Investigation to Understand and Optimize Psilocybin

NCT ID: NCT06512194

Last Updated: 2025-05-23

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: PHASE2
• Total Enrollment: 141 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-05-13
• Study Completion Date: 2029-05-31

Brief Summary

This study will examine the effects of a single dose of psilocybin, administered with psychological support, on symptoms of depression. It will also assess whether different post-dosing interventions, including a non-invasive technique called transcutaneous auricular Vagus Nerve Stimulation (taVNS), influence various psychological and behavioral outcomes. In addition, the study will explore objective measures of real-world social behavior and identify early behavioral responses that may be associated with long-term treatment outcomes.

Detailed Description

One hundred forty-one adults ages 18 to 70 experiencing a major depressive episode of at least 60 days duration of moderate or greater severity at screening will be enrolled to obtain evaluable data on approximately 120 subjects.

All subjects will receive a single 25 mg dose of psilocybin using a "set and setting" therapeutic approach that will include 1) several hours of preparatory sessions prior to dosing and 2) the presence of two facilitators throughout the dosing session; and 3) several post dosing integration sessions with a facilitator.

Following the psilocybin dosing session, subjects will be randomized to 1) taVNS (7 days of twice daily taVNS), 2) sham taVNS (7 days of twice daily sham taVNS), or 3) no taVNS.

Both taVNS and sham sessions will include guided prompts encouraging participants to reflect on key aspects of their psychedelic experience, accompanied by music previously used during the psilocybin dosing session.

Participants will complete assessments at multiple time points to evaluate depression, anxiety, well-being, functional disability, quality of life, social behavior, suicidal ideation, and adverse events before and after psilocybin dosing.

Conditions

Depression

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

Group 1: Psilocybin + taVNS

Participants in this arm will receive a single 25 mg dose of psilocybin, followed by twice-daily sessions of taVNS for 7 consecutive days. Each taVNS session will be paired with music and prompts related to the participant's psilocybin experience.

Group Type: EXPERIMENTAL

Psilocybin

Intervention Type: DRUG

The psilocybin used in this study is synthesized under Good Manufacturing Practice (GMP) guidelines and is provided in a capsule containing 25 mg of synthetic psilocybin.

Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)

Intervention Type: DEVICE

Participants will be provided with a taVNS device and trained on its use. The device delivers gentle stimulation to the left ear.

Group 2: Psilocybin + Sham taVNS

Participants in this arm will receive a single 25 mg dose of psilocybin, followed by twice-daily sham taVNS sessions for 7 consecutive days. Each sham session will be paired with music and prompts related to the participant's psilocybin experience.

Group Type: SHAM_COMPARATOR

Psilocybin

Intervention Type: DRUG

The psilocybin used in this study is synthesized under Good Manufacturing Practice (GMP) guidelines and is provided in a capsule containing 25 mg of synthetic psilocybin.

Sham taVNS

Intervention Type: DEVICE

Participants will be provided with a taVNS device and trained on its use. The device delivers gentle stimulation to the left ear. In the sham condition, the device will simulate the sensations of active taVNS without delivering therapeutic stimulation.

Group 3: Psilocybin + No taVNS

Participants in this arm will receive a single 25 mg dose of psilocybin, followed by no additional intervention. They will receive the standard psychological support related to their psilocybin experience, but no taVNS or sham device will be used.

Group Type: ACTIVE_COMPARATOR

Psilocybin

Intervention Type: DRUG

The psilocybin used in this study is synthesized under Good Manufacturing Practice (GMP) guidelines and is provided in a capsule containing 25 mg of synthetic psilocybin.

Interventions

Psilocybin

The psilocybin used in this study is synthesized under Good Manufacturing Practice (GMP) guidelines and is provided in a capsule containing 25 mg of synthetic psilocybin.

Intervention Type: DRUG

Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)

Participants will be provided with a taVNS device and trained on its use. The device delivers gentle stimulation to the left ear.

Intervention Type: DEVICE

Sham taVNS

Participants will be provided with a taVNS device and trained on its use. The device delivers gentle stimulation to the left ear. In the sham condition, the device will simulate the sensations of active taVNS without delivering therapeutic stimulation.

Intervention Type: DEVICE

Other Intervention Names

Psilocybine; Psilocibin; Usona Institute Psilocybin; taVNS

Eligibility Criteria

Inclusion Criteria

Current diagnosis of Major Depressive Disorder (MDD), with a depressive episode lasting ≥ 60 consecutive days at the time of screening, as confirmed by structured clinical interview

Medically healthy, as determined by the screening physician, with no significant medical conditions that would interfere with participation or affect the safety of the subject.

Exclusion Criteria

History or presence of any psychiatric or medical condition that, in the opinion of the investigator, could pose a safety risk, interfere with participation, or confound study results (e.g., bipolar disorder, psychosis, seizure disorder, or cardiovascular disease).

Known family history of a psychotic disorder (e.g., schizophrenia or schizoaffective disorder) in a first-degree relative (biological parent, full sibling, or child).

Current active suicidal ideation with a specific plan within the prior 2 weeks, as assessed via clinical interview and validated instrument (e.g., C-SSRS).

Suicide attempt within the prior 6 months, regardless of intent or lethality.

Current diagnosis of a substance use disorder

Abnormal ECG at screening that may increase risk during participation (e.g., prolonged QTc, arrhythmias, or other clinically significant findings as determined by the study physician).

Unwilling or unable to discontinue prescription psychotropic medications (e.g., antidepressants, antipsychotics, anxiolytics, lithium, anticonvulsants, or mood stabilizers) for the duration of study participation, including any necessary washout period as determined by the investigator.

Any condition, finding, or behavior (including suspected deception or noncompliance) that, in the opinion of the investigator, renders the participant unsuitable for the study or likely to interfere with the integrity of the data or safety of the subject.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Usona Institute

OTHER

Sponsor Role: collaborator

Tiny Blue Dot Foundation

OTHER

Sponsor Role: collaborator

Steadman Philippon Research Institute

OTHER

Sponsor Role: collaborator

Emory University

OTHER

Sponsor Role: collaborator

Charles Raison

OTHER

Sponsor Role: lead

Responsible Party

Charles Raison

Vail Health Behavioral Health Innovation Center Director

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Charles Raison, MD

Role: PRINCIPAL_INVESTIGATOR

Vail Health Behavioral Health

Locations

Vail Health Behavioral Health

Edwards, Colorado, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Program Manager

Role: CONTACT

bhic@vailhealth.org

(970) 855-7374

Facility Contacts

Program Manager

Role: primary

bhic@vailhealth.org

(970) 855-7374

Other Identifiers

20243954

Identifier Type: -

Identifier Source: org_study_id