Psilocybin-Assisted Therapy in Treatment-Resistant Depression

NCT06303739 | Active Not Recruiting Phase 3 FDA Drug

• 1 other identifier: 22-1421
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The goal of this clinical trial is to test how well psilocybin-assisted therapy works in treating people with depression. The main questions this study aims to answer are:

• Does psilocybin with assisted therapy help improve symptoms for people with depression?
• How long do the effects of this treatment last? Participants will:
• Take part in a couple of screening and preparation visits.
• Be given psilocybin in one or two treatment sessions.
• Attend a series of follow-up sessions over the following year.
• Complete forms and surveys to test how their symptoms have changed and what they thought of their experience. Researchers will also compare whether one treatment or two treatments help improve symptoms more for participants.

Conditions

Refractory Depression; Treatment Resistant Depression

Keywords

psilocybin; psychedelic; refractory depression; psychedelic-assisted therapy; treatment-resistant depression; TRD; depression

Outcome Measures

Primary Outcomes (4)

• Change in HAM-D-17 Scores between Baseline and 2 Weeks after Treatment

  The change in Hamilton Depression Rating Scale 17 item (HAM-D-17) scores between baseline and 2 weeks after treatment The HAM-D-17 is a 17-item questionnaire used to measure severity of depression. The score ranges from 0 to 52. Higher scores indicate more severe depression.

  Baseline, 2 weeks

• Change in QIDS SR-16 Scores between Baseline and 2 Weeks after Treatment

  The change between depression scores as reported by Quick Inventory of Depressive Symptomatology Short Response-16 (QIDS SR-16) scores between baseline and 2 weeks after treatment The QIDS SR-16 is a 16-item questionnaire used to measure severity of depression. The scores range from 0 to 45. Higher scores indicate more severe depression.

  Baseline, 2 weeks

• Number of Participants Achieving Remission 2 Weeks after Treatment

  Number of participants achieving remission (defined as a HAM-D-17 score less than 10) 2 weeks after treatment

  up to 2 weeks

• Number of Participants Achieving Response 2 weeks after treatment

  Number of participants achieving response (defined as a HAM-D-17 score that has decreased by greater than or equal to 50 percent compared to baseline) 2 weeks after treatment

  up to 2 weeks

Secondary Outcomes (22)

• Number of Participants Achieving Remission at 6 Weeks

  up to 6 weeks

• Number of Participants Achieving Response at 6 Weeks

  up to 6 weeks

• Number of Participants Achieving Remission at 3 Months

  up to 3 months

• Number of Participants Achieving Response at 3 Months

  up to 3 months

• Number of Participants Achieving Remission at 6 Months

  up to 6 months

Study Arms (2)

Single Psilocybin Treatment

EXPERIMENTAL

Participants will be administered one dose of a 25mg capsule of psilocybin. This will be administered one time.

Drug: psilocybin

Two Psilocybin Treatments

ACTIVE COMPARATOR

Participants will be administered one dose of a 25mg capsule of psilocybin. Two weeks later, the participant will be administered one more dose of a 25mg capsule of psilocybin.

Drug: psilocybin

Interventions

psilocybin DRUG

25mg of psilocybin administered during treatment session, accompanied by preparation before, integration after, and assistive therapy during the session.

Single Psilocybin Treatment; Two Psilocybin Treatments

Eligibility Criteria

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

You may qualify if:

• Provision of signed and dated informed consent form.
• Willingness to comply with all study procedures and availability for the study.
• Diagnostic and Statistical Manual of Mental Disorders 5 (DSM-V) diagnosis of major depressive disorder.
• Currently experiencing a major depressive episode, lasting at least 3 months
• Failure to respond or inability to tolerate at least 2 guideline-concordant pharmacological treatments from different pharmacologic classes during the current major depressive episode
• Good health evidenced by medical history and routine lab tests
• No central nervous system (CNS) or neurocognitive impairment
• Ability to take oral medication and to follow to the psilocybin-assisted therapy protocol
• Identified support person to accompany patient home after dosing
• Use of effective contraception throughout the study by those with child-bearing potential
• Use of condoms or other effective contraceptive methods by males with reproductive potential
• Fully vaccinated and up to date on vaccination against COVID-19, as defined by Center for Disease Control guidelines
• Following Lifestyle Considerations throughout study (no nicotine containing products in clinical unit, refrain from operating heavy machinery for the duration of treatment day, no more than two servings 8 hours prior to treatment, no psychoactive drugs 72 hours before treatment, refrain from consuming foods that would interfere with drug absorption, minimize interaction with household immunocompromised contacts)

