Anandamide Is Related to Clinical and Cardiorespiratory Benefits of Aerobic Exercise Training in Migraine Patients: A Randomized Controlled Clinical Trial

Introduction: Since endocannabinoids have been implicated in migraine pathophysiology, we conducted a randomized, controlled clinical trial to test the effects of a 12-week aerobic exercise intervention on plasma anandamide (AEA) and its relation with clinical, psychological, and cardiorespiratory outcomes. Materials and Methods: Episodic migraine patients taking no preventive drugs and nonheadache individuals were recruited from Hospital São Paulo and a tertiary headache clinic between March 2012 and March 2015. Participants were randomly assigned to receive aerobic exercise or enter the waitlist. Primary outcome was changes in plasma AEA; secondary outcome was number of days with migraine/month; and other clinical variables, mood scores, and cardiorespiratory fitness were chosen as tertiary outcomes. Measurements were taken on headache-free days. Data were analyzed by generalized linear models. Discussion: Fifty participants concluded the study (mean±SD age=36.2±10.9, and BMI=26.5±4.5). The plasma AEA reduced in migraine exercise (p<0.05) and control exercise groups (p<0.01). The number of days with migraine (p<0.01), migraine attacks (p<0.05), and abortive medication used (p<0.05) reduced in the migraine exercise group, whereas cardiorespiratory fitness increased in migraine exercise and control exercise groups (both p<0.05). Anxiety, depression, anger, and fatigue scores improved in the migraine exercise group (p<0.05 for all). Significant correlations between reduction in abortive medication used and cardiorespiratory fitness (r=−0.81 p<0.001), and reduced AEA (r=0.68 p<0.05) were found. Conclusions: This study suggests that peripheral AEA metabolism may be partly linked to the clinical and cardiorespiratory benefits of regular aerobic exercise in migraine patients. Trials registration: #NCT01972607.