Psilocybin-Assisted Therapy as a Treatment for Depression

Official title

A Pilot Mechanistic Study of Psilocybin-Assisted Therapy as a Treatment for Depression

Overview

Depression is the leading cause of disability worldwide, affecting an estimated 300 million people. Despite available treatments, response rates remain modest, and treatment resistance is common. Novel treatments are needed that act rapidly, produce lasting effects and work differently than existing antidepressants. In clinical trials, psilocybin has shown promise as a treatment for depression due to its rapid onset of antidepressant effects and sustained benefits. This study will use MRI scanning of the brain and other biological measures (biomarkers) to investigate how psilocybin affects brain activity and psychological flexibility before, during, and after receiving psilocybin in participants with depressive symptoms.

Interventions

• Drug Psilocybin (Usona Institute)
  Capsule containing 25 mg of synthetic psilocybin

Primary outcome measures

• Characterize ACUTE (~1 week post-dose) and PERSISTING (~30 days post-dose) effects of PAT in depressed adults at two possible administrations on depression symptom severity using the Montgomery-Asberg Depression Rating Scale (MADRS) score. [Time frame: 1 week and 30 days post-dose for both administration sessions]
• Characterize ACUTE (~1 week post-dose) and PERSISTING (~30 days post-dose) effects of PAT in depressed adults at two possible administrations on psychological flexibility using the Multidimensional Psychological Flexibility Inventory (MPFI). [Time frame: 1 week and 30 days post-dose for both administration sessions]

Eligibility criteria

Inclusion criteria

• Age > 18 years
• Participants of childbearing potential must agree to practice 2 forms of effective birth control throughout the duration of the study
• Females of childbearing potential must have a negative urine pregnancy test at Screening and prior to dosing on Dosing Day
• Diagnosis of depression at Screening via the SCID-5-CT interview and MADRS score of ≥7
• Have an identified support person Agree to be accompanied home (or to an otherwise safe destination) by the support person, or another responsible party, following dosing

Exclusion criteria

• Unable to read or understand English
• Is currently pregnant or breastfeeding, or plan to become pregnant or breastfeed within the study period
• Has had Electroconvulsive Therapy, Transmagnetic Stimulation, Vagus Nerve Stimulation or Deep Brain Stimulation treatment within the last 12 months

a. Participants with VNS or DBS devices in place- including devices that are inactive or turned off will not be eligible to participate in the imaging portion of the study

• Is currently taking a medication on the prohibited medications list, such as heterocyclic (tricyclic, tetracyclic) antidepressants, monoamine oxidase inhibitors (MAOIs), antipsychotic augmentation therapy, or is taking more than one medication for the treatment of depression:

• Participants who are taking a single prescription medication for depression must be on a stable, minimally therapeutic/tolerated dose for at least 4 weeks prior to Screening.
• Psychostimulants for the treatment of attention-deficit/hyperactivity disorder (ADHD) are allowed, if used at a stable dose or pattern for at least 6-weeks prior to Screening and not used on Dosing Day(s).
• Has a primary psychotic disorder diagnosis
• Has a first-degree relative with a known history of a psychotic disorder
• Meets criteria for substance use disorder or diagnosis of substance use disorder within 6 months prior to Screening
• Has an unstable medical condition or serious abnormalities of complete blood count, chemistries, or ECG, or taking medications that in the opinion of the study clinician would preclude safe participation in the trial
• Is at risk for hypertensive crisis defined as:

• BP at Screening AND Baseline >140/90 mmHG
• BP on Dosing Day prior to dosing >140/90 mmHG
• Has used a serotonergic hallucinogenic substance (e.g., psilocybin, lysergic acid diethylamide (LSD), mescaline, N,N-dimethyltryptamine (DMT), 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT), ibogaine, 3,4-methylenedioxymethamphetamine (MDMA), or other related substances) within 6 months of Screening.
• Has a known sensitivity to psychedelic medications
• Has a positive urine drug test including amphetamines, barbiturates, buprenorphine, benzodiazepines, cocaine, methamphetamine (unless prescribed), MDMA, methadone, opiates, and phencyclidine (PCP)
• Is at high risk for suicide (e.g., active suicidal ideation and or current intent or plan) and unable to be managed safely (i.e., unwilling to be hospitalized)

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

N/A

Model

Single group

Masking

Open label

Primary purpose

Basic science

Study locations

United States · 1 center

• Washington University School of Medicine — St Louis

Publications

• Siegel JS, Subramanian S, Perry D, Kay BP, Gordon EM, Laumann TO, Reneau TR, Metcalf NV, Chacko RV, Gratton C, Horan C, Krimmel SR, Shimony JS, Schweiger JA, Wong DF, Bender DA, Scheidter KM, Whiting FI, Padawer-Curry JA, Shinohara RT, Chen Y, Moser J, Yacoub E, Nelson SM, Vizioli L, Fair DA, Lenze EJ, Carhart-Harris R, Raison CL, Raichle ME, Snyder AZ, Nicol GE, Dosenbach NUF. Psilocybin desynchr PMID 39020167

Identifiers

NCT: NCT07582120 · 202603029

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