The ENHANCE Study: taVNS and Psilocybin

Last updated: January 21, 2026
Sponsor: University of Wisconsin, Madison
Overall Status: Active - Recruiting

Phase

1

Condition

N/A

Treatment

Transcutaneous auricular Vagus Nerve Stimulation (taVNS)

Treatment as Usual (TAU)

Sham taVNS

Clinical Study ID

NCT05866471
2024-0463
Protocol Version 10/25/24
A538900
Protocol Version 4/16/24
Protocol Version 1/13/25
Protocol Version 12/30/25
Protocol Version 3/20/25
Protocol Version 3/20/24
Protocol Version 6/24/25
  • Ages 18-70
  • All Genders
  • Accepts Healthy Volunteers

Study Summary

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.

Eligibility Criteria

Inclusion

Inclusion Criteria:

  • 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 ofchildbearing potential)

Exclusion

Exclusion Criteria:

  • Clinically significant safety lab abnormalities (i.e., Complete Blood Count withDifferential, Comprehensive Metabolic Panel, and urinalysis)

  • Current or clinically significant psychiatric disorder that, in the investigator'sjudgment, would interfere with participation or increase risk

  • Current use of drugs or medications, prescribed or otherwise, that may interact withpsilocybin

  • 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

Study Design

Total Participants: 108
Treatment Group(s): 7
Primary Treatment: Transcutaneous auricular Vagus Nerve Stimulation (taVNS)
Phase: 1
Study Start date:
January 27, 2025
Estimated Completion Date:
January 31, 2028

Study Description

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.

Connect with a study center

  • University of Wisconsin - Madison

    Madison, Wisconsin 53715
    United States

    Site Not Available

  • University of Wisconsin - Madison

    Madison 5261457, Wisconsin 5279468 53715
    United States

    Active - Recruiting

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