Treatment With Psilocybin for Chronic Neuropathic Pain and Depression (TRANSCEND)

Inclusion Criteria: 1. Adults 18 to 65 years old; 2. Are outpatients; 3. Must be deemed to have capacity to provide informed consent; 4. Must sign and date the informed consent form; 5. Stated willingness to comply with all study procedures; 6. Ability to read and communicate in English, such that their literacy and comprehension is sufficient for understanding the consent form and study questionnaires, as evaluated by study staff obtaining consent; 7. Primary DSM-5 diagnosis of non-psychotic MDD, single or recurrent, based on the Structured Clinical Interview for DSM-5 (SCID-5) administered at the first screening visit; 8. Participants diagnosed with treatment-resistant depression defined as individuals with a baseline HamD-17 score \> 14 and that have not responded to two or more separate trials of antidepressants at an adequate dosage and duration (an antidepressant resistance rating score of three or more is considered an adequate trial) based on the Antidepressant Treatment History Form (ATHF) (Sackeim \& Sackeim, 2001); there is no upper limit on the number of treatment failures; 9. Diagnosis of chronic neuropathic pain as determined by a pain specialist and confirmed with the standardized Leeds Assessment of Neuropathic Symptoms and Signs (LANSS) questionnaire 10. Moderate-to-severe neuropathic pain determined by Patient Reported Outcomes Measurement Information System (PROMIS) Pain Interference score of ≥ 60, as well as mean pain intensity scores ≥ 5 on a numeric rating scale 11. Previous trials of at least two medications recommended in the Canadian consensus guidelines on the management of neuropathic pain with no self-reported meaningful improvement in symptoms 12. Ability to take oral medication; 13. Individuals with an eGFR above 40mL/min/1.73m² and all blood work on clinical laboratory tests assessed as not clinically significant by study delegate physician at Screening (V1) 14. Individuals who are capable of becoming pregnant: use of highly effective contraception for at least 1 month prior to screening and agreement to use such a method during study participation; 15. Individuals who are willing to taper off current antidepressant and antipsychotic medications for a minimum of 2-weeks (or more depending on the medication) prior to Baseline (V2) and for the duration of the study and whose physician confirms that it is safe for them to do so; and 16. Agreement to adhere to Lifestyle Considerations (section 4.5) throughout study duration. Excl…