Phase 4
N=37
Cannabidiol for Bilateral Total Knee Arthroplasty
Pain, Postoperative · Opioid Use · Knee Osteoarthritis
Bottom Line
View on ClinicalTrials.gov: NCT04749628 ↗Enrolled (actual)
37
Serious AEs
5.6%
Results posted
May 2026
Primary outcome: Primary: Cumulative Opioid Usage in First 72 Hours Postoperatively — 209.0; 144.0; 203.2 Morphine Milligram Equivalents (MME)
Study Design & Population
- Study type
- Interventional
- Phase
- Phase 4
- Interventions
- cannabidiol (Drug); Ora-sweet SF (Other)
- Age
- Adult, Older Adult · 18+ yrs
- Sex
- All
- Sponsor
- Hospital for Special Surgery, New York
- Primary completion
- Oct 2024
Outcome Measures
| Outcome | Result | p-value |
|---|---|---|
| PRIMARY Cumulative Opioid Usage in First 72 Hours Postoperatively |
209.0; 144.0; 203.2 | — |
| SECONDARY Pharmacokinetics of CBD |
0.00; 0.00; 0.00; 0.00; 0.22; 9.22 | — |
| SECONDARY Levels of Plasma Inflammatory Marker Interleukin-6 |
12.3; 20.6; 17.7 | — |
| SECONDARY NRS Pain at Rest |
7.0; 7.5; 7.5; 7.5; 5.0; 7.5 | — |
| SECONDARY NRS Pain With Movement |
7.0; 7.0; 5.5; 8.5; 5.5; 6.0 | — |
| SECONDARY Brief Pain Inventory Short Form |
4.3; 5.1; 4.8; 4.9; 4.3; 6.4 | — |
| SECONDARY Incidence of Adverse Events |
0; 0; 0; 0; 0; 0 | — |
| SECONDARY Opioid Related Symptom Distress Scale (ORSDS) |
0.4; 0.5; 1.0; 0.4; 0.5; 0.7 | — |
| SECONDARY Anxiety Levels |
3.0; 6.5; 6.0; 2.5; 3.0; 5.0 | — |
| SECONDARY Cumulative Inpatient Analgesic Use (Non-opioid) |
7600; 7700; 8100; 50.0; 47.5; 51.3 | — |
| SECONDARY Number of Participants With Opioid and Non-opioid Medication Use |
8; 8; 7; 8; 7; 7 | — |
| SECONDARY Opioid & Non-opioid Analgesic Consumption |
364.8; 282.3; 360.4; 14100; 15300; 16000 | — |
| SECONDARY Number of Participants With Opioid and Non-opioid Medication Use |
8; 8; 7; 8; 7; 7 | — |
| SECONDARY Hospital Length of Stay |
66.4; 81.3; 81.5 | — |
| SECONDARY Blinding Assessment |
0.17; 0.00; 0.17; -0.33; 0.67; 0.83 | — |
| SECONDARY Time to Reach Discharge Physical Therapy Goals |
45.1; 55.5; 66.8; 39.5; 40.7; 45.4 | — |
| SECONDARY Range of Motion |
120.0; 110.0; 106.5; 0.0; 0.0; 0.0 | — |
| SECONDARY Actigraphy Sleep Efficiency |
64.8; 59.2; 64.9; 72.2; 66.1; 81.0 | — |
| SECONDARY Actigraphy Sleep Time |
272.0; 248.5; 272.5; 303.0; 277.5; 340.0 | — |
| SECONDARY Sleep Quality |
13.9; 15.2; 13.4; 8.8; 10.2; 10.6 | — |
Summary
In light of the opioid epidemic and evidence suggesting that cannabis may be opioid-sparing, we are in a unique position to conduct a novel, high-impact study that would set the stage for future RCTs examining the effects of a nonintoxicating and nonaddictive cannabinoid in an orthopedic patient population. Epidiolex®, an oral cannabidiol (CBD) solution, is the first ever cannabis-derived medication to be approved by the Food & Drug Administration. Our aim is to conduct a pilot study using a placebo oral solution, 400mg and 800mg Epidiolex® to gather data on its effects on patients undergoing bilateral total knee arthroplasty (BTKA). We will be estimating whether Epidiolex® is associated with minimal opioid use and adequate analgesia. We will also assess its tolerability, pharmacokinetics, and effects on inflammatory markers in the perioperative setting.
Eligibility Criteria
Inclusion Criteria
- Age 18 to 75
- Scheduled for same-day bilateral total knee replacements with participating surgeons
- American Society of Anesthesiologists (ASA) Physical Status 1 or 2
Exclusion Criteria
- ASA 3 and higher
- Weight 3 months)
- Coumadin use
- Current use of SSRI or SNRIs
- History of substance abuse or dependence
- Active or history of major psychiatric illness
- Severe cardiovascular disorder
- Severe hepatic or renal insufficiency (transaminase levels above ULN)
- History of epilepsy
- Diagnosis of rheumatic disease, autoimmune disease, or immunodeficiency (e.g. rheumatoid arthritis, psoriatic arthritis, inflammatory bowel disease, multiple sclerosis, etc.)
- Use of valproate or clobazam
- Known or suspected hypersensitivity, allergy, or contraindication to cannabinoids or any of the excipients in the study medications (i.e. sesame oil, sucralose, strawberry flavor)
- Active use of steroids - oral steroids upon admission
- Stress dose steroids
- Non-English speakers
- Planned discharge to home without caregiver(s)
Data sourced from ClinicalTrials.gov (NCT04749628). Outcome figures and adverse-event rates are extracted automatically from the registry's posted results and are provided for clinician reference, not as a substitute for the primary publication.