Acceptability & Safety of Two Sequential Doses of Psilocybin in Bipolar Disorder II Depression and Suicidality

July 15, 2025 updated by: Thomas D. Meyer, PhD, The University of Texas Health Science Center, Houston
The purpose of the study is to assess the safety and acceptability of up to two sequential administrations of 25 mg psilocybin with additional therapeutic support in decreasing suicidality in patients with Bipolar Disorder (BD II) depression.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

This study aims to determine whether psilocybin paired with psychotherapy is a safe, feasible, and acceptable treatment for Bipolar II (BD II) depression, specifically, individuals experiencing suicidal ideation (without having an active plan or intention to act). The design is a non-randomized clinical trial, where patients will receive up to 2 doses of 25mg psilocybin in the context of psychological support informed by mindfulness-based CBT and typical elements of psychedelic treatments (e.g., preparation, intention setting, integration). The investigators will measure suicidality, depression, and acute experiences using validated questionnaires at multiple time points in the study. If this study shows psilocybin to be a feasible, acceptable, and safe treatment option, this would have huge implications for improving outcomes because highly effective treatment for suicidality in patients with Bipolar Disorder is still lacking.

Study Type

Interventional

Enrollment (Estimated)

10

Phase

  • Phase 2

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • United States
    • Texas
      • Houston, Texas, United States, 77006
        • Recruiting
        • The University of Texas Health Science Center at Houston
        • Contact:
        • Contact:
        • Sub-Investigator:
          • Jair C. Soares, MD, PhD
        • Sub-Investigator:
          • Joao De Quevedo, MD, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Must have completed written informed consent
  • Must be at 25 years of age or older at screening (but below age of 70)
  • Confirmed Diagnostic and Statistical Manual of Mental Disorders (DSM-5) diagnosis of BD-II using clinical records and Diagnostic Interview for Anxiety, Mood, and Obsessive-compulsive disorder (OCD) and Related Neuropsychiatric Disorders (DIAMOND)
  • Must meet criteria for suicidality according to the INQ cutoff scores: A score of at least 12 on the Perceived Burden (PB) subscale and at least a score of 36 on the Thwarted Belongingness (TB) subscale indicating substantial risk for passive suicidal ideation
  • Must meet criteria for depression according to the MADRS cutoff scores: A score of 7-34 indicating mild to moderate depression
  • Must pass medical examination (physical exam, personal/family medical history, including consultation with current medical provider, ECG, about 4 tablespoons blood draw, psychiatric/psychological assessments, urine drug test)
  • Willingness to taper down mood stabilizers and other relevant medications (including but not limited to: antidepressants, antipsychotics, lithium, benzodiazepines, Monoamine oxidase inhibitors (MAOIs), Selective serotonin reuptake inhibitors (SSRIs), Serotonin and norepinephrine reuptake inhibitors (SNRIs), A serotonin-norepinephrine-dopamine reuptake inhibitors (SNDRIs), Tricyclic antidepressants (TCAs), stimulants, cannabis, and other medications, supplements or therapeutics that affect serotonergic function) for the duration of the study before and during administration days (starting 5 weeks before administration), and be off medication for at least 2 weeks prior to administration
  • Willingness to stop allowed medication at least 24 h prior to administration of psilocybin as advised by study physician (e.g., benzodiazepines)
  • Ability to complete all protocol required assessment tools without any assistance or alteration to the copyrighted assessments, and to comply with all study visits

Exclusion Criteria:

  • Participants who do not read/speak English
  • Active suicidal ideation with at least some intent and/or plan (i.e., a current score of 4 or 5 on the C-SSRS)
  • History of medically significant suicide attempt in the last 6 months
  • Current or past history of Bipolar I disorder, psychotic symptoms or psychotic disorder, (including but not limited to schizophrenia, delusional disorder, schizoaffective disorder) clinically relevant personality disorder (such as borderline, antisocial, narcissistic or paranoid personality disorder), or any serious psychiatric comorbidity considered negatively impacting participation or safety (e.g., PTSD or severe substance use or alcohol disorder) assessed by medical history and/or a structured clinical interview
  • Have a first or second degree relative with Bipolar I disorder or a psychotic disorder
  • Currently experiencing a hypomanic or mixed-symptom episode
  • Have a psychiatric or other condition judged to be incompatible with establishment of rapport or safe exposure to psilocybin
  • Any indication of a Personality Disorder (PD) such as but not limited to Borderline, Narcissistic, Antisocial, Paranoid, or Schizotypal PD based on Structured Clinical Interview for DSM-5 for PD and/or clinical judgment

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Psilocybin with therapeutic support
Up to two sequential administrations of 25 mg psilocybin with additional therapeutic support.
Drug: Psilocybin
Two sequential administrations of 25 mg psilocybin, 4 weeks apart.
Behavioral: Therapeutic Support

Five preparatory in-person psychotherapy sessions will be offered before the first administration session during weeks 1, 2, 3, 4, and 5. The optional second administration session will be preceded by a shorter 60 min preparatory session the day before.

