Cannabis and Brain Disorders: Cannabinoids Targeting the Endocannabinoid System and Receptors As A Means to CURE


Below are studies that show how cannabis affects the central nervous system.  These studies suggest that cannabis can aid in treating brain disorders.  With more research we can prove that marijuana does have medicinal value and can greatly aid or cure many ailments.  These are published medical studies that I encourage you to research and share your findings with everyone.  Spread the truth!
Information gathered by David Worrell edited by Cherry Girl

It is not important that you fully understand all the scientific mumbo-jumbo. What is important, what you need to understand, is that there are “Functional Neuronal CB2 Cannabinoid Receptors in the Central Nervous System”  ~ D.W.

Functional Neuronal CB2 Cannabinoid Receptors in the Central Nervous System
“Cannabinoids are the constituents of the marijuana plant (Cannabis sativa). The recent progress in marijuana-cannabinoid research include the discovery of an endocannabinoid system with specific genes coding for cannabinoid receptors (CBRs) that are activated by smoking marijuana, and that the human body and brain makes its own marijuana-like substances called endocannabinoids that also activate CBRs.”
‎”Commentary: Functional Neuronal CB2 Cannabinoid Receptors in the CNS.
Onaivi ES.  SourceWilliam Paterson University, Wayne NJ and Molecular Neurobiology Branch, National Institute on Drug Abuse, NIH, Baltimore, USA.

Abstract
Cannabinoids are the constituents of the marijuana plant (Cannabis sativa). There are numerous cannabinoids and other natural compounds that have been reported in the cannabis plant. The recent progress in marijuana-cannabinoid research include the discovery of an endocannabinoid system with specific genes coding for cannabinoid receptors (CBRs) that are activated by smoking marijuana, and that the human body and brain makes its own marijuana-like substances called endocannabinoids that also activate CBRs. This new knowledge and progress about cannabinoids and endocannabinoids indicate that a balanced level of endocannabinoids is important for pregnancy and that the breast milk in animals and humans has endocannabinoids for the growth and development of the new born. There are two well characterized cannabinoid receptors termed CB1-Rs and CB2-Rs and these CBRs are perhaps the most abundant G-protein coupled receptors that are expressed at high levels in many regions of the mammalian brain. The expression of CB1-Rs in the brain and periphery and the identification of CB2-Rs in immune cells and during inflammation has been extensively studied and characterized. However, the expression of functional neuronal CB2-Rs in the CNS has been much less well established and characterized in comparison to the expression of abundant brain CB1-Rs and functional neuronal CB2-Rs has ignited debate and controversy. While the issue of the specificity of CB2-R antibodies remains, many recent studies have reported the discovery and functional characterization of functional neuronal CB2-Rs in the CNS beyond neuro-immuno cannabinoid activity.”   http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3137183/?tool=pubmed


Targeting the Endocannabinoid System in Treating Brain Disorders.
“Many studies on cannabinoids indicate important progress for protection against several neurodegenerative disorders.This review highlights recent studies implicating the endocannabinoid system in neuroprotection against different disorders of the CNS.” (Central Nervous System)
‎”Targeting the endocannabinoid system in treating brain disorders.Bahr BA, Karanian DA, Makanji SS, Makriyannis A. SourceDepartment of Pharmaceutical Sciences, University of Connecticut, Storrs, CT 06269, USA. Bahr@uconn.edu

Abstract
Recent cannabinoid research has a primary focus on developing therapeutics against human diseases. Many studies on Cannabinoids indicate important progress for protection against several Neurodegenerative disorders.  Agonists of cannabinoid receptors activate signalling pathways in the brain that are linked to neuronal repair and cell maintenance, and endogenous ligands can also activate neuroprotective responses. These endocannabinoids are bioactive fatty acid amides and esters that are synthesised in the brain and include arachidonoyl ethanolamide (anandamide) and 2-arachidonoyl glycerol. Endocannabinoids are released in response to pathogenic events, thus representing a potential compensatory repair mechanism. Enhancing this on-demand action of endocannabinoids is a strategy with which to promote endogenous repair signalling. For such enhancement, considerable work has gone into modulating the availability of endocannabinoids by blocking the processes of their deactivation. The targets include the anandamide-hydrolysing enzyme fatty acid amide hydrolase, the carrier-mediated anandamide transport system and 2-arachidonoyl glycerol-deactivating enzyme monoacylglycerol lipase. The activity of endocannabinoids is terminated through transport and degradation and, accordingly, selective inhibitors of these processes effectively exploit the protective nature of cannabinergic responses. This review highlights recent studies implicating the endocannabinoid system in neuroprotection against different disorders of the Central Nervous System.”  http://www.ncbi.nlm.nih.gov/pubmed/16548785

Cannabinoids: A New Group of Agonists of PPARs
Cannabinoids have been used medicinally for thousands of years. In preclinical studies cannabinoids displayed many of the characteristics of nonsteroidal anti-inflammatory drugs (NSAIDs) and seem to be free of unwanted side effects. An increasing number of therapeutic actions of cannabinoids are being reported…
Sun Y, Bennett A.  SourceSchool of Biomedical Sciences, University of Nottingham Medical School, Nottingham NG7 2UH, UK. stxys3@nottingham.ac.uk

