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Cardiovascular System

The heart, the blood & the cannabinoids

Best reviews

2022: This review looks at the potential of CBD for treating cardiovascular diseases

The Potential of Cannabidiol in the Treatment of Cardiovascular Disease

https://www.sciresliterature.org/Cardiovascular/IJCDD-ID47.pdf

2021: This review looks at CBD, the ECS & heart disease

The Endocannabinoid System and Cannabidiol: Past, Present, and Prospective for Cardiovascular Diseases

https://www.mdpi.com/1424-8247/14/9/936

2021: An overview of how the cannabinoids may help with heart diseases

An overview on plants cannabinoids endorsed with cardiovascular effects

https://pubmed.ncbi.nlm.nih.gov/34332376/

2017: A review from an endocannabinoid hero, Dr. Cecilia Hillard, on all of the studies that have been done relating the levels of endocannabinoids in your blood to your health status

Circulating Endocannabinoids: From Whence Do They Come and Where are They Going?

https://pubmed.ncbi.nlm.nih.gov/28653665/

2021: A review of how the ECS is involved in the development of blood cells, the immune system in the brain & neuroinflammation
Endocannabinoid system: Role in blood cell development, neuroimmune interactions and associated disorders
https://www.sciencedirect.com/science/article/abs/pii/S016557282100028X

2020: A review of how the ECS helps with metabolic syndrome & the related cardiovascular problems
Cannabinoids in Metabolic Syndrome and Cardiac Fibrosis
https://pubmed.ncbi.nlm.nih.gov/33089434/

2020: A review of why it makes sense to use CBD for heart problems
Therapeutic Applications of Cannabinoids in Cardiomyopathy and Heart Failure
https://pubmed.ncbi.nlm.nih.gov/33194003/

2020: This meta-review suggests targeting the ECS for the heart problems related to obesity
Therapeutic Interventions of Endocannabinoid Signaling in Obesity-Related Cardiovascular Dysfunction
https://link.springer.com/chapter/10.1007%2F978-3-030-47336-5_14

2020: Clinical review of how changing the ECS system affects heart therapies
Key Aspects to Consider about Beneficial and Harmful Effects on the Central Nervous System by the Endocannabinoid Modulation Linked to New Cardiovascular Therapies
http://www.remedypublications.com/annals-of-pharmacology-and-pharmaceutics-abstract.php?aid=5519

2020: For the heart, this meta-review touches on the many positive effects of CBD that have been seen in experimental models of heart disease as well as its general safety profile for the heart
The Effects of Cannabidiol, a Non-Intoxicating Compound of Cannabis, on the Cardiovascular System in Health and Disease
https://pubmed.ncbi.nlm.nih.gov/32937917/

 

2020: This meta-review looks at the role of the ECS in the heart & the potential for targeting the ECS for diseases of the heart
Naturally Occurring Cannabinoids and their Role in Modulation of Cardiovascular Health
https://pubmed.ncbi.nlm.nih.gov/32677481/

 

2019: This review found that “CBD can protect against cardiac injuries, mainly through its anti-oxidant, anti-inflammatory, and anti-apoptotic effects on the basis of non-clinical studies”
The protective mechanism of cannabidiol in cardiac injury: A systematic review of non-clinical studies
https://www.ncbi.nlm.nih.gov/pubmed/31291873

 

Chart Gallery

Timeline of Research

2022: In men with HIV who used cannabis, they had lower levels of proteins linked to heart disease risk

Plasma C-reactive protein is lower among marijuana using HIV-negative individuals but not among persons living with HIV

https://pubmed.ncbi.nlm.nih.gov/33649360/

2022: In mice, a combination of CBD & swimming training protected their hearts

Effect of eight weeks of swimming training and consumption of CBD oil on the expression of NF-kB and 5­HT1A genes in heart tissue of rats with myocardial infraction

https://ebnesina.ajaums.ac.ir/browse.php?a_id=986&sid=1&slc_lang=en

2022: In a rat model of obesity, CBD treatment protected their hearts via several measures

