Trial Outcomes & Findings for Effects of Psilocybin in Major Depressive Disorder (NCT NCT03181529)

Last Updated: 2021-12-15

Results Overview

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)

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

27 participants

Primary outcome timeframe

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.

Results posted on

2021-12-15

Participant Flow

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.

Participant milestones

Participant milestones
Measure	Immediate Treatment 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.	Delayed Treatment 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.
Overall Study STARTED	15	12
Overall Study COMPLETED	13	11
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Immediate Treatment 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.	Delayed Treatment 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.
Overall Study Withdrawal by Subject	1	1
Overall Study Dropped out of study due to sleep difficulties. Sleep difficulties were also reported at screening	1	0

Baseline Characteristics

Effects of Psilocybin in Major Depressive Disorder

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Immediate Treatment n=13 Participants 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.	Delayed Treatment n=11 Participants 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 n=24 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	13 Participants n=5 Participants	11 Participants n=7 Participants	24 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Continuous	43.6 years STANDARD_DEVIATION 13.0 • n=5 Participants	35.2 years STANDARD_DEVIATION 9.9 • n=7 Participants	39.8 years STANDARD_DEVIATION 12.2 • n=5 Participants
Sex: Female, Male Female	9 Participants n=5 Participants	7 Participants n=7 Participants	16 Participants n=5 Participants
Sex: Female, Male Male	4 Participants n=5 Participants	4 Participants n=7 Participants	8 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) White	13 Participants n=5 Participants	9 Participants n=7 Participants	22 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	13 Participants n=5 Participants	11 Participants n=7 Participants	24 Participants n=5 Participants

PRIMARY outcome

Timeframe: 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 measures

Outcome measures
Measure	Immediate Treatment n=13 Participants 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.	Delayed Treatment n=11 Participants 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.
The GRID-Hamilton Depression Rating Scale (GRID-HAMD) Baseline	22.9 units on a scale Standard Deviation 3.6	22.5 units on a scale Standard Deviation 4.4
The GRID-Hamilton Depression Rating Scale (GRID-HAMD) Week 5 Waitlist-Period (Delayed Group Only)	NA units on a scale Standard Deviation NA This group did not have a waitlist period	23.8 units on a scale Standard Deviation 5.4
The GRID-Hamilton Depression Rating Scale (GRID-HAMD) Week 8 Waitlist-Period (Delayed Group Only)	NA units on a scale Standard Deviation NA This group did not have a waitlist period	23.5 units on a scale Standard Deviation 6.0
The GRID-Hamilton Depression Rating Scale (GRID-HAMD) Week 1 Post Psilocybin Treatment	8.0 units on a scale Standard Deviation 7.1	9.5 units on a scale Standard Deviation 8.3

