Psilocybin-assisted therapy for treatment-resistant depression

Induction Protocol for Psilocybin-Assisted Therapy in Treatment-Resistant Depression (TRD): A Pilot Study

This study is testing if therapy combined with psilocybin can help people with treatment-resistant depression feel better over time.

Quick facts

• Phase: PHASE3
• Study type: Interventional
• Enrollment: 20 (estimated)
• Ages: 18 Years to 70 Years
• Sex: All
• Sponsor: University of North Carolina, Chapel Hill (other)
• Locations: 1 site (Chapel Hill, North Carolina)
• Trial ID: NCT06303739 on ClinicalTrials.gov

What this trial studies

This clinical trial aims to evaluate the effectiveness of psilocybin-assisted therapy in individuals suffering from treatment-resistant depression (TRD). Participants will undergo screening and preparation visits, receive psilocybin in one or two treatment sessions, and attend follow-up sessions over the course of a year. The study will assess symptom changes and participant experiences through forms and surveys, while comparing the outcomes of one versus two treatment sessions. The goal is to determine both the immediate and long-term effects of psilocybin on depressive symptoms.

Who should consider this trial

Good fit: Ideal candidates are adults diagnosed with major depressive disorder who have not responded to at least two different classes of antidepressant medications.

Not a fit: Patients who do not have a diagnosis of major depressive disorder or those who have not experienced treatment resistance may not benefit from this study.

Why it matters

Potential benefit: If successful, this treatment could provide a novel and effective option for patients with treatment-resistant depression.

How similar studies have performed: Previous studies have shown promising results for psilocybin in treating depression, indicating potential for success in this approach.

Eligibility criteria

Inclusion Criteria:

* 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)

Exclusion Criteria:

* 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 6 months) of esketamine, ketamine or classic hallucinogens (psilocybin-containing mushrooms or LSD) or use of psychedelics 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.
* 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).
* Current treatment with buproprion greater than 300mg/day.
* Current use of tramadol.
* Prior participation in psilocybin-assisted therapy trial and or regular use of hallucinogens
* Treatment with another investigational drug or other intervention during study period.

Where this trial is running

Chapel Hill, North Carolina

• UNC Chapel Hill Medical Center — Chapel Hill, North Carolina, United States (RECRUITING)

Study contacts

• Principal investigator: Robert K McClure, MD — Director of Interventional Psychiatry
• Study coordinator: Brittania Ricketts

Conditions: Refractory Depression, Treatment Resistant Depression, psilocybin, psychedelic, refractory depression, psychedelic-assisted therapy, treatment-resistant depression, TRD