Effects of Psilocybin in Major Depressive Disorder
Condition: Major Depressive Disorder
MeSH terms: Depressive Disorder; Depression; Depressive Disorder, Major
Intervention: Psilocybin
Intervention description: 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.
Intervention MeSH terms: Psilocybin
Phase: Phase 2
Study type: Interventional
Primary purpose: Treatment
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.
Enrollment: 27.0
Sex: All
Minimum age: 21 Years
Maximum age: 75 Years
Healthy volunteers: No

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.
    

Eligibility criteria:

        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)