Patient description: A 46-year-old Asian woman with MDD complains of persistent feelings of sadness and loss of interest in daily activities. She states that her mood is still depressed most of the days. She complains of loss of energy and feelings of worthlessness nearly every day. She is on anti-depressants for the past 6 months, but the symptoms are still present. She does not drink alcohol or smoke. She used to exercise every day for at least 30 min., but she doesn't have enough energy to do so for the past 3 weeks. She also has some digestive issues recently. She is married and has 4 children. She is menopausal. Her husband was diagnosed with colon cancer a year ago and is undergoing chemotherapy. Her past medical history is unremarkable. Her family history is negative for any psychologic problems. Her HAM-D score is 20.

Clinical trial eligibility criteria: eligible ages (years): 18.0-999.0,  Major Depressive Disorder Signed ICF 2. 18 years of age or above at Screening (V1) 3. Currently meet 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)  Psychiatric 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 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 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