The Safety and Efficacy of Psilocybin in Cancer Patients With Major Depressive Disorder

This is a Phase II, single-center, fixed dose, open label trial to explore the safety, tolerability and efficacy of a 25mg dose of psilocybin in cancer patients with MDD. The study population will include adult men and women, 18 years of age or above, with MDD, diagnosed with a malignant neoplasm. MDD is defined as those who meet DSM 5 diagnostic criteria for a single or recurrent episode of MDD without psychotic features. A diagnosis of a malignant neoplasm is defined as having a diagnostic code from C00 to C97 according to the ICD-10.

Recent randomized, placebo-controlled clinical trials of psilocybin therapy for anxiety and depression associated with cancer diagnosis showed significant improvement in study endpoints reflecting psychological distress, as compared to placebo. The effects of a single psilocybin therapy session endured for up to six months with no specific follow-up care. In this study, we aim to explore the safety and efficacy of psilocybin therapy in cancer patients, diagnosed with Major Depressive Disorder (MDD).

Eligibility Criteria:
Inclusion Criteria:

1. Signed ICF
2. 18 years of age or above at Screening (V1)
3. Currently meet criteria for MDD (single or recurrent episode as defined by DSM 5; if single episode, duration of more or equal to 3 months) based on medical records, clinical assessment and documented completion of the MINI version 7.0.2
4. A diagnosis of a malignant neoplasm with a diagnostic code from C00 to C97 according to the International Classification of Diseases and Related Health Problems, 10th Revision (ICD-10)
5. HAM D 17 score ≥18 at Screening (V1) and at Baseline (V2)
6. Are not currently taking any antidepressant and/or antipsychotic medications, or medical cannabis, at Screening (V1)
7. Able to complete all protocol required assessment tools without any assistance or alteration to the copyrighted assessments, and to comply with all study visits
8. Has capacity to consent (assessed via investigator judgement)

Exclusion Criteria:

Psychiatric Exclusion Criteria:

1. Current or past history of schizophrenia, psychotic disorder, bipolar disorder, delusional disorder, paranoid personality disorder, schizoaffective disorder, or borderline personality disorder, as assessed by medical history and a structured clinical interview (MINI version 7.0.2)
2. Current (within the past year) alcohol or drug use disorder as defined by DSM 5 (MINI 7.0.2) at Screening (V1)
3. Significant suicide risk as defined by (1) suicidal ideation as endorsed on items 4 or 5 on the C-SSRS within the past year, at Screening or at Baseline, or; (2) suicidal behaviors within the past year, or; (3) clinical assessment of significant suicidal risk during subject interview
4. Other personal circumstances and behaviour judged to be incompatible with establishment of rapport or safe exposure to psilocybin

   General Medical Exclusion Criteria:
5. Women who are pregnant, nursing, or planning a pregnancy. Women and men of child bearing potential and who are sexually active must agree to use an acceptable contraceptive method throughout their participation in the study. Women of child bearing potential must have a negative urine pregnancy test at Screening (V1) and Baseline (V2)
6. Cardiovascular conditions: recent stroke (\<1 year from signing of ICF), recent myocardial infarction (\<1 year from signing of ICF), uncontrolled hypertension (blood pressure \>140/90) or clinically significant arrhythmia within 1 year of signing the ICF
7. Uncontrolled or insulin dependent diabetes
8. Seizure disorder
9. Positive urine drug screen for illicit drugs or drugs of abuse at V1 and V2. Any positive urine drug test will be reviewed with participants to determine the pattern of use and eligibility will be determined at the investigator's discretion in conjunction with the medical monitor
10. Current enrollment in any investigational drug or device study or participation in such within 30 days of Screening.
11. Abnormal and clinically significant results on the physical examination, vital signs, ECG, or laboratory tests at Screening (V1) that in the investigator's opinion may consistute a risk for an individual who is explosed to psilocybin. This includes platelets below 50,000 platelets per cubic millimeter of blood, liver function tests three times the upper limit of normal, creatine two times above the normal range. Clinically significant abnormal electrolytes or low hemoglobin (below 8 g/L) should be corrected and rechecked
12. Any other clinically significant cardiovascular, pulmonary, gastrointestinal, hepatic, renal or any other major concurrent illness that, in the opinion of the investigator, may interfere with the interpretation of the study results or constitute a health risk for the participant if he/she takes part in the study
13. Use of psychedelics, including psilocybin but excluding medical marijuana, within the past 12 months and use of psychedelics during the current episode of depression
14. Concurrent or recent chemotherapy or radiation therapy, that impairs general level of phsyical functioning.