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

NCT ID: NCT06706232

Last Updated: 2025-07-18

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

PHASE2

Total Enrollment

10 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-07-07

Study Completion Date

2027-01-31

Brief Summary

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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.

Detailed Description

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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.

Conditions

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Bipolar II Disorder Depression, Bipolar Suicidality

Study Design

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Allocation Method

NA

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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Psilocybin with therapeutic support

Up to two sequential administrations of 25 mg psilocybin with additional therapeutic support.

Group Type EXPERIMENTAL

Psilocybin

Intervention Type DRUG

Two sequential administrations of 25 mg psilocybin, 4 weeks apart.

Therapeutic Support

Intervention Type BEHAVIORAL

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.

Interventions

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Psilocybin

Two sequential administrations of 25 mg psilocybin, 4 weeks apart.

Intervention Type DRUG

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.

Intervention Type BEHAVIORAL

Eligibility Criteria

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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
Minimum Eligible Age

25 Years

Maximum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Anne and Don Fizer Foundation

UNKNOWN

Sponsor Role collaborator

The University of Texas Health Science Center, Houston

OTHER

Sponsor Role lead

Responsible Party

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Thomas D. Meyer, PhD

Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Thomas Meyer, PhD

Role: PRINCIPAL_INVESTIGATOR

The University of Texas Health Science Center, Houston

Locations

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The University of Texas Health Science Center at Houston

Houston, Texas, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Thomas Meyer, PhD

Role: CONTACT

713-486-2643

Lauren Vale, MA

Role: CONTACT

713-486-2643

Facility Contacts

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Thomas Meyer, PhD

Role: primary

713-486-2643

Lauren Vale, MA

Role: backup

713-486-2643

References

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Aaronson ST, van der Vaart A, Miller T, LaPratt J, Swartz K, Shoultz A, Lauterbach M, Sackeim HA, Suppes T. Single-Dose Synthetic Psilocybin With Psychotherapy for Treatment-Resistant Bipolar Type II Major Depressive Episodes: A Nonrandomized Open-Label Trial. JAMA Psychiatry. 2024 Jun 1;81(6):555-562. doi: 10.1001/jamapsychiatry.2023.4685.

Reference Type BACKGROUND
PMID: 38055270 (View on PubMed)

Bogenschutz MP, Ross S, Bhatt S, Baron T, Forcehimes AA, Laska E, Mennenga SE, O'Donnell K, Owens LT, Podrebarac S, Rotrosen J, Tonigan JS, Worth L. Percentage of Heavy Drinking Days Following Psilocybin-Assisted Psychotherapy vs Placebo in the Treatment of Adult Patients With Alcohol Use Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2022 Oct 1;79(10):953-962. doi: 10.1001/jamapsychiatry.2022.2096.

Reference Type BACKGROUND
PMID: 36001306 (View on PubMed)

Carhart-Harris RL, Bolstridge M, Day CMJ, Rucker J, Watts R, Erritzoe DE, Kaelen M, Giribaldi B, Bloomfield M, Pilling S, Rickard JA, Forbes B, Feilding A, Taylor D, Curran HV, Nutt DJ. Psilocybin with psychological support for treatment-resistant depression: six-month follow-up. Psychopharmacology (Berl). 2018 Feb;235(2):399-408. doi: 10.1007/s00213-017-4771-x. Epub 2017 Nov 8.

Reference Type BACKGROUND
PMID: 29119217 (View on PubMed)

Davis AK, Barrett FS, May DG, Cosimano MP, Sepeda ND, Johnson MW, Finan PH, Griffiths RR. Effects of Psilocybin-Assisted Therapy on Major Depressive Disorder: A Randomized Clinical Trial. JAMA Psychiatry. 2021 May 1;78(5):481-489. doi: 10.1001/jamapsychiatry.2020.3285.

Reference Type BACKGROUND
PMID: 33146667 (View on PubMed)

Goodwin GM, Aaronson ST, Alvarez O, Arden PC, Baker A, Bennett JC, Bird C, Blom RE, Brennan C, Brusch D, Burke L, Campbell-Coker K, Carhart-Harris R, Cattell J, Daniel A, DeBattista C, Dunlop BW, Eisen K, Feifel D, Forbes M, Haumann HM, Hellerstein DJ, Hoppe AI, Husain MI, Jelen LA, Kamphuis J, Kawasaki J, Kelly JR, Key RE, Kishon R, Knatz Peck S, Knight G, Koolen MHB, Lean M, Licht RW, Maples-Keller JL, Mars J, Marwood L, McElhiney MC, Miller TL, Mirow A, Mistry S, Mletzko-Crowe T, Modlin LN, Nielsen RE, Nielson EM, Offerhaus SR, O'Keane V, Palenicek T, Printz D, Rademaker MC, van Reemst A, Reinholdt F, Repantis D, Rucker J, Rudow S, Ruffell S, Rush AJ, Schoevers RA, Seynaeve M, Shao S, Soares JC, Somers M, Stansfield SC, Sterling D, Strockis A, Tsai J, Visser L, Wahba M, Williams S, Young AH, Ywema P, Zisook S, Malievskaia E. Single-Dose Psilocybin for a Treatment-Resistant Episode of Major Depression. N Engl J Med. 2022 Nov 3;387(18):1637-1648. doi: 10.1056/NEJMoa2206443.

Reference Type BACKGROUND
PMID: 36322843 (View on PubMed)

Other Identifiers

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HSC-MS-23-0905

Identifier Type: -

Identifier Source: org_study_id

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