A randomized clinical trial by University of Florida researchers has found that a low-THC, full-spectrum oral cannabidiol preparation provided postoperative pain control comparable to codeine plus acetaminophen following photorefractive keratectomy, or PRK, a laser eye procedure known for producing several days of significant corneal discomfort. The prospective crossover study involved 35 adults who underwent PRK on one eye and then the other, allowing every participant to receive both treatments in randomized order and effectively serve as their own comparison. The findings were published online July 29, 2026, in the Journal of Cataract & Refractive Surgery.
Pain reached its highest level on the second postoperative day under both treatments, and investigators detected no significant difference between CBD and codeine-acetaminophen in either average or maximum pain ratings. Visual recovery was also similar, with uncorrected visual acuity improving substantially by three months regardless of which pain treatment had been used. The authors concluded that low-THC oral CBD provided non-inferior pain control with similar recovery outcomes and suggested it could eventually become an opioid-sparing option in refractive surgery. The finding is promising, but the small trial does not demonstrate that CBD can replace opioids after surgery generally, and several details of the design make that distinction especially important.
How Researchers Compared CBD With an Opioid
The study used an unusual paired-eye crossover design. Participants undergoing bilateral PRK had their surgeries approximately two weeks apart rather than treating both eyes simultaneously. After one surgery, the patient received the CBD regimen; after the other, the patient received codeine-acetaminophen. The order was randomized, meaning roughly half received CBD first and the remainder began with the opioid combination. Because pain sensitivity varies considerably among individuals, comparing two treatments within the same person can reduce some of the biological variability that complicates conventional parallel-group pain trials.
The CBD regimen delivered 50 milligrams twice daily beginning on the morning of surgery and continuing through postoperative day four. The protocol specified a full-spectrum CBD product containing less than 0.3 percent THC by weight and sourced from a single tested lot to reduce chemical variation. During the opioid condition, patients received codeine 30 milligrams combined with acetaminophen 300 milligrams for breakthrough pain, with use allowed as needed up to once every four hours. The published abstract summarizes the comparison as oral CBD versus codeine-acetaminophen, but the underlying protocol makes clear that the opioid medication was available for breakthrough pain rather than necessarily taken around the clock.
What the Trial Actually Found
Patient pain diaries showed a similar postoperative pattern under both treatment strategies. Pain increased after PRK, peaked on postoperative day two and then declined. Statistical analysis found no significant difference between the CBD and codeine-acetaminophen conditions in mean or maximum pain scores, with a reported P value of 0.538. The researchers therefore described CBD as providing non-inferior pain control. Other patient-reported outcomes were broadly similar between treatments.
The pain medication also did not appear to interfere with the ultimate purpose of surgery. Uncorrected visual acuity improved significantly by postoperative month three, with no treatment-related difference between the CBD and opioid conditions. The investigators additionally assessed outcomes using established refractive-surgery and ocular-surface questionnaires, including measures related to visual function, quality of life and dry-eye symptoms. Those outcomes did not reveal meaningful disadvantages associated with CBD. Together, the findings suggest that the cannabinoid regimen controlled pain without compromising the recovery being achieved by PRK itself.
CBD Was Not the Only Pain Treatment Patients Received
One of the most important details is easy to miss in headlines describing CBD as matching an opioid. Neither CBD nor codeine-acetaminophen was used as the only postoperative analgesic. According to the registered protocol, every participant received a bandage contact lens along with moxifloxacin, ketorolac, fluorometholone and lubricating eye drops after surgery. Patients were also prescribed 800 milligrams of ibuprofen three times daily for the first 48 hours and instructed to use cold packs on the closed eyelids. The experimental question was therefore whether CBD could function similarly to codeine-acetaminophen within a broader multimodal pain-control program.
That context does not diminish the result, but it changes what the result means. The trial did not establish that someone experiencing severe postoperative pain can simply replace all conventional analgesics with CBD. Instead, it suggests that in this particular procedure, among otherwise healthy adults already receiving aggressive non-opioid and topical pain management, scheduled low-THC CBD produced pain outcomes similar to having codeine-acetaminophen available for breakthrough pain. That is still clinically relevant because reducing or eliminating the need for opioid exposure is a longstanding goal of postoperative medicine, but larger trials will need to determine whether the same strategy works in other operations and with different background analgesic protocols.
Why PRK Provides an Interesting Test of CBD for Acute Pain
PRK corrects refractive errors by removing the corneal epithelium and reshaping underlying corneal tissue with a laser. Unlike LASIK, which creates a corneal flap, PRK requires the surface epithelium to regenerate following surgery. That healing period can produce substantial pain, tearing, irritation and light sensitivity, particularly during the first several postoperative days. The University of Florida protocol specifically identified postoperative discomfort as one reason PRK is sometimes less attractive than LASIK despite advantages it may offer selected patients.
There is already controlled evidence that the opioid comparator used in the new study genuinely relieves PRK pain. A 2017 randomized, double-blind, placebo-controlled trial tested codeine plus acetaminophen following PRK and found the combination significantly superior to placebo for pain control. That makes the new comparison more informative than testing CBD only against an inactive placebo: researchers compared the cannabinoid strategy with a medication combination that already has evidence of efficacy in this specific pain model.
There Is a Biological Reason to Study Cannabinoids in Corneal Pain
The possibility that cannabinoids could influence eye pain is not based solely on anecdotal cannabis use. Experimental research has identified cannabinoid-sensitive pathways in ocular tissues. In a 2018 animal study, researchers induced superficial corneal injury in mice and found that topical CBD reduced both corneal hyperalgesia and inflammatory neutrophil infiltration. The analgesic and anti-inflammatory effects of CBD in that experiment appeared to involve 5-HT1A serotonin receptors rather than the conventional CB1 pathway usually associated with THC.
