Cannabis Cannabinoid Res 5(1): 6-11

Endocannabinoids and Stroke Prevention: Review of Clinical Studies

^{Department of Neurology, Mayo Clinic, Rochester, Minnesota.}

^{Community Internal Medicine, Mayo Clinic, Rochester, Minnesota.}

^{Address correspondence to: Eugene L. Scharf, MD, Department of Neurology, Mayo Clinic, 200 First Street SW, Rochester, MN 55905}ude.oyam@enegue.frahcs

Abstract

The societal burden of ischemic stroke suggests a need for additional therapeutic categories in stroke prevention. Modulation of the endocannabinoid system (ECS) is a rational target for stroke prevention because of its effects on inflammation, vascular tone, and metabolic balance, all well-described stroke risk factors. In this article, we summarize the existing ECS clinical studies in human subjects' research as they relate to conventional vascular risk factors associated with ischemic stroke. To date, 2-arachidonoylglycerol (2-AG) derivative endocannabinoids are consistently reported to be elevated in insulin resistance, whereas the N-arachidonoylethanolamine (AEA) endocannabinoid derivatives are elevated in obesity. The ECS role in metabolic health should examine the effects of 2-AG reduction and AEA augmentation as a means of stroke risk reduction. Cannabinoid receptors are reported on macrophages within atherosclerotic plaques and suggest a role for immunomodulation as a therapeutic for atherosclerosis through both peripheral immune cell CB1 antagonism and/or CB2 agonist. The effects of ECS on hypertension, smoking, physical activity, obstructive sleep apnea, heart failure, and atrial fibrillation are incompletely described and deserve further study. A limitation to ECS research is significant overlap with noncannabinoid molecular targets. Further exploration of the ECS needs to include the larger metabolomics context for a greater understanding of its therapeutic potential. Clinical translational studies in stroke prevention should be directed at ECS in metabolic balance and atherosclerosis.

Keywords: 2-AG, AEA, anandamide, cannabinoid receptors, endocannabinoid system, stroke prevention

Abstract

Abbreviations Used

2-AG	2-arachidonoylglycerol
AEA	N-arachidonoylethanolamine
BMI	body mass index
CB1	type one cannabinoid receptor
CB2	type two cannabinoid receptor
CBD	cannabidiol
ECS	endocannabinoid system
FAAH	fatty acid amide hydrolase
HDL	high density lipoprotien
HOMA-IR	homeostatic model of insulin resistance
IL	interleukin
MAGL	monoacylglycerol lipase
MMP	matrix metalloproteinase
mRNA	messenger RNA
NEA	N-acylethanolamines
PPAR	peroxisome proliferator-activated receptor
THCV	tetrahydrocannabivarin

Abbreviations Used

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