Effects of Psilocybin in Major Depressive Disorder

NCT03181529 | Completed Phase 2 Results DMC FDA Drug

• 1 other identifier: IRB00101821
• Study Type: interventional
• Target: 27
• Locations: 1 country
• Sites: 1

Brief Summary

The proposed pilot study will assess whether people with major depressive disorder experience psychological and behavioral benefits and/or harms from psilocybin. This study will investigate acute and persisting effects of psilocybin on depressive symptoms and other moods, attitudes, and behaviors. The primary hypothesis is that psilocybin will lead to rapid and sustained antidepressant response, as measured with standard depression rating scales.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• The GRID-Hamilton Depression Rating Scale (GRID-HAMD)

  The GRID-Hamilton Depression Rating Scale is a 17-item clinician-administered rating scale designed to assess severity of depressive symptoms. The score range for the GRID-HAMD is 0 to 52, with higher score indicating more severe depression. For this clinician-rated measure, a clinically significant response was defined as ⩾50% decrease in measure relative to Baseline; symptom remission was defined as ⩾50% decrease in measure relative to Baseline and a score of ⩽7 on the GRID-HAMD * Week 0 Baseline = Initial baseline assessment * Week 5 Waitlist-Period (Delayed Group Only) = 5 weeks post enrollment, but pre-study drug in the Delayed Treatment group only. * Week 8 Waitlist-Period (Delayed Group Only) = 8 weeks post enrollment, but pre-study drug in the Delayed Treatment group only. * Week 1 Post Psilocybin Treatment = 1 week after the second psilocybin session in both the Immediate Treatment group (Week 5) and Delayed Treatment group (Week 13)

  Baseline (Week 0) to 1-week after second psilocybin session (Week 8 in Immediate Treatment; Week 13 in Delayed Treatment). The first psilocybin session (20 mg/70 kg) and second psilocybin session (30 mg/70 kg) are spaced approximately 1 week apart.

Study Arms (2)

Immediate Treatment

EXPERIMENTAL

Participants will begin psilocybin intervention immediately after study enrollment.

Drug: Psilocybin

Delayed Treatment

EXPERIMENTAL

Participants will begin the psilocybin intervention 8 weeks after study enrollment.

Drug: Psilocybin

Interventions

Psilocybin DRUG

Participants will receive a moderately high psilocybin dose in the first session and will receive either a moderately high or high psilocybin dose in the second session.

Delayed Treatment; Immediate Treatment

Eligibility Criteria

• Age: 21 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• to 75 years old
• Have given written informed consent
• Have at least a high-school level of education or equivalent (e.g. GED).
• Have a confirmed Diagnostic Statistical Manual (DSM-5) diagnosis of Major Depressive Disorder and currently experiencing a major depressive episode.
• No antidepressant medication for at least 2 weeks (4 weeks for fluoxetine) prior to enrollment.
• Concurrent psychotherapy is allowed if the type and frequency of the therapy has been stable for at least two months prior to screening and is expected to remain stable during participation in the study.
• Be medically stable as determined by screening for medical problems via a personal interview, a medical questionnaire, a physical examination, an electrocardiogram (ECG), and routine medical blood and urinalysis laboratory tests
• Agree to consume approximately the same amount of caffeine-containing beverage (e.g., coffee, tea) that he/she consumes on a usual morning, before arriving at the research unit on the mornings of drug session days. If the participant does not routinely consume caffeinated beverages, he/she must agree not to do so on session days.
• Agree to refrain from using any psychoactive drugs, including alcoholic beverages and nicotine, within 24 hours of each drug administration. The exception is caffeine. Participants will be required to be non-smokers.
• Agree not to take any Pro re nata (PRN) medications on the mornings of drug sessions
• Agree not to take sildenafil (Viagra®), tadalafil, or similar medications within 72 hours of each drug administration.
• Agree that for one week before each drug session, he/she will refrain from taking any nonprescription medication, nutritional supplement, or herbal supplement except when approved by the study investigators. Exceptions will be evaluated by the study investigators and will include acetaminophen, non-steroidal anti-inflammatory drugs, and common doses of vitamins and minerals.

You may not qualify if:

• Women who are pregnant (as indicated by a positive urine pregnancy test assessed at intake and before each drug session) or nursing; women who are of child-bearing potential and sexually active who are not practicing an effective means of birth control.
• Cardiovascular conditions: coronary artery disease, stroke, angina, uncontrolled hypertension, a clinically significant ECG abnormality (e.g., atrial fibrilation), prolonged QTc interval (i.e., QTc \> 450 msec), artificial heart valve, or Transient Ischemic Attack (TIA) in the past year
• Epilepsy with history of seizures
• Insulin-dependent diabetes; if taking oral hypoglycemic agent, then no history of hypoglycemia
• Currently taking psychoactive prescription medication on a regular (e.g., daily) basis
• Currently taking on a regular (e.g., daily) basis any medications having a primary centrally-acting serotonergic effect, including Mono-Amine Oxidase Inhibitors (MAOIs). For individuals who have intermittent or PRN use of such medications, psilocybin sessions will not be conducted until at least 5 half-lives of the agent have elapsed after the last dose.
• More than 25% outside the upper or lower range of ideal body weight according to Metropolitan Life height and weight table
• Current antidepressant use
• Current or past history of meeting DSM-5 criteria for schizophrenia spectrum or other psychotic disorders (except substance/medication-induced or due to another medical condition), or Bipolar I or II Disorder
• Current or history within one year of meeting DSM-5 criteria for a moderate or severe alcohol, tobacco, or other drug use disorder (excluding caffeine)
• Have a first or second-degree relative with schizophrenia spectrum or other psychotic disorders (except substance/medication-induced or due to another medical condition), or Bipolar I or II Disorder
• Has failed to respond to electroconvulsive therapy during the current major depressive episode
• Has a psychiatric condition judged to be incompatible with establishment of rapport or safe exposure to psilocybin
• Head trauma
• Claustrophobia incompatible with scanning

Sponsors & Collaborators

• Johns Hopkins University: lead

Study Sites (1)

Behavioral Pharmacology Research Unit, Johns Hopkins Bayview Medical Center

Baltimore, Maryland, 21224, United States

Location

Related Publications (2)

• Levin AW, Lancelotta R, Sepeda ND, Gukasyan N, Nayak S, Wagener TL, Barrett FS, Griffiths RR, Davis AK. The therapeutic alliance between study participants and intervention facilitators is associated with acute effects and clinical outcomes in a psilocybin-assisted therapy trial for major depressive disorder. PLoS One. 2024 Mar 14;19(3):e0300501. doi: 10.1371/journal.pone.0300501. eCollection 2024.

  PMID: 38483940 DERIVED

• 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 DERIVED

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Psilocybin

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Intervention Hierarchy (Ancestors)

Indole Alkaloids; Alkaloids; Heterocyclic Compounds; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Tryptamines; Indolizidines; Indolizines

Results Point of Contact

• Title: Dr. Roland Griffiths
• Organization: Johns Hopkins University

rgriff@jhmi.edu

410-550-0034

Study Officials

• Roland R Griffiths, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: Primary outcome measure (GRID-HAMD) will be assessed by raters blinded to randomization condition.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: June 7, 2017
• First Posted: June 8, 2017
• Study Start: August 10, 2017
• Primary Completion: December 2, 2020
• Study Completion: December 2, 2020
• Last Updated: December 15, 2021
• Results First Posted: December 15, 2021

Record last verified: 2021-11

Locations

US (1)