Author Archives: David Worrell

[Cardiac and vascular effects of cannabinoids: toward a therapeutic use?].

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“Interest in cannabinoid pharmacology developed rapidly since the discovery of cannabinoids receptors and endocannabinoids. Modulation of this system is becoming a hot topic in cardiovascular pharmacology mainly at the light of recent findings.

Among them, cardiac effects of cannabinoids were described with respect to their probable participation to the well-studied preconditioning phenomenon.

Beneficial effects of post-infarction cannabinoids administration against ischemia-reperfusion injury were also reported.

Finally, pathological situations concerning the cardiovascular system and including brain ischemia, hemorrhagic and endotoxic shocks were reported to be linked with endocannabinoids.

However, the clinical use of cannabinoid receptors agonists or antagonists will depend on the development of non psychoactive compounds.”

http://www.ncbi.nlm.nih.gov/pubmed/15828464

Ligand activation of cannabinoid receptors attenuates hypertrophy of neonatal rat cardiomyocytes.

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“Endocannabinoids are bioactive amides, esters, and ethers of long-chain polyunsaturated fatty acids.

Evidence suggests that activation of the endocannabinoid pathway offers cardioprotection against myocardial ischemia, arrhythmias, and endothelial dysfunction of coronary arteries.

In conclusion, CB-13 inhibits cardiomyocyte hypertrophy through AMPK-eNOS signaling and may represent a novel therapeutic approach to cardioprotection.”

http://www.ncbi.nlm.nih.gov/pubmed/24979612

The endocannabinoid-CB2 receptor axis protects the ischemic heart at the early stage of cardiomyopathy.

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“Ischemic heart disease is associated with inflammation, interstitial fibrosis and ventricular dysfunction prior to the development of heart failure.

Endocannabinoids and the cannabinoid receptor CB2 have been claimed to be involved, but their potential role in cardioprotection is not well understood. We therefore explored the role of the cannabinoid receptor CB2 during the initial phase of ischemic cardiomyopathy development prior to the onset of ventricular dysfunction or infarction.

… the endocannabinoid-CB2 receptor axis plays a key role in cardioprotection during the initial phase of ischemic cardiomyopathy development.”

http://www.ncbi.nlm.nih.gov/pubmed/24980781

Role of cyclic nucleotides and NO synthase in mechanisms of cardioprotective effects of cannabinoid HU-210.

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“The cardioprotective effect of HU-210 remained unchanged under condition of NO synthase inhibition.

The results of the experiment suggest that the cardioprotective effect of HU-210 can be determined by a decrease in cAMP level in the myocardium during reperfusion. cGMP and NO synthase do not contribute to cytoprotective effect of HU-210.”

Signaling Pathways Involved in the Cardioprotective Effects of Cannabinoids

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jphs

“The aim of the present article is to review the cardioprotective properties of cannabinoids, with an emphasis on the signaling pathways involved.

Cannabinoids have been reported to protect against ischemia in rat isolated hearts, as well as in rats and mice in vivo.

Finally, although nitric oxide (NO) was shown to exert both pro and anti-apoptotic effects on cardiomyocytes, with an apparently controversial effect on myocardial survival, our data suggest that NO may contribute to the cardioprotective effect of some cannabinoids.”

“Signaling pathways involved in the cardioprotective effects of cannabinoids.”  http://www.ncbi.nlm.nih.gov/pubmed/17031075

https://www.jstage.jst.go.jp/article/jphs/102/2/102_2_155/_article

6B.09: EFFECT OF CANNABINOID RECEPTOR ACTIVATION ON ABERRANT MITOCHONDRIAL BIOENERGETICS IN HYPERTROPHIED CARDIAC MYOCYTES.

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“We recently reported that activation of endocannabinoid receptors attenuates cardiac myocyte hypertrophy. Mitochondrial dysfunction has emerged as a critical determinant of aberrant myocyte energy production in cardiac hypertrophy. Thus, we determined endocannabinoid influence on mitochondrial function in the hypertrophied cardiac myocyte…

The cardioprotective actions of liganded cannabinoid receptors extend to the mitochondrial level. Therefore, a cannabinoid-based treatment for cardiac disease remains a potential therapeutic strategy that warrants further study.”

http://www.ncbi.nlm.nih.gov/pubmed/26102932

The endocannabinoid anandamide during lactation increases body fat content and CB1 receptor levels in mice adipose tissue.

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“Type 1 cannabinoid receptors (CB1R) modulate energy balance; thus, their premature activation may result in altered physiology of tissues involved in such a function.

Activation of CB1R mainly occurs after binding to the endocannabinoid Anandamide (AEA).

The objective of this study was to evaluate the effects of AEA treatment during lactation on epididymal and body fat content, in addition to CB1R protein level at weaning.

This in vivo study shows for the first time that a progressive increase in body fat accumulation can be programmed in early stages of life by oral treatment with the endocannabinoid AEA, a fact associated with an increased amount of epididymal fat pads and a higher expression of CB1R in this tissue.”

http://www.ncbi.nlm.nih.gov/pubmed/26098446

Topical cannabinoid receptor 1 agonist attenuates the cutaneous inflammatory responses in oxazolone-induced atopic dermatitis model.

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“This study was performed to investigate the effects of CBR agonists on skin inflammation, using acute and chronic inflammation animal models.

All of the results suggest that topical application of CB1R-specific agonist can be beneficial for alleviating the inflammatory symptoms in chronic skin diseases, including atopic dermatitis.”

http://www.ncbi.nlm.nih.gov/pubmed/26095080

CB2R orchestrates fibrogenesis through regulation of inflammatory response during the repair of skeletal muscle contusion.

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“Skeletal muscle injuries repair typically is an overlapping event between inflammation and tissue repair.

Our previous study has demonstrated that activation of cannabinoid receptor type 2 (CB2R) alleviates fibrosis in the repair of rat skeletal muscle contusion. Meanwhile, accumulated data show that CB2R stimulation exerts anti-inflammatory property in sepsis and cystitis…

In this study, we used selective agonist or antagonist of CB2R to observe the role of CB2R on inflammation and fibrogenesis during the repair of contused skeletal muscles in rats…

Our study demonstrated that CB2R orchestrates fibrogenesis through regulation of inflammatory response during the repair of skeletal muscle contusion.”

http://www.ncbi.nlm.nih.gov/pubmed/26097533

 

Minor oxygenated cannabinoids from high potency Cannabis sativa L.

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“Nine oxygenated cannabinoids were isolated from a high potency Cannabis sativa L. variety. Structure elucidation was achieved using spectroscopic techniques, including 1D and 2D NMR, HRMS and GC-MS.

These minor compounds include four hexahydrocannabinols, four tetrahydrocannabinols, and one hydroxylated cannabinol, namely 9α-hydroxyhexahydrocannabinol, 7-oxo-9α-hydroxyhexa-hydrocannabinol, 10α-hydroxyhexahydrocannabinol, 10aR-hydroxyhexahydrocannabinol, Δ9-THC aldehyde A, 8-oxo-Δ9-THC, 10aα-hydroxy-10-oxo-Δ8-THC, 9α-hydroxy-10-oxo-Δ6a,10a-THC, and 1’S-hydroxycannabinol, respectively.

The latter compound showed moderate anti-MRSa (IC50 10.0μg/mL), moderate antileishmanial (IC50 14.0μg/mL) and mild antimalarial activity against Plasmodium falciparum (D6 clone) and P. falciparum (W2 clone) with IC50values of 3.4 and 2.3μg/mL, respectively.”

http://www.ncbi.nlm.nih.gov/pubmed/26093324