Tag Archives: endocannabinoids

Marijuana & Stroke: Pot Compounds Protect Brain, New Meta-Study Shows

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“Cannabinoids, chemicals related to those found in cannabis could be effective in restoring neurological function by shrinking the area of the brain affected by stroke, according to a new study led by Dr. Tim England, Honorary Consultant Stroke Physician at the University of Nottingham and Royal Derby Hospital.

Stroke, a leading cause of adult disability in the UK leaves over half of all survivors dependent on others for life. Over one million people are living with the effects of stroke and it is reported that in the UK alone, over 150,000 people have a stroke every year. Finding new treatments to help survivors recover quickly has never been more important.

The authors examined 94 studies evaluating the effects of cannabinoids on 1022 mice, monkeys, and male rats. Cannabinoids can be classified into endocannabinoids that occur naturally in the body, phytocannabinoids that are obtained from plant extracts, and synthetic cannabinoids.

A meta-analysis of experimental studies conducted by the researchers at the University of Nottingham identifies the potential of all three categories of these compounds potential to reduce brain damage caused by stroke and help improve brain function after an attack.

The U.S. government sought a patent in 2001 for the naturally occuring marijuana molecule, cannabidiol, for use as a brain protector during stroke. ”

http://blog.sfgate.com/smellthetruth/2013/12/11/marijuana-stroke-pot-compounds-protect-brain-new-meta-study-shows/

Cannabinoids and Neuroprotection in Stroke

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“One of the most recently described neural signaling systems is that mediated by endogenous cannabinoids (endocannabinoids). Cannabinoids have recently been shown to attenuate neuronal injury induced by hypoxia and glucose deprivation in cell culture, as well as injury induced in rat brain following both global and focal cerebral ischemia in vivo.

Two endocannabinoids have been characterized in detail: N-arachidonylethanolamide and 2-arachidonylglycerol. Cannabinoid CB1 and CB2receptors have been cloned and an alternatively spliced CB1A isoform has been identified.

The development of metabolically stable, synthetic, enantiomeric cannabinoid receptor agonists and of CB1 and CB2 receptor antagonists has greatly aided the characterization of cannabinoid receptor-mediated processes, although certain aspects of cannabinoid signaling in some systems remain poorly understood.

Indirect evidence suggests that cannabinoids might serve as endogenous regulators of ischemic neuronal injury, but several recent reports provide more direct evidence bearing on such a role.

The author’s own findings provide evidence for CB1 receptor-mediated neuroprotection in vivo, but non-receptor-mediated protection in vitro.”

http://journals.prous.com/journals/servlet/xmlxsl/pk_journals.xml_summary_pr?p_JournalId=3&p_RefId=129&p_IsPs=Y

Cannabis compounds may limit stroke damage

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“Chemical compounds found in cannabis may help to reduce brain damage following a stroke, new research has revealed.

Researchers at the University of Nottingham conducted a meta-analysis of experimental studies into cannabinoids; chemicals related to those found in cannabis, some of which also occur naturally in the body.

The findings showed that the compounds could reduce the size of stroke and improve .

Cannabinoids can be classified into those found naturally in the body (endocannabinoids), those made artificially (synthetic cannabinoids) or those derived from extracts from the plant cannabis sativa (phytocannabinoids).

The research, announced at the annual UK Stroke Forum, indicates that all three classes of cannabinoid could be effective in shrinking the area of the brain affected by stroke and in recovering neurological function.”

http://healthmedicinet.com/i/cannabis-compounds-may-limit-stroke-damage/

The endocannabinoid system modulates stress, emotionality, and inflammation.

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“The physiological and behavioral effects of stress are well characterized.

Endocannabinoids are produced on demand and function to attenuate many of the physiological effects of the stress response.

The endocannabinoid system is made up of cannabinoid receptors, the fatty acid signaling molecules that bind to and activate these receptors, and the enzymes that synthesize and catabolize these endocannabinoid signaling molecules.

Cannabinoid research has recently grown substantially, due in no small part to the development of genetic research models as well as highly selective pharmaceutical tools.

