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AHS 2022 | The endocannabinoid system in headache disorders: future reserach goals

Tally Largent-Milnes, PhD, University of Arizona, College of Medicine, Tucson, AZ, discusses future research goals concerning the endocannabinoid system in headache disorders. A future goal is to see if there are any additional benefits in combining targeting strategies. These strategies have multiple sites of action, affecting the blood vessels and pre- and post-synaptic neurons when combined. These sites of action are highly expressed in various brain regions, highlighting the potential of polypharmacy for treating individuals with headache disorders. When moving to a clinical setting from a pre-clinical standpoint, work is also needed to further understand the side effect profiles; targeting the cannabinoid system could lead to concern over reward liability. THC abuse may have a sedative effect, diminishing quality of life even with a reduction in pain. With the endocannabinoid system demonstrating a role in maintaining respiratory drive, it is also important to establish whether any manipulations of the system are not detrimental to life. Furthermore, from a mechanistic perspective, there is also great consideration of how 2-AG works through the cannabinoid receptors; this would increase our scientific understanding of one of the highest density systems throughout the nervous system. As there is currently little knowledge on the system and how it is regulated, there is an emphasis required on the basic science, how it changes over time through behavior and environmental stimuli. This interview took place at the 2022 American Headache Society (AHS) meeting in Denver, CO.