You may not qualify if:

• Family history (first- or second-degree relatives) or diagnosis of bipolar disorder with psychotic features, schizophrenia, schizoaffective disorder, hallucinogen-induced psychosis, anti-social personality disorder, or other psychotic disorder.
• Borderline personality disorder, defined by DSM-V criteria, that in the judgement of the Investigator is likely to complicate the assessment of clinical response to study treatments or limits the patient's ability to comply with study procedures.
• Alcohol or other substance use disorder (except tobacco/nicotine) that has been active within the 6 months prior to enrollment.
• Recent use (within past 4 weeks) of esketamine, ketamine or classic hallucinogens (psilocybin-containing mushrooms or LSD) or use of psychedelics within the past 6 months or more than 10 times in lifetime.
• Participants with active suicidal ideation or plan with a Columbia Suicide Severity Rating Scale (C-SSRS) score greater than or equal to 4.
• Current active self-injurious behavior, requiring medical attention or per investigator discretion.
• Diagnosis of Obsessive-compulsive disorder or post-traumatic stress disorder.
• Within 72 hours of psilocybin administration, use of nicotine, alcohol, or other controlled substances (use related to over-the-counter or prescribed medications may be allowed per the Primary Investigator's discretion).
• Current delirium, dementia, amnestic disorder, or other cognitive disorders.
• Any current or past medical or neurological illness (including chronic pain syndromes and/or history of cerebrovascular event (excluding migraine)) that, in the opinion of the investigator, may confound the interpretation of study assessments
• Known allergic reactions to components of psilocybin.
• Medically instability at screening, including hepatic, renal, circulatory, cardiac (arrhythmia, uncontrolled hypertension, systolic BP \> 140 mmHg or diastolic BP \> 90 mmHg, abnormal QTc), pulmonary or CNS (seizure disorder or treatment with antiepileptic drugs) impairment.
• Current pregnancy or lactation.
• Febrile illness in last 3 weeks.
• Current use or use within 4 weeks of psilocybin administration of Monoamine oxidase inhibitors (MAOIs), alcohol dehydrogenase inhibitors and antipsychotics (concomitant medications will be allowed per investigator discretion).

Sponsors & Collaborators

• Foundation of Hope, North Carolina: collaborator
• University of North Carolina, Chapel Hill: lead

Study Sites (1)

UNC Chapel Hill Medical Center

Chapel Hill, North Carolina, 27514, United States

Location

Related Publications (15)

• Demyttenaere K, Van Duppen Z. The Impact of (the Concept of) Treatment-Resistant Depression: An Opinion Review. Int J Neuropsychopharmacol. 2019 Feb 1;22(2):85-92. doi: 10.1093/ijnp/pyy052.

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• Dold M, Kasper S. Evidence-based pharmacotherapy of treatment-resistant unipolar depression. Int J Psychiatry Clin Pract. 2017 Mar;21(1):13-23. doi: 10.1080/13651501.2016.1248852. Epub 2016 Nov 16.

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• Keller MB, Shapiro RW, Lavori PW, Wolfe N. Recovery in major depressive disorder: analysis with the life table and regression models. Arch Gen Psychiatry. 1982 Aug;39(8):905-10. doi: 10.1001/archpsyc.1982.04290080025004.

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• Griffiths RR, Johnson MW, Carducci MA, Umbricht A, Richards WA, Richards BD, Cosimano MP, Klinedinst MA. Psilocybin produces substantial and sustained decreases in depression and anxiety in patients with life-threatening cancer: A randomized double-blind trial. J Psychopharmacol. 2016 Dec;30(12):1181-1197. doi: 10.1177/0269881116675513.