The purpose of this minireview is to discuss a subset of the many parallels between cannabinoid and behavioral neuroimmunology research, with specific discussion of interactions between the endocannabinoid system and psychological stress, emotionality, and inflammation.”

http://www.ncbi.nlm.nih.gov/pubmed/24953427

Role of Endocannabinoid Activation of Peripheral CB1 Receptors in the Regulation of Autoimmune Disease.

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“The impact of the endogenous cannabinoids (AEA, 2-AG, PEA, and virodamine) on the immune cell expressed cannabinoid receptors (CB1, CB2, TRPV-1, and GPR55) and consequent regulation of immune function is an exciting area of research with potential implications in the prevention and treatment of inflammatory and autoimmune diseases.

Despite significant advances in understanding the mechanisms through which cannabinoids regulate immune functions, not much is known about the role of endocannabinoids in the pathogenesis or prevention of autoimmune diseases.

Inasmuch as CB2 expression on immune cells and its role has been widely reported, the importance of CB1 in immunological disorders has often been overlooked especially because it is not highly expressed on naive immune cells.

Therefore, the current review aims at delineating the effect of endocannabinoids on CB1 receptors in T cell driven autoimmune diseases. This review will also highlight some autoimmune diseases in which there is evidence indicating a role for endocannabinoids in the regulation of autoimmune pathogenesis.

Overall, based on the evidence presented using the endocannabinoids, specifically AEA, we propose that the peripheral CB1 receptor is involved in the regulation and amelioration of inflammation associated with autoimmune diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/24911431

Do cannabinoids have a therapeutic role in transplantation?

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Figure 1

“Cannabinoids are a group of terpenophenolic compounds structurally similar to delta-9-tetrahydrocannabinol (THC) from the plant Cannabis sativa.

Cannabinoids have emerged as powerful drug candidates for the treatment of inflammatory and autoimmune diseases due to their immunosuppressive properties.

Significant clinical and experimental data on the use of cannabinoids as anti-inflammatory agents exist in many autoimmune disease settings, but virtually no studies have been undertaken on their potential role in transplant rejection. Here we suggest a theoretical role for the use of cannabinoids in preventing allograft rejection.

…manipulation of endocannabinoids in vivo by activating their biosynthesis and inhibiting cellular uptake and metabolism may offer another pathway to regulate immune response during allograft rejection.

…cannabinoids have emerged as novel anti-inflammatory agents because of their efficacy in the treatment of many immune-mediated disorders such as multiple sclerosis, rheumatoid arthritis and autoimmune hepatitis.

Transplantation is one critical area of medicine that requires the use of immunosuppressants.

 Inasmuch as, immune cells constitute an important resource of endocannabinoids, it may be easier to manipulate their levels during an immune response, which could have a direct and immediate impact on such cells that determine the fate of the allograft.

In summary, targeting cannabinoid receptors and understanding the role and use of exo-and endocannabinoids in experimental allograft rejection models may provide an exciting new beginning with significant translational impact.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2923447/

Signaling through cannabinoid receptor 2 suppresses murine dendritic cell migration by inhibiting matrix metalloproteinase 9 expression

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“The cannabinoid system consists of cannabinoid receptors and their ligands, including endocannabinoids, synthetic cannabinoid receptor agonists and antagonists, and phytocannabinoids.

Administration of cannabinoid receptor 2 (CB2R) agonists in inflammatory and autoimmune disease and CNS injury models results in significant attenuation of clinical disease, and reduction of inflammatory mediators.

…cannabinoids contribute to resolve acute inflammation and to reestablish homeostasis.

Selective CB2R agonists might be valuable future therapeutic agents for the treatment of chronic inflammatory conditions by targeting activated immune cells, including DCs.

Because of their anti-inflammatory functions targeting various immune cells, CB2R agonists could represent valuable therapeutic agents for the treatment of chronic inflammatory conditions.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3488886/

Cannabinoid-induced apoptosis in immune cells as a pathway to immunosuppression.

