The Endocannabinoid System and its Relationship to Migraine: Tally Largent-Milnes, PhD

WATCH TIME: 5 minutes

“We used a preventative paradigm as well as a reversal paradigm targeting the ABHD6 enzyme—the enzyme that's responsible for 2-AG levels before it's released as a neuromodulator. It was able to completely prevent induction of cephalic allodynia as a result of cortical spreading depression, and it did so in a cannabinoid-independent manner. We're still following that up, but it was suggestive that by targeting this enzyme, at least in part, we could prevent a headache altogether.”­­

Recently, clinical observations have suggested that clinical endocannabinoid deficiency (CED) might be a possible migraine mechanism for a portion of this patient population, though evidence in the literature has been sparse. Although, some have been conducting basic science investigations into the potential of this as a therapeutic pathway, including Tally Largent-Milnes, PhD, and colleagues.

Largent-Milnes, an assistant professor of pharmacology at the University of Arizona College of Medicine Tucson, gave a talk on this subject as part of the hot topics in headache session at the 2022 American Headache Society (AHS) Annual Scientific Meeting, June 9-11, in Denver, Colorado.¹ In it, she detailed the constitution of the endocannabinoid system and offered perspective on its role in, and how it is altered during, pain-related conditions such as migraine. The CED phenomenon has been observed in patients with chronic migraine, medication overuse headache, fibromyalgia, and irritable bowel syndrome. These individuals, she explained, appear to have lower levels of 2 circulating endocannabinoid lipids: anandamide, known as AEA, and 2-arachidonoylglycerol, or 2-AG.

While on-site in Denver, Largent-Milnes sat down with NeurologyLive® to talk further about her presentation and this research. She offered perspective on the modeling that her group has done in migraine and spoke about the endocannabinoid system’s potential as a therapeutic target for this patient population.

Click here for more coverage of AHS 2022.

REFERENCE
1. Largent-Milnes TM. How Does the Endocannabinoid System Affect Headache and Disorders? Presented at: AHS Annual Scientific Meeting; June 9-11, 2022; Denver, CO.