Cannabidiol for Postoperative Opioid Reduction in Primary Total Knee Arthroplasty

Inclusion Criteria: * Willing and able to read, understand, and sign the informed consent (English) * Willingness to participate in all study measures and restrictions, including patient-reported outcomes and longitudinal follow-up * Scheduled for surgery: primary total knee arthroplasty * Primary diagnosis of osteoarthritis of the surgical knee * Individuals of reproductive potential must agree to use acceptable birth control (defined in manual of operating procedures). This includes currently practicing an effective form of two types of birth control for women of childbearing potential, which are defined as those, alone or in combination, that result in a low failure rate (i.e., less than 1% per year) when used consistently and correctly from the screening visit until 28 days after the last study drug administration. * Participants must also agree not to donate sperm or eggs during study drug administration * Ability to take and to swallow the study medication and be willing to adhere to the treatment regimen * Agreement to adhere to Lifestyle Considerations (see protocol) throughout study duration Exclusion Criteria: * Revision or bilateral total knee arthroplasty * Individuals receiving or actively applying for worker's compensation or disability and other aspects associated with potential secondary gain * Severe physical impairment or clinically significant illness (e.g., blindness, paraplegia) * Co-morbid medical conditions that may significantly impair physical functional status (e.g., current non-skin malignancies, solid organ transplant in the past year) * Illicit drug use (other than cannabis). Unreported opioid use would be exclusionary but reported prescribed opioid use is allowed (e.g. patient denies opioid use but is found to be positive on the urine drug screen) * Use of cannabis products in the past 30 days (self-report and confirmed with urinalysis). Note - may be rescreened with appropriate wash-out period (see protocol) * High daily preoperative opioid dose * Individuals with major neurological disorders, such as dementia, Parkinson's disease, cognitive impairment, epilepsy, history of traumatic brain injury/head injury, and seizures * Individuals with significant illness (e.g., cancer) and/or clinically significant labs (e.g. labs measured by complete blood count (CBC) and basic chemistry with values meaningfully outside of the normal range \[abnormal levels to be reviewed by the Principal Investigator or prescribing provider\]) * Medical or psychiatric conditions that in the judgment of study personnel would preclude participation in this study (e.g., psychosis, suicidal ideation; note that stable anxiety and depression are not exclusions) * Pregnant or nursing women (total joint arthroplasty is typically not indicated in this group of patients) * Self-reported liver cirrhosis * Self-reported uncontrolled diabetes * Self-reported active hepatitis (any etiology, including infectious, autoimmune, or alcohol-related) * Blood pressure at screening above 180 millimeters of mercury (mmHg) systolic and/or 120 mmHg diastolic; if value exceeds the set point, potential participants will have repeat assessment within 5 minutes for up to two additional measurements. * Resting heart rate at screening less than 50 beats per minute (bpm) or greater than 100 bpm; if value exceeds the set point, potential participants will have repeat assessment within 5 minutes for up to two additional measurements. * Elevated liver enzymes and bilirubin (measured by blood test at screening) * Serum total bilirubin ≥ 2.5 milligrams (mg) per deciliter (dL) (mg/dL); or, * Alanine transaminase (ALT) or Alanine transaminase (AST) ≥ 3x upper limit normal (ULN); or, * Alkaline phosphatase ≥ 2x ULN * Severe cardiovascular disease (e.g., current unstable angina, current congestive heart failure, or current severe valvular abnormalities) that is self-reported by patient or in medical record * Current valproate, clobazam, or warfarin use per self-report or medical records * Current use of strong inducers of cytochrome p450 (CYP) enzymes CYP3A4 and CYP2C19, or CYP2C19 substrates with a narrow therapeutic index * Self-reported allergies to sesame oil, strawberries, opioids, or cannabis/cannabinoids * Any impairment, activity, behavior, or situation that in the judgment of the study team would prevent satisfactory completion of the study protocol * Self-reported severe side effects to opioids precluding the use of opioids for post-surgical pain and/or clear plan not to use any opioids after surgery * Participation in other clinical trials over the course of this study