Combining cannabis with opioids offers no added pain relief for knee arthritis patients: Study

Combining cannabis with an opioid did not improve acute pain for people with knee arthritis, according to results of a study published in the May issue of Anesthesiology, the peer-reviewed medical journal of the American Society of Anesthesiologists (ASA).

While animal studies have suggested that the two drugs might work better together to relieve pain, the results of a randomized, double-blind, placebo-controlled study found no added benefit while undergoing laboratory pain testing. The findings showed neither cannabis nor opioids alone provided significant pain relief and using them together did not improve results.

“Some patients believe combining cannabis with opioids can help with pain, and clinicians may recommend or prescribe it in states where cannabis is legal,” said Katrina R. Hamilton, Ph.D., Department of Psychology, Ohio University, Athens, Ohio and Department of Psychiatry and Behavioral Sciences, Johns Hopkins School of Medicine, Baltimore, Maryland and lead author of the study. “Our study suggests that isn’t the case and patients may experience more side effects when the drugs are combined.”

The study included 21 patients with knee osteoarthritis. Each took part in four sessions, receiving different combinations of pills each time: two placebos (inactive pills); hydromorphone (an opioid) and a placebo; dronabinol (a pharmaceutical form of THC, the psychoactive compound in cannabis) and a placebo; and hydromorphone and dronabinol. All patients received all four combinations in a random order.

The researchers used a range of tests to assess how the drugs affected pain, including measuring participants' sensitivity to pressure, heat and cold, how well their bodies naturally reduced pain and how much knee pain they were experiencing. They also assessed thinking and memory, physical functioning and how the drugs made participants feel overall (including side effects), to understand the full impact on both body and mind.

They determined that taking opioids and cannabis, either alone or in combination, did not provide robust acute pain relief while undergoing laboratory pain testing. The opioid alone reduced pain sensitivity, while the cannabis did not, but neither meaningfully reduced participants’ self-reported pain during the study visits. When the two drugs were combined, side effects such as drowsiness, dizziness and impaired thinking were stronger and more noticeable, without added pain relief.

An accompanying editorial notes that the participants had never used cannabis before, received a single relatively high dose and that the results may not fully represent how cannabis is used in the real world. It adds that cannabis may still address symptoms related to pain, such as sleep, mood and anxiety, even if its direct effect on pain is limited.

“In the real world, people often use cannabis differently, including lower starting doses, using gradually stronger doses, which may affect both benefits and side effects,” said Dr. Hamilton. “More research is needed to better understand how cannabis affects pain when used in real-world settings.”

Reference:

Hamilton, Katrina R. Ph.D.1; Mun, Chung Jung Ph.D.2; Sadik, Eliot M.D.3; Bergeria, Cecilia L. Ph.D.4; Huhn, Andrew S. Ph.D., M.B.A.5; Speed, Traci J. M.D., Ph.D.6; Vandrey, Ryan Ph.D.7; Dunn, Kelly E. Ph.D., M.B.A.8; Campbell, Claudia M. Ph.D.9. Evaluating the Acute Effects of the Cannabinoid Dronabinol and the Opioid Hydromorphone Alone and in Combination: A Double-blind, Randomized, Placebo-controlled Trial in Knee Osteoarthritis. Anesthesiology 144(5):p 1187-1198, May 2026. | DOI: 10.1097/ALN.0000000000005925