Proceedings of the 2022 Cannabis Clinical Outcomes Research Conference (CCORC) Orlando, FL, USA, May 19-20, 2022

Objective: Migraine is a debilitating disorder characterized by recurrent headaches accompanied by symptoms of anxiety and abnormal sensory sensitivity, including photophobia. Migraine is often inadequately managed by existing treatments. Thus, additional treatment options with improved efficacy and reduced side effects are a research priority. Surprisingly, despite the extensive historical use of Cannabis in headache disorders, there is limited research on the non-psychoactive cannabidiol (CBD) for migraine and there is no scientific evidence to prove that CBD is an effective treatment. Here, we test the efficacy of CBD in preventing and treating prominent symptoms of acute and chronic, pharmacolog-ically-evoked, migraine-like states in mice. Methods: We developed and characterized in our laboratory an animal model of acute and chronic migraine that involved measures of periorbital allodynia associated with intraperitoneal (i.p.) administration of the migraine-triggering agent calcitonin-gene related peptide (CGRP, 0.1 mg/kg). Periorbital allodynia was assessed through mechanical stimulation of the mouse periorbital region using von Frey fila-ments applied according to an up down method. CBD (10 and 30 mg/kg, i.p.) was tested for its ability to decrease this and other CGRP-induced migraine-like symptoms, including facial grimace, photophobia and anxiety in male and female C57BL/6J mice. Results: A single administration of CGRP induced facial hypersensitivity in both male and female mice. Repeated CGRP treatment produced progressively increased levels of basal hyperalgesia in females, but not male mice. A single CBD administration pro-tected mice from hyperalgesia induced by a single CGRP injection, in both males and females. Repeated CBD administration pre-vented increased levels of basal hyperalgesia induced by repeated CGRP treatment in female mice. CBD, injected after CGRP, reversed CGRP-evoked allodynia. CBD also reduced spontaneous pain traits induced by CGRP administration in female mice. CBD failed in providing protection from CGRP-induced photophobia. Finally, CBD blocked CGRP-induced anxiety in male mice. Conclusion: Collectively, these results demonstrate the efficacy of CBD in preventing episodic, as well as chronic headache, particularly in female subjects. Importantly, CBD may serve as an abortive agent for treating migraine attacks. CBD also shows efficacy for headache-related conditions such as anxiety and spontaneous pain, but does not seem to protect from photophobia.