Cannabidiol Downregulates Myocardial de Novo Ceramide Synthesis Pathway in a Rat Model of High-Fat Diet-Induced Obesity

https://pubmed.ncbi.nlm.nih.gov/35216351/

2022: In heart cells stressed by high levels of glucose (a model of diabetes), CBD protected them from arrythmia & cytotoxicity via inhibition of the sodium channels

Cannabidiol protects against high glucose-induced oxidative stress and cytotoxicity in cardiac voltage-gated sodium channels

https://pubmed.ncbi.nlm.nih.gov/32077098/

2021: In rats with heart problems, chronic treatment with CBD protected their aorta & small arteries

Vasoprotective Endothelial Effects of Chronic Cannabidiol Treatment and Its Influence on the Endocannabinoid System in Rats with Primary and Secondary Hypertension

https://www.mdpi.com/1424-8247/14/11/1120

2021: In a mouse model of heart failure, CBD nanoparticles protected against the formation of scar tissue

Cannabidiol Loaded Nanoparticles Exhibit an Anti-Fibrotic Effect in a Mouse Model of Non-Ischemic Heart Failure

https://www.ahajournals.org/doi/abs/10.1161/circ.144.suppl_1.10708

2021: In rats poisoned by aluminum phosphide (a common pesticide that causes toxicity in humans across the world), CBD protected their hearts from the usual damage, restored mitochondrial function (powerhouse of the cell) & prevented heart cell death

Modification of the hemodynamic and molecular features of phosphine, a potent mitochondrial toxicant in the heart, by cannabidiol

https://pubmed.ncbi.nlm.nih.gov/34711111/

2021: In rat heart tissue, THC protected the heart from the negative effects of toxic gas

Inhibition of Mitochondria Permeability Transition Pore and Antioxidant Effect of Delta-9-Tetrahydrocannabinol Reduces Aluminum Phosphide-Induced Mitochondrial Dysfunction and Cytotoxicity

https://assets.researchsquare.com/files/rs-998530/v1/aaffbd8f-32b0-4606-a7c7-26530d81c600.pdf?c=1635174312

2021: In mice with no CB1 receptor, researchers found that the CB1 receptor helped the smooth muscle of the heart to relax during its dilation phase & that during an infarct (a small area of dead tissue due to lack of blood flow), mice with no CB1 receptors had larger areas of dead tissue

Impaired vessel relaxation response and increased infarct size in smooth muscle cannabinoid receptor 1 knockout mice

https://pubmed.ncbi.nlm.nih.gov/34655603/ 

2021: In rats with heart problems from diabetes, a combination of CB2 activation & L-arginine decreased oxidative stress, reduced inflammation & protected the heart

CB2 receptor agonist and L- arginine combination attenuates diabetic cardiomyopathy in rats via NF-ĸβ inhibition

https://pubmed.ncbi.nlm.nih.gov/34860602/

2021: A study "provides evidence supporting an association between recent cannabis use and history of [myocardial infarction] in young adults"

Recent cannabis use and myocardial infarction in young adults: a cross-sectional study

https://pubmed.ncbi.nlm.nih.gov/34493564/

2021: In rats given ZnO nanoparticles (a treatment for cancer & diabetes), it modified the response of their hearts to the cannabinoid receptors

ZnO Nanoparticles Induce Dyslipidemia and Atherosclerotic Lesions Leading to Changes in Vascular Contractility and Cannabinoid Receptors Expression as Well as Increased Blood Pressure

https://www.mdpi.com/2079-4991/11/9/2319

 

2021: In mice undergoing swimming training, consuming CBD oil improved their heart’s markers for MAPK & PPARα gene expression while showing that the interventions of CBD & swimming combined worked better than either method alone

Effect of Eight Weeks of Swimming Training and CBD Oil Consumption on MAPK, Pparα Gene Expression in the Heart Tissue of Myocardial Infarction Rats

https://www.jorjanijournal.goums.ac.ir/article-1-840-en.html

2021: In a rat’s aorta, the drug affinin (a painkiller with a structure similar to anandamide) appears to act via the CB1, TRPV1 & TRPA1 receptors to cause vasodilation in the heart

