Category Archives: Endocannabinoid System

Activation of CB2 receptors as a potential therapeutic target for migraine: evaluation in an animal model.

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“Experimental animal models of migraine have suggested the existence of interactions between the endocannabinoid system and pain mediation in migraine.

Extensive evidence has demonstrated a role for the cannabinoid-1 (CB1) receptor in antinociception.

…recent research suggests that also CB2 receptors, especially located outside the central nervous system, play a role in the perception of pain…

In this study we evaluated the role of CB2 receptors in two animal models of pain that may be relevant for migraine…

CONCLUSION:

These findings suggest that the pharmacological manipulation of the CB2 receptor may represent a potential therapeutic tool for the treatment of migraine.”

http://www.ncbi.nlm.nih.gov/pubmed/24636539

Cannabinoids for treatment of Alzheimer’s disease: moving toward the clinic.

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“The limited effectiveness of current therapies against Alzheimer’s disease (AD) highlights the need for intensifying research efforts devoted to developing new agents for preventing or retarding the disease process. During the last few years, targeting the endogenous cannabinoid system has emerged as a potential therapeutic approach to treat Alzheimer.

The endocannabinoid system is composed by a number of cannabinoid receptors, including the well-characterized CB1 and CB2 receptors… Several findings indicate that the activation of both CB1 and CB2 receptors by natural or synthetic agonists, at non-psychoactive doses, have beneficial effects in Alzheimer experimental models…

Moreover, endocannabinoid signaling has been demonstrated to modulate numerous concomitant pathological processes, including neuroinflammation, excitotoxicity, mitochondrial dysfunction, and oxidative stress.

The present paper summarizes the main experimental studies demonstrating the polyvalent properties of cannabinoid compounds for the treatment of AD, which together encourage progress toward a clinical trial.”

http://www.ncbi.nlm.nih.gov/pubmed/24634659

“Considering the numerous complex pathological mechanisms involved in the progression of AD, treatments targeting a single causal or modifying factor offer limited benefit. Cannabinoids, however, exhibit pleiotropic activity, targeting in parallel several processes that play key roles in AD…”

Full: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3942876/

“Prevention of Alzheimer’s disease pathology by cannabinoids: neuroprotection mediated by blockade of microglial activation…Our results indicate that cannabinoid receptors are important in the pathology of AD and that cannabinoids succeed in preventing the neurodegenerative process occurring in the disease.” http://www.jneurosci.org/content/25/8/1904.long

Therapeutic Potential of Cannabinoids in Schizophrenia.

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“Increasing evidence suggests a close relationship between the endocannabinoid system and schizophrenia.

The endocannabinoid system comprises of two G protein-coupled receptors (the cannabinoid receptors 1 and 2 [CB1 and CB2] for marijuana’s psychoactive principle Δ9-tetrahydrocannabinol), their endogenous small lipid ligands (namely anandamide [AEA] and 2-arachidonoylglycerol [2-AG], also known as endocannabinoids), and proteins for endocannabinoid biosynthesis and degradation.

…antipsychotic compounds which manipulate this system may provide a novel therapeutic target for the treatment of schizophrenia.

The present article reviews current available knowledge on herbal, synthetic and endogenous cannabinoids with respect to the modulation of schizophrenic symptomatology.

Furthermore, this review will be highlighting the therapeutic potential of cannabinoid-related compounds and presenting some promising patents targeting potential treatment options for schizophrenia.”

http://www.ncbi.nlm.nih.gov/pubmed/24605939

Effects of cannabinoid drugs on the deficit of prepulse inhibition of startle in an animal model of schizophrenia: the SHR strain

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“Clinical and neurobiological findings suggest that the cannabinoids and the endocannabinoid system may be implicated in the pathophysiology and treatment of schizophrenia.

Our results reinforce the role of the endocannabinoid system in the sensorimotor gating impairment related to schizophrenia, and point to cannabinoid drugs as potential therapeutic strategies.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3915876/

Care and Feeding of the Endocannabinoid System: A Systematic Review of Potential Clinical Interventions that Upregulate the Endocannabinoid System

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“The “classic” endocannabinoid (eCB) system… An emerging literature documents the “eCB deficiency syndrome” as an etiology in migraine, fibromyalgia, irritable bowel syndrome, psychological disorders, and other conditions. We performed a systematic review of clinical interventions that enhance the eCB system—ways to upregulate cannabinoid receptors, increase ligand synthesis, or inhibit ligand degradation.

Evidence indicates that several classes of pharmaceuticals upregulate the eCB system, including analgesics (acetaminophen, non-steroidal anti-inflammatory drugs, opioids, glucocorticoids), antidepressants, antipsychotics, anxiolytics, and anticonvulsants.

Clinical interventions characterized as “complementary and alternative medicine” also upregulate the eCB system: massage and manipulation, acupuncture, dietary supplements, and herbal medicines. Lifestyle modification (diet, weight control, exercise, and the use of psychoactive substances—alcohol, tobacco, coffee, cannabis) also modulate the eCB system.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3951193/#!po=4.79452

 

“Clinical endocannabinoid deficiency (CECD): can this concept explain therapeutic benefits of cannabis in migraine, fibromyalgia, irritable bowel syndrome and other treatment-resistant conditions? Migraine, fibromyalgia, IBS and related conditions display common clinical, biochemical and pathophysiological patterns that suggest an underlying clinical endocannabinoid deficiency that may be suitably treated with cannabinoid medicines.”

 http://www.ncbi.nlm.nih.gov/pubmed/18404144

A drug discovery case history of ‘delta-9-tetrahydrocannabinol, cannabidiol’.