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Fig. 1

“Cannabinoids are a group of compounds found in the marijuana plant (Cannabis sativaL.). Marijuana has been used both for recreational and medicinal purposes for several centuries.

Cannabinoids have been shown to be effective in the treatment of nausea and vomiting associated with cancer chemotherapy, anorexia and cachexia seen in HIV/AIDS patients, as well as neuropathic pain, and spasticity in multiple sclerosis.

More recently, the anti-inflammatory properties of cannabinoids are drawing significant attention. In the last 15 years, studies with marijuana cannabinoids led to the discovery of cannabinoid receptors (CB1 and CB2) and their endogenous ligands, which make up what is known as the endocannabinoid system.

Cannabinoids are a group of compounds present in Cannabis plant (Cannabis sativa L.). They mediate their physiological and behavioral effects by activating specific cannabinoid receptors. With the recent discovery of the cannabinoid receptors (CB1 and CB2) and the endocannabinoid system, research in this field has expanded exponentially.

Cannabinoids have been shown to act as potent immunosuppressive and anti-inflammatory agents and have been shown to mediate beneficial effects in a wide range of immune-mediated diseases such as multiple sclerosis, diabetes, septic shock, rheumatoid arthritis, and allergic asthma.

Cannabinoid receptor 1 (CB1) is mainly expressed on the cells of the central nervous system as well as in the periphery. In contrast, cannabinoid receptor 2 (CB2) is predominantly expressed on immune cells. The precise mechanisms through which cannabinoids mediate immunosuppression is only now beginning to be understood…

In this review, we will focus on apoptotic mechanisms of immunosuppression mediated by cannabinoids on different immune cell populations and discuss how activation of CB2 provides a novel therapeutic modality against inflammatory and autoimmune diseases as well as malignancies of the immune system, without exerting the untoward psychotropic effects…

…cannabinoids do induce apoptosis in immune cells, alleviating inflammatory responses and protecting the host from acute and chronic inflammation.

The cumulative effect of cannabinoids on all cell populations of the immune system can be beneficial, when there is a need for immune suppression.

For example, in patients with autoimmune diseases such as multiple sclerosis, arthritis and lupus, or in those with septic shock, where the disease is caused by activated immune cells, targeting the immune cells via CB2 agonists may trigger apoptosis and act as anti-inflammatory therapy.

CB2 select agonists are not psychoactive and because CB2 is expressed primarily in immune cells, use of CB2 agonists could provide a novel therapeutic modality against autoimmune and inflammatory diseases.

In addition to the use of exogenous cannabinoids, in vivo manipulation of endocannabinoids may also offer novel treatment opportunities against cancer and autoimmune diseases.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005548/

Common polymorphism in the cannabinoid type 1 receptor gene (CNR1) is associated with microvascular complications in type 2 diabetes.

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“Endocannabinoids exert their biological effects via interaction with G-protein coupled cannabinoid receptors CB1 and CB2. Polymorphisms in the CNR1 gene (encoding CB1 receptor) were previously found to be associated with dyslipidemia and cardiovascular diseases. We investigated a role of the polymorphism in CNR1 gene in type 2 diabetes and its complications…

The novel finding of our study is the association of the G1359A polymorphism with diabetic nephropathy and diabetic retinopathy in patients with T2DM. This polymorphism was also associated with cardiovascular disease in the patient group.”

http://www.ncbi.nlm.nih.gov/pubmed/24075694

CB1 cannabinoid receptors couple to focal adhesion kinase to control insulin release.

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“Endocannabinoid signaling has been implicated in modulating insulin release from β cells of the endocrine pancreas. β Cells express CB1cannabinoid receptors (CB1Rs), and the enzymatic machinery regulating anandamide and 2-arachidonoylglycerol bioavailability…

We conclude that FAK downstream from CB1Rs mediates endocannabinoid-induced insulin release by allowing cytoskeletal reorganization that is required for the exocytosis of secretory vesicles.

These findings suggest a mechanistic link between increased circulating and tissue endocannabinoid levels and hyperinsulinemia in type 2 diabetes.”

http://www.ncbi.nlm.nih.gov/pubmed/24089517