Table 1 Inclusion and exclusion criteria

Inclusion criteria:

 1. Age 18 years or older

 2. CDH diagnosis according to the International Classification of Headache Disorder – 3rd edition [18]

 3. Normal liver and kidney function

Exclusion criteria:

 1. Pregnant or breastfeeding participants

 2. Pre-existing renal impairment: stage 4 chronic kidney disease

 3. Pre-existing liver impairment, defined as alanine transaminase (ALT) and/or aspartate aminotransferase (AST) greater than two times the upper normal limit, an elevated total bilirubin (TB), an elevated alkaline phosphatase (AP), an elevated international normalized ratio (INR) for prothrombin time, and/or an elevated blood urea nitrogen (BUN)

 4. Chronic benzodiazepine or antipsychotic medication use

 5. History of a cerebrovascular event

 6. Significant and untreated hypertension and severe cardiac decompensation

 7. Pheochromocytoma

 8. Hyperthyroidism

 9. Glaucoma

 10. Concomitant use of strong CYP2B6 or CYP2C8 inhibitor

 11. Allergy or intolerance to ketamine

 12. Any significant cognitive or language barriers that impede participation

 13. Use of calcitonin gene-related peptide antagonists in one month or onabotulinum-toxin A in 3 months prior to the trial medication infusion, that is associated with greater than 30% reduction in headache intensity or number of migraine days

 14. Active diagnosis of post-traumatic stress disorder

 15. Active diagnosis of substance use disorder

 16. Daily oral morphine equivalent (OME) of 80 mg or higher