Effects of Psilocybin in Major Depressive Disorder

• Sponsor: Johns Hopkins University (Other)
• Overall Status: Completed
• CT.gov ID: NCT03181529
• Collaborator: (none)
• Enrollment: 27
• Location: 1
• Arms: 2
• Actual Duration (Months): 39.8
• Patients Per Site Per Month: 0.7

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Major Depressive Disorder	Drug: Psilocybin	Phase 2

Study Design

• Study Type: Interventional
• Actual Enrollment: 27 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Masking Description: Primary outcome measure (GRID-HAMD) will be assessed by raters blinded to randomization condition.
• Primary Purpose: Treatment
• Official Title: Effects of Psilocybin in Major Depressive Disorder
• Actual Study Start Date: Aug 10, 2017
• Actual Primary Completion Date: Dec 2, 2020
• Actual Study Completion Date: Dec 2, 2020

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Immediate Treatment Participants will begin psilocybin intervention immediately after study enrollment.	Drug: Psilocybin; 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.
Experimental: Delayed Treatment Participants will begin the psilocybin intervention 8 weeks after study enrollment.	Drug: Psilocybin; 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.

Outcome Measures

Primary Outcome Measures

1. The GRID-Hamilton Depression Rating Scale (GRID-HAMD) [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.]

   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)

Eligibility Criteria

Criteria

• Ages Eligible for Study: 21 Years to 75 Years
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• 21 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.

Exclusion Criteria:

• 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

Psychiatric Exclusion Criteria:

• 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

Additional Magnetic Resonance Imaging (MRI) Exclusion Criteria:

• Head trauma

• Claustrophobia incompatible with scanning

• Cardiac pacemaker

• Implanted cardiac defibrillator

• Aneurysm brain clip

• Inner ear implant

• Prior history as a metal worker and/or certain metallic objects in the body

• History of clinically significant vertigo, seizure disorder, middle ear disorder, or double vision

• Poor vision not adequately corrected (in order to complete emotional processing task)

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Behavioral Pharmacology Research Unit, Johns Hopkins Bayview Medical Center	Baltimore	Maryland	United States	21224

Sponsors and Collaborators

• Johns Hopkins University

Investigators

• Principal Investigator: Roland R Griffiths, PhD, Johns Hopkins University

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Jul 8, 2020

More Information

Publications

None provided.

• Responsible Party: Johns Hopkins University
• ClinicalTrials.gov Identifier: NCT03181529
• Other Study ID Numbers: IRB00101821
• First Posted: Jun 8, 2017
• Last Update Posted: Dec 15, 2021
• Last Verified: Nov 1, 2021

• Studies a U.S. FDA-regulated Drug Product: Yes
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major; Psilocybin

Study Results

Participant Flow

Recruitment Details	Target recruitment for this study was 24 study completers. Due to participant drop outs (reasons described in Figure 1 of the study manuscript), we enrolled a total of 27 participants to achieve our target recruitment goals.

Arm/Group Title	Immediate Treatment	Delayed Treatment
Arm/Group Description	Participants will begin psilocybin intervention immediately after study enrollment. Psilocybin: Participants will receive a moderately high psilocybin dose in the first session (20 mg/70 kg) and a high dose in the second session (30 mg/70 kg), spaced approximately 1-week apart.	Participants will begin the psilocybin intervention 8 weeks after study enrollment. Psilocybin: Participants will receive a moderately high psilocybin dose in the first session (20 mg/70 kg) and a high dose in the second session (30 mg/70 kg), spaced approximately 1-week apart.
Period Title: Overall Study
STARTED	15	12
COMPLETED	13	11
NOT COMPLETED	2	1

