Investigating the Analgesic Potential of (2R,6R)-HNK in Acute Pain in Healthy Volunteers

* INCLUSION CRITERIA: In order to be eligible to participate in this study, an individual must meet all of the following criteria: 1. Provision of signed and dated informed consent form 2. Stated willingness to comply with all study procedures and availability for the duration of the study 3. Aged 18-60 4. In good general health as evidenced by medical history 5. Ability to take intravenous medication and be willing to adhere to the (2R,6R)-HNK regimen 6. For females of reproductive potential: Use of highly effective contraception starting at the time of enrollment and agreement to use such a method during study participation and for an additional four weeks after the end of participation 7. For males of reproductive potential: Use of condoms or other effective contraceptive methods from the time of enrollment, and for an additional 90 days after the end of participation 8. Agreement to adhere to Lifestyle Considerations throughout study duration 9. Ability of participant to understand and the willingness to sign a written informed consent document EXCLUSION CRITERIA: An individual who meets any of the following criteria will be excluded from participation in this study:00 1. Current use of disallowed concomitant medications. 2. Presence of ferromagnetic devices or any devices that could pose a risk relating to the safety of the fMRI procedure, including implanted cardiac pacemaker or auto-defibrillator, insulin pump, ferromagnetic metal in the cranial cavity or eye (e.g. aneurysm clip, implanted neural stimulator, cochlear implant, ocular foreign body), and irremovable body piercings. 3. Pregnancy or lactation. 4. Has a clinically important acute or active chronic disease 5. Has a history of any clinically important cardiovascular findings 6. Has a history of serious medical illness, including but not limited to the following body systems and organs or those that in the judgment of the Principal Investigator and Medical Advisory Investigator pose a risk to the participant s ability to safely participate in the study: 1. Hepatic diseases (e.g. active viral hepatitis infection or cirrhosis of the liver) 2. Cardiovascular disease (including ischemic heart disease, coronary artery disease, congestive heart failure, poorly controlled hypertension due to risk of further blood pressure elevation and increase in demand on cardiac function from study drug) 3. Renal/urologic (e.g chronic kidney disease or acute kidney injury, history of bladder dysfunction due to theoretical risk of ketamine-induced cystitis) 4. Endocrinologic (including diabetes due to association with progressive abnormality of the microvasculature and nervous system) 5. Central nervous system disorder, neuromuscular disease, or other neurologic disorder (e.g. stroke, brain damage, elevated intraocular pressure or history of or presence of diseases that are associated with elevated intracranial pressure). 6. Pulmonary disease (e.g., asthma, emphysema, chronic bronchitis) 7. Has a clinically important vital sign, ECG, or clinical laboratory finding. 8. Has a major medical condition or medical history that in a clinician's assessment could affect heat sensitivity, pain thresholds, or somatosensation (e.g., Raynaud s disease, peripheral neuropathy, or circulatory disorder) 9. Has a significant current psychiatric condition (including mood disorders, anxiety disorders, or substance use disorders) or has a history of psychosis, hospitalization for a mental health condition, or recurrent psychiatric episodes. 10. Has a current chronic pain condition or has had chronic pain in the past (painful condition lasting more than six months). 11. Has a dermatological condition that might influence cutaneous sensibility such as scars or burns, or has a tattoo in the testing region 12. Unable to comply with study procedures or follow-up visits. 13. Those with an abnormality on a structural MRI. 14. Individuals who are left-handed (based on self-report or score on handedness questionnaire). 15. Participants who are currently using drugs (except for caffeine, nicotine, or cannabis) must not have used illicit substances or known drugs of abuse in the two weeks prior to screen and must have a negative drug urine test at baseline and on each research visit prior to infusion. Cannabis use is exclusionary if the use is daily, or if participants are unable to abstain during the study, or if function of daily life is impaired by use as determined by a clinician. 16. Participants with a history of head injury that resulted in loss of consciousness exceeding five minutes. 17. Participants with unstable clinical hyperthyroidism or hypothyroidism. 18. Participants with one or more seizures without a clear and resolved etiology. 19. Clinically significant abnormal laboratory tests specifically defined by: 1. Alkaline phosphatase (Alk Phos) \> 150 U/L 2. Alanine aminotransferase (ALT) \>55 U/L 3. Aspartate aminotransferase (AST) \> 34 U/L 4. Total bilirubin (TB) \> 1.2 mg/dL 5. Direct bilirubin (DB) \> 0.5 mg/dL 6. 25-hydroxyvitamin D \< 20 ng/mL 7. Folate \< 2ng/mL 8. Vitamin B12 \< 200 pg/mL 20. Positive Human Immunodeficiency Virus (HIV) test. 21. Participants with Coronavirus Disease 2019 (COVID-19) or suspected COVID-19. 22. NIH employee who is a subordinate/relative/co-worker of any investigator on the protocol. 23. Inability to read and understand English. Non-English speakers will not be eligible as most of the required monitoring and rating instruments are not validated in languages other than English. 24. Participants may not use any prescription or nonprescription drugs including OTC, herbal medicine, or dietary supplements within 14 days or 5 half-lives, whichever is longer, prior to drug administration.