“Cannabidiol (CBD) is the second most abundant phytocannabinoid, after Δ9-tetrahydrocannabinol (THC) and was first isolated from the cannabis extract in 1940. Given the increasing clinical use of CBD, and the numerous effects of CBD in the cardiovascular system, the aim of the present study was to systematically review and analyse in vivo studies evaluating the effects of CBD on alterations in haemodynamics. From the limited data available, we conclude that acute and chronic administration of CBD had no effect on BP or HR under control conditions, but reduces BP and HR in stressful conditions, and increases cerebral blood flow (CBF) in mouse models of stroke. This meta-analysis and systematic review has highlighted the haemodynamic effects of CBD administration in vivo. The positive effects induced by CBD include maintaining the fall in BP after global hypoxia, reducing the increase in MBP and HR post-stress, and increasing BF in ischaemia-reperfusion models. It is possible that beneficial effects of CBD on haemodynamics occurs when the cardiovascular system is abnormally altered, suggesting that CBD may be used as a treatment for various cardiovascular disorders, such as hypertension, myocardial infarction and stroke.” http://journal.frontiersin.org/article/10.3389/fphar.2017.00081/full]]>
Category Archives: Cardiovascular Disease
Cannabinoid signaling in health and disease.
“Cannabis sativa has long been used for medicinal purposes.
To improve safety and efficacy, compounds from C. sativa were purified or synthesized and named under an umbrella group as cannabinoids.
Currently, several cannabinoids may be prescribed in Canada for a variety of indications such as nausea and pain.
More recently, an increasing number of reports suggest other salutary effects associated with endogenous cannabinoid signaling including cardioprotection.
The therapeutic potential of cannabinoids is therefore extended; however, evidence is limited and mechanisms remain unclear.
In addition, the use of cannabinoids clinically has been hindered due to pronounced psychoactive side effects.
This review provides an overview on the endocannabinoid system, including known physiological roles, and conditions in which cannabinoid receptor signaling has been implicated.”
The role of exercise training and the endocannabinoid system in atherosclerotic plaque burden and composition in Apo-E-deficient mice.
“We investigated the effect of combining exercise training and treatment with an endocannabinoid receptor 1 inhibitor (Rimonabant) on atherosclerosis burden and composition. Both exercise and rimonabant treatments induced plaque regression and promoted plaque stability. The combined treatment failed to show additive or synergistic benefits relative to either intervention alone.” https://www.ncbi.nlm.nih.gov/pubmed/28254386]]>
CB2 cannabinoid receptors modulate HIF-1α and TIM-3 expression in a hypoxia-ischemia mouse model.
“The role of CB2 cannabinoid receptors (CB2R) in global brain lesions induced by hypoxia-ischemia (HI) insult is still unresolved. The aim of this study was to evaluate the involvement of CB2R in the behavioural and biochemical underpinnings related to brain damage induced by HI in adult mice, and the mechanisms involved. Our results indicate that CB2R may have a crucial neuroprotective role following HI insult through the modulation of the inflammatory-related HIF-1α/TIM-3 signalling pathway in microglia.” https://www.ncbi.nlm.nih.gov/pubmed/28253997]]>
Cannabidiol attenuates OGD/R-induced damage by enhancing mitochondrial bioenergetics and modulating glucose metabolism via pentose-phosphate pathway in hippocampal neurons
“Deficient bioenergetics and diminished redox conservation have been implicated in the development of cerebral ischemia/reperfusion injury. In this study, the mechanisms underlying the neuroprotective effects of cannabidiol (CBD), a nonpsychotropic compound derived from Cannabis sativa with FDA-approved antiepilepsy properties, were studied in vitro using an oxygen–glucose-deprivation/reperfusion (OGD/R) model in a mouse hippocampal neuronal cell line. This study is the first to document the neuroprotective effects of CBD against OGD/R insult, which depend in part on attenuating oxidative stress, enhancing mitochondrial bioenergetics, and modulating glucose metabolism via the pentose-phosphate pathway, thus preserving both energy and the redox balance. Cannabidiol (CBD) is a nonpsychoactive cannabinoid derived from Cannabis sativa and a weak CB1 and CB2 cannabinoid receptor antagonist, with very low toxicity for humans. It has recently been demonstrated in vivo and in vitro that CBD has a variety of therapeutic properties, exerting antidepressant, anxiolytic, anti-inflammatory, immunomodulatory, and neuroprotective effects. Our results provide novel insight into the neuroprotective properties of CBD, which involves the regulation of the mitochondrial bioenergetics and the glucose metabolism of hippocampal neurons during OGD/R injury. In summary, our results suggest that CBD exerts a potent neuroprotective effect against ischemia/reperfusion injury by attenuating intracellular oxidative stress, enhancing mitochondrial bioenergetics, and optimizing glucose metabolism via the pentose-phosphate pathway, thus strengthening the antioxidant defenses and preserving the energy homeostasis of neurons. More in-depth studies are required to investigate the precise mechanism underlying the success of CBD treatment and to determine the actual role of CBD in cerebral ischemia.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5247568/
“Cannabidiol may soon be used in the emergency room to fight effects of stroke and cardiac emergencies” http://www.naturalnews.com/2017-02-21-cannabidiol-may-soon-be-used-in-the-emergency-room-to-fight-effects-of-stroke-cardiac-emergencies.html
]]>The potential for clinical use of cannabinoids in treatment of cardiovascular diseases.