Endothelial TRP channels and cannabinoid receptors are involved in affinin-induced vasodilation

https://pubmed.ncbi.nlm.nih.gov/34237389/

2021: In humans with Hermansky–Pudlak syndrome (a rare genetic disorder leading to fatal adult scarring of the heart), treatment with MRI-1867 (a dual inhibitor of the CB1 receptor & enzyme that creates the signaling molecule nitric oxide) prevented heart scarring & revered dysfunction of the mitochondria (the powerhouse of the cell)

CB1R and iNOS are distinct players promoting pulmonary fibrosis in Hermansky–Pudlak syndrome

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8255071/

2021: In a rat model of myocardial ischemia reperfusion (the return of blood flow to the heart after a heart attack), pretreatment with CBD protected the heart from damage

Cannabidiol-mediated RISK PI3K/AKT and MAPK/ERK pathways decreasing reperfusion myocardial damage

https://pubmed.ncbi.nlm.nih.gov/34176244/

2021: In diabetic mice, injections of 2-AG protected their hearts from the cardiac pathology of the disease

2-Arachidonoylglycerol Attenuates Fibrosis in Diabetic Mice via the TGF-β1/Smad Pathway

https://europepmc.org/article/ppr/ppr344998

2021: In mice with heart disease, CBD caused less inflammation, lower levels of reactive oxygen species & protection of the mitochondria

Cannabidiol attenuates pulmonary arterial hypertension by improving vascular smooth muscle cells mitochondrial function

https://pubmed.ncbi.nlm.nih.gov/33859746/

2021: In mice with their left carotid artery tied off, a combination of PEA & rutin (a helpful plant pigment) reduces inflammation, oxidative stress & vascular damage

Micro Composite Palmitoylethanolamide/Rutin Reduces Vascular Injury through Modulation of the Nrf2/HO-1 and NF-kB Pathways

https://pubmed.ncbi.nlm.nih.gov/33781184/

2021: In humans with a valve disease of the heart, the endocannabinoid system is suggested as a potential target to limit disease progression

Role of the Endocannabinoid System in Modulation of the Inflammatory Reaction in Aortic Valve Degeneration

https://www.thieme-connect.com/products/ejournals/html/10.1055/s-0041-1725674

2021: In rats, β-Caryophyllene (usually the most common terpene in hemp) protects the heart from cardiotoxicity of a widely used chemotherapy drug via the CB2 receptor

β-Caryophyllene, a natural bicyclic sesquiterpene attenuates doxorubicin-induced chronic cardiotoxicity via activation of myocardial cannabinoid type-2 (CB 2) receptors in rats

https://pubmed.ncbi.nlm.nih.gov/30836069/

2021: In rats, activating the CB2 receptor protects the heart during a model of a heart attack

AM1241 alleviates myocardial ischemia-reperfusion injury in rats by enhancing Pink1/Parkin-mediated autophagy

https://pubmed.ncbi.nlm.nih.gov/33607150/

2021: In megakaryocyte cells (the bone marrow cells that produce platelets), the endocannabinoid virodhamine helps to control the differentiation process via the mitochondria (the powerhouse of the cell)

Virodhamine, an endocannabinoid, induces megakaryocyte differentiation by regulating MAPK activity and function of mitochondria

https://pubmed.ncbi.nlm.nih.gov/32696508/

2021: In rat arteries, CBD lessened contraction in the small arteries but not the large ones

Cannabidiol selectively inhibits the contraction of rat small resistance arteries: Possible role for CGRP and voltage-gated calcium channels

https://www.sciencedirect.com/science/article/pii/S0014299920308591

2020: In a mouse model of cardiomyopathy, the liver-heart axis is heavily involved & a CB2 agonist seems to help

Interplay of Liver-Heart Inflammatory Axis and Cannabinoid 2 Receptor Signaling in an Experimental Model of Hepatic Cardiomyopathy

https://pubmed.ncbi.nlm.nih.gov/31469200/

2020: In heart preparations from rabbits & guinea-pigs, they looked at the effects of CBD