The new human trial did not test that mechanism, however, and its CBD was administered orally rather than directly to the cornea. Oral CBD undergoes absorption and metabolism before reaching systemic circulation, so the mechanisms involved could include central pain processing, inflammation, anxiety or several interacting pathways. The trial therefore demonstrates a clinical signal rather than proving how CBD produced it. It also cannot determine whether CBD alone was responsible because the tested product was full-spectrum and contained very small quantities of THC and potentially other medical cannabis constituents.
Human CBD Pain Research Has Produced Mixed Results
The PRK study joins a small but expanding group of randomized trials suggesting that CBD may have analgesic effects in some acute-pain settings. A 2022 double-blind randomized trial involving 99 patients undergoing arthroscopic rotator-cuff repair found that buccally absorbed CBD reduced pain on the first postoperative day and increased patient satisfaction compared with placebo, although differences disappeared later and opioid consumption was not significantly reduced. Patients received either 25 or 50 milligrams of CBD three times daily depending on body weight.
A 2024 randomized trial of acute dental pain also produced positive results. Sixty-one patients with moderate-to-severe toothache received oral CBD at 10 or 20 milligrams per kilogram or placebo. Both CBD doses significantly reduced pain compared with placebo, with the higher dose producing an earlier response; investigators reported a maximum median pain reduction of 73 percent at three hours. Yet other trials have been less encouraging. A randomized study of CBD-rich cannabis extract given before endodontic treatment found no significant reduction in postoperative pain compared with placebo. These divergent findings reinforce an important point: “CBD for pain” is not a single intervention. Dose, formulation, route, timing and type of pain may profoundly influence whether a benefit appears.
More recently, a 2026 randomized crossover trial of high-dose purified CBD in people with chronic neuropathic pain after spinal-cord injury found a statistically significant but modest reduction in pain compared with placebo. Participants were titrated as high as 800 milligrams per day—far above the 100-milligram daily dose used in the PRK trial. The contrast illustrates how widely CBD dosing differs across clinical research and why positive findings from one formulation cannot automatically be transferred to another.
Mild Changes in Sensorium Were Detected
Safety results were generally encouraging in the PRK study, but CBD was not entirely free of noticeable effects. Researchers reported significantly higher “sensorium” scores when participants received CBD during their first eye surgery, an effect that was not observed when CBD was used following the second operation. The authors interpreted this as a first-exposure effect and characterized the changes as mild. The protocol had anticipated possible sleepiness, fatigue, gastrointestinal symptoms and other CBD-related adverse effects and instructed participants not to drive until they understood how the medication affected them.
The product’s very low THC concentration is also relevant. Less than 0.3 percent THC by weight does not necessarily mean absolutely zero THC exposure, particularly with a full-spectrum preparation. The study therefore should not be interpreted as testing chemically pure CBD. It also does not validate every hemp-derived CBD gummy sold commercially. Investigators used material from the same lot, confirmed its cannabinoid profile through independent laboratory testing and screened for contaminants such as heavy metals, pesticides and microorganisms—controls that may not be identical across consumer products.
Important Limitations Keep the Result Preliminary
The study’s greatest limitation is its size. Thirty-five participants can reveal a meaningful signal, particularly in a crossover design, but the sample is too small to reliably identify uncommon adverse effects or determine whether the result applies to diverse patient populations. Participants were also generally healthy adults eligible for elective PRK. The protocol excluded people with several cardiovascular, neurological, liver, kidney and ocular conditions, as well as those with a history of opioid misuse. Results therefore cannot simply be generalized to medically complex surgical populations.
Blinding was another important limitation. The registered protocol explicitly states that masking participants to treatment was not possible because CBD and codeine-acetaminophen differed in appearance and dosing schedule. Pain is inherently subjective, so knowing which treatment one is receiving can affect expectations and reported symptoms. The crossover design reduces many person-to-person differences, but it cannot eliminate expectation effects or differences between experiencing a first operation and returning two weeks later already knowing what PRK recovery feels like. The abstract’s description of CBD as “non-inferior” is therefore encouraging, but independent replication in larger, preferably better-masked studies would make the conclusion substantially stronger.
Could CBD Become an Opioid-Sparing Option After Surgery?
The most interesting implication is not that CBD has been proven equal to opioids in general. It is that researchers have now directly randomized patients to a standardized cannabis-derived preparation or an established opioid-containing pain treatment and obtained similar pain outcomes in a clearly defined postoperative setting. Compared with observational surveys asking people whether cannabis helps their pain, that represents a considerably stronger experimental test of the idea that cannabinoids might reduce reliance on opioids.
What comes next should be larger randomized trials measuring not only pain scores but actual opioid consumption, rescue-medication requirements, functional recovery, adverse effects and patient preferences. Comparisons against optimized non-opioid regimens would also be valuable, because modern postoperative pain management is increasingly multimodal rather than simply opioid versus cannabis. For now, the University of Florida study provides one of the more intriguing pieces of clinical evidence for CBD in acute postoperative pain: a carefully controlled 35-person crossover trial in which low-THC oral CBD produced pain and recovery outcomes similar to codeine-acetaminophen after PRK. It is not yet evidence that CBD can replace opioids throughout surgery, but it is strong enough to justify finding out whether it can reduce how often they are needed.
