By Roger Chriss, PNN Columnist

The opioid-sparing effect of cannabis is routinely touted as a reason for marijuana legalization. The hope is that cannabis combined with opioid medication will produce equal analgesia at lower opioid doses, thus reducing the risks associated with opioid therapy.

But evidence in favor of the opioid-sparing effect is largely pre-clinical and often involves animals or healthy volunteers, not the real world conditions that pain patients live with.

A recent study on rhesus monkeys, for example, at the University of Texas found that combining cannabinoids with morphine did not significantly increase the impulsivity or memory impairment of the monkeys.

A 2018 study by Ziva Cooper and colleagues on healthy cannabis smokers concluded that cannabis enhances the analgesic effect of oxycodone, suggesting there is a synergy between the two.

And a 2017 systematic review of over two dozen studies in the journal Neuropsychopharmacology reported “robust evidence of the opioid-sparing effect of cannabinoids.”

But evidence against the opioid-sparing effect of cannabis is mounting, based on clinical findings in real-world chronic pain patients.

Andrew Rogers of the University of Houston reported at the 2019 American Pain Society Scientific Meeting that chronic pain patients who used both prescription opioids and recreational marijuana showed higher levels of anxiety, depression and substance abuse problems than those who used opioids alone. There was no difference between the two groups in pain levels.

"The things psychologists would be most worried about were worse, but the thing patients were using the cannabis to hopefully help with — namely pain — was no different,” Rogers told MedPageToday. "Co-use of substances generally leads to worse outcomes. As you pour on more substances to regulate anxiety and depression, symptoms can go up."

A large Australian study in The Lancet Public Health found that cannabis use was common in patients with chronic non-cancer pain who were prescribed opioids, but “there was no evidence that cannabis use reduced pain severity or interference or exerted an opioid-sparing effect.”

This research, known as the Australia POINT study, followed over 1,500 chronic pain patients for almost four years. Although its methodology has limitations, it is one of the largest long-term studies of opioids and cannabis under real-world conditions.

“At each assessment, participants who were using cannabis reported greater pain and anxiety, were coping less well with their pain, and reported that pain was interfering more in their life, compared to those not using cannabis,” said lead author Gabrielle Campbell, PhD, of the University of New South Wales.

In other words, the opioid-sparing effect of cannabis seems not to work well in the real world, despite its apparent success under laboratory conditions. There are several possible factors at work.

First, laboratory conditions are artificial. Studies often use lab animals or healthy human volunteers. But people with chronic health conditions may be different. Or perhaps people who are experienced with cannabis and willing to spend a day in a laboratory being subjected to painful stimuli are different.

Second, laboratory studies are often short term, but chronic pain is long term. The cumulative risks of opioids and cannabis, as well as the complex interactions between them, may take time to unfold and discover. It is possible that an initial opioid-sparing benefit washes away quickly and is replaced by nontrivial risks.

Third, real-world studies emphasize patient outcomes, a factor that laboratory work cannot assess. Because outcomes are so important, studies that focus on them must be given greater weight. 

More research will be needed to sort out the effects of combining cannabis and opioids in chronic pain management. But at present, clinical studies point to more risks and harms than benefits. Perhaps a subset of patients or a particular combination of a specific opioid and cannabis preparation will change this. Or perhaps combining cannabis and opioids is not such a great idea. 

Roger Chriss lives with Ehlers Danlos syndrome and is a proud member of the Ehlers-Danlos Society. Roger is a technical consultant in Washington state, where he specializes in mathematics and research.

The information in this column should not be considered as professional medical advice, diagnosis or treatment. It is for informational purposes only and represents the author’s opinions alone. It does not inherently express or reflect the views, opinions and/or positions of Pain News Network.