Reduction by Δ9-tetrahydrocannabinol in the blood pressure of hypertensive rats bearing regenerated adrenal glands

Posted on April 1, 2015 by David

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“A suspension of (−)-Δ9-trans-tetrahydrocannabinol (Δ9-THC) was administered daily for one week by i.p. injection to female rats showing the syndrome of adrenal regeneration hypertension (ARH)…

The findings indicate that Δ9-THC, at a moderate dose for the rat, is capable of lowering the blood pressure in rats suffering from adrenal regeneration hypertension and that chronic administration of Δ9-THC does not appear to stimulate the pituitary-adrenal axis, in contrast to reported effects of acute administration.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1776093/

http://www.thctotalhealthcare.com/category/hypertension-high-blood-pressure/

Endocannabinoid-mediated modulation of Gq/11 protein-coupled receptor signaling-induced vasoconstriction and hypertension.

Posted on January 18, 2015 by David

“Activation of G protein-coupled receptors (GPCRs) can induce vasoconstriction via calcium signal-mediated and Rho-dependent pathways…

Our aim was to provide evidence that GPCR signaling-induced 2-AG production and activation of vascular type1 cannabinoid receptors (CB1R) is capable of reducing agonist-induced vasoconstriction and hypertension…

Pharmacological or genetic loss of CB1R function augmented AngII-induced blood pressure rise in mice.

These data demonstrate that vasoconstrictor effect of GPCR agonists is attenuated via Gq/11-mediated vascular endocannabinoid formation.

Agonist-induced endocannabinoid-mediated CB1R activation is a significant physiological modulator of vascular tone.

Thus, the selective modulation of GPCR signaling-induced endocannabinoid release has a therapeutic potential in case of increased vascular tone and hypertension.”

http://www.ncbi.nlm.nih.gov/pubmed/25595485

http://www.thctotalhealthcare.com/category/hypertension-high-blood-pressure/

Δ(9)-THC and N-arachidonoyl glycine regulate BV-2 microglial morphology and cytokine release plasticity: implications for signaling at GPR18.

Posted on January 17, 2014 by David

“Microglial cells are extremely plastic and undergo a variety of CNS-prompted shape changes relative to their location and current role. Signaling molecules from neurons also regulate microglial cytokine production. Neurons are known to employ the endogenous cannabinoid system to communicate with other cells of the CNS.

N-arachidonoyl glycine (NAGly) and Δ(9)-tetrahydrocannabinol (Δ(9)-THC) signaling via GPR18 has been introduced as an important new target in microglial-neuronal communication…

These data add to an emerging profile that emphasizes NAGly as a component of an endogenous system present in the CNS that tightly integrates microglial proliferation, recruitment, and adhesion with neuron-glia interactivity and tissue remodeling.”

http://www.ncbi.nlm.nih.gov/pubmed/24427137

The Novel Endocannabinoid Receptor GPR18 is Expressed in the Rostral Ventrolateral Medulla and Exerts Tonic Restraining Influence on Blood Pressure.

Posted on January 17, 2014 by David

“Systemic administration of the GPR18 agonist abnormal cannabidiol (Abn CBD) lowers blood pressure (BP).

These findings are the first to demonstrate GPR18 expression in the RVLM, and to suggest sympathoinhibitory role for this receptor. The findings yield new insight into the role of a novel cannabinoid receptor (GPR18) in central BP control.”

http://www.ncbi.nlm.nih.gov/pubmed/24431468PR

Preventive and treatment effects of a hemp seed (Cannabis sativa L.) meal protein hydrolysate against high blood pressure in spontaneously hypertensive rats.

Posted on December 8, 2013 by David

“This work determined the ability of hemp seed meal protein hydrolysate (HMH)-containing diets to attenuate elevated blood pressure (hypertension) development in spontaneously hypertensive rats (SHRs)…

CONCLUSIONS: The results suggest that HMH with strong hypotensive effects in SHRs could be used as a therapeutic agent for both the prevention and treatment of hypertension.”

http://www.ncbi.nlm.nih.gov/pubmed/24292743

Therapeutic potential of cannabinoid medicines.

Posted on September 6, 2013 by David

Drug Testing and Analysis

“Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines.

The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology.

In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/24006213

http://onlinelibrary.wiley.com/doi/10.1002/dta.1529/abstract

The endocannabinoid system and its therapeutic exploitation.

Posted on May 24, 2013 by David

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“The term ‘endocannabinoid’ – originally coined in the mid-1990s after the discovery of membrane receptors for the psychoactive principle in Cannabis, Delta9-tetrahydrocannabinol and their endogenous ligands – now indicates a whole signalling system that comprises cannabinoid receptors, endogenous ligands and enzymes for ligand biosynthesis and inactivation. This system seems to be involved in an ever-increasing number of pathological conditions. With novel products already being aimed at the pharmaceutical market little more than a decade since the discovery of cannabinoid receptors, the endocannabinoid system seems to hold even more promise for the future development of therapeutic drugs. We explore the conditions under which the potential of targeting the endocannabinoid system might be realized in the years to come.” http://www.ncbi.nlm.nih.gov/pubmed/15340387

http://www.nature.com/nrd/journal/v3/n9/full/nrd1495.html

Cannabidiol as an Emergent Therapeutic Strategy for Lessening the Impact of Inflammation on Oxidative Stress

Posted on January 10, 2013 by David

“Growing evidence suggests that the endocannabinoid system, which includes the CB₁ and CB₂ G protein-coupled receptors and their endogenous lipid ligands, may be an area that is ripe for therapeutic exploitation. In this context, the related nonpsychotropic cannabinoid cannabidiol, which may interact with the endocannabinoid system, but has actions that are distinct, offers promise as a prototype for anti-inflammatory drug development.

