Cannabidiol limits Tcell-mediated chronic autoimmune myocarditis: implications to autoimmune disorders and organ transplantation.

Posted on January 17, 2016 by David

“Myocarditis is a major cause of heart failure and sudden cardiac death in young adults and adolescents. Many cases of myocarditis are associated with autoimmune processes in which cardiac myosin is a major autoantigen.

Conventional immunosuppressive therapies often provide unsatisfactory results and are associated with adverse toxicities during the treatment of autoimmune myocarditis.

Cannabidiol (CBD) is a non-psychoactive constituent of Marijuana which exerts antiinflammatory effects independent from classical cannabinoid receptors.

Recently 80 clinical trials have been reported investigating the effects of CBD in various diseases from inflammatory bowel disease to graft-versus-host disease.

CBD-based formulations are used for the management of multiple sclerosis in numerous countries, and CBD also received FDA approval for the treatment of refractory childhood epilepsy and glioblastoma multiforme.

Herein, using a well-established mouse model of experimental autoimmune myocarditis (EAM) induced by immunization with cardiac myosin emmulsified in adjuvant resulting in T cell-mediated inflammation, cardiomyocyte cell death, fibrosis and myocardial dysfunction, we studied the potential beneficial effects of CBD…

CBD may represent a promising novel treatment for management of autoimmune myocarditis and possibly other autoimmune disorders, and organ transplantation.”

http://www.ncbi.nlm.nih.gov/pubmed/26772776

Cannabinoid receptor-2 agonist inhibits macrophage induced EMT in non-small cell lung cancer by downregulation of EGFR pathway.

Posted on January 12, 2016 by David

“JWH-015, a cannabinoid receptor 2 (CB2) agonist has tumor regressive property in various cancer types.

These data confer the impact of this cannabinoid on anti-proliferative and anti-tumorigenic effects, thus enhancing our understanding of its therapeutic efficacy in NSCLC.

Our findings open new avenues for cannabinoid receptor CB2 agonist-JWH-015 as a novel and potential therapeutic target based on EGFR downregulation mechanisms in NSCLC.”

http://www.ncbi.nlm.nih.gov/pubmed/26741322

Purified Cannabidiol, the main non-psychotropic component of Cannabis sativa, alone, counteracts neuronal apoptosis in experimental multiple sclerosis.

Posted on January 9, 2016 by David

“Multiple Sclerosis (MS) is a global concern disease leading to a progressive, chronic and demyelinating condition, affecting the central nervous system (CNS).

The pathology has an inflammatory/autoimmune origin; nevertheless, neuronal cell death mechanisms are not to be underestimated.

The present study was designed to test the effects of intraperitoneal administration of cannabidiol (CBD), the main non-psychotropiccannabinoid of Cannabis sativa (CS), in an experimental model of MS. The aim is to evaluate the capability of CBD administration to thwart the cascade of mediators involved in MS-induced apoptosis.

We have demonstrated that, alone, purified CBD possesses an anti-apoptotic power against the neurodegenerative processes underlying MS development. This represents an interesting new profile of CBD that could lead to its introduction in the clinical management of MS.”

http://www.ncbi.nlm.nih.gov/pubmed/26744883

http://www.thctotalhealthcare.com/category/multiple-sclerosis-ms/

Cannabidiol Post-Treatment Alleviates Rat Epileptic-Related Behaviors and Activates Hippocampal Cell Autophagy Pathway Along with Antioxidant Defense in Chronic Phase of Pilocarpine-Induced Seizure.

Posted on January 8, 2016 by David

“Abnormal and sometimes severe behavioral and molecular symptoms are usually observed in epileptic humans and animals.

To address this issue, we examined the behavioral and molecular aspects of seizure evoked by pilocarpine. Autophagy can promote both cell survival and death, but there are controversial reports about the neuroprotective or neurodegenerative effects of autophagy in seizure.

Cannabidiol has anticonvulsant properties in some animal models when used as a pretreatment.

In this study, we investigated alteration of seizure scores, autophagy pathway proteins, and antioxidant status in hippocampal cells during the chronic phase of pilocarpine-induced epilepsy after treatment with cannabidiol.

Cannabidiol (100 ng, intracerebroventricular injection) delayed the chronic phase of epilepsy.

Single administration of cannabidiol during the chronic phase of seizure significantly diminished seizure scores such as mouth clonus, head nodding, monolateral and bilateral forelimb clonus and increased the activity of catalase enzyme and reduced glutathione content.

Such a protective effect in the behavioral scores of epileptic rats was also observed after repeated administrations of cannabidiol at the onset of the silent phase.

Moreover, the amount of Atg7, conjugation of Atg5/12, Atg12, and LC3II/LC3I ratio increased significantly in epileptic rats treated with repeated injections of cannabidiol.

In short, our results suggest that post-treatment of Cannabidiol could enhance the induction of autophagy pathway and antioxidant defense in the chronic phase of epilepsy, which could be considered as the protective mechanisms of cannabidiol in a temporal lobe epilepsy model.”

http://www.ncbi.nlm.nih.gov/pubmed/26738731

http://www.thctotalhealthcare.com/category/epilepsy-2/

Cannabidiol Effective and Safe at 3 Months for Epilepsy

Posted on January 4, 2016 by David

“New open-label data from the expanded-access treatment program involving the cannabidiol Epidiolex(GW Pharma) show the median reduction in frequency of convulsive seizures after 3 months of treatment was 45% in all patients but higher in those with Dravet syndrome, among the most severe types of epilepsy.