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• Carhart-Harris R, Giribaldi B, Watts R, Baker-Jones M, Murphy-Beiner A, Murphy R, Martell J, Blemings A, Erritzoe D, Nutt DJ. Trial of Psilocybin versus Escitalopram for Depression. N Engl J Med. 2021 Apr 15;384(15):1402-1411. doi: 10.1056/NEJMoa2032994.

  PMID: 33852780 BACKGROUND

• Carhart-Harris RL, Bolstridge M, Rucker J, Day CM, Erritzoe D, Kaelen M, Bloomfield M, Rickard JA, Forbes B, Feilding A, Taylor D, Pilling S, Curran VH, Nutt DJ. Psilocybin with psychological support for treatment-resistant depression: an open-label feasibility study. Lancet Psychiatry. 2016 Jul;3(7):619-27. doi: 10.1016/S2215-0366(16)30065-7. Epub 2016 May 17.

  PMID: 27210031 BACKGROUND

• 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.

  PMID: 29119217 BACKGROUND

• 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.

  PMID: 33146667 BACKGROUND

• Gukasyan N, Davis AK, Barrett FS, Cosimano MP, Sepeda ND, Johnson MW, Griffiths RR. Efficacy and safety of psilocybin-assisted treatment for major depressive disorder: Prospective 12-month follow-up. J Psychopharmacol. 2022 Feb;36(2):151-158. doi: 10.1177/02698811211073759.

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• Barrett FS, Johnson MW, Griffiths RR. Validation of the revised Mystical Experience Questionnaire in experimental sessions with psilocybin. J Psychopharmacol. 2015 Nov;29(11):1182-90. doi: 10.1177/0269881115609019. Epub 2015 Oct 6.

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• Maclean KA, Leoutsakos JM, Johnson MW, Griffiths RR. Factor Analysis of the Mystical Experience Questionnaire: A Study of Experiences Occasioned by the Hallucinogen Psilocybin. J Sci Study Relig. 2012 Dec;51(4):721-737. doi: 10.1111/j.1468-5906.2012.01685.x.

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• Murphy R, Kettner H, Zeifman R, Giribaldi B, Kartner L, Martell J, Read T, Murphy-Beiner A, Baker-Jones M, Nutt D, Erritzoe D, Watts R, Carhart-Harris R. Therapeutic Alliance and Rapport Modulate Responses to Psilocybin Assisted Therapy for Depression. Front Pharmacol. 2022 Mar 31;12:788155. doi: 10.3389/fphar.2021.788155. eCollection 2021.

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• Bond FW, Hayes SC, Baer RA, Carpenter KM, Guenole N, Orcutt HK, Waltz T, Zettle RD. Preliminary psychometric properties of the Acceptance and Action Questionnaire-II: a revised measure of psychological inflexibility and experiential avoidance. Behav Ther. 2011 Dec;42(4):676-88. doi: 10.1016/j.beth.2011.03.007. Epub 2011 May 25.

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MeSH Terms

Conditions

Depressive Disorder, Treatment-Resistant; Depression

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders; 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

• Robert K McClure, MD

  Director of Interventional Psychiatry

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Due to the nature of the study and limitations of study staffing, only those conducting assessments and ratings throughout the study will be masked to the treatments. All others, including participants, therapists, investigators, and study coordinator, will not be masked to the number of treatments a participant receives.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are randomized into one of two groups and will receive either one single treatment of psilocybin-assisted therapy with follow-up therapy and assessments or two treatments spaced two weeks apart with follow-up therapy and assessments.

Study Record Dates

• First Submitted: February 27, 2024
• First Posted: March 12, 2024
• Study Start: April 19, 2024
• Primary Completion: April 9, 2026
• Study Completion (Estimated): March 26, 2027
• Last Updated: May 6, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Data will be provided beginning 9 and continuing for 36 months following publication.
• Access Criteria: Investigator has approved IRB, IEC, or REB and an executed data use/sharing agreement with UNC.

Locations

US (1)