Investigation to Understand and Optimize Psilocybin

NCT06512194 | Recruiting Phase 2 DMC FDA Drug FDA Device

• 1 other identifier: 20243954
• Study Type: interventional
• Target: 141
• Locations: 1 country
• Sites: 1

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.

Conditions

Depression

Keywords

depression; psilocybin; psychedelics; transcutaneous auricular vagus nerve stimulation; depressive symptoms; well-being; adverse events; ecological momentary assessment; electronically activated recorder; dynamical complexity assessment

Outcome Measures

Primary Outcomes (3)

• Montgomery-Åsberg Depression Rating Scale (MADRS) score

  The MADRS is a 10-item depression rating scale that includes questions on the following symptoms: 1. Reported sadness, 2. Apparent sadness, 3. Inner tension, 4. Reduced sleep, 5. Reduced appetite, 6. Concentration difficulties, 7. Lassitude, 8. Inability to feel, 9. Pessimistic thoughts, and 10. Suicidal thoughts. Items are scored via a blinded clinical interview and rated to capture the patient's clinical state over the prior week. Each item yields a score of 0 to 6, and higher scores indicate more severe depression. The overall score ranges from 0 to 60. For this study, the structured MADRS interview will be used.

  Baseline 2, Week 8 Post-Psilocybin Dosing

• PROMIS Ability to Participate in Social Roles and Activities - Short Form 8a

  An 8-item validated measure assessing an individual's perceived ability to engage in social roles and activities, such as work, family responsibilities, and leisure. Participants rate each item on a 5-point Likert scale. Total score can range from 8 to 40 with higher scores indicating greater functional ability and social participation.

  Baseline 2, Week 8 Post-Dose

• Quality of Life Enjoyment and Satisfaction Questionnaire Short-Form (Q-LES-Q) score

  The Short Form version (Q-LES-Q-SF) will be used in this trial. The measure contains 16 items that assess quality of life. A total score is derived from summing the first 14 items on the scale, with the last 2 items serving as stand-alone queries. Total score can range from 14 to 70 with higher scores indicating better quality of life.

  Baseline 2, Week 8 Post-Dose

Secondary Outcomes (11)

• Electronically Activated Recorder (EAR)

  Up to 55 days

• Voicediary

  Up to 35 days

• Ecological Momentary Assessment (EMA)

  Up to 35 days

• Challenging Experiences Questionnaire (CEQ) score

  Day 1 Post-Dose, Week 8 Post-Dose

• Warwick-Edinburgh Mental Wellbeing Scale (WEMWBS) score

  Baseline 1, Baseline 2, Week 2 Post-Dose, Week 4 Post-Dose, Week 8 Post-Dose

Study Arms (3)

Group 1: Psilocybin + taVNS

EXPERIMENTAL

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.

Drug: Psilocybin; Device: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)

Group 2: Psilocybin + Sham taVNS

SHAM COMPARATOR

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.

Drug: Psilocybin; Device: Sham taVNS

Group 3: Psilocybin + No taVNS

ACTIVE COMPARATOR

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.

Drug: Psilocybin

Interventions

Psilocybin 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.

Also known as: Psilocybine, Psilocibin, Usona Institute Psilocybin

Group 1: Psilocybin + taVNS; Group 2: Psilocybin + Sham taVNS; Group 3: Psilocybin + No taVNS

Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) DEVICE

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

Also known as: taVNS

Group 1: Psilocybin + taVNS

Sham taVNS 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 2: Psilocybin + Sham taVNS

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Charles Raison: lead
• Usona Institute: collaborator
• Tiny Blue Dot Foundation: collaborator
• Steadman Philippon Research Institute: collaborator
• Emory University: collaborator

Study Sites (1)

Vail Health Behavioral Health

Edwards, Colorado, 81632, United States

RECRUITING

MeSH Terms

Conditions

Depression

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Study Officials

• Charles Raison, MD

  Vail Health Behavioral Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Program Manager

CONTACT

(970) 855-7374; bhic@vailhealth.org

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Vail Health Behavioral Health Innovation Center Director

Model Details: All subjects will receive a single 25 mg dose of psilocybin administered within a "set and setting" (SaS) framework of psychological support provided by trained clinicians. Post-dosing, subjects will be randomized to 1) taVNS, 2) sham taVNS, or 3) no taVNS.

Study Record Dates

• First Submitted: July 16, 2024
• First Posted: July 22, 2024
• Study Start: May 13, 2025
• Primary Completion (Estimated): May 1, 2029
• Study Completion (Estimated): May 1, 2029
• Last Updated: May 23, 2025

Record last verified: 2025-05

Data Sharing

• IPD Sharing: Will share
• Time Frame: Following publication of primary study findings.
• Access Criteria: EAR/ Voicediary/ EMA Data: Data sharing will adhere to ethical guidelines and those set by the Tiny Blue Dot Foundation, with only de-identified and aggregated data shared in accordance with FAIR principles. Sharing of data collected as part of the EAR/ Voicediary procedures will be limited to protect subject confidentiality, because raw speech data are inherently identifiable and classified as Protected Health Information (PHI). Aggregated behavioral codings and linguistic derivates of these data will be included in data files shared in accordance with the FAIR principles, but speech data and transcripts will not be shared beyond the study team. All data: Following publication of primary study findings, de-identified data will be made available to qualified researchers in a way that protects subject confidentiality and adheres to HIPAA policies. Informed consent documents will provide sufficient detail about the intent to archive, share, and re-analyze data.

Locations

US (1)