Ketamine-assisted Therapy for Advanced GI Cancer

Inclusion Criteria: 1. Must have a diagnosis of a stage 3 or 4 primary GI (i.e., pancreatic, colorectal, hepatocellular, biliary, and gastro-esophageal) cancer. 2. Must be willing to sign the informed consent form (ICF) and follow the study procedures as outlined in the ICF for the duration of the study. 3. Must be 18 years or older. 4. Must speak English and/or Spanish 5. Must have a Palliative Performance Score (PPS) v. 2.0 greater than or equal to 40%. 6. Must be able to swallow liquid oral medication. 7. Clinically significant moderate to severe demoralization as assessed by the Demoralization Scale-II (DS-II). 8. Must discontinue the following medications and refrain from taking following medications for the duration of study participation (participants who require these medications will be taken off study): 1. Lamotrigine 2. Clozapine 3. as-needed (PRN) anxiolytics. Note: Benzodiazepine use may be allowed if used in a regular, scheduled way. Consultation with the Principal Investigator is recommended. 4. Dopamine agonists 5. Lithium 9. Female-born participants of child-bearing potential with male-born partners must use highly effective contraception for at least 1 month prior to ketamine administration (on day 0) and agree to use such a method for an additional 2 months after ketamine administration. 10. Male-born participants with female-born partners of child-bearing potential must use highly effective contraception for at least 1 month prior to ketamine administration and agree to use such a method for an additional 2 months after ketamine administration. Note: Highly effective contraception include: * Intrauterine device (IUD) * Intrauterine hormone-releasing system (IUS) * Non-oral hormonal methods, including injected, intravaginal, implanted, transdermal * Oral hormones plus a barrier contraception (condom, diaphragm, or spermicide) * Double barrier method (at least two of the following: condom, diaphragm, and spermicide) * Vasectomy * Abstinence from penile-vaginal intercourse\* \*The reliability of abstinence should be evaluated carefully with the participant in relation to their general lifestyle. An additional acceptable birth control method should be discussed with the participant in case participants decide to engage in penile-vaginal intercourse during the course of the study. 11. Must agree to the following life-style considerations: 1. Continue receiving psychotherapy or other behavioral interventions for mental health as usual. Current interventions should not be stopped and new interventions should not be started during the study period once participants are enrolled in the study. 2. Consume no more than a modest quantity (e.g., 1 cup) of caffeine or xanthine-containing products (e.g., coffee or tea) the morning of receiving ketamine (on Day 0/Visit 4). 3. Abstain from alcohol for 24 hours before receiving ketamine. 4. Abstain from using any nicotine-containing products (including nicotine patches) for 3 hours before receiving ketamine. 5. If cannabis products are used regularly, participants will be asked to continue using regular amount but will be asked not to use cannabis within 24 hours prior to receiving ketamine. 6. If prescribed a regular dose of benzodiazepines, participants will be asked not to take medication the morning of the ketamine administration visit. 7. If taking any psychostimulants (e.g., methylphenidate), participants will be asked not to take psychostimulant drugs (other than caffeine) the morning of the ketamine administration visit. 8. Will be advised to maintain their usual opioid regimen. Note: Input will be obtained from the participant's regular clinical providers on appropriate pain management for the participant during the study, particularly in the case of analgesics associated with adverse reactions of concern with ketamine (e.g., tramadol and any opioid may increase risk of respiratory depression from ketamine). Exclusion Criteria: 1. Has a known allergic or severe reactions to the non-psychoactive components of liquid ketamine. 2. Has received treatment with another investigational drug or intervention within 1 month of signing Informed Consent Form (ICF). 3. Is deemed by clinical judgment of the study investigators to be unsafe for undergoing the intervention. 