Activating Neuroplasticity to ENHANCE the Perception Box Expanding Effects of Psilocybin
试验速览
- 阶段
- 1 期
- 状态
- 招募中
- 入组人数
- 108
- 试验地点
- 1
- 主要终点
- Memory Experiences Questionnaire (MEM-Q-PSIL): Comparison of taVNS Administration vs. Treatment as Usual
研究概览
简要总结
This study will examine whether combining a single dose of psilocybin with non-invasive transcutaneous auricular vagus nerve stimulation (taVNS), a potential inducer of neuroplasticity and enhanced memory formation, will enhance the long-term beneficial behavioral effects of psilocybin when compared to sham taVNS or no VNS by allowing memory for insights gained during the psychedelic experience to remain vivid after they will have faded in subjects who receive psilocybin followed by sham taVNS or no VNS.
详细描述
One hundred and eight medically healthy adult volunteers with a modest decrement in wellbeing will receive a single open-label 25 mg dose of psilocybin administered within a "set and setting" (SaS) framework of psychological support provided by trained facilitators, such as has been successfully employed in prior psychedelic studies at UW-Madison. The SaS protocol will include 2-4 hours of preparation, a 6- to 8-hour psilocybin dosing session and an hour-long integration session 1 day and 9 days post dosing. All subjects will receive various combinations of active taVNS or sham taVNS prior to, or following, psilocybin dosing.
Active and sham taVNS sessions will last 20 minutes and will occur twice daily (morning and afternoon/evening) for 7 consecutive days, using an "at home" protocol that has been used safely and effectively by study collaborators. taVNS is a non-invasive low-risk procedure.
Subjects will be randomized with equal allocation to one of four conditions: 1) seven days of sham taVNS prior to psilocybin dosing and 7 days of active taVNS post- psilocybin dosing (Group 1: n=27); 2) seven days of sham taVNS prior to psilocybin dosing and 7 days of sham taVNS post- psilocybin dosing (Group 2: n=27); 3) seven days of sham taVNS prior to psilocybin dosing and psilocybin with psychosocial support post-dosing (Group 3: n=27); and 4) seven days of active taVNS prior to psilocybin dosing and 7 days of sham taVNS post- psilocybin dosing (Group 4: n=27). Importantly, participants in all groups will receive psychosocial support in addition to their randomization status (i.e., taVNS or sham taVNS prior to, or following psilocybin, or psychosocial support alone), as the provision of psychosocial support is the current standard of care for the use of psychedelics in FDA-regulated clinical trials (FDA 2023). It is anticipated that a total sample of 108 subjects will be enrolled to provide 100 subjects who complete study activities/assessments sufficient to provide evaluable data for testing study primary and exploratory outcomes.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Factorial
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 年龄范围
- 18 Years 至 70 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •English speaking
- •Ability/willingness to complete all study activities
- •Modest reduction in emotional well-being
- •Medically healthy (does not meet criteria for an exclusionary medical condition)
- •Blood pressure and heart rate within established ranges at screening
- •Use of acceptable contraceptive methods (sexually active males and women of childbearing potential)
排除标准
- •Clinically significant safety lab abnormalities (i.e., Complete Blood Count with Differential, Comprehensive Metabolic Panel, and urinalysis)
- •Current or clinically significant psychiatric disorder that, in the investigator's judgment, would interfere with participation or increase risk
- •Current use of drugs or medications, prescribed or otherwise, that may interact with psilocybin
- •Use of investigational drugs, biologics, or devices within 30 days of enrollment
- •Use of psychedelic or related agents within three months of Dosing Day
- •Clinically significant electrocardiogram (ECG)
- •Vitals outside acceptable range
- •Pregnancy and currently breastfeeding
- •Unwillingness to go without tobacco products for 12 hours or more
- •Inability to undergo fMRI scanning
- •Recent ear trauma, hearing loss (if clinically significant), or deafness
- •Family history of a psychotic disorder in a first degree relative
研究组 & 干预措施
Group 1: Sham taVNS + Psilocybin + taVNS
Group 1 will receive twice daily sham taVNS for 7 days immediately prior to psilocybin dosing. Post-psilocybin dosing, they will receive twice-daily taVNS paired with psychedelic session contextual cues for 7 days.
干预措施: Psilocybin (Drug)
Group 3: Sham taVNS + Psilocybin + Psychosocial Support Alone
Group 3 will receive twice daily sham taVNS for 7 days immediately prior to psilocybin dosing. Post-psilocybin dosing, they will receive psychosocial support alone, comprised of an integration session 1 day and 1-week post-psilocybin dosing. They will not receive active or sham taVNS post-psilocybin.
