Inflammatory disease and anxiety: could endocannabinoids be a mechanism of comorbidity?

Written by Sharon Salt, Editor

Matthew Hill is an Associate Professor at the Hotchkiss Brain Institute at the University of Calgary (Canada). His research primarily focuses on trying to understand the endocannabinoid system and how it regulates emotions and stress circuits in the brain to modulate anxiety and stress-related psychiatric disorders, such as post-traumatic stress disorder.

In this interview, Matthew speaks to us about his talk on endocannabinoids as a mechanism of comorbidity between inflammatory disease and anxiety, including what the next steps of his research will be. He also discusses if the controversial elements behind term ‘cannabinoid’ provide any limitations to research.


You’re presenting a talk here at FENS (7–11 July, Berlin, Germany) on endocannabinoids as a mechanism of comorbidity between inflammatory disease and anxiety – can you tell us more about this?

…one of the other disease classes that you see quite regularly with individuals who self-medicate with cannabis are inflammatory diseases…

We have done a lot of work looking into how endocannabinoids are involved in the effects of stress on anxiety. It’s interesting because when you look at populations of people who use marijuana for medical benefit, or things that they believe help them, we’d always look into post-traumatic stress disorder as a potential. However, one of the other disease classes that you see quite regularly with individuals who self-medicate with cannabis are inflammatory diseases like irritable bowel syndrome or colitis, arthritis or even multiple sclerosis. We became intrigued by the fact that these inflammatory diseases are quite often comorbid with psychiatric issues including anxiety and depression.

If you look at a lot of the survey data that has been done in individuals who have inflammatory diseases and use cannabis in a medical sense, more often than not, you see that the use of cannabis improves the psychiatric comorbidities more than the disease state itself, for example. This made us wonder if perhaps this was related to the fact that there might be changes in brain endocannabinoid function from inflammatory disease that are involved in the generation of comorbidities such as anxiety, and this could explain why external augmentation of cannabinoid function with something like delta-9-tetrahydrocannabinol in cannabis might help improve some of the anxiety effects. What we found was that, indeed, persistent peripheral inflammation like colitis resulted in a reduction in endocannabinoid function in the brain, and if we boost endocannabinoid function in the brain, we are able to reverse some of those changes in anxiety.

What are your next steps for this? Do you think this could be translated into a benefit for patients with anxiety or these effects with inflammatory disease?

There’s a lot of interest from the pharmaceutical industry about using drugs that inhibit endocannabinoid metabolism, sort of like an endocannabinoid-selective serotonin reuptake inhibitor. They elevate endocannabinoid levels in the brain, and in the context of psychiatric issues, particularly anxiety, there has been a lot of interest, but also there has been an interest in looking at inflammatory diseases and colitis. Irritable bowel syndrome has actually been one of the targets that people have talked about. Therefore, we think that from a translational perspective, these data are really interesting because they might help provide a two-pronged therapeutic approach. This is because by using a drug that elevates endocannabinoid function, you may be able to treat the inflammation associated with colitis but also treat some of the comorbidities as well, such as the changes in anxiety.

Cannabinoids is a bit of a buzzword, especially in the media, and it can be seen as slightly more controversial than other areas of medical research. Do you think this controversial element provides any limitations or challenges with research, if any?

I think focusing on endocannabinoids and the development of pharmaceutical drugs that target the endocannabinoids system strips away a lot of that controversy.

I would say if you were studying cannabis directly, then yes, it’s a lot trickier. There’s so much variance in cannabis through different strains and some patients have reported a lot of benefit and others have adverse reactions. The clinical studies haven’t demonstrated overwhelmingly large effects, if any.

I think focusing on endocannabinoids and the development of pharmaceutical drugs that target the endocannabinoids system strips away a lot of that controversy. There’s a lot of interest from multiple major pharmaceutical companies, as they can be seen as bypassing the cannabis route and going for endocannabinoids.

For the research that we do, it relates a lot more to that. We think that our data may help explain some of the cannabis effects in humans that some individuals have reported, but we are much more focused on endocannabinoids, and so it’s a little less controversial.

Looking ahead, do you think we are likely to see more treatments, perhaps harnessing these endocannabinoids, in 10 years from now for patients for a whole spectrum of diseases?

I would probably estimate for less than 10 years. There are several drug companies that are already doing Phase II clinical trials right now with a lot of these drugs. There were at least two studies going on that related to anxiety-type psychiatric issues. There’s a company in California (USA) that has developed drugs that target different endocannabinoids than the one we are looking at, and they have already done some preliminary trials in humans looking at diseases like tic disorders.

I think that perhaps in the psychiatric domain, we may see something like that in a short while. It may be possible in pain but the first pain trial that was done with these drugs didn’t work out very well, so this is an area of uncertainty. Hopefully for inflammatory disorders we’ll be able to see an advance too.

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The opinions expressed in this interview are those of the interviewee and do not necessarily reflect the views of Neuro Central or Future Science Group.