This review discusses recent studies suggesting that cannabidiol may have utility in treating a number of human diseases and disorders now known to involve activation of the immune system and associated oxidative stress, as a contributor to their etiology and progression. These include rheumatoid arthritis, types I and II diabetes, atherosclerosis, Alzheimer’s disease, hypertension, the metabolic syndrome, ischemia-reperfusion injury, depression, and neuropathic pain.

Cannabidiol (CBD) is the major nonpsychotropic cannabinoid compound derived from the plant Cannabis sativa, commonly known as marijuana…

Conclusions

Inflammation and oxidative stress are intimately involved in the genesis of many human diseases. Unraveling that relationship therapeutically has proven challenging, in part because inflammation and oxidative stress “feed off” each other. However, CBD would seem to be a promising starting point for further drug development given its anti-oxidant (although relatively modest) and anti-inflammatory actions on immune cells, such as macrophages and microglia. CBD also has the advantage of not having psychotropic side effects. Studies on models of human diseases support the idea that CBD attenuates inflammation far beyond its antioxidant properties, for example, by targeting inflammation-related intracellular signaling events. The details on how CBD targets inflammatory signaling remain to be defined.

The therapeutic utility of CBD is a relatively new area of investigation that portends new discoveries on the interplay between inflammation and oxidative stress, a relationship that underlies tissue and organ damage in many human diseases.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3085542/

From cannabis to the endocannabinoid system: refocussing attention on potential clinical benefits.

Posted on November 20, 2012 by David

“Cannabis sativa is one of the oldest herbal remedies known to man. Over the past four thousand years, it has been used for the treatment of numerous diseases but due to its psychoactive properties, its current medicinal usage is highly restricted. In this review, we seek to highlight advances made over the last forty years in the understanding of the mechanisms responsible for the effects of cannabis on the human body and how these can potentially be utilized in clinical practice. During this time, the primary active ingredients in cannabis have been isolated, specific cannabinoid receptors have been discovered and at least five endogenous cannabinoid neurotransmitters (endocannabinoids) have been identified. Together, these form the framework of a complex endocannabinoid signalling system that has widespread distribution in the body and plays a role in regulating numerous physiological processes within the body. Cannabinoid ligands are therefore thought to display considerable therapeutic potential and the drive to develop compounds that can be targeted to specific neuronal systems at low enough doses so as to eliminate cognitive side effects remains the ‘holy grail’ of endocannabinoid research.”

http://www.ncbi.nlm.nih.gov/pubmed/23155985

Cannabis and endocannabinoid modulators: Therapeutic promises and challenges

Posted on November 6, 2012 by David

Abstract

“The discovery that botanical cannabinoids such as delta-9 tetrahydrocannabinol exert some of their effect through binding specific cannabinoid receptor sites has led to the discovery of an endocannabinoid signaling system, which in turn has spurred research into the mechanisms of action and addiction potential of cannabis on the one hand, while opening the possibility of developing novel therapeutic agents on the other. This paper reviews current understanding of CB1, CB2, and other possible cannabinoid receptors, their arachidonic acid derived ligands (e.g. anandamide; 2 arachidonoyl glycerol), and their possible physiological roles. CB1 is heavily represented in the central nervous system, but is found in other tissues as well; CB2 tends to be localized to immune cells. Activation of the endocannabinoid system can result in enhanced or dampened activity in various neural circuits depending on their own state of activation. This suggests that one function of the endocannabinoid system may be to maintain steady state. The therapeutic action of botanical cannabis or of synthetic molecules that are agonists, antagonists, or which may otherwise modify endocannabinoid metabolism and activity indicates they may have promise as neuroprotectants, and may be of value in the treatment of certain types of pain, epilepsy, spasticity, eating disorders, inflammation, and possibly blood pressure control.”

Summary

“The discovery of an endocannabinoid signaling system has opened new possibilities for research into understanding the mechanisms of marijuana actions, the role of the endocannabinoid system in homeostasis, and the development of treatment approaches based either on the phytocannabinoids or novel molecules. CB1 agonists may have roles in the treatment of neuropathic pain, spasticity, nausea and emesis, cachexia, and potentially neuroprotection after stroke or head injury. Agonists and antagonists of peripheral CB receptors may be useful in the treatment of inflammatory and autoimmune disorders, as well as hypertension and other cardiovascular diseases. CB1 antagonists may find utility in management of obesity and drug craving. Other novel agents that may not be active at CB receptor sites, but might otherwise modify cannabinoid transport or metabolism, may also have a role in therapeutic modification of the endocannabinoid system. While the short and long term toxicities of the newer compounds are not known, one must expect that at least some of the acute effects (psychotropic effects; hypotension) may be shared by CB agonists. While there are few, long-term serious toxicities attributable to marijuana, extrapolation to newer and more potent agonists, antagonists, and cannabinoid system modulators cannot be assumed. CB1 agonists have the potential in animal models to produce drug preference and drug seeking behaviors as well as tolerance and abstinence phenomena similar to, though not generally as severe as those of other drugs of addiction. There is increasing evidence from human observations that withdrawal from the phytocannabinoids can produce an abstinence syndrome characterized primarily by irritability, sleep disturbance, mood disturbance, and appetite disturbance in chronic heavy users, therefore, such possible effects will need to be considered in the evaluation of newer shorter acting and more potent agonists.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2544377/