Adverse Events

Session #1 Through 1-week Post-session #1 Follow-up

Serious events: 0 serious events

Other events: 9 other events

Deaths: 0 deaths

Session #2 Through 1-week Post-session #2 Follow-up

Serious events: 0 serious events

Other events: 11 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Session #1 Through 1-week Post-session #1 Follow-up n=24 participants at risk 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.	Session #2 Through 1-week Post-session #2 Follow-up n=24 participants at risk Participants received a high psilocybin dose (30 mg/70 kg) in the second session, and were assessed for adverse events at follow-up visits.
Vascular disorders Headache	29.2% 7/24 • Number of events 7 • Psilocybin session #1 to 1-week after psilocybin session #2 (3 weeks). Immediate treatment group: Weeks 3-5; delayed treatment group: Weeks 11-13. 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.	29.2% 7/24 • Number of events 7 • Psilocybin session #1 to 1-week after psilocybin session #2 (3 weeks). Immediate treatment group: Weeks 3-5; delayed treatment group: Weeks 11-13. 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.
General disorders Physical discomfort	4.2% 1/24 • Number of events 1 • Psilocybin session #1 to 1-week after psilocybin session #2 (3 weeks). Immediate treatment group: Weeks 3-5; delayed treatment group: Weeks 11-13. 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.	0.00% 0/24 • Psilocybin session #1 to 1-week after psilocybin session #2 (3 weeks). Immediate treatment group: Weeks 3-5; delayed treatment group: Weeks 11-13. 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.
Musculoskeletal and connective tissue disorders Mild controllable muscle motion	4.2% 1/24 • Number of events 1 • Psilocybin session #1 to 1-week after psilocybin session #2 (3 weeks). Immediate treatment group: Weeks 3-5; delayed treatment group: Weeks 11-13. 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.	0.00% 0/24 • Psilocybin session #1 to 1-week after psilocybin session #2 (3 weeks). Immediate treatment group: Weeks 3-5; delayed treatment group: Weeks 11-13. 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.
Eye disorders Visual distortion	4.2% 1/24 • Number of events 1 • Psilocybin session #1 to 1-week after psilocybin session #2 (3 weeks). Immediate treatment group: Weeks 3-5; delayed treatment group: Weeks 11-13. 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.	8.3% 2/24 • Number of events 2 • Psilocybin session #1 to 1-week after psilocybin session #2 (3 weeks). Immediate treatment group: Weeks 3-5; delayed treatment group: Weeks 11-13. 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.
Musculoskeletal and connective tissue disorders Tenseness/soreness	0.00% 0/24 • Psilocybin session #1 to 1-week after psilocybin session #2 (3 weeks). Immediate treatment group: Weeks 3-5; delayed treatment group: Weeks 11-13. 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.	8.3% 2/24 • Number of events 2 • Psilocybin session #1 to 1-week after psilocybin session #2 (3 weeks). Immediate treatment group: Weeks 3-5; delayed treatment group: Weeks 11-13. 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.
Musculoskeletal and connective tissue disorders Chest tightness	0.00% 0/24 • Psilocybin session #1 to 1-week after psilocybin session #2 (3 weeks). Immediate treatment group: Weeks 3-5; delayed treatment group: Weeks 11-13. 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.	4.2% 1/24 • Number of events 1 • Psilocybin session #1 to 1-week after psilocybin session #2 (3 weeks). Immediate treatment group: Weeks 3-5; delayed treatment group: Weeks 11-13. 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.
General disorders Vivid dreams	0.00% 0/24 • Psilocybin session #1 to 1-week after psilocybin session #2 (3 weeks). Immediate treatment group: Weeks 3-5; delayed treatment group: Weeks 11-13. 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.	4.2% 1/24 • Number of events 1 • Psilocybin session #1 to 1-week after psilocybin session #2 (3 weeks). Immediate treatment group: Weeks 3-5; delayed treatment group: Weeks 11-13. 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.
General disorders Altered body sensation	0.00% 0/24 • Psilocybin session #1 to 1-week after psilocybin session #2 (3 weeks). Immediate treatment group: Weeks 3-5; delayed treatment group: Weeks 11-13. 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.	4.2% 1/24 • Number of events 1 • Psilocybin session #1 to 1-week after psilocybin session #2 (3 weeks). Immediate treatment group: Weeks 3-5; delayed treatment group: Weeks 11-13. 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.
Vascular disorders Blood pressure event	4.2% 1/24 • Number of events 2 • Psilocybin session #1 to 1-week after psilocybin session #2 (3 weeks). Immediate treatment group: Weeks 3-5; delayed treatment group: Weeks 11-13. 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.	0.00% 0/24 • Psilocybin session #1 to 1-week after psilocybin session #2 (3 weeks). Immediate treatment group: Weeks 3-5; delayed treatment group: Weeks 11-13. 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.
Cardiac disorders Heart rate event	8.3% 2/24 • Number of events 7 • Psilocybin session #1 to 1-week after psilocybin session #2 (3 weeks). Immediate treatment group: Weeks 3-5; delayed treatment group: Weeks 11-13. 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.	8.3% 2/24 • Number of events 5 • Psilocybin session #1 to 1-week after psilocybin session #2 (3 weeks). Immediate treatment group: Weeks 3-5; delayed treatment group: Weeks 11-13. 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.

Additional Information

Dr. Roland Griffiths

Johns Hopkins University

Phone: 410-550-0034

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place