The electrophysiological effect of cannabidiol on hERG current and in guinea-pig and rabbit cardiac preparations

https://pubmed.ncbi.nlm.nih.gov/32999428/

2020: In rats, CBD lowered hypertension of the heart

Cannabidiol Ameliorates Monocrotaline-Induced Pulmonary Hypertension in Rats

https://pubmed.ncbi.nlm.nih.gov/32992900/

2020: In mammal heart preparations, high levels of CBD altered the electrophysiology

The electrophysiological effect of cannabidiol on hERG current and in guinea-pig and rabbit cardiac preparations

https://www.nature.com/articles/s41598-020-73165-2

 

2020: In rabbit hearts, CBD affected several of the ion channels causing a shorter action potential & slightly decreased amplitude

Cannabidiol inhibits multiple cardiac ion channels and shortens ventricular action potential duration in vitro

https://www.sciencedirect.com/science/article/abs/pii/S0014299920306348

2020: In endothelial cells (those that line your blood vessels), CBD helped them to survive via heme oxygenase-1, an enzyme that helps to regulate programmed cellular suicide

Cannabidiol Promotes Endothelial Cell Survival by Heme Oxygenase-1-Mediated Autophagy

https://www.mdpi.com/2073-4409/9/7/1703

2020: In alcoholic mice, activating the CB2 receptor protects the heart from damage

Pharmacological activation of CB2 receptor protects against ethanol-induced myocardial injury related to RIP1/RIP3/MLKL-mediated necroptosis

https://pubmed.ncbi.nlm.nih.gov/32681290/

2020: In rats exposed to the chemotherapeutic agent bleomycin, CB2 activation protected the heart against inflammation & scarring (fibrosis)

Effects of cannabinoid receptor 2 synthetic agonist, AM1241, on bleomycin induced pulmonary fibrosis

https://www.tandfonline.com/doi/abs/10.1080/10520295.2020.1758343

2020: In this clinical trial, they found that the benefits of flaxseed oil for your heart seems to be mediated by the ECS

Effect of flaxseed oil supplementation on the erythrocyte membrane fatty acid composition and endocannabinoid system modulation in patients with coronary artery disease: a double-blind randomized controlled trial

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7201600/

2020: In rats, a look at how PEA causes vasodepression (the lowering of blood pressure) via the heart's CB1, TRPV1 and probably GPR55 receptors, but not by CB2

Potential Mechanisms Involved in Palmitoylethanolamide-Induced Vasodepressor Effects in Rats

https://www.ncbi.nlm.nih.gov/pubmed/32248195

2020: In rats, activation of CB1 helped lower hypertension without affecting blood pressure

Stimulation of brain cannabinoid CB1 receptors can ameliorate hypertension in spontaneously hypertensive rats

https://www.ncbi.nlm.nih.gov/pubmed/32141630

2020: In a cell culture mimicking heart cells in a diabetic, CBD protected from all the negative effect of high glucose: elevated reactive oxygen species, shift of voltage by sodium channels, and prolongation of action potential (hyperexcitability)

Cannabidiol protects against high glucose-induced oxidative stress and cytotoxicity in cardiac voltage-gated sodium channels

https://www.ncbi.nlm.nih.gov/pubmed/32077098

2020: In rats with high blood pressure, CBD did not help to lower their blood pressure - but it did help with oxidative stress

Chronic Cannabidiol Administration Fails to Diminish Blood Pressure in Rats with Primary and Secondary Hypertension Despite Its Effects on Cardiac and Plasma Endocannabinoid System, Oxidative Stress and Lipid Metabolism

https://www.mdpi.com/1422-0067/21/4/1295

2020: In lambs, a look at how activating the CB1 receptor protects from the oxidative stress of fetal ischemia (cutting off the blood flow)

Cannabinoid-mediated Modulation of Oxidative Stress and Early Inflammatory Response after Hypoxia–Ischemia

https://www.mdpi.com/1422-0067/21/4/1283

2020: In a cell culture, a look at how CBD modulates the important sodium channels in the cell membrane

Mechanism of Sodium Channel Inhibition by Cannabidiol

https://www.cell.com/biophysj/pdf/S0006-3495(19)33690-2.pdf

 

2020: In a cell culture, CBD seems to protect the heart against high glucose levels via anti-oxidant effects & inhibition of the sodium channels

