Clinical TrialHealthy VolunteersPsilocybinPsilocybinPsilocybinPsilocybinRecruiting

Pairing Psilocybin With Transauricular Vagus Nerve Stimulation (ENHANCE)

Randomised, triple-blind Phase I factorial trial (n=108 planned) testing whether adjunctive taVNS enhances the long-term beneficial effects of a single open-label 25 mg psilocybin dose in medically healthy adults with modest reductions in wellbeing.

Target Enrollment
108 participants
Study Type
Phase I interventional
Design
Randomized, triple Blind

Detailed Description

A factorial, randomized study in healthy volunteers comparing combinations of active or sham transcutaneous auricular vagus nerve stimulation (taVNS) delivered before and after a single open-label 25 mg psilocybin dose to examine whether taVNS enhances retention of insights and long-term beneficial behavioural effects.

Participants receive 2–4 hours of preparatory support, a 6–8 hour psilocybin dosing session, and integration sessions at 1 day and ~1 week post-dosing; taVNS (active or sham) is delivered 20 minutes twice daily for 7 days according to randomisation.

Study Protocol

Preparation

1 sessions
180 min each

Dosing

1 sessions
360 min each

Integration

2 sessions
60 min each

Therapeutic Protocol

support

Study Arms & Interventions

Sham pre → taVNS post

experimental

Sham taVNS for 7 days pre-psilocybin; active taVNS twice daily for 7 days post-psilocybin.

Interventions

  • Psilocybin25 mg
    via Oral• single dose• 1 doses total

    Single open-label 25 mg psilocybin capsule administered in set-and-setting.

  • Compound
    via Other• twice daily x7 days

    Sham taVNS twice daily for 7 days prior to dosing (pre); active taVNS 20 min twice daily for 7 days post-dosing (post).

Sham pre → Sham post

inactive

Sham taVNS twice daily for 7 days pre- and post-psilocybin.

Interventions

  • Psilocybin25 mg
    via Oral• single dose• 1 doses total

    Single open-label 25 mg psilocybin capsule.

  • Compound
    via Other• twice daily x7 days

    Sham taVNS 20 min twice daily for 7 days pre- and post-dosing.

Sham pre → Psychosocial post

active comparator

Sham taVNS twice daily for 7 days pre-psilocybin; psychosocial support alone post-psilocybin (integration sessions).

Interventions

  • Psilocybin25 mg
    via Oral• single dose• 1 doses total

    Single open-label 25 mg psilocybin capsule.

  • Compound
    via Other• integration sessions

    Sham taVNS twice daily for 7 days pre-dosing; post-dosing receive psychosocial support (integration at 1 day and ~1 week) instead of active taVNS.

  • Compound
    via Other• integration sessions

    Psychosocial support: SaS framework; integration sessions 1 day and 9 days post-dosing (1 hour each).

taVNS pre → Sham post

active comparator

Active taVNS twice daily for 7 days pre-psilocybin; sham taVNS twice daily for 7 days post-psilocybin.

Interventions

  • Psilocybin25 mg
    via Oral• single dose• 1 doses total

    Single open-label 25 mg psilocybin capsule.

  • Compound
    via Other• twice daily x7 days

    Active taVNS 20 min twice daily for 7 days pre-dosing; sham taVNS 20 min twice daily for 7 days post-dosing.

Participants

Ages
18 – 70
Sexes
Male & Female

Inclusion Criteria

  • 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

  • Exclusion Criteria:
  • Clinically significant safety lab abnormalities (i.e., Complete Blood Count with Differential, Comprehensive Metabolic Panel, and urinalysis)
  • Current exclusionary medical illness or Diagnostic and Statistical Manual (DSM-5) psychiatric diagnosis
  • 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)
  • Hypertension or tachycardia
  • 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), deafness, or colorblindness
  • Family history of a psychotic disorder in a first degree relative

Study Details

Locations

University of Wisconsin - Madison — Madison, Wisconsin, United States

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