Endocannabinoid deficiency may play a role in migraine

DENVER — There may be a link between migraine and clinical endocannabinoid deficiency, a speaker said at the American Headache Society’s annual scientific meeting.

“That has really come from this idea that if you measure endocannabinoid lipid levels, from platelets or [cerebrospinal fluid] from migraine patients or those who have medication overuse, they actually have significantly lower levels of circulating endocannabinoid lipids,” Tally Largent-Milnes, PhD, assistant professor of pharmacology at the University of Arizona, said.

Largent-Milnes noted that when comparing endocannabinoid levels in cerebrospinal fluid and platelets, there were no 2-arachidonoylglycerol (2-AG) endocannabinoid lipids.

“This is very odd, because 2-AG is actually the more dominant endocannabinoid lipid, and it's expressed and made at 200-fold more concentrated levels than anandamide itself,” she said.

Largent-Milnes and colleagues utilized preclinical models to understand the link between migraine and endocannabinoid deficiency. They used medication overuse models and measured periorbital withdrawal thresholds and endocannabinoid lipids.

According to Largent-Milnes, 2-AG were still low, while anandamide was elevated, which suggests a “unique pattern” for the endocannabinoid system.

“I've shown you that endocannabinoids do play a role in headache, both headache pathogenesis and maintenance, and that they may be targeted at the enzyme level for treating different types of headache pains,” she said.