Effects of Psilocybin on Speech Fluency, Struggle, and Brain Activity in People Who Stutter

NCT07296328 | Not Yet Recruiting Phase 2 DMC FDA Drug

• 1 other identifier: 25-00244
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

Brief Summary

This Phase 2a clinical trial is an open-label, single-group, within-subjects pilot study designed to evaluate the safety, feasibility, and preliminary efficacy of psilocybin as a therapeutic intervention for adults with developmental stuttering. This pilot study will assess whether further research to explore the potential benefits of psilocybin-assisted therapy for improving clinical outcomes in individuals who stutter, is warranted. The aims of this study include:

• Aim 1: Assess the safety and feasibility of psilocybin as a therapeutic agent for stuttering.
• Aim 2: Evaluate the effects of psilocybin on objective and subjective measures of stuttering severity, struggle, and well-being.
• Aim 3: Explore the therapeutic neural mechanisms of psilocybin in stuttering.

Conditions

Stuttering

Keywords

Stuttering; Psilocybin; Stutter

Outcome Measures

Primary Outcomes (5)

• Change in Stuttering Severity Instrument - 4th Edition (SSI-4) total score

  The Stuttering Severity Instrument-4th Edition (SSI-4) provides a total score that is compared to age-specific norms to determine severity, with ranges for "Very Mild" to "Very Severe". The SSI-4 calculates individual scores for frequency (2-18), duration (2-18), and physical concomitants (0-20). These individual scores are combined to create a total score, which is then ranked against norms to provide a verbal severity descriptor, such as mild, moderate, severe, or very severe.

  Week 4, Week 12

• Change in frequency subcomponent score of the SSI-4

  The Stuttering Severity Instrument-4th Edition (SSI-4) provides a total score that is compared to age-specific norms to determine severity, with ranges for "Very Mild" to "Very Severe". The SSI-4 calculates individual scores for frequency (2-18), duration (2-18), and physical concomitants (0-20). These individual scores are combined to create a total score, which is then ranked against norms to provide a verbal severity descriptor, such as mild, moderate, severe, or very severe.

  Week 4, Week 12

• Change in duration subcomponent score of the SSI-4

  The Stuttering Severity Instrument-4th Edition (SSI-4) provides a total score that is compared to age-specific norms to determine severity, with ranges for "Very Mild" to "Very Severe". The SSI-4 calculates individual scores for frequency (2-18), duration (2-18), and physical concomitants (0-20). These individual scores are combined to create a total score, which is then ranked against norms to provide a verbal severity descriptor, such as mild, moderate, severe, or very severe.

  Week 4, Week 12

• Change in physical concomitants subcomponent score of the SSI-4

  The Stuttering Severity Instrument-4th Edition (SSI-4) provides a total score that is compared to age-specific norms to determine severity, with ranges for "Very Mild" to "Very Severe". The SSI-4 calculates individual scores for frequency (2-18), duration (2-18), and physical concomitants (0-20). These individual scores are combined to create a total score, which is then ranked against norms to provide a verbal severity descriptor, such as mild, moderate, severe, or very severe.

  Week 4, Week 12

• Change in Overall Assessment of the Speaker's Experience of Stuttering - Adults (OASES-A) score

  The OASES-A is a tool used by speech-language pathologists to measure the adverse impact of stuttering on an adult's life. It consists of 100 questions rated on a 5-point scale (1-5). The scores from individual questions are added together to create an overall score. The total score is then used to determine the "Impact Rating" on a scale from mild to severe. Higher scores indicate higher levels of negative impact.

  Week 4, Week 12

Secondary Outcomes (5)

• Change in self-reported stuttering severity Wright and Ayre Stuttering Self-Rating Profile (WASSP) score

  Week 4, Week 12

• Change in the Brief Version of the Unhelpful Thoughts and Beliefs About Stuttering Scales (UTBAS-6) total score

  Week 4, Week 12

• Change in Brief Fear of Negative Evaluation Scale (BFNE-S) total score

  Week 4, Week 12

• Change in the Social Interaction Anxiety Scale (SIAS) score

  Week 4, Week 12

• Change in Stuttering Anticipation Scale (SAS) score

  Week 4, Week 12

Study Arms (1)

Adult stutterers

EXPERIMENTAL

Participation will occur over an 8-week, 10-session period. Six sessions speech therapy; one preparatory therapy session prior to the drug administration session; one 8-hour drug administration session (25 mg of psilocybin); two follow-up therapy sessions following the drug administration session.

Drug: Psilocybin; Behavioral: Speech therapy

Interventions

Psilocybin DRUG

Participants will receive a single oral high-dose of psilocybin, 25 mg.

Adult stutterers

Speech therapy BEHAVIORAL

Speech therapy will consist of standard stuttering modification therapy, which includes four phases: Identification, Desensitization, Modification, Stabilization.

