Cannabinoids could make opioids more effective, meaning pain relief with lower doses and reduced risk of dependency

In animal studies, four times less morphine and ten times less codeine was needed when cannabinoids were given at the same time.

The higher the dose of opioid pain relievers, the more likely it is a patient will experience side effects and complications. With the opioid epidemic becoming a pressing problem, researchers are working to find ways to provide pain relief with less risk. To understand whether therapeutic cannabinoids could be an effective strategy to reduce opioid use, researchers at the University of New South Wales and the Centre for Addiction and Mental Health analysed data from 19 pre-clinical studies and nine clinical trials. We spoke with author Suzanne Nielsen to learn more.

ResearchGate: What motivated this study?

Suzanne Nielsen: There have been serious harms associated with use of high-dose opioids in the US and Australia, including the current prescription opioid overdose epidemic in North America. Despite this, few strategies exist to assist people who are using prescribed opioids for chronic pain to reduce their opioid dose without compromising their pain relief.

Medications used to enhance the effect of opioids and enable lower doses are called “opioid-sparing” medications. This is what we are very interested in. There have been a number of recent observational studies (i.e. surveys with people who have uses medical marijuana) in the US that found that those using cannabis for therapeutic purposes have reported greatly reducing their need for opioid pain medications, or even being able to cease opioids altogether. These studies highlight the potential beneficial effects of combining opioids and cannabinoids, but did not have the scientific quality to change clinical practice. We were really interested to explore the scientific literature to understand whether the use of therapeutic cannabinoids may be an effective strategy to help people reduce their need for high-dose opioids for pain relief.


“These studies highlight the potential beneficial effects of combining opioids and cannabinoids”


RG: What did you find?

Nielsen: We found there were quite a few animal studies (nineteen in total) that examined the synergistic effects of opioids and cannabinoids, and almost all of these confirmed that by combing opioids and cannabinoids, much lower doses of opioids are needed for effective pain relief. For example, the dose of morphine needed was four times lower when cannabinoids were given at the same time, and for codeine it was ten times lower. While this is very powerful, we often find that results in humans are quite different from those seen in animals.

We also looked at studies with humans but didn't find as many. Most of the studies in which patients were given opioids and cannabinoids didn't specifically measure if there was a change in opioid dose, or even instructed patients not to change their opioid dose to measure the effect of cannabinoids on pain. In the few studies that did examine the effects of combined opioids and cannabinoids, the results were inconsistent. Only one smaller, low quality report showed promising results. This is an area where more research is needed.

RG: What do you think explains the difference between pre-clinical and clinical results? 

Nielsen: Studies in animals are very tightly controlled, so results are often a lot more consistent. With this consistency, the effect of medications can be easier to detect than it is in human studies. This is because patients clinical trials tend different from each other in important ways. This can be because of differences in age, weight, gender, other health conditions, other medications people take the different ways people experience pain.  A medication might work really well in one person, and not at all in the next, so the average effect is diluted. These differences between people and responses to different drugs tend to make a lot of “noise” in the results so it can be harder to detect an effect, or only some patients respond, so the effect seen is smaller.


“We hope that our review will support the need for more research in this area, and we are currently seeking funding to do just that.”


RG: How do you hope your findings will be applied?

Nielsen: While the preclinical findings were very promising, more research is needed before cannabinoids could be recommended as an opioid-sparing medication for patients with chronic pain. We hope that our review will support the need for more research in this area, and we are currently seeking funding to do just that: establish a human study to test the opioid-sparing effects of cannabinoids.

RG: What should the public take away from your findings?

Nielsen: We think there are two important things. Animal studies can highlight potential areas of opportunity for human research, but it is important not to jump to conclusions until high quality studies have been conducted that replicate pre-clinical findings in those with chronic pain. Secondly, having the right study design is needed to really test how well cannabinoids may help people with chronic pain that want to reduce their opioid doses. Many study designs we found were measuring other things, such as analgesia, but didn't measure opioid-sparing effects.

RG: Could there be drawbacks from using cannabinoids to reduce opioid?

Nielsen: It is clearly important to make sure that patients with chronic pain won’t experience other unexpected harms from cannabinoids as we attempt to reduce harms from opioids, such as fatal overdoses. Opioids are associated with an enormous number of deaths every year, but there are concerns with the potential for people to become addicted to cannabinoids, or experience other side effects such as psychosis. There are many areas where there isn’t enough scientific data to know that, for an individual patient, the benefits of cannabinoids will outweigh the harms. This is one of the reasons why we think well-designed and conducted studies are really critical to explore the potential therapeutic uses of cannabinoids before recommending then widely for clinical use.


Featured image courtesy of Be.Futureproof.