation to the left ear.
Participants will be provided with a taVNS device and trained on its use. The device delivers gentle stimulation to the left ear. In the sham condition, the device will simulate the sensations of active taVNS without delivering therapeutic stimulation.
Vail Health Behavioral Health
Edwards, Colorado, United States
RECRUITINGMontgomery-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.
Time frame: Baseline 2, Week 8 Post-Psilocybin Dosing
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.
Time frame: Baseline 2, Week 8 Post-Dose
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.
Time frame: Baseline 2, Week 8 Post-Dose
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.
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Time frame: Up to 55 days
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).
Time frame: Up to 35 days
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.
Time frame: Up to 35 days
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.
Time frame: Day 1 Post-Dose, Week 8 Post-Dose
Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS) score
The WEMWBS has 14 questions scored using a five-point Likert scale. The items are all worded positively and cover both feeling and functioning aspects of mental wellbeing. Items on the questionnaire are rated on a 5-point scale, where 1= "None of the time", 2= "rarely", 3= "some of the time", 4= "often", 5= "all the time". The scale is scored by summing the response to each item. The minimum scale score is 14 and the maximum is 70. Scores reflect feelings and thoughts in the two weeks prior to answering the questionnaire with higher scores indicating better well-being.
Time frame: Baseline 1, Baseline 2, Week 2 Post-Dose, Week 4 Post-Dose, Week 8 Post-Dose
Psychedelic Assisted Therapy Adverse Events (PATAE)
The PATAE was developed to assess pre-dosing and post-acute dosing adverse events that may occur during psychedelic-assisted therapy due to the pharmacologic and psychotherapeutic components, as well as their interaction. The PATAE consists of 54 items that assess across 7 domains: sociocultural, psychospiritual, interpersonal, behavioral, psychotherapy-related, and perceptual.
Time frame: Baseline 1, Baseline 2, Day 1 Post-Dose, Week 1 Post-Dose, Week 2 Post-Dose, Week 4 Post-Dose, Week 8 Post-Dose
30-item Mystical Experiences Questionnaire (MEQ30) score
The MEQ30 is a 30-item self-report measure developed to assess the effects of classic psychedelics in laboratory studies. It covers the major dimensions of the classic mystical experience: unity, transcendence, noetic quality, sacredness, positive mood, and ineffability/paradoxicality. The MEQ has 4 sub scales: 1) transcendence, 2) positive mood, 3) ineffability, and 4) mystical. The total possible range for each sub scale and total score is 0-100% with higher percentages indicating a larger mystical experience. Typically, a complete mystical experience is defined as scoring 60% or more on all four MEQ30 sub scales.
Time frame: Day 1 Post-Dose, Week 8 Post-Dose
Emotional Breakthrough Inventory (EBI) score
The EBI is a 6-item self-report scale that assesses the presence and severity of emotionally challenging/distressing experiences that occur during a psychedelic experience. The scale utilizes visual analog responses captured on a line anchored by "not at all" on one end and "very much so" on the other. Experiences queried include 1) facing emotionally difficult feelings that are usually pushed aside; 2) experiencing a resolution of a personal conflict/trauma; 3) being able to explore challenging emotions and memories; 4) having an emotional breakthrough; 5) getting a sense of closure on an emotional problem, and 6) achieving an emotional release followed by a sense of relief. The total possible score ranges from 0-100 with higher scores indicating a greater emotional breakthrough.
Time frame: Day 1 Post-Dose, Week 8 Post-Dose
Psychological Insight Questionnaire (PIQ) score
The PIQ is a 23-item instrument designed to query self-perceived attainment of insight during a psychedelic experience. It comprises two subscales: (a) Avoidance and Maladaptive Patterns Insights and Goals; and (b) Adaptive Patterns Insights. Sub scale and total scores range from 0 to 5 with a higher score indicating great psychological insight.
Time frame: Day 1 Post-Dose, Week 8 Post-Dose
Ego Dissolution Inventory (EDI) score
The EDI is an 8-item self-report scale designed to measure ego-dissolution. Each item is scored on a visual analogue scale from 0 to 100 with the following statements at the lower and upper end, respectively: "No, not more than usually" and "Yes, I experienced this completely/entirely." The total possible range of scores for the EDI is 0-100 with higher scores indicating a greater ego dissolution.
Time frame: Day 1 Post-Dose, Week 8 Post-Dose
Awe Experiences Questionnaire - Short Form (AWE-SF) score
The AWE-SF is a 12-item self-report scale that measures the state of awe. Each items is rated on a scale of 1 to 7, with 1 representing "Strongly Disagree" and 7 representing "Strongly Agree". The total possible range of scores for the AWE is 12-84 with higher scores indicating a greater awe.
Time frame: Day 1 Post-Dose, Week 8 Post-Dose