AAN 2026 | Preliminary research on the endocannabinoid system in migraine pathology and treatment

I had an interesting path going into the cannabinoid research in my lab. An alumnus of Iowa, George Pappas, approached me, and he had done some work as a businessman with cannabinoids in the Netherlands, of all places. In the Netherlands, there’s a lot of cannabinoids. And I said, I really think it’s going to be useful for migraine. And so a postdoc in my lab said, yeah, I’d like to look at that. So it was a total veer-off for my work on CGRP and PACAP to look at cannabinoids. And we got some interesting results there. We published in Encephalagia and the Journal of Headache over the past couple of years. The upshot was you need a combination of CBD and THC. Which kind of builds off the whole pharmacological process of why the two would work together better than one or the other on their own. But we proved that with the mice. And it builds on a whole concept of combinatorial treatment, I think, that no one drug will be the one drug to treat all of migraine. I don’t think that cannabinoids will be the one drug either. We’ll need a combination. From cannabinoids, though, the disorder then grew with another postdoc in my lab, Adriana de la Pietra, who had worked with endocannabinoids in her graduate work. And so she then started thinking, well, if cannabinoids from plants are working, how can we tap into the body’s endocannabinoids? And so avoid any sort of regulatory problems or concerns about people getting high and all that’s concerns with THC by using a drug that she developed as a graduate student to inhibit the breakdown of endocannabinoids. So inhibiting the enzymes, the hydrolases that break down the body’s own endocannabinoids, keep the levels higher. So she got a very prestigious fellowship, the Marie Curie Fellowship from Europe, to begin that work in my lab. She’s working on that now. And then she’ll go to Phil Holland’s lab in London in another year or so to continue the work there as part of the exchange between European and American research enterprises. Her preliminary work is just that, very preliminary, and she’ll probably scream at me for saying this, but it’s very exciting. So I think that, in short, that this is going to be a good target. Take advantage of what the body already has there with these endocannabinoids that decrease the pain. And I think, I really think that the endocannabinoid is going to circle back and be influencing the glymphatic flow as well.

This transcript is AI-generated. While we strive for accuracy, please verify this copy with the video.