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By Pat Anson

Combining a low dose of opioids with a cannabis-based medicine did not improve acute pain for people with arthritis, according to results of a small clinical study published in the journal Anesthesiology.

Animal studies have suggested that the two drugs might have a synergistic effect and provide better pain relief, but the study of 21 people with knee osteoarthritis found no added benefit. 

“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 lead author Katrina Hamilton, PhD, a Psychiatry Professor at Johns Hopkins School of Medicine. “Our study suggests that isn’t the case and patients may experience more side effects when the drugs are combined.”

There are some important caveats to the study that diminish its findings.

One is the design of the study and its small size – just 21 patients – who received placebo pills, hydromorphone alone, dronabinol alone, and a combination of hydromorphone and dronabinol. 

Participants received all four combinations prior to having pain induced by sticking their hands in cold water or having their skin rubbed with a “hot” capsaicin cream. That means the researchers were evaluating acute pain induced in a laboratory, not the chronic pain caused by arthritis.

Second, dronabinol (Marinol) is not cannabis. Dronabinol is a synthetic version of THC, the active ingredient in cannabis. It is FDA-approved to treat nausea and vomiting in chemotherapy patients, and to improve appetite in AIDS patients. Dronabinol was never intended to provide pain relief and has little in common with the various forms of cannabis (edibles, smoking, vaping) used in the real world. 

Third, while hydromorphone is a potent opioid, the oral dose (2 mg) that was used is relatively low – about 10 morphine milligram equivalents (MME). The research team had previously conducted a similar study using 4mg of hydromorphone. That also produced little pain relief for participants, so it’s not surprising that 2mg didn’t help either, although researchers say the lower dose has a “better safety profile.” 

The researchers found that taking hydromorphone and dronabinol, either alone or in combination, did not provide significant relief from acute pain. The opioid alone reduced pain sensitivity, while dronabinol did not, but neither meaningfully reduced participants’ self-reported pain.

When the two drugs were combined, side effects such as drowsiness, dizziness and impaired thinking were stronger and more noticeable, but without added pain relief.

“Opioid and cannabinoid medications failed to produce robust analgesia in experimentally induced pain among patients with knee osteoarthritis. In contrast to preclinical studies, there was no evidence of synergistic analgesic effects by combining hydromorphone and dronabinol,” researchers concluded.

While the dose of hydromorphone was low, the 10mg dose of dronabinol that was used in the study is a hefty amount. Interestingly, participants reported more of a “high” sensation from the dronabinol than from hydromorphone. But again, dronabinol is a synthetic version of cannabis and has little in common with what most cannabis consumers use.    

“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 Hamilton, acknowledging the limits of her study. “More research is needed to better understand how cannabis affects pain when used in real-world settings.”