CB1 worsens and CB2 protects the heart during ischemia, but cannabis also raises cardiovascular risk factors

Both CB1 and CB2 receptors and their endogenous ligands (anandamide and 2-AG) are upregulated in the ischemic heart. CB1 activation aggravates the inflammatory response during cardiac ischemia, while CB2 activation reduces inflammation by affecting immune cell attraction, macrophage polarization, and lymphocyte clusters. However, cannabis consumption may trigger arrhythmias and myocardial infarction, and CB1 activation is linked to impaired lipid/glucose metabolism, obesity, and diabetes.

Narrative review of preclinical and clinical literature on cannabinoid receptors (CB1, CB2, GPR55) in cardiac physiology, ischemia, and cardiovascular risk factors.

The opposing roles of CB1 and CB2 in the heart present both danger and opportunity. Understanding which receptor does what could enable selective targeting: blocking CB1 to reduce cardiovascular risk while activating CB2 for cardiac protection.

Cannabis is a blunt instrument affecting both CB1 and CB2 simultaneously. The therapeutic future likely lies in selective cannabinoid receptor drugs: CB2 agonists for cardiac protection and CB1 antagonists for metabolic benefits, without the mixed effects of whole cannabis.

Narrative review (not systematic); much evidence from animal models; clinical translation of receptor-specific effects uncertain; cannabis delivery method effects not well differentiated; GPR55 cardiac role poorly characterized.