“Cannabinoids, the constituents of the marijuana plant and their analogs, have not only neurobehavioral but also cardiovascular effects. Great advances in the last couple of decades have led to better understanding of the physiological effects of the cannabinoids and of their role in various cardiovascular pathologies. The potential therapeutic use of cannabinoids in various cardiac diseases, such as ischemic injury, heart failure, and cardiac arrhythmias, has been studied in animal models. The purpose of this article is to review the physiological cardiovascular properties of cannabinoids and to summarize the knowledge related to their potential therapeutic use.” https://www.ncbi.nlm.nih.gov/pubmed/20946323
“Cannabinoid system as a potential target for drug development in the treatment of cardiovascular disease.” https://www.ncbi.nlm.nih.gov/pubmed/15320476
]]>The endocannabinoid system: no longer anonymous in the control of nitrergic signalling?
“The endocannabinoid system (ECS) is a key cellular signalling system that has been implicated in the regulation of diverse cellular functions. Importantly, growing evidence suggests that the biological actions of the ECS may, in part, be mediated through its ability to regulate the production and/or release of nitric oxide, a ubiquitous bioactive molecule, which functions as a versatile signalling intermediate. Herein, we review and discuss evidence pertaining to ECS-mediated regulation of nitric oxide production, as well as the involvement of reactive nitrogen species in regulating ECS-induced signal transduction by highlighting emerging work supporting nitrergic modulation of ECS function. Importantly, the studies outlined reveal that interactions between the ECS and nitrergic signalling systems can be both stimulatory and inhibitory in nature, depending on cellular context. Moreover, such crosstalk may act to maintain proper cell function, whereas abnormalities in either system can undermine cellular homoeostasis and contribute to various pathologies associated with their dysregulation. Consequently, future studies targeting these signalling systems may provide new insights into the potential role of the ECS -: nitric oxide signalling axis in disease development and/or lead to the identification of novel therapeutic targets for the treatment of nitrosative stress-related neurological, cardiovascular, and metabolic disorders.” https://www.ncbi.nlm.nih.gov/pubmed/28130308]]>
Diuretic effects of cannabinoid agonists in mice
“Cannabinoids both increase urine output and decrease urinary frequency in human subjects. However, these effects have not been systematically evaluated in intact mice, a species commonly used to evaluate the effects of novel cannabinoids.
The present studies investigated whether cannabinoid agonists reliably produce diuresis in mice at doses comparable to those that produce other cannabinoid effects and, further, identified the receptors that may mediate these effects.
These findings suggest that mice may provide a model for understanding the mixed effects of marijuana on urine output, as described in clinical studies, and aid in the development of targeted cannabinoid based therapies for bladder dysfunction.
Clinical studies have reported beneficial effects of smoked or aerosolized cannabis on bladder dysfunction in patients with multiple sclerosis, primarily by decreasing urinary frequency in these subjects following marijuana use. These reports contrast with the earlier clinical reports demonstrating increase in urine output after cannabis administration.
Our findings in mice demonstrate a dose related increase or decrease in urine output, providing a platform for understanding the mixed effects on urine output observed with marijuana in various clinical studies. As noted earlier in a study with rats, the diuresis induced by THC in mice also is weakly naturetic compared to furosemide and further investigations in this area may yield a new, clinically beneficial diuretic.
In contrast, our data suggest that development of peripherally selective cannabinoid CB1 agonists may be beneficial for patients suffering from bladder dysfunction.”
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3872476/Diuretic effects of cannabinoids.
“These data indicate that cannabinoids have robust diuretic effects in rats that are mediated via CB1 receptor mechanisms. Overall, our data indicate that diuresis is a CB1-mediated effect that may serve as a reliable and objective physiologic measure of cannabinoid action in rats; the circumstances under which these results represent a potential therapeutic benefit or potential liability of cannabinoids remain to be determined. The implications of these findings currently are poorly understood, although a better understanding of mechanisms and sites of action by which cannabinoids increase urine loss may lead to the rational development of novel cannabinergic medications.” https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3533417/
“Diuretics are medicines that help reduce the amount of water in the body. Diuretics are used to treat the buildup of excess fluid in the body that occurs with some medical conditions such ascongestive heart failure, liver disease, and kidney disease. Some diuretics are also prescribed to treat high bloodpressure. These drugs act on the kidneys to increase urine output. This reduces the amount of fluid in the bloodstream,which in turn lowers blood pressure.” http://medical-dictionary.thefreedictionary.com/diuretics
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Cannabis, Tobacco, Alcohol Use, and the Risk of Early Stroke
“Current knowledge on cannabis use in relation to stroke is based almost exclusively on clinical reports. By using a population-based cohort, we aimed to find out whether there was an association between cannabis use and early-onset stroke, when accounting for the use of tobacco and alcohol.
Conclusions—We found no evident association between cannabis use in young adulthood and stroke, including strokes before 45 years of age. Tobacco smoking, however, showed a clear, dose–response shaped association with stroke.”
http://stroke.ahajournals.org/content/early/2016/12/27/STROKEAHA.116.015565 “New Study: Cigarettes Tied To Increased Stroke Risk But Not Marijuana” http://www.weednews.co/new-study-cigarettes-tied-to-increased-stroke-risk-but-not-marijuana/
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