4. Recent use of ketamine for non-anesthesia purposes. 5. Frequent use of ketamine over lifetime. 6. Has a history of intra-cerebral hemorrhage. 7. Has cognitive impairment sufficient to impede the ability to complete study tasks. 8. Has had delirium/encephalopathy within 3 months of signing ICF. 9. Has a history of intracranial hemorrhage. 10. Has had a stroke (embolic) within 12 months of signing ICF. 11. Has had a seizure within 6 months of signing ICF. 12. Currently has an intracranial mass (e.g., primary tumor or brain metastasis). 13. Has an advanced stage of a neurologic disease that puts participants at elevated risk for psychosis (e.g., Parkinson or Huntington disease). 14. Has a history of a primary psychotic disorder or primary bipolar disorder I or II (determined by Quick Structured Clinical Interview for Diagnostic and Statistical Manual version 5 Disorders (QuickSCID-5)). 15. Has a history of dissociative disorder. 16. Recent active suicidal ideation. Note: This does not include requesting medical aid in dying. 17. Is currently receiving electroconvulsive therapy (ECT), transcranial magnetic stimulation (TMS) or similar somatic therapies. 18. Has baseline hypertension (≥150 SBP or ≥90 DBP), after repeated measurements. Note: Participants with hypertension that has been controlled by medication down to \<150 Systolic blood pressure (SBP) and \<90 diastolic blood pressure (DBP) will be allowed participate. 19. Has a history of aneurysmal vascular disease or dissection (including thoracic and abdominal aorta, intracranial and peripheral arterial vessels) or arteriovenous malformation. 20. Has had cardiac arrest within 12 months of signing ICF. 21. Has had a myocardial infarction within 12 months of signing ICF. 22. Has QT Corrected for Heart Rate using Fridericia's Formula (QTcf) \>480msec on 12-lead EKG. Note: Participants may qualify for the study if corrected QT Interval (QTc) 480-500 msec on one EKG, but then \<=480 msec on repeat EKG taken \>1 day later. If QT-prolonging medications are started or increased in dose after enrollment and prior to ketamine administration, a repeat EKG must be done \>12-hours after this change in order to assure continued safe enrollment in the trial. 23. Has clinically significant arrhythmia defined as 1. Ventricular fibrillation or ventricular tachycardia within 1 year of signing ICF 2. Bradycardia, severe, within 1 year of signing ICF Note: Participants with pacemakers will be considered to be eligible at the discretion of the Principal Investigator. 3. Atrial fibrillation, without rate or rhythm control 4. Supraventricular tachycardia (SVT), without standard treatment 5. Other clinically significant arrhythmias (e.g., Wolf Parkinson White) 24. Has symptomatic congestive heart failure (NYHA Class II-IV) 25. Has severe obstructive intracardiac abnormalities (e.g., aortic stenosis) 26. Has any current condition where physical activity is associated with palpitations, anginal pain or syncope. 27. Is unable to protect their own airway due to dysphagia, difficulty swallowing or a neurologic disease resulting in a risk of aspiration. 28. Has a history of flash pulmonary edema within 12 months of signing ICF. 29. Has a diagnosis of moderate or severe pulmonary hypertension. 30. Needs supplemental oxygen (intermittent or continuous). 31. Has current intractable nausea/vomiting/diarrhea. 32. Meets the following laboratory parameters: 1. Asymptomatic alanine aminotransferase (ALT) or aspartate aminotransferase (AST) \>=5x upper limit of normal (ULN). 2. Symptomatic ALT or AST \>= 2x ULN. 3. Total bilirubin \> 2x ULN (Gilbert syndrome is allowed) 4. Alkaline phosphatase \>5x ULN 5. International Normalized Ratio (INR) \> 2.5 for patients with any history of cirrhosis or gastrointestinal bleeding within 6 months of signing ICF. 6. Renal insufficiency (i.e., estimated glomerular filtration rate (eGFR) \< 30 milliliter/minute (mL/min) /1.73 m\^2 (using the 2021 Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) Creatinine Equation), Creatinine Clearance (CrCl) \< 30 mL/min (using the Cockcroft-Gault Equation), or current dialysis)). 33. Is currently pregnant or breastfeeding. 34. Has insulin-dependent diabetes with diabetes-related hospitalization within 6 months of signing ICF.