Adult stutterers

Eligibility Criteria

• Age: 18 Years - 50 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Are able to provide voluntary informed consent
• Are able to read, speak, and understand English, as documented during the informed consent process.
• o Non-English-speaking subjects will be excluded because the study is using only validated English-language versions of assessment instruments.
• Are 18 to 50 years old, inclusive, at Screening visit.
• Have diagnosis of mild-moderate to severe stuttering based on either the SSI-4 or OASES; also confirmed stuttering by stuttering specialist.
• Are able and willing to adhere to all study requirements, including attending all study visits and therapy sessions, and completing all assessments.
• Agree to refrain from any non-prescribed psychotropic substance or illicit drug use for at least 72 hours prior to investigational product (IP) administration, and for at least 24 hours before each fMRI assessment visit, with the exceptions of nicotine and caffeine. Regarding nicotine, they must agree not to use nicotine for at least 1 hour before and 6 hours following IP administration, and for at least 1 hour before fMRI scans. Regarding caffeine, they must agree to consume approximately their usual amount of caffeine on the morning of Day 0 (prior to IP administration).
• Agree to refrain from taking all non-prescription medications and supplements (nutritional and herbal) for at least 1 week prior to the IP administration session unless approved by the Investigator.
• Can swallow capsules.
• Subjects who are able to become pregnant must comply with the following conditions:
• A. Subjects are considered able to become pregnant unless they
• Do not have a uterus;
• Are postmenopausal (has had 12 months of natural amenorrhea with a matching clinical profile \[age, history of vasomotor symptoms\]) prior to Screening Part 2; or
• Are surgically sterile (documented hysterectomy, bilateral salpingectomy, or bilateral oophorectomy).
• B. Subjects who are able to become pregnant must

You may not qualify if:

• Pregnancy or lactation.
• Any medical condition that would preclude safe participation in the study, including the following, as determined by medical history review, physical examination, electrocardiogram (ECG), and clinical laboratory tests:
• Seizure disorder
• Significantly impaired liver function, defined as 1) alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) \> 5 × upper limit of normal (ULN); 2) ALT or AST \> 3 × ULN with concomitant total bilirubin \> 2.0 × ULN; or 3) ALT or AST ≥ 3 × ULN with the appearance of fatigue, nausea, vomiting, right upper quadrant pain or tenderness, fever, rash, and/or eosinophilia.
• Cardiovascular disease including coronary artery disease, angina, history of arrhythmia (unless a successful ablation has been performed), heart failure, history of heart valve replacement, and history of cerebrovascular accident or transient ischemic attack.
• Uncontrolled hypertension with systolic blood pressure \> 140 mmHg or diastolic blood pressure \> 90 mmHg. (Note: participants who otherwise meet all eligibility criteria during the screening visit will have 3 opportunities to produce 1 blood pressure reading ≤ 140/90 mmHg (each reading will be collected at least 15 minutes apart). If blood pressure at Screening is consistently elevated (\> 140/90 mmHg across all 3 attempts), participants may be referred to their primary care provider (PCP) for management of hypertension. Participants may continue study participation if the Investigator believes that it is likely that hypertension can be controlled prior to the IP administration session, and the patient is able to provide documentation of adequate control (BP \< 140/90 mmHg) prior to the PI administration session.)
• Resting heart rate \> 100 bpm (Note: participants will have an opportunity to return once within the 30-day screening window to make 3 additional attempts at a resting heart rate ≤ 100 bpm.).
• Serious ECG abnormalities (e.g., evidence of ischemia, myocardial infarction, QT interval corrected for heart rate \[QTc\] prolongation (QTc \> 0.450 seconds), arrhythmia, or conduction abnormalities that increase the risk of arrhythmia.
• Hyperthyroidism
• Insulin-dependent diabetes
• Bradycardia (e.g., heart rate \<50 bpm)
• Orthostatic hypotension
• Schizotypal and paranoid personality disorders
• Any other medical condition which precludes safe participation in the study in the medical opinion of the Investigator. (Note: medical history will be updated on Day 0. Those not meeting the criterion may be rescheduled once within 14 days if the criterion is likely to resolve within 14 days in the judgement of the Investigator.)
• Have any of the following Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-5) psychiatric disorders, as determined by the Mini International Neuropsychiatric Interview (MINI) and Psychiatric History at the Screening Visit: (Note: psychiatric history will be re-evaluated on Day 0, but the MINI will not be re-administered on Day 0)

Sponsors & Collaborators

• NYU Langone Health: lead

Study Sites (1)

NYU Langone Health

New York, New York, 10016, United States

Location

MeSH Terms

Conditions

Stuttering

Interventions

Psilocybin; Speech Therapy

Condition Hierarchy (Ancestors)

Speech Disorders; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Nervous System Diseases; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines; Rehabilitation of Speech and Language Disorders; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics

Study Officials

• Michael Bogenschutz, MD

  NYU Langone Health

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Eric Jackson, PhD

CONTACT

212-992-9470; Ej34@nyu.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: December 18, 2025
• First Posted: December 22, 2025
• Study Start: January 15, 2026
• Primary Completion (Estimated): April 1, 2027
• Study Completion (Estimated): April 1, 2027
• Last Updated: December 22, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP
• Time Frame: Beginning 9 months and ending 36 months following article publication or as required by a condition of awards and agreements supporting the research.
• Access Criteria: The investigator who proposed to use the data will be granted access upon reasonable request. Requests should be directed to Michael.bogenschutz@nyulangone.org. To gain access, data requestors will need to sign a data access agreement. This instance of data sharing will also require separate IRB review as well as review from NYU Langone's DSSB.

Locations

US (1)