Investigation to Understand and Optimize Psilocybin
Purpose
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.
Condition
- Depression
Eligibility
- Eligible Ages
- Between 18 Years and 70 Years
- Eligible Genders
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
Current diagnosis of Major Depressive Disorder (MDD), with a depressive episode lasting ≥ 60 consecutive days at the time of screening, as confirmed by structured clinical interview Medically healthy, as determined by the screening physician, with no significant medical conditions that would interfere with participation or affect the safety of the subject.
Exclusion Criteria
History or presence of any psychiatric or medical condition that, in the opinion of the investigator, could pose a safety risk, interfere with participation, or confound study results (e.g., bipolar disorder, psychosis, seizure disorder, or cardiovascular disease). Known family history of a psychotic disorder (e.g., schizophrenia or schizoaffective disorder) in a first-degree relative (biological parent, full sibling, or child). Current active suicidal ideation with a specific plan within the prior 2 weeks, as assessed via clinical interview and validated instrument (e.g., C-SSRS). Suicide attempt within the prior 6 months, regardless of intent or lethality. Current diagnosis of a substance use disorder Abnormal ECG at screening that may increase risk during participation (e.g., prolonged QTc, arrhythmias, or other clinically significant findings as determined by the study physician). Unwilling or unable to discontinue prescription psychotropic medications (e.g., antidepressants, antipsychotics, anxiolytics, lithium, anticonvulsants, or mood stabilizers) for the duration of study participation, including any necessary washout period as determined by the investigator. Any condition, finding, or behavior (including suspected deception or noncompliance) that, in the opinion of the investigator, renders the participant unsuitable for the study or likely to interfere with the integrity of the data or safety of the subject.
Study Design
- Phase
- Phase 2
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel Assignment
- Intervention Model Description
- All subjects will receive a single 25 mg dose of psilocybin administered within a "set and setting" (SaS) framework of psychological support provided by trained clinicians. Post-dosing, subjects will be randomized to 1) taVNS, 2) sham taVNS, or 3) no taVNS.
- Primary Purpose
- Treatment
- Masking
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Arm Groups
Arm | Description | Assigned Intervention |
---|---|---|
Experimental Group 1: Psilocybin + taVNS |
Participants in this arm will receive a single 25 mg dose of psilocybin, followed by twice-daily sessions of taVNS for 7 consecutive days. Each taVNS session will be paired with music and prompts related to the participant's psilocybin experience. |
|
Sham Comparator Group 2: Psilocybin + Sham taVNS |
Participants in this arm will receive a single 25 mg dose of psilocybin, followed by twice-daily sham taVNS sessions for 7 consecutive days. Each sham session will be paired with music and prompts related to the participant's psilocybin experience. |
|
Active Comparator Group 3: Psilocybin + No taVNS |
Participants in this arm will receive a single 25 mg dose of psilocybin, followed by no additional intervention. They will receive the standard psychological support related to their psilocybin experience, but no taVNS or sham device will be used. |
|
Recruiting Locations
More Details
- Status
- Recruiting
- Sponsor
- Charles Raison
Detailed Description
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 subjects. All subjects 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, subjects 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.