The ENHANCE Study: Psilocybin and Vagus Nerve Stimulation

This study, called the ENHANCE Study, is looking at whether combining a single dose of psilocybin (a psychedelic compound) with transcutaneous auricular Vagus Nerve Stimulation (taVNS), a gentle electrical stimulation applied to the ear, can improve well-being. Researchers want to see if this combination helps people remember positive insights from their psychedelic experience for longer. You might be eligible if you are a healthy adult between 18 and 70 years old, speak English, and have a modest reduction in your emotional well-being. The study will measure success by looking at your memory of the experience, brain activity using fMRI (functional Magnetic Resonance Imaging), and overall mental well-being after 8 weeks. The current status of this study is unclear.

Study design
This interventional study plans to enroll 108 healthy adult volunteers. Participants will be randomized into one of four groups, receiving different combinations of active or sham taVNS before and after a single open-label 25 mg dose of psilocybin.
What's involved
You would receive a single 25 mg dose of psilocybin with psychological support. You would also use a taVNS device at home twice daily for 20 minutes for 7 consecutive days, either before or after psilocybin dosing. There will be preparation and integration sessions, and assessments at Day 1, Day 56, and 8 weeks post-psilocybin dose.
Compensation
Not stated in the trial record.
Follow-up
Your memory experiences and mental well-being will be assessed at 8 weeks. Functional MRI will be conducted at Day 1 and Day 56 after the psilocybin dose.

AI-generated from the public study record. Only the study team can confirm whether you're eligible — confirm details with them before making decisions.

NCT05866471

The ENHANCE Study: taVNS and Psilocybin

Recruiting
PHASE1Ages 18–70InterventionalBasic science
University of Wisconsin, Madison
~108 participants
Updated 2026-07-29 on ClinicalTrials.gov
What's tested:PsilocybinTranscutaneous auricular Vagus Nerve Stimulation (taVNS)Psychosocial Support AloneSham taVNS

At a glance

Recruiting sites
1 of 1 listed site is recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Memory Experiences Questionnaire (MEM-Q-PSIL): Comparison of taVNS Administration vs. Treatment as Usual
Measured over 8 weeks
+3 more outcomes measured
Healthy
Psychedelic Experiences
Vagus Nerve Stimulation
1 sites across 1 states
Wisconsin1
  • Charles Raison, MD · PRINCIPAL_INVESTIGATOR · University of Wisconsin, Madison

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Do you actually qualify for this trial?

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Eligibility criteria

Inclusion

English speaking
Ability/willingness to complete all study activities
Modest reduction in emotional well-being

Exclusion

Blood pressure and heart rate within established ranges at screening
Use of acceptable contraceptive methods (sexually active males and women of childbearing potential)
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
  • Memory Experiences Questionnaire (MEM-Q-PSIL): Comparison of taVNS Administration vs. Treatment as Usual8 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 UsualDay 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 Usual8 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 Eventsup to 8 weeks

    Adverse events (AEs) categorized by CTCAE v5.0 criteria at all assessments (6 study visits).