Major Depressive Disorder
Conditions
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.
Interventions
DRUGPsilocybin
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.
Sponsors
Johns Hopkins University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Masking description
Primary outcome measure (GRID-HAMD) will be assessed by raters blinded to randomization condition.
Eligibility
Sex/Gender
ALL
Age
21 Years to 75 Years
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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) |
Countries
United States
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.
Participants by arm
| Arm | Count |
|---|---|
| Immediate Treatment 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. | 13 |
| 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 and will receive either a moderately high or high psilocybin dose in the second session. | 11 |
| Total | 24 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Dropped out of study due to sleep difficulties. Sleep difficulties were also reported at screening | 1 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 |
Baseline characteristics
| Characteristic | Immediate Treatment | Delayed Treatment | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 13 Participants | 11 Participants | 24 Participants |
| Age, Continuous | 43.6 years STANDARD_DEVIATION 13 | 35.2 years STANDARD_DEVIATION 9.9 | 39.8 years STANDARD_DEVIATION 12.2 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 13 Participants | 9 Participants | 22 Participants |
| Region of Enrollment United States | 13 Participants | 11 Participants | 24 Participants |
| Sex: Female, Male Female | 9 Participants | 7 Participants | 16 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 8 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 24 | 0 / 24 |
| other Total, other adverse events | 9 / 24 | 11 / 24 |
| serious Total, serious adverse events | 0 / 24 | 0 / 24 |
Outcome results
Primary
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)
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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Immediate Treatment | The GRID-Hamilton Depression Rating Scale (GRID-HAMD) | Week 5 Waitlist-Period (Delayed Group Only) | NA units on a scale | — |
| Immediate Treatment | The GRID-Hamilton Depression Rating Scale (GRID-HAMD) | Baseline | 22.9 units on a scale | Standard Deviation 3.6 |
| Immediate Treatment | The GRID-Hamilton Depression Rating Scale (GRID-HAMD) | Week 8 Waitlist-Period (Delayed Group Only) | NA units on a scale | — |
| Immediate Treatment | The GRID-Hamilton Depression Rating Scale (GRID-HAMD) | Week 1 Post Psilocybin Treatment | 8.0 units on a scale | Standard Deviation 7.1 |
| Delayed Treatment | The GRID-Hamilton Depression Rating Scale (GRID-HAMD) | Week 1 Post Psilocybin Treatment | 9.5 units on a scale | Standard Deviation 8.3 |
| Delayed Treatment | The GRID-Hamilton Depression Rating Scale (GRID-HAMD) | Week 8 Waitlist-Period (Delayed Group Only) | 23.5 units on a scale | Standard Deviation 6 |
| Delayed Treatment | The GRID-Hamilton Depression Rating Scale (GRID-HAMD) | Baseline | 22.5 units on a scale | Standard Deviation 4.4 |
| Delayed Treatment | The GRID-Hamilton Depression Rating Scale (GRID-HAMD) | Week 5 Waitlist-Period (Delayed Group Only) | 23.8 units on a scale | Standard Deviation 5.4 |