“Preventive treatment with cannabinoid agonists has been reported to reduce the infarct size in a mouse model of myocardial ischemia/reperfusion.
Here we investigated the possible cardioprotective effect of selective CB(2) cannabinoid receptor activation during ischemia.
Our data suggest that administration during ischemia reduces the infarct size in a mouse model of myocardial ischemia/reperfusion through a direct cardioprotective activity on cardiomyocytes and neutrophils.”
“Post-myocardial infarction (MI) heart failure is a major public health problem in Western countries and results from ischemia/reperfusion (IR)-induced cell death, remodeling, and contractile dysfunction.
Ex vivo studies have demonstrated the cardioprotective anti-inflammatory effect of the cannabinoid type 2 (CB2) receptor agonists within hours after IR.
Herein, we evaluated the in vivo effect of CB2 receptors on IR-induced cell death, fibrosis, and cardiac dysfunction and investigated the target role of cardiac myocytes and fibroblasts… CB2 receptor activation may protect against post-IR heart failure through direct inhibition of cardiac myocyte and fibroblast death and prevention of myofibroblast activation…
In conclusion, modulation of the endocannabinoid system is emerging as a novel approach for the therapy of various inflammatory, metabolic, cardiovascular, hepatic, and neurodegenerative disorders.
CB1 receptors exert cardioprotective effects in cirrhotic rats and against doxorubicin toxicity. Pharmacological inhibition of the endocannabinoid degradative pathway, fatty acid aminohydrolase, represents a novel protective strategy against chronic inflammation, oxidative and nitrative stresses, and apoptosis associated with cardiovascular aging and atherosclerosis.
CB2 receptor activation is thought to be anti-inflammatory and involved in protective mechanisms during atherosclerosis. In addition, selective CB2 agonists protect against cerebral and hepatic IR injuries.
We demonstrated a highly protective role of CB2 receptors in post-IR cardiac remodeling, potentially related to activation of antiapoptotic, prosurvival, and antifibrogenic pathways.
Our results infer that CB2 agonists may be useful in preventing reperfusion injury in acute coronary syndrome and provide novel evidence for the pivotal role of CB2 receptors in post-IR-induced cardiomyopathy.”
“Although cannabinoids have been recreationally employed for thousands of years, it was not until the discovery of their specific receptors, in the early nineties, that the molecular basis of cannabinoid activity have began to be understood.
Growing research in this field has demonstrated not only that the action of cannabinoids in mammals is mainly receptor-mediated, but also that endogenous cannabinoids, such as anandamide, are produced, metabolized, and taken up across the cell membrane through a facilitated uptake process.
The exogenous administration of cannabinoids, as well as the manipulation of their endogenous levels have been related to a variety of effects, such as analgesia, (temporary) impairment of cognition and learning, appetite enhancement and peripheral vasodilation.
Hence, the endocannabinoid system, including the CB1 and CB2 receptors, the metabolizing enzyme fatty acid amide hydrolase and the anandamide transporter, is a potential target for the development of novel therapeutic drugs in the treatment of various conditions, such as pain, feeding disorders and vascular disease among others.
Although most of the research in the field of cannabinoids has been focused on their effects in the central nervous system, a growing line of evidence indicates that cannabinoids can also play a major role in the control of physiopathological functions in the cardiovascular system.
In this context, endocannabinoids have been proposed as novel possible hypotensive agents, and have been involved in the hypotension observed in septic shock, acute myocardial infarction and cirrhosis. In addition, a protective role for endocannabinoids has been described in ischemia.”
“The psychoactive properties of cannabinoids, the biologically active constituents of the marijuana plant, have long been recognized. Recent research has revealed that cannabinoids elicit not only neurobehavioral, and immunological, but also profound cardiovascular effects.
Similar effects can be elicited by the endogenous ligand arachidonyl ethanolamine (anandamide) and 2-arachidonoyl-glycerol.
The biological effects of cannabinoids are mediated by specific receptors.
Two cannabinoid receptors have been identified so far: CB1-receptors are expressed by different cells of the brain and in peripheral tissues, while CB2-receptors were found almost exclusively in immune cells.
Through the use of a selective CB1 receptor antagonist and CB1 receptor-knockout mice the hypotensive and bradycardic effects of cannabinoids in rodents could be attributed to activation of peripheral CB1 receptors. In hemodynamic studies using the radioactive microsphere technique in anesthetized rats, cannabinoids were found to be potent CB1-receptor dependent vasodilators in the coronary and cerebrovascular beds.
Recent findings implicate the endogenous cannabinoid system in the pathomechanism of haemorrhagic, endotoxic and cardiogenic shock.
Finally, there is evidence that the extreme mesenteric vasodilation, portal hypertension and systemic hypotension present in advanced liver cirrhosis are also mediated by the endocannabinoid system.
These exciting, recent research developments indicate that the endogenous cannabinoid system plays an important role in cardiovascular regulation, and pharmacological manipulation of this system may offer novel therapeutic approaches in a variety of pathological conditions.”
“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.”
“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.”
“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.”
“Cannabinoid receptor type 1 (CB1R) plays an important role in the development of myocardial hypertrophy and fibrosis-2 pathological features of uremic cardiomyopathy. However, it remains unknown whether CB1R is involved in the pathogenesis of uremic cardiomyopathy.
Here, we aimed to elucidate the role of CB1R in the development of uremic cardiomyopathy via modulation of Akt signalling…
CB1R inhibition exerts anti-fibrotic effects via modulation of Akt signaling in H9c2 myofibroblasts.
Therefore, the development of drugs targeting CB1R may have therapeutic potential in the treatment of uremic cardiomyopathy.”
“Stress affects a constellation of physiological systems in the body and evokes a rapid shift in many neurobehavioral processes.
A growing body of work indicates that the endocannabinoid (eCB) system is an integral regulator of the stress response.
In the current review, we discuss the evidence to date that demonstrates stress-induced regulation of eCB signaling and the consequential role changes in eCB signaling play with respect to many of the effects of stress.
Across a wide array of stress paradigms, studies have generally shown that stress evokes bidirectional changes in the two eCB molecules, anandamide (AEA) and 2-arachidonoyl glycerol (2-AG), with stress exposure reducing AEA levels and increasing 2-AG levels.
Additionally, in almost every brain region examined, exposure to chronic stress reliably causes a down-regulation or loss of cannabinoid type 1 (CB1) receptors.
With respect to the functional role of changes in eCB signaling during stress, studies have demonstrated that the decline in AEA appears to contribute to the manifestation of the stress response, including activation of the hypothalamic-pituitary-adrenal (HPA) axis and increases in anxiety behavior, while the increased 2-AG signaling contributes to termination and adaptation of the HPA axis, as well as potentially contributing to changes in pain perception and synaptic plasticity.
More so, translational studies have shown that eCB signaling in humans regulates many of the same domains and appears to be a critical component of stress regulation, and impairments in this system may be involved in the vulnerability to stress-related psychiatric conditions, such as depression and post-traumatic stress disorder.
Collectively, these data create a compelling argument that eCB signaling is an important regulatory system in the brain that largely functions to buffer against many of the effects of stress and that dynamic changes in this system contribute to different aspects of the stress response.”
“We investigated the capacity of intrathecal arachidonyl-2′-chloroethylamide (ACEA), a cannabinoid-1 receptor (CB1R) agonist, to inhibit referred hyperalgesia and increased bladder contractility resulting from acute acrolein-induced cystitis in rats…
These findings suggest that pain arising from cystitis may be inhibited by activation of spinal CB1R but the acute local response of the bladder appeared to be unaffected by stimulation of spinal CB1R.”