Cannabidiol in Headache: Preliminary Results of a Scoping Review.

Abstract

Background. Headache represents a frequent cause of disability and impaired quality of life. Despite therapeutic advances, some patients show an insufficient response to conventional treatments, which has prompted the search for strategies aimed at modulating mechanisms related to trigeminovascular nociception, neuroinflammation, and calcitonin gene-related peptide signaling. In this context, cannabidiol has been proposed as an intervention with analgesic, anti-inflammatory, and endocannabinoid system-modulating potential; however, the available evidence in headache remains limited and heterogeneous. Objective. To describe the therapeutic potential of cannabidiol in headache according to published studies. Materials and methods. A literature search was conducted in PubMed using algorithms based on the following Medical Subject Headings (MeSH) and search terms: (“Headache” OR “Headaches” OR “Cephalalgia” OR “Cephalalgias” OR “Cephalgia” OR “Cephalgias” OR “Cephalodynia” OR “Cephalodynias” OR “Cranial Pain” OR “Cranial Pains” OR “Pain, Cranial” OR “Pains, Cranial” OR “Head Pain” OR “Head Pains” OR “Pain, Head” OR “Pains, Head” OR “Generalized Headache” OR “Generalized Headaches” OR “Headache, Generalized” OR “Headaches, Generalized”) AND Cannabidiol. Preclinical studies, clinical studies, or reviews addressing the use of cannabidiol, alone or in combination with other cannabinoids, in headache, migraine, or related experimental models were included. Study selection was performed in two stages, title/abstract and full-text screening, in duplicate. Finally, a narrative synthesis was reported under PRISMA parameters based on the following variables: article type, population or experimental model, route of administration, dose, therapeutic outcomes, adverse effects, and quality of life or functional benefits. Results. A total of 74 articles were identified, of which 7 were included. The evidence identified included narrative reviews, preclinical studies, a clinical protocol, and a retrospective study in chronic migraine. Preclinical studies suggest that cannabidiol reaches structures related to migraine pathophysiology and may reduce trigeminal hyperalgesia, CGRP levels, and inflammatory mediators. In murine models, cannabidiol-based combinations showed reductions in photophobia, spontaneous pain, and migraine-like behaviors. In humans, oral cannabinoid preparations were associated with reduced pain intensity and use of acute medication, although without a significant reduction in migraine days. Conclusions. In conclusion, cannabidiol shows preliminary therapeutic potential in headache, mainly through its possible effects on trigeminovascular nociception, CGRP signaling, and neuroinflammation. However, direct clinical evidence remains scarce, heterogeneous, and limited by uncontrolled or preclinical designs. Randomized clinical trials are required to define efficacy, safety, dose, route of administration, and functional outcomes in patients with headache.