The data are “very positive and promising,” said lead author Orrin Devinsky, MD, professor, neurology, neurosurgery and psychiatry, and director, New York University Comprehensive Epilepsy Center.” http://www.medscape.com/viewarticle/855768

“More Positive Results With Cannabidiol in Epilepsy” http://www.medscape.com/viewarticle/853781

http://www.thctotalhealthcare.com/category/epilepsy-2/

Cannabidiol induces rapid-acting antidepressant-like effects and enhances cortical 5-HT/glutamate neurotransmission: Role of 5-HT1A receptors.

Posted on December 30, 2015 by David

“Cannabidiol (CBD), the main non-psychotomimetic component of marihuana…

…we have evaluated the effects of CBD following acute and chronic administration in the olfactory bulbectomy mouse model of depression…

In conclusion, our findings indicate that CBD could represent a novel fast antidepressant drug, via enhancing both serotonergic and glutamate cortical signalling through a 5-HT1A receptor-dependent mechanism.”

http://www.ncbi.nlm.nih.gov/pubmed/26711860

The cross-talk between electrophiles, antioxidant defence and the endocannabinoid system in fibroblasts and keratinocytes after UVA and UVB irradiation.

Posted on December 19, 2015 by David

“UV, including UVA and UVB radiation, is one of the most ubiquitous environmental stress factors to human skin and leads to redox imbalance and, consequently, photoaging and cancer development. The aim of the study was to verify which skin cells, keratinocytes or fibroblasts, were more susceptible to UVA or UVB irradiation.

The results presented in this paper demonstrate a strong relationship between UV-induced oxidative stress and changes in the endocannabinoid system.

The differences demonstrated in the response of the tested cells to UV irradiation allow for a better understanding of the mechanisms occurring in the human skin, which may be exploited for future therapies in dermatology.”

http://www.ncbi.nlm.nih.gov/pubmed/26674123

The Role of the Brain’s Endocannabinoid System in Pain and Its Modulation by Stress.

Posted on December 8, 2015 by David

“Stress has a complex, bidirectional modulatory influence on pain. Stress may either reduce (stress-induced analgesia) or exacerbate (stress-induced hyperalgesia) pain depending on the nature, duration, and intensity of the stressor.

The endogenous cannabinoid (endocannabinoid) system is present throughout the neuroanatomical pathways that mediate and modulate responses to painful stimuli.

The specific role of the endocannabinoid system in the brain in pain and the modulation of pain by stress is reviewed herein.

We first provide a brief overview of the endocannabinoid system, followed by a review of the evidence that the brain’s endocannabinoid system modulates pain.

We provide a comprehensive evaluation of the role of the endocannabinoid system supraspinally, and particularly in the rostral ventromedial medulla, periaqueductal gray, amygdala, and prefrontal cortex, in pain, stress-induced analgesia, and stress-induced hyperalgesia.

Increased understanding of endocannabinoid-mediated regulation of pain and its modulation by stress will inform the development of novel therapeutic approaches for pain and its comorbidity with stress-related disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/26638768

Prevention of Diet-Induced Obesity Effects on Body Weight and Gut Microbiota in Mice Treated Chronically with Δ9-Tetrahydrocannabinol.

Posted on December 4, 2015 by David

“Acute administration of cannabinoid CB1 receptor agonists, or the ingestion of cannabis, induces short-term hyperphagia. However, the incidence of obesity is lower in frequent cannabis users compared to non-users.

Gut microbiota affects host metabolism and altered microbial profiles are observed in obese states. Gut microbiota modifies adipogenesis through actions on the endocannabinoid system. This study investigated the effect of chronic THC administration on body weight and gut microbiota in diet-induced obese (DIO) and lean mice.

THC reduced weight gain, fat mass gain and energy intake in DIO but not lean mice. DIO-induced changes in select gut microbiota were prevented in mice chronically administered THC.

Chronic THC treatment reduced energy intake and prevented high fat diet-induced increases in body weight and adiposity; effects that were unlikely to be a result of sedation or altered gastrointestinal transit. Changes in gut microbiota potentially contribute to chronic THC-induced actions on body weight in obesity.”

http://www.ncbi.nlm.nih.gov/pubmed/26633823

“Prevention of Diet-Induced Obesity Effects on Body Weight and Gut Microbiota in Mice Treated Chronically with Δ9-Tetrahydrocannabinol… To follow up on our hypothesis that exposure to THC may produce weight loss, in the current study we investigated whether chronic THC inhibits weight gain in lean and diet-induced obese (DIO) mice… We present data showing that chronic administration of the CB1/CB2 receptor partial agonist, THC, prevents weight gain in DIO mice. Furthermore, we show evidence that DIO-mediated modifications in gut microbiota are prevented in chronically THC treated mice… In conclusion, we present data showing the CB1/CB2 receptor partial agonist THC, induces hypophagia and prevents weight gain in obesity and suggest these actions may be mediated in part by modifications of the gut microbiota.” http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0144270

Involvement of PAR-4 in cannabinoid-dependent sensitization of osteosarcoma cells to TRAIL-induced apoptosis.

Posted on December 3, 2015 by David

“Osteosarcoma is the most common malignant bone tumor in childhood and adolescence.

Cannabinoids (CBs), the active constituents of Cannabis sativa, are known to exert a wide range of central and peripheral effects.

Recently, numerous studies evidenced the role of cannabinoids in the regulation of cell death and survival, focusing the anti-proliferative effects of these compounds in various tumours… cannabinoids can also activate autophagic process…

The aim of the present study was to investigate the effects induced by cannabinoids in osteosarcoma cells and the molecular pathway…

The synthetic cannabinoid WIN 55,212-2 is a potent cannabinoid receptor agonist with anticancer potential.

Moreover, we indicate that a key role in WIN action is played by the tumor suppressor protein PAR-4.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4007360/