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“…the Cannabis sativa herb has been known for its therapeutic benefit for centuries… interest in the clinical potential of cannabinoid-based drugs escalated after the discovery of the endocannabinoid system… therapeutic applications of cannabinoids (plant-derived or synthetic)… may constitute a useful addition to the pharmacotherapeutic armamentarium in chronic conditions insufficiently alleviated by existing drugs.”  http://www.ncbi.nlm.nih.gov/pubmed/22646020

“The endocannabinoid system and its therapeutic exploitation.” http://www.ncbi.nlm.nih.gov/pubmed/15340387

“Cannabinoid receptors as therapeutic targets.” http://www.ncbi.nlm.nih.gov/pubmed/16402900

“Cannabinoids.” http://www.ncbi.nlm.nih.gov/pubmed/16266285

“Plant, synthetic, and endogenous cannabinoids in medicine.” http://www.ncbi.nlm.nih.gov/pubmed/16409166

Brain Innate Immunity In The Regulation Of Neuroinflammation: Therapeutic Strategies By Modulating Cd200-Cd200r Interaction Involve The Cannabinoid System.

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“The central nervous system (CNS) innate immune response includes an arsenal of molecules and receptors expressed by professional phagocytes, glial cells and neurons that is involved in host defence and clearance of toxic and dangerous cell debris. However, any uncontrolled innate immune responses within the CNS are widely recognized as playing a major role in the development of autoimmune disorders and neurodegeneration, with multiple sclerosis (MS) and Alzheimer’s disease (AD) being primary examples. Hence, it is important to identify the key regulatory mechanisms involved in the control of CNS innate immunity and which could be harnessed to explore novel therapeutic avenues. Neuroimmune regulatory proteins (NIReg) such as CD95L, CD200, CD47, sialic acid, complement regulatory proteins (CD55, CD46, fH, C3a), HMGB1, may control the adverse immune responses in health and diseases. In the absence of these regulators, when neurons die by apoptosis, become infected or damaged, microglia and infiltrating immune cells are free to cause injury as well as an adverse inflammatory response in acute and chronic settings. We will herein provide new emphasis on the role of the pair CD200-CD200R in MS and its experimental models: experimental autoimmune encephalomyelitis (EAE) and Theiler’s virus induced demyelinating disease (TMEV-IDD). The interest of the cannabinoid system as inhibitor of inflammation prompt us to introduce our findings about the role of endocannabinoids (eCBs) in promoting CD200-CD200 receptor (CD200R) interaction and the benefits caused in TMEV-IDD. Finally, we also review the current data on CD200-CD200R interaction in AD, as well as, in the aging brain.”

http://www.ncbi.nlm.nih.gov/pubmed/24588829

Role of the Endocannabinoid System in the Neuroendocrine Responses to Inflammation.

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“… the endocannabinoid system has been recognized as a major neuromodulatory system whose main functions are to exert and maintain the body homeostasis.

The coordinated neural, immune, behavioral and endocrine responses to inflammation are orchestrated to provide an important defense against infections and help homeostasis restoration in the body. These responses are executed and controlled mainly by the hypothalamic-pituitary adrenal axis. Also, the hypothalamic-neurohypophyseal system is essential for survival and plays a role recovering the homeostasis under a variety of stress conditions, including inflammation and infection.

Since the endocannabinoid system components are present at sites involved in the hypothalamic-pituitary axis regulation, several studies were performed in order to investigate the endocannabinoid-mediated neurotransmitters and hormones secretion under physiological and pathological conditions.

In the present review we focused on the endocannabinoids actions on the neuroendocrine response to inflammation and infection. We provide a detailed overview of the current understanding of the role of the endocannabinoid system in the recovering of homeostasis as well as potential pharmacological therapies based on the manipulation of endocannabinoid system components that could provide novel treatments for a wide range of disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/24588819

Multiple sleep alterations in mice lacking cannabinoid type 1 receptors.

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“Cannabinoid type 1 (CB1) receptors are highly expressed in the brain… Endogenous cannabinoid signaling is modulated by high-fat diet (HFD).

We investigated the consequences of congenital lack of CB1 receptors on sleep in mice fed standard diet (SD) and HFD.

CB1 cannabinoid receptor knock-out (KO) and wild-type (WT) mice were fed SD or HFD for 4 months .

The occurrence of multiple sleep alterations in KO indicates important roles of CB1 cannabinoid receptors in limiting arousal during the active period of the day, in sleep regulation, and in sleep EEG in mice.”

http://www.ncbi.nlm.nih.gov/pubmed/24586776

Endocannabinoid system in cancer cachexia.

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“More than 60% of advanced cancer patients suffer from anorexia and cachexia.

This review focuses on the possible mechanisms by which the endocannabinoid system antagonizes cachexia-anorexia processes in cancer patients and how it can be tapped for therapeutic applications.

Cannabinoids stimulate appetite and food intake…

Cannabinoid type 1 receptor activation stimulates appetite and promotes lipogenesis and energy storage.

Further study of cancer-cachexia pathophysiology and the role of endocannabinoids will help us to develop cannabinoids without psychotropic properties, which will help cancer patients suffering from cachexia and improve outcomes of clinical antitumor therapy.”

http://www.ncbi.nlm.nih.gov/pubmed/17563462