Recruiting
Phase 1

Psilocybin & taVNS

Sponsor:

University of Wisconsin, Madison

Code:

NCT05866471

Conditions

Healthy

Psychedelic Experiences

Vagus Nerve Stimulation

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Accepted

Interventions

Psilocybin

Transcutaneous auricular Vagus Nerve Stimulation (taVNS)

Psychosocial Support Alone

Sham taVNS

Study Details

Brief 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.

Conditions

Healthy

Psychedelic Experiences

Vagus Nerve Stimulation

Study ID

NCT05866471

Start date

Jan 27, 2025

Status verified date

Jul, 2026

Completion date

Jan, 2028

Anticipated

Primary completion date

Nov, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70

Healthy Volunteers: Accepted

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 of childbearing potential)

Exclusion Criteria:

  • 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

Study Design

Enrollment

108 participants

Anticipated

Allocation

Randomized

Intervention Model

Factorial

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: 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.

sham comparator: 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.

active comparator: 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.

active comparator: 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.

Interventions

Psilocybin

The psilocybin is produced under Good Manufacturing Practice and is in a capsule that contains 25 mg of botanically-derived psilocybin.

Transcutaneous auricular Vagus Nerve Stimulation (taVNS)

For both the active and sham taVNS procedure, participants will be provided with, and trained on, taVNS devices that apply gentle stimulation to the left ear via either electrodes or an earpiece that fits over the left ear.

Psychosocial Support Alone

Participants assigned to Psychosocial Support Alone will not receive taVNS following psilocybin dosing.

Sham taVNS

For both the active and sham taVNS procedure, participants will be provided with, and trained on, taVNS devices that apply gentle stimulation to the left ear via either electrodes or an earpiece that fits over the left ear.

Primary outcome measure

  • Memory Experiences Questionnaire (MEM-Q-PSIL): Comparison of taVNS Administration vs. Treatment as Usual [ Time Frame: 8 weeks ]
  • Functional Magnetic Resonance Imaging (fMRI): Comparison of taVNS Administration vs. Treatment as Usual [ Time Frame: Day 1 and Day 56 Post- Psilocybin Dose ]
  • Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS): Comparison of taVNS Administration vs. Treatment as Usual [ Time Frame: 8 weeks ]
  • Summary of Adverse Events [ Time Frame: up to 8 weeks ]

Central Contacts and Locations

Central contacts

Program Manager

608-265-4987enhance@psychiatry.wisc.edu

Locations

University of Wisconsin - Madison

Recruiting

Madison, Wisconsin, United States, 53715

Contacts

Program Manager

enhance@psychiatry.wisc.edu

More Information

Sponsor

University of Wisconsin, Madison

Last update posted

Jul 29, 2026

Last verified

Jul, 2026

Keywords

  • Psilocybin
  • Psychedelics
  • Vagus Nerve Stimulation
  • Healthy Volunteer

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Wisconsin, Madison on 2026-07-29.