Protective Effect of Cannabidiol Against Oxidative Stress and Cytotoxicity Evoked by High Glucose in Cardiac Voltage-Gated Sodium Channels

https://www.cell.com/biophysj/pdf/S0006-3495(19)34071-8.pdf

2020: The CB1 receptor helps to modulate the cardiovascular response to stress

Cannabinoid receptor type 1 in the bed nucleus of the stria terminalis modulates cardiovascular responses to stress via local N-methyl-D-aspartate receptor/neuronal nitric oxide synthase/soluble guanylate cyclase/protein kinase G signaling

https://journals.sagepub.com/doi/abs/10.1177/0269881119897556

2020: During reduced blood flow to the heart, 2-AG levels elevate

Endocannabinoid 2-arachidonoylglycerol is elevated in the coronary circulation during acute coronary syndrome

https://www.ncbi.nlm.nih.gov/pubmed/31887202

2020: in humans, one dose of CBD reduced blood pressure

A single dose of cannabidiol reduces blood pressure in healthy volunteers in a randomized crossover study

https://www.ncbi.nlm.nih.gov/pubmed/28614793

2020: CBD causes vasodilation in arteries of the lung and the bowel and this effect was reduced by high blood pressure and obesity

Vasodilatory effects of cannabidiol in human pulmonary and rat small mesenteric arteries: modification by hypertension and the potential pharmacological opportunities

https://www.ncbi.nlm.nih.gov/pubmed/31800399

2020: In humans, heart effects of CBD: initially lowers blood pressure – but tolerance develops after 7 days. However, CBD continues to protect against the tendency of stress to increase blood pressure. Also reduces arterial stiffness & improves endothelial function

The effects of acute and sustained cannabidiol dosing for seven days on the haemodynamics in healthy men: a randomised controlled trial

https://nottingham-repository.worktribe.com/output/3780903/the-effects-of-acute-and-sustained-cannabidiol-dosing-for-seven-days-on-the-haemodynamics-in-healthy-men-a-randomised-controlled-trial

 

2019: In rats, activation of the CB1 receptor protects against mitochondrial damage in the heart induced by a toxin

Activation of Cannabinoid Receptors Attenuates Endothelin-1-induced Mitochondrial Dysfunction in Rat Ventricular Myocytes

https://journals.lww.com/cardiovascularpharm/Abstract/publishahead/Activation_of_Cannabinoid_Receptors_Attenuates.98463.aspx

2019: CBD's ability to cause vasodilation may be helpful for heart disease treatment

Vasodilatory effects of cannabidiol in human pulmonary and rat small mesenteric arteries

https://journals.lww.com/jhypertension/Abstract/publishahead/Vasodilatory_effects_of_cannabidiol_in_human.97067.aspx

2017: In diabetic rats, CBD improves vasorelaxation in arteries via COX & NO

In Vivo Cannabidiol Treatment Improves Endothelium-Dependent Vasorelaxation in Mesenteric Arteries of Zucker Diabetic Fatty Rats

https://pubmed.ncbi.nlm.nih.gov/28572770/

2016: in a mouse model of MS, CBD largely attenuated the CD3+ and CD4+ T cell-mediated inflammatory response and injury, myocardial fibrosis and cardiac dysfunction

Cannabidiol Limits T Cell-Mediated Chronic Autoimmune Myocarditis: Implications to Autoimmune Disorders and Organ Transplantation

https://www.ncbi.nlm.nih.gov/pubmed/26772776

2015: In rat heart cells, CBD depressed contractility via calcium channels & inhibits excitation-contraction coupling

Effects of cannabidiol on contractions and calcium signaling in rat ventricular myocytes

https://pubmed.ncbi.nlm.nih.gov/25711828/

2015: In a mouse, CBD protected against the negative heart effects of doxorubicin, a chemotherapy agent

