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

Abstract

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.

Keywords: cardiorespiratory fitness; endocannabinoids; exercise; headache disorders; mood; physical activity.

Conflict of interest statement

No competing financial interests exist.

Copyright 2019, Mary Ann Liebert, Inc., publishers.

Figures

FIG. 1.

Participants' flow in the study.

FIG. 2.

Primary outcome variable plasma AEA concentrations. Data are shown as mean±SEM. *p<0.05; **p<0.01, pairwise comparisons of repeated-measure ANOVA. AEA, anandamide.

FIG. 3.

Correlations between changes in medication consumed and AEA (a), and between medication consumed and VO2Peak(b). VO2Peak, peak oxygen uptake.

FIG. 4.

Correlations between changes in AEA and adherence to the exercise training program.