干预措施: Sham taVNS (Other)
Group 1: Sham taVNS + Psilocybin + taVNS
Group 1 will receive twice daily sham taVNS for 7 days immediately prior to psilocybin dosing. Post-psilocybin dosing, they will receive twice-daily taVNS paired with psychedelic session contextual cues for 7 days.
干预措施: Transcutaneous auricular Vagus Nerve Stimulation (taVNS) (Device)
Group 1: Sham taVNS + Psilocybin + taVNS
Group 1 will receive twice daily sham taVNS for 7 days immediately prior to psilocybin dosing. Post-psilocybin dosing, they will receive twice-daily taVNS paired with psychedelic session contextual cues for 7 days.
干预措施: Sham taVNS (Other)
Group 2: Sham taVNS + Psilocybin + Sham taVNS
Group 2 will receive twice daily sham taVNS for 7 days immediately prior to psilocybin dosing. Post-psilocybin dosing, they will receive twice-daily sham taVNS paired with psychedelic session contextual cues for 7 days.
干预措施: Sham taVNS (Other)
Group 3: Sham taVNS + Psilocybin + Psychosocial Support Alone
Group 3 will receive twice daily sham taVNS for 7 days immediately prior to psilocybin dosing. Post-psilocybin dosing, they will receive psychosocial support alone, comprised of an integration session 1 day and 1-week post-psilocybin dosing. They will not receive active or sham taVNS post-psilocybin.
干预措施: Psychosocial Support Alone (Behavioral)
Group 4: taVNS + Psilocybin + Sham taVNS
Group 4 will receive twice daily taVNS for 7 days immediately prior to psilocybin dosing. Post-psilocybin dosing, they will receive twice-daily sham taVNS paired with psychedelic session contextual cues for 7 days.
干预措施: Transcutaneous auricular Vagus Nerve Stimulation (taVNS) (Device)
Group 4: taVNS + Psilocybin + Sham taVNS
Group 4 will receive twice daily taVNS for 7 days immediately prior to psilocybin dosing. Post-psilocybin dosing, they will receive twice-daily sham taVNS paired with psychedelic session contextual cues for 7 days.
干预措施: Sham taVNS (Other)
Group 4: taVNS + Psilocybin + Sham taVNS
Group 4 will receive twice daily taVNS for 7 days immediately prior to psilocybin dosing. Post-psilocybin dosing, they will receive twice-daily sham taVNS paired with psychedelic session contextual cues for 7 days.
干预措施: Psilocybin (Drug)
Group 3: Sham taVNS + Psilocybin + Psychosocial Support Alone
Group 3 will receive twice daily sham taVNS for 7 days immediately prior to psilocybin dosing. Post-psilocybin dosing, they will receive psychosocial support alone, comprised of an integration session 1 day and 1-week post-psilocybin dosing. They will not receive active or sham taVNS post-psilocybin.
干预措施: Psilocybin (Drug)
Group 2: Sham taVNS + Psilocybin + Sham taVNS
Group 2 will receive twice daily sham taVNS for 7 days immediately prior to psilocybin dosing. Post-psilocybin dosing, they will receive twice-daily sham taVNS paired with psychedelic session contextual cues for 7 days.
干预措施: Psilocybin (Drug)
结局指标
主要结局
Memory Experiences Questionnaire (MEM-Q-PSIL): Comparison of taVNS Administration vs. Treatment as Usual
时间窗: 8 weeks
The MEM-Q is 31-item self-report scales designed to measure 10 phenomenological qualities of autobiographical memories: Vividness, Coherence, Accessibility, Time Perspective, Sensory Details, Visual Perspective, Emotional Intensity, Sharing, Distancing and Valence. Ratings are made on a 5-point Likert scale, ranging from 1 (strongly disagree) to 5 (strongly agree).
Functional Magnetic Resonance Imaging (fMRI): Comparison of taVNS Administration vs. Treatment as Usual
时间窗: Day 1 and Day 56 Post- Psilocybin Dose
Activation in brain regions associated with cued autobiographical memory retrieval will be assessed with fMRI. Group comparisons will examine differences in whole brain blood oxygenated level dependent (BOLD) signal and connectivity based on previously established seed-based methods using a priori brain regions implicated in autobiographical memory retrieval corresponding dosing session stimuli. The study team will update with more specific information when the details are confirmed.
Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS): Comparison of taVNS Administration vs. Treatment as Usual
时间窗: 8 weeks
The WEMWBS is a 14-item self-report scale that was designed to measure the psychological well-being of a population. The questions use 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". A total scale score is calculated by summing the 14 individual item scores. The total possible range of scores for the WEMWBS is 14-70 with higher scores indicating a greater well-being.
Summary of Adverse Events
时间窗: up to 8 weeks
Adverse events (AEs) categorized by CTCAE v5.0 criteria at all assessments (6 study visits).
次要结局
未报告次要终点