Clinical Evidence of Cannabinoids in Migraine: A Narrative Review

Abstract

The endocannabinoid system (ECS) influences many biological functions, and hence, its pharmacological modulation may be useful for several disorders, such as migraine. Preclinical studies have demonstrated that the ECS is involved in the modulation of trigeminal excitability. Additionally, clinical data have suggested that an endocannabinoid deficiency is associated with migraine. Given these data, phytocannabinoids, as well as synthetic cannabinoids, have been tried as migraine treatments. In this narrative review, the current clinical evidence of potential ECS involvement in migraine pathogenesis is summarized. Furthermore, studies exploring the clinical effects of phytocannabinoids and synthetic cannabinoids on migraine patients are reviewed.

Salivary Endocannabinoid Profiles in Chronic Orofacial Pain and Headache Disorders: An Observational Study Using a Novel Tool for Diagnosis and Management

“…Since these dissimilarities were found in different biofluids (CSF versus saliva), and since PEA is hydrolyzed by various enzyme classes, namely, FAAH and N -acylethanolamine acid amidase (NAAA), which catabolize PEA and AEA at significantly different rates [ 22 ], it is possible that the differences in the quality and quantity of these enzymes in the examined fluids caused the disparity. Nonetheless, our study strengthened the evidence of a dysregulated ECS ‘tone’ with reduced eCB activity, which may play a role in migraines [ 14 ].…”

“…The released eCBs are retrieved by a membrane transporter. AEA is degraded by fatty acid amide hydrolase (FAAH), whereas monoglyceride lipase (MAGL) is the main 2-AG hydrolase [ 14 ]. 2-AG is a full agonist of CB1 and CB2 receptors, whereas AEA shows slight selectivity for CB1 over CB2 [ 11 ].…”

“…AEA also acts on other receptors implicated in pain processing, such as TRPV1 and PPARs [ 13 ]. ECS components are expressed ubiquitously throughout pain-processing pathways [ 11 ], which balance GABAergic inhibitory activity and glutamatergic excitatory activity by eCBs released from postsynaptic neurons that stimulate presynaptic CB1 [ 14 ]. Based on their neuromodulatory role [ 12 ], it is reasonable to consider eCBs as reliable biomarkers for chronic pain conditions.…”

Nutraceuticals and migraine: further strategy for the treatment of specific conditions

“…Cannabis The endocannabinoid system has a neuro-modulatory role that influences many physiological functions, including pain processing and modulation of trigeminal excitability, pathophysiological assumption supporting the possible usefulness in the treatment of migraine. As found in a recent review [10], the growing body of supporting evidence consists of retrospective studies, online surveys, case series, and case reports, and migraine patients enrolled in these studies usually used different cannabis preparations through different routes of administration, making it difficult to explore the therapeutic potential of the Cannabis plant. Proper placebo-controlled trials are needed to establish the therapeutic role for cannabinoids (plant-derived or synthetic) in migraine treatment.…”

Efficacy and Safety of Medical Marijuana in Migraine Headache: A Systematic Review

“…But many anti-migraine medications have side effects, posing a difficulty that has led to the halt of research and development of prospective anti-migraine drugs [ 4 ]. As a result, the current situation necessitates more investigation, particularly for individuals who do not benefit from or tolerate regularly recommended drugs [ 6 ]. Evidence-based guidelines from the United States, Canada, and Europe also offer consistent advice, such as lifestyle changes, trigger avoidance, and coping techniques [ 7 ].…”