Oral and Sublingual Ketamine

Inclusion Criteria: * Participants must meet all the following criteria to be eligible for the study. Appendix B is a checklist that will be used by Dr. Hammound for screening, based on the following inclusion and exclusion criteria. 1. Age: Between 18 and 65 years (inclusive) at the time of screening. 2. Weight: Equal to or greater than 50 kg (110 lbs). 3. Diagnosis: A current diagnosis of Major Depressive Disorder (MDD), moderate to severe in intensity, as defined by the DSM-5 criteria. 4. Current Episode: Experiencing a moderate to severe Major Depressive Episode (MDE) at screening. 5. Ongoing Treatment: Actively receiving pharmacological treatment for MDD at the time of enrollment. 6. Treatment Resistance: Documented history of inadequate response to at least two antidepressant medications, each from a different pharmacological class, administered at an adequate dose and duration. 7. Capacity and Consent: Able and willing to provide written informed consent after understanding the nature, risks, and potential benefits of the study. 8. Clinical Oversight: Currently under the regular care of a psychiatrist or general practitioner (GP). 9. Support System: Has a responsible adult (e.g., family member or caregiver) who can accompany them from study visits or ensure safe transportation after ketamine has been used. 10. Able to speak, read and understand English Exclusion Criteria: * Participants will be excluded if any of the following criteria apply: 1. Suicidality: Active suicidal ideation with plan or intent, or suicidal behavior, within the past 3 months. 2. Concomitant Medications: Use of medications that may pose a risk of respiratory depression or serious adverse events when combined with ketamine (e.g., benzodiazepines, opioids, barbiturates). 3. Medical Comorbidities: Presence or history of significant or unstable medical conditions that could interfere with study participation or pose a safety risk, including but not limited to cerebrovascular accident, cardiac decompensation, large vessel aneurysms, glaucoma etc.. Participants with clinically significant laboratory abnormalities, as determined by the investigator, will also be excluded. 4. Hypersensitvity to ketamine 5. Uncontrolled hypertension (blood pressure ≥140/90 mmHg at screening, which may be repeated after 30 minutes rest) 6. Psychiatric Comorbidities: Diagnosis of bipolar disorder, psychotic disorders, or history of psychotic symptoms. 7. Substance Use: Clinically significant alcohol or substance use disorder within the last 6 months, as defined by DSM-5 criteria. 8. Cognitive Impairment: Any condition resulting in impaired capacity to understand or consent to participation or to comply with study procedures. 9. Pregnancy and Lactation: Pregnant or breastfeeding individuals. 10. Concurrent Research Participation: Participation in another interventional clinical trial or use of an investigational drug within the 30 days prior to screening. 11. Current or recent (within 90 days) treatment with ketamine (oral, IV or intranasal). 12. ECG demonstrates abnormalities like Qtc interval\>470 ms or any arrhythmia reported as clinically significant or abnormal by the interpreting physician. Exclusionary findings would include uncontrolled atrial fibrillation, ventricular arrhythmias, heart block, or other abnormalities that could pose a safety risk with ketamine administration