Baseline Characteristics

Arm/Group Title	Immediate Treatment	Delayed Treatment	Total
Arm/Group Description	Participants will begin psilocybin intervention immediately after study enrollment. Psilocybin: 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.	Participants will begin the psilocybin intervention 8 weeks after study enrollment. Psilocybin: 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.	Total of all reporting groups
Overall Participants	13	11	24
Age (Count of Participants)
<=18 years	0 0%	0 0%	0 0%
Between 18 and 65 years	13 100%	11 100%	24 100%
>=65 years	0 0%	0 0%	0 0%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	43.6 (13.0)	35.2 (9.9)	39.8 (12.2)
Sex: Female, Male (Count of Participants)
Female	9 69.2%	7 63.6%	16 66.7%
Male	4 30.8%	4 36.4%	8 33.3%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	0 0%	1 9.1%	1 4.2%
Native Hawaiian or Other Pacific Islander	0 0%	0 0%	0 0%
Black or African American	0 0%	1 9.1%	1 4.2%
White	13 100%	9 81.8%	22 91.7%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	0 0%	0 0%	0 0%
Region of Enrollment (Count of Participants)
United States	13 100%	11 100%	24 100%

Outcome Measures

1. Primary Outcome

Title	The GRID-Hamilton Depression Rating Scale (GRID-HAMD)
Description	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)
Time Frame	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.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Immediate Treatment	Delayed Treatment
Arm/Group Description	Participants will begin psilocybin intervention immediately after study enrollment. Psilocybin: 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.	Participants will begin the psilocybin intervention 8 weeks after study enrollment. Psilocybin: 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.
Measure Participants	13	11
Baseline	22.9 (3.6)	22.5 (4.4)
Week 5 Waitlist-Period (Delayed Group Only)	NA (NA)	23.8 (5.4)
Week 8 Waitlist-Period (Delayed Group Only)	NA (NA)	23.5 (6.0)
Week 1 Post Psilocybin Treatment	8.0 (7.1)	9.5 (8.3)

Adverse Events

Time Frame	Psilocybin session #1 to 1-week after psilocybin session #2 (3 weeks). Immediate treatment group: Weeks 3-5; delayed treatment group: Weeks 11-13.
Adverse Event Reporting Description	At each study visit, participants were asked to report on any adverse events since their last study visit. At the psilocybin Session #1, participants were administered 20 mg/70 kg. At the psilocybin Session #2, participants were administered 30 mg/70 kg. Therefore, adverse events are reported here by session number to indicate the rate of adverse events after each drug administration session. No adverse events related to the study were reported prior to drug administration.
Arm/Group Title	Session #1 Through 1-week Post-session #1 Follow-up		Session #2 Through 1-week Post-session #2 Follow-up
Arm/Group Description	Participants received a moderately high psilocybin dose (20 mg/70 kg) in the first session, and were assessed for adverse events at follow-up visits.		Participants received a high psilocybin dose (30 mg/70 kg) in the second session, and were assessed for adverse events at follow-up visits.
All Cause Mortality
	Session #1 Through 1-week Post-session #1 Follow-up		Session #2 Through 1-week Post-session #2 Follow-up
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/24 (0%)
Serious Adverse Events
	Session #1 Through 1-week Post-session #1 Follow-up		Session #2 Through 1-week Post-session #2 Follow-up
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/24 (0%)		0/24 (0%)
Other (Not Including Serious) Adverse Events
	Session #1 Through 1-week Post-session #1 Follow-up		Session #2 Through 1-week Post-session #2 Follow-up
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	9/24 (37.5%)		11/24 (45.8%)
Cardiac disorders
Heart rate event	2/24 (8.3%)	7	2/24 (8.3%)	5
Eye disorders
Visual distortion	1/24 (4.2%)	1	2/24 (8.3%)	2
General disorders
Physical discomfort	1/24 (4.2%)	1	0/24 (0%)	0
Vivid dreams	0/24 (0%)	0	1/24 (4.2%)	1
Altered body sensation	0/24 (0%)	0	1/24 (4.2%)	1
Musculoskeletal and connective tissue disorders
Mild controllable muscle motion	1/24 (4.2%)	1	0/24 (0%)	0
Tenseness/soreness	0/24 (0%)	0	2/24 (8.3%)	2
Chest tightness	0/24 (0%)	0	1/24 (4.2%)	1
Vascular disorders
Headache	7/24 (29.2%)	7	7/24 (29.2%)	7
Blood pressure event	1/24 (4.2%)	2	0/24 (0%)	0

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.