Each administration session will be followed by 3 integration sessions and will adopt a Mindfulness-based CBT approach (M-CBT), in which a therapist will help the participant to process their experience and how to translate this into actual changes in everyday life.

If participants prefer more psychological support after the second administration session, they will be offered additional, optional therapy sessions for the duration of the trial regardless if they opted for a second administration session or not.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Acceptability of Two Dosing Sessions as Assessed by Number of Participants who Choose to Participate in a Second Administration Session
Time Frame: 11 weeks after first administration session
11 weeks after first administration session
Score on the Thwarted Belongingness (TB) Items of the Interpersonal Needs Questionnaire (INQ-15)
Time Frame: baseline, 3 weeks after first administration session
The Thwarted Belongingness (TB) section of the INQ-15 has a total score range from 9 to 63, with a higher score indicating greater TB.
baseline, 3 weeks after first administration session
Score on the Perceived Burdensomeness (PB) Items of the Interpersonal Needs Questionnaire (INQ-15)
Time Frame: baseline, 3 weeks after first administration session
The Perceived Burdensomeness (PB) section of the INQ-15 has a total score range from 6 to 42, with a higher score indicating greater PB.
baseline, 3 weeks after first administration session
Score on the Columbia-Suicide Severity Rating Scale (C-SSRS)
Time Frame: baseline, 3 weeks after first administration session
The total score on the C-SSRS ranges from 0-5, with 5 indicating the highest level of suicidal ideation.
baseline, 3 weeks after first administration session
Feasibility as Assessed by Number of Participants who Complete the Trial (Overall Retention)
Time Frame: from baseline to 3 weeks after first administration session
This is assessed by number of participants who complete the trial, that is, the number of participants who complete the first dose and follow-up visits up to 3 weeks after the first dose.
from baseline to 3 weeks after first administration session
Feasibility as Assessed by Number of Therapy Sessions Attended
Time Frame: from baseline to 3 weeks after first administration session
from baseline to 3 weeks after first administration session
Feasibility as Assessed by Number of Assessments Completed
Time Frame: from baseline to 3 weeks after first administration session
from baseline to 3 weeks after first administration session
Acceptability as Assessed by Number of Therapy Sessions Attended
Time Frame: from baseline to 11 weeks after first administration session
from baseline to 11 weeks after first administration session
Acceptability as Assessed by Number of Assessments Completed
Time Frame: from baseline to 11 weeks after first administration session
from baseline to 11 weeks after first administration session

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Score on the Montgomery-Åsberg Depression Rating Scale (MADRS)
Time Frame: baseline, 3 weeks after first administration session
The total score on the MADRS ranges from 0 to 60, with a higher score indicating a greater depression.
baseline, 3 weeks after first administration session
Score on the Quick Inventory of Depressive Symptomatology (QIDS-SR16)
Time Frame: baseline, 3 weeks after first administration session
Total score on the QIDS-SR16 ranges from 0 to 27, where higher scores indicate a higher occurence of depressive symptoms.
baseline, 3 weeks after first administration session
Score on the Altman Self-Rating Mania Scale (ASRM)
Time Frame: baseline, 3 weeks after first administration session
The total score on the ASRM ranges from 5-25, with higher scores indicating more severity of mania.
baseline, 3 weeks after first administration session
Score on the Young Mania Rating Scale (YMRS)
Time Frame: baseline, 3 weeks after first administration session
The total score on the YMRS ranges from 0 to 60, with higher scores indicating greater severity of mania.
baseline, 3 weeks after first administration session
Psychiatric Symptoms as Assessed by Score on the Brief Psychiatric Rating Scale (positive symptom subscale) (BPRS+)
Time Frame: baseline, 3 weeks after first administration session
The total score on the BPRS+ ranges from 4 to 28, with higher scores indicating a higher severity of psychopathology.
baseline, 3 weeks after first administration session

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

The University of Texas Health Science Center, Houston

Collaborators

Anne and Don Fizer Foundation

Investigators

  • Principal Investigator: Thomas Meyer, PhD, The University of Texas Health Science Center, Houston

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

July 7, 2025

Primary Completion (Estimated)

January 1, 2027

Study Completion (Estimated)

January 1, 2027

Study Registration Dates

First Submitted

November 22, 2024

First Submitted That Met QC Criteria

November 22, 2024

First Posted (Actual)

November 26, 2024

Study Record Updates

Last Update Posted (Actual)

July 18, 2025

Last Update Submitted That Met QC Criteria

July 15, 2025

Last Verified

July 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • HSC-MS-23-0905

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

Yes

Studies a U.S. FDA-regulated device product

No

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Depression, Bipolar

Clinical Trials on Psilocybin

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

CROs by country

CROs in Liberia

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Subscribe