What is the mechanism of action of this treatment?

Psilocybin induces psychological insights by acting on serotonin receptors, particularly the 5-HT2A receptor, leading to altered perception and cognition. Transcutaneous auricular vagus nerve stimulation (taVNS) enhances neuroplasticity and memory formation by stimulating the vagus nerve. Combining these treatments could amplify the beneficial effects of psilocybin, making psychological insights more vivid and long-lasting. This is significant for healthy subjects as it may improve cognitive function, emotional well-being, and overall mental health.

What side effects are associated with this type of intervention?

Psilocybin, a psychedelic compound, is known to cause side effects such as nausea, dizziness, anxiety, and transient increases in heart rate and blood pressure. Psychological effects can include hallucinations, altered perception of time, and emotional variability. Transcutaneous auricular vagus nerve stimulation (taVNS) is generally well-tolerated but can cause mild side effects such as skin irritation at the site of stimulation, headache, and dizziness. Combining these treatments may enhance neuroplasticity and memory formation but also requires careful monitoring for compounded side effects.

What prior FDA approvals exist?

The FDA has not approved any treatments specifically for healthy subjects that combine psychedelics like psilocybin with neuroplasticity-enhancing methods such as taVNS. However, psilocybin has been studied for its potential to treat various psychiatric conditions, and vagus nerve stimulation (VNS) has been approved for treatment-resistant depression and epilepsy. These treatments are generally targeted at specific medical conditions rather than healthy individuals.

What other types of research exist?

<ol> <li>SM-10888: A CNS-selective cholinesterase inhibitor that has shown to enhance habituation and improve passive avoidance responses at lower doses compared to other cholinesterase inhibitors, indicating potential for cognitive enhancement.</li> <li></li> </ol> CX516: An ampakine that has demonstrated marked facilitation of short-term memory performance in rats, suggesting potential benefits for memory enhancement in humans. 3. Methylene Blue and Photobiomodulation: Both have shown cognitive improvement in hepatic encephalopathy models, indicating potential for cognitive enhancement through different mechanisms.

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Psychedelic

Psilocybin + taVNS for Enhancing Psychedelic Experiences (ENHANCE Trial)

Phase 1

Recruiting

Led By Charles Raison, MD

Research Sponsored by University of Wisconsin, Madison

Eligibility Criteria Checklist

Specific guidelines that determine who can or cannot participate in a clinical trial

Must have

Be older than 18 years old

Timeline

Screening 3 weeks

Treatment Varies

Follow Up day 1 and day 56 post- psilocybin dose

Summary

This trial is testing if combining psilocybin with a gentle nerve stimulation technique can make the positive effects of psilocybin last longer. The study involves adults who will receive a dose of psilocybin and either real or fake nerve stimulation. The goal is to see if the nerve stimulation helps keep the memories from the psilocybin experience vivid and beneficial.

Who is the study for?

This trial is for English-speaking, medically healthy individuals who can swallow pills and agree to use contraception if they are sexually active. They should have a slight decrease in emotional well-being but no current serious medical conditions, psychiatric diagnoses, abnormal lab results, heart issues like hypertension or tachycardia, and not be pregnant or breastfeeding.

What is being tested?

The study tests if transauricular vagus nerve stimulation (taVNS) can make the positive effects of psilocybin last longer. Participants will take a single dose of psilocybin and then receive either real taVNS treatment, sham taVNS treatment without actual stimulation, or usual care with no additional intervention.

What are the potential side effects?

Psilocybin may cause changes in perception, mood swings, nausea, headache or increased heart rate. The taVNS could potentially lead to mild discomfort at the site of application. Side effects vary from person to person.

Timeline

Screening ~ 3 weeks3 visits

Treatment ~ Varies

Follow Up ~ day 1 and day 56 post- psilocybin dose

Screening ~ 3 weeks

Treatment ~ Varies

Follow Up ~day 1 and day 56 post- psilocybin dose

This trial's timeline: 3 weeks for screening, Varies for treatment, and day 1 and day 56 post- psilocybin dose for reporting.

Treatment Details

Study Objectives

Study objectives can provide a clearer picture of what you can expect from a treatment.

Primary study objectives

Functional Magnetic Resonance Imaging (fMRI): Comparison of taVNS Administration vs. Treatment as Usual

Memory Experiences Questionnaire (MEM-Q): Comparison of taVNS Administration vs. Treatment as Usual

Summary of Adverse Events

+1 more

Trial Design

4Treatment groups

Experimental Treatment

Active Control

Placebo Group

Group I: Group 1: Sham taVNS + Psilocybin + taVNSExperimental Treatment3 Interventions

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.

Group II: Group 3: Sham taVNS + Psilocybin + Psychosocial Support AloneActive Control3 Interventions

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.

Group III: Group 4: taVNS + Psilocybin + Sham taVNSActive Control3 Interventions

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.

Group IV: Group 2: Sham taVNS + Psilocybin + Sham taVNSPlacebo Group2 Interventions

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.

Treatment

First Studied

Drug Approval Stage

How many patients have taken this drug

Psilocybin

2021

Completed Phase 2

~530

Do I qualify?Apply below to find out

Research Highlights

Information in this section is not a recommendation. We encourage patients to speak with their healthcare team when evaluating any treatment decision.

Mechanism Of Action

Side Effect Profile

Prior Approvals

Other Research

Psilocybin induces psychological insights by acting on serotonin receptors, particularly the 5-HT2A receptor, leading to altered perception and cognition. Transcutaneous auricular vagus nerve stimulation (taVNS) enhances neuroplasticity and memory formation by stimulating the vagus nerve. Combining these treatments could amplify the beneficial effects of psilocybin, making psychological insights more vivid and long-lasting. This is significant for healthy subjects as it may improve cognitive function, emotional well-being, and overall mental health.

Role of the 5-HT2A Receptor in Self- and Other-Initiated Social Interaction in Lysergic Acid Diethylamide-Induced States: A Pharmacological fMRI Study.Chocolate and the brain: neurobiological impact of cocoa flavanols on cognition and behavior.