Abstract
Cannabinoids have been used medicinally and recreationally for thousands of years and their effects were proposed to occur mainly via activation of the G-protein-coupled receptor CB1/CB2 (cannabinoid receptor 1/2). Discovery of potent synthetic analogs of the natural cannabinoids as clinically useful drugs is the sustained aim of cannabinoid research. This demands that these new compounds be free of the psychotropic effects that connected with the recreational use of cannabinoids. In preclinical studies cannabinoids displayed many of the characteristics of nonsteroidal anti-inflammatory drugs (NSAIDs) and it seems to be free of unwanted side effects. An increasing number of therapeutic actions of cannabinoid are being reported that do not appear to be mediated by either CB1 or CB2, and recently nuclear receptor superfamily PPARs (peroxisome-proliferator-activated receptors) have been suggested as the target of certain cannabinoids. This review summarizes the evidence for cannabinoid activation on PPARs and possible associated remedial potentials.”
‎”In summary, there is strong evidence to suggest that some cannabinoids can act on PPARs through either direct or indirect pathways. These discoveries not only broaden the promising usage of cannabinoids as therapeutic agents, but also support PPARs as new targets for some neuroprotective treatment.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2220031/?tool=pubmed

Cannabinoid Activation of PPARα; A Novel Neuroprotective Mechanism
“Conclusions and implications:These data demonstrate the potential for a range of cannabinoid compounds, of diverse structures, to activate PPAR alpha and suggest that at least some of the neuroprotective properties of these agents could be mediated by nuclear receptor activation.”
‎”Cannabinoid activation of PPAR alpha; a novel neuroprotective mechanism.
Sun Y, Alexander SP, Garle MJ, Gibson CL, Hewitt K, Murphy SP, Kendall DA, Bennett AJ.
SourceSchool of Biomedical Sciences, University of Nottingham Medical School, Nottingham, UK.

Abstract
BACKGROUND AND PURPOSE: Although CB(1) receptor activation evokes neuroprotection in response to cannabinoids, some cannabinoids have been reported to be peroxisome proliferator activated receptor (PPAR) ligands, offering an alternative protective mechanism. We have, therefore, investigated the ability of a range of cannabinoids to activate PPAR alpha and for N-oleoylethanolamine (OEA), an endogenous cannabinoid-like compound (ECL), to evoke neuroprotection.

EXPERIMENTAL APPROACH:
Assays of PPAR alpha occupancy and gene transactivation potential were conducted in cell-free and transfected HeLa cell preparations, respectively. In vivo estimates of PPAR alpha activation through fat mobilization and gene transcription were conducted in mice. Neuroprotection in vivo was investigated in wild-type and PPAR alpha gene-disrupted mice.

KEY RESULTS: The ECLs OEA, anandamide, noladin ether and virodhamine were found to bind to the purified PPAR alpha ligand binding domain and to increase PPAR alpha-driven transcriptional activity. The high affinity synthetic CB(1/2) cannabinoid agonist WIN 55212-2 bound to PPAR alpha equipotently with the PPARalpha agonist fenofibrate, and stimulated PPARalpha-mediated gene transcription. The phytocannabinoid delta 9 tetrahydrocannabinol was without effect. OEA and WIN 55212-2 induced lipolysis in vivo, while OEA pre-treatment reduced infarct volume from middle cerebral artery occlusion in wild-type, but not in PPAR alpha-null mice. OEA treatment also led to increased expression of the NFkappa B-inhibitory protein, Ikappa B, in mouse cerebral cortex, while expression of the NFkappa B-regulated protein COX-2 was inhibited. Conclusions and implications:These data demonstrate the potential for a range of cannabinoid compounds, of diverse structures, to activate PPAR alpha and suggest that at least some of the neuroprotective properties of these agents could be mediated by nuclear receptor activation.”

‎”In summary, the data presented here provide strong evidence that selected cannabinoids (WIN 55212-2, OEA, noladin ether and virodhamine) are PPARα agonists, and suggest a novel means by which the multiple effects of cannabinoids, in boththe CNS and periphery, could be brought about. In addition to its well-recognized role in lipid metabolism, PPARα activation showed obvious beneficial effects in ischaemic brain damage, which is likely to be connected with its anti-inflammatory action through the NF–κB pathway. These discoveries not only broaden the potential use of cannabinoids as therapeutic agents, but also support PPARα as a new target for neuroprotectiv treatment.” http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2190030/?tool=pubmed


Cannabinoids and PPARalpha Signalling

“Cannabinoids have been shown to possess anti-inflammatory and neuroprotective properties.This review summarizes the evidence for cannabinoid activation of PPARs and identifies a new intracellular target for cannabinoids as therapeutic agents for neuroprotective treatment.”
‎”Cannabinoids and PPARalpha signalling. Sun Y, Alexander SP, Kendall DA, Bennett AJ. SourceSchool of Biomedical Sciences, University of Nottingham, Nottingham NG7 2UH, UK. stxys3@nottingham.ac.uk

Abstract
Cannabinoids have been shown to possess anti-inflammatory and neuroprotective properties, which were proposed to occur mainly via activation of the G-protein-coupled receptor CB(1) (cannabinoid receptor 1). Recently, certain cannabinoids have been reported to be ligands for members of the nuclear receptor transcription factor superfamily known as PPARs (peroxisome-proliferator-activated receptors). This review summarizes the evidence for cannabinoid activation of PPARs and identifies a new intracellular target for cannabinoids as therapeutic agents for neuroprotective treatment.”
http://www.ncbi.nlm.nih.gov/pubmed/17073758

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