Cannabidiol Protects against Doxorubicin-Induced Cardiomyopathy by Modulating Mitochondrial Function and Biogenesis

https://pubmed.ncbi.nlm.nih.gov/25569804/

2015: in rat model of anxiety, a FAAH inhibitor protects the heart

Cardioprotective effects of fatty acid amide hydrolase inhibitor URB694, in a rodent model of trait anxiety

https://pubmed.ncbi.nlm.nih.gov/26656183/

2015: In rabbits with a heart attack, CBD infusion before the attack protected the heart in multiple ways

Pharmacologic Effects of Cannabidiol on Acute Reperfused Myocardial Infarction in Rabbits: Evaluated With 3.0T Cardiac Magnetic Resonance Imaging and Histopathology

https://pubmed.ncbi.nlm.nih.gov/26065843/

2015: In mice with arrythmias, CBD conferred protection, probably via the adenosine A1 receptor

The effect of cannabidiol on ischemia/reperfusion-induced ventricular arrhythmias: the role of adenosine A1 receptors

https://pubmed.ncbi.nlm.nih.gov/24853683/

2015: in humans, CBD causes relaxation of the arteries in the heart via activation of CB1 & TRP channels

Cannabidiol causes endothelium-dependent vasorelaxation of human mesenteric arteries via CB1 activation

https://www.ncbi.nlm.nih.gov/pubmed/26092099

2014: pathway of platelet activation by ECs

Mechanism of platelet activation induced by endocannabinoids in blood and plasma.

http://www.ncbi.nlm.nih.gov/pubmed/23789792

2014: In diabetic rats, CBD improves vasorelaxation via COX1 & COX2

Cannabidiol improves vasorelaxation in Zucker diabetic fatty rats through cyclooxygenase activation

https://pubmed.ncbi.nlm.nih.gov/25212218/

2013: in mice, CBD protects from cardiotoxicity of doxorubicin

Cardioprotective effect of cannabidiol in rats exposed to doxorubicin toxicity

https://www.ncbi.nlm.nih.gov/pubmed/23721741

2012: In human females with depression, the AEA & 2AG levels in their blood correlated to their blood pressure

Serum contents of endocannabinoids are correlated with blood pressure in depressed women

https://pubmed.ncbi.nlm.nih.gov/22373123/

2011: FAAH is a key protector of the heart

Fatty acid amide hydrolase is a key regulator of endocannabinoid-induced myocardial tissue injury

https://www.ncbi.nlm.nih.gov/pubmed/21070851/

2011: In the mouse brain model of sepsis, CBD helped to stabilize the vasculature & lower inflammation

Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: an intravital microscopy study

https://pubmed.ncbi.nlm.nih.gov/21244691/

2010: In a mouse model of diabetes, CBD protected the heart by lowering oxidative stress, inflammation, cell death and fibrosis

Cannabidiol attenuates cardiac dysfunction, oxidative stress, fibrosis, and inflammatory and cell death signaling pathways in diabetic cardiomyopathy

https://pubmed.ncbi.nlm.nih.gov/21144973/

2010: In rats, CBD protects the heart from insult by reducing arrhythmias & size of infarct (dead tissue)

Acute administration of cannabidiol in vivo suppresses ischaemia-induced cardiac arrhythmias and reduces infarct size when given at reperfusion

https://www.ncbi.nlm.nih.gov/pubmed/20590615

2009: In rats, AEA decreased blood pressure in those with hypertension but not those without via mechanisms besides CB1

Acute hypertension reveals depressor and vasodilator effects of cannabinoids in conscious rats

https://pubmed.ncbi.nlm.nih.gov/19133994/

2009: In rat aortas, CBD causes vasorelaxation via the calcium channels & also binds to PPARgamma

Time-dependent vascular actions of cannabidiol in the rat aorta

https://pubmed.ncbi.nlm.nih.gov/19285060/

2007: in the heart of rats, CBD protected against ischemia

Cannabidiol, a nonpsychoactive Cannabis constituent, protects against myocardial ischemic reperfusion injury

https://www.ncbi.nlm.nih.gov/pubmed/17890433

2006: In rats with conditioned fear, CBD lessened anxiety & cardiovascular effects of fear

Effects of cannabidiol and diazepam on behavioral and cardiovascular responses induced by contextual conditioned fear in rats

https://pubmed.ncbi.nlm.nih.gov/16780966/


 

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