Pairing Psilocybin With Transcutaneous Auricular Vagus Nerve Stimulation

Healthy Clinical Trial

— ENHANCE  

Official title:

Activating Neuroplasticity to ENHANCE the Perception Box Expanding Effects of Psilocybin

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT05866471
• Other study ID #: 2024-0463
• Secondary ID: A538900Protocol
• Status: Not yet recruiting
• Phase: Phase 1
• Start date: August 2024
• Est. completion date: October 2027

Study information

• Verified date: May 2024
• Source: University of Wisconsin, Madison
• Contact: Program Manager
• Phone: 608-265-4987
• Email: raisonlab[@]psychiatry.wisc.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This study will examine whether combining a single dose of psilocybin with non-invasive transcutaneous auricular vagus nerve stimulation (taVNS), a known inducer of neuroplasticity and enhanced memory formation, will enhance the long-term beneficial behavioral effects of psilocybin when compared to sham taVNS 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.

Description:

One hundred and eight adults 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 University of Wisconsin-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 treatment as usual post- psilocybin 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). 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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 108
• Est. completion date: October 2027
• Est. primary completion date: July 2027
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 70 Years

Eligibility

Inclusion Criteria:

• English speaking

• Ability/willingness to complete all study activities

• Modest decrement 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 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 screening

• 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, deafness, or colorblindness

Related Conditions & MeSH terms

• Healthy
• Psychedelic Experiences
• Vagus Nerve Stimulation

Intervention

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

Device:
• 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.
• 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.

Behavioral:
• Treatment as Usual (TAU)
Participants assigned to TAU will not receive taVNS following psilocybin dosing.

Locations

Country	Name	City	State
United States	University of Wisconsin - Madison	Madison	Wisconsin

Sponsors (2)

Lead Sponsor	Collaborator
University of Wisconsin, Madison	Tiny Blue Dot Foundation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Memory Experiences Questionnaire (MEM-Q): Comparison of taVNS Administration vs. Treatment as Usual	The MEM-Q is a 63-item self-report scale 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).	8 weeks
Primary	Functional Magnetic Resonance Imaging (fMRI): Comparison of taVNS Administration vs. Treatment as Usual	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.	Day 1 and Day 56 Post- Psilocybin Dose
Primary	Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS): Comparison of taVNS Administration vs. Treatment as Usual	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.	8 weeks
Primary	Summary of Adverse Events	Adverse events (AEs) categorized by CTCAE v5.0 criteria at all assessments (6 study visits).	up to 8 weeks