Recruiting
Phase 2

Cannabidiol

Sponsor:

Chad Brummett

Code:

NCT06234631

Conditions

Knee Replacement Surgery

Osteoarthritis, Knee

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

Interventions

Epidiolex oral solution

Placebo

Study Details

Brief summary:

The goal of this study is to better understand how daily treatment with cannabidiol (CBD) affects the need for opioid pain medication, as well as pain, inflammation and other related symptoms, after knee replacement surgery. The information collected in this study is necessary to help understand whether CBD may be a useful medication before and/or after surgery.

The study hypothesis is that CBD exerts opioid-sparing effects through anti-inflammatory, analgesic, and anxiolytic mechanisms.

Conditions

Knee Replacement Surgery

Osteoarthritis, Knee

Study ID

NCT06234631

Start date

Mar 13, 2024

Status verified date

Apr, 2026

Completion date

Jan, 2029

Anticipated

Primary completion date

Jan, 2029

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 70+

Healthy Volunteers: Not accepted

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 (postoperative disability for recovery is permitted)
  • 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)
  • Self-reported use of cannabis products within the 7 days prior to starting study drug
  • Self-reported use of cannabis products within the 8-30 days prior to starting study drug AND either a failed drug screen or inability to confirm successful washout (Note - may be rescreened with appropriate wash-out period)
  • 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 and confirmed by the investigator during screening
  • 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 and confirmed by the investigator during screening
  • Participation in other clinical trials over the course of this study (note: outside of active period is permissible as determined by the investigator during screening)

Study Design

Enrollment

380 participants

Anticipated

Allocation

Randomized

Intervention Model

Factorial

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

experimental: Pre - and post-operative CBD

Participants will take 300 milligrams (mg)/day on days 1-36 (150mg twice a day \[b.i.d.\])

experimental: Pre-operative placebo plus post-operative CBD

Participants will take placebo prior to surgery days 1-7, then days 8-36 participants will take CBD 300 milligrams (150mg twice a day \[b.i.d.\])

experimental: Pre-operative CBD plus post-operative placebo

Participants will take CBD 300 milligrams (mg) /day prior to surgery on days 1-7 (150mg twice a day \[b.i.d.\]), then days 8-36 will take placebo twice a day \[b.i.d.\]

placebo comparator: Pre- and post-operative placebo

Participants will take placebo on days 1-36 twice a day \[b.i.d.\]

Interventions

Epidiolex oral solution

Participants assigned to CBD will take the medication one hour before or two hours after eating a meal.

If participants can't tolerate the full-strength dose, the participant can decrease the dosing to 0.75 milliliter twice a day. If this is still not well tolerated, dosing can further be decreased to 0.75 milliliter once per day in the evening.

Placebo

Participants will be instructed to take one hour before or two hours after eating a meal.

Primary outcome measure

  • Total postoperative opioid consumption (measured in oral morphine equivalents) during the 28 days after surgery [ Time Frame: 28 days (after surgery) ]

Central Contacts and Locations

Central contacts

Kendall Dubois

734-232-0324kendalld@med.umich.edu

Locations

University of Michigan

Recruiting

Ann Arbor, Michigan, United States, 48109

Contacts

Kendall Dubois

734-232-0324kendalld@med.umich.edu

Principal Investigator:

Chad Brummet, MD

More Information

Sponsor

Chad Brummett

Last update posted

Apr 15, 2026

Last verified

Apr, 2026

Keywords

  • Epidiolex
  • Pain medication

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Chad Brummett on 2026-04-15.