Randomized, Controlled Cross-over Comparison of Oral Cannabidiol to Oral Opioid for Postoperative Photorefractive Keratectomy Pain Control

Purpose: To compare the safety and efficacy of low-THC oral cannabidiol (CBD) with oral codeine-acetaminophen for postoperative pain control following photorefractive keratectomy. Setting: Academic outpatient clinical practice Design: Prospective, randomized, crossover, self-controlled clinical trial Methods: Thirty-five adults underwent bilateral sequential PRK, receiving oral CBD (50 mg twice daily) for one eye and oral T3 (codeine-acetaminophen 30mg-300mg every 4 hours) for the contralateral eye in a randomized sequence. Primary outcomes included pain and uncorrected visual acuity at month 3. Secondary outcomes included diary-reported symptoms, and patient-reported quality-of-life scores: Patient Reported Outcomes with LASIK (PROWL), Quality of Life Impact of Refractive Correction (QIRC), and Ocular Surface Disease Index (OSDI) Results: Pain scores peaked on postoperative day 2 across both interventions with no significant difference in mean or maximum pain ratings (p = 0.538). Visual acuity improved significantly by POM3 (p < 0.001), with no treatment-related differences (p = 0.928). Sensorium was significantly higher when taking CBD for the first eye, and not the second eye, indicating first exposure effect ( p = 0.035). Other symptoms and outcomes were equivalent between treatments. Conclusions: Low-THC oral CBD provides non-inferior pain control to codeine-acetaminophen following PRK with similar recovery outcomes and minimal side effects. Mild sensorium changes may occur in surgically naïve patients taking CBD. CBD may represent a viable opioid-sparing alternative in refractive surgery or acute pain management.