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

The takeaway

A review of the cardiac endocannabinoid system found CB1 receptors aggravate and CB2 receptors mitigate heart inflammation during ischemia, while cannabis use itself may trigger arrhythmias and heart attacks.

Cardiologists, cardiovascular researchers, and pharmacologists developing cannabinoid-based cardiac therapies.

CB1 aggravates, CB2 mitigates cardiac ischemic inflammation

What the researchers found

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.

Why it matters

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.

The numbers in context

CB1 antagonism reduces plasma triglycerides, LDL cholesterol, leptin, insulin, and glucose; CB2 activation mitigates ischemia-induced inflammation; GPR55 prevents impaired adrenoceptor responsiveness.

How the study worked

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

What this study cannot tell us

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.

How to read the evidence

Moderate: comprehensive mechanistic review drawing on animal and human data, but not systematic.

When this study was published

Published 2020.

The bigger picture

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.

Questions still open

Would a selective CB2 agonist protect the heart during a heart attack? Can the metabolic benefits of CB1 antagonism be achieved without psychiatric side effects?

Common questions

Is cannabis good or bad for the heart?

Both. CB2 receptor activation appears to protect the heart during ischemia by reducing inflammation, while CB1 activation worsens inflammation and is linked to metabolic risk factors. Cannabis activates both receptors, creating mixed effects.

Could cannabinoid drugs help after a heart attack?

Potentially. CB2-selective agonists reduced cardiac inflammation in animal models of ischemia. However, whole cannabis or THC (which also activates CB1) may worsen outcomes. Selective drugs targeting CB2 alone are the most promising approach.

Read the original research

Cannabinoid-sensitive receptors in cardiac physiology and ischaemia.

Biochimica et biophysica acta. Molecular cell research, 1867(3), 118462

View on PubMed ↗Publisher’s paper ↗

Citation

Puhl, Sarah-Lena. (2020). Cannabinoid-sensitive receptors in cardiac physiology and ischaemia.. Biochimica et biophysica acta. Molecular cell research, 1867(3), 118462. https://doi.org/10.1016/j.bbamcr.2019.03.009