Category Archives: Endocannabinoid System

Cannabis and cancer: toward a new understanding

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“The treatment of cancer, including the disease itself and the symptoms associated with cancer and its therapy, is one of the most important emerging frontiers in cannabinoid therapeutics.

This Current Oncology supplement brings together the work of some of the leading minds around the world who have dedicated themselves and their laboratories to understanding the role of cannabis and cannabinoids in the pathophysiology and management of cancer.

It is an unfortunate reality of 2016 that many doctors still lack the basic knowledge about cannabis, cannabinoids, and the endocannabinoid system that would enable them to have an informed discussion with their patients, and that the knowledge gap gives rise to stigmatization, alienation, and a fracture of the doctor–patient relationship.

Our patient describes her experience in trying to find answers and assistance, and with the help of her treating oncologist, she succeeds in securing legal access to cannabinoids, with remarkable results. Stories of this kind are occurring too often to be ignored or written off as placebo responses or outliers. As a medical profession, we are duty-bound to follow up on such experiences with critical and balanced investigation.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4791146/

Endocannabinoid Signaling Regulates Sleep Stability.

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“Since antiquity cannabinoids have been used as a treatment for insomnia, and the first reports in western medical literature regarding the therapeutic utility and physiological effects of cannabis preparations note their hypnogenic properties.

The hypnogenic properties of cannabis have been recognized for centuries, but endogenous cannabinoid (endocannabinoid) regulation of vigilance states is poorly characterized.

We report findings from a series of experiments in mice measuring sleep with polysomnography after various systemic pharmacological manipulations of the endocannabinoid system.

Our findings demonstrate that eCB signaling is necessary and sufficient for the control of sleep stability, but this neurotransmitter system is not necessary for sleep homeostasis.

 These results support the hypothesis that endocannabinoid signaling through CB1 is necessary for NREM stability but it is not necessary for sleep homeostasis.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4816426/

http://www.thctotalhealthcare.com/category/insomnia/

Beyond the CB1 Receptor: Is Cannabidiol the Answer for Disorders of Motivation?

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“The Cannabis sativa plant has been used to treat various physiological and psychiatric conditions for millennia.

Current research is focused on isolating potentially therapeutic chemical constituents from the plant for use in the treatment of many central nervous system disorders.

Of particular interest is the primary nonpsychoactive constituent cannabidiol (CBD).

Unlike Δ9-tetrahydrocannabinol (THC), CBD does not act through the cannabinoid type 1 (CB1) receptor but has many other receptor targets that may play a role in psychiatric disorders.

Here we review preclinical and clinical data outlining the therapeutic efficacy of CBD for the treatment of motivational disorders such as drug addiction, anxiety, and depression.

Across studies, findings suggest promising treatment effects and potentially overlapping mechanisms of action for CBD in these disorders and indicate the need for further systematic investigation of the viability of CBD as a psychiatric pharmacotherapy.”

http://www.ncbi.nlm.nih.gov/pubmed/27023732

Experimental cannabinoid 2 receptor inhibition in CNS injury-induced immunodeficiency syndrome.

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“Severe central nervous system (CNS) injury, such as stroke, traumatic brain injury or spinal cord injury, is known to increase susceptibility to infections. The increased susceptibility to infection is due to an impaired immune response and is referred to as CNS injury-induced immune deficiency syndrome (CIDS).

The cannabinoid 2 receptor (CB2 R) on immune cells presents a potential therapeutic target in CIDS as activation of this receptor has been shown to be involved in immunosuppression.

Our findings suggest that inhibition of CB2 R signaling in animals with CIDS challenged with endotoxin restored peripheral leukocyte recruitment without detrimental impact on infarct size.

We conclude that the endocannabinoid system is involved in the impaired immune response following CNS injury and future studies should further explore the CB2 R pathway in order to develop novel therapies for CIDS.”

http://www.ncbi.nlm.nih.gov/pubmed/26999797

Cannabinoids Occlude the HIV-1 Tat-Induced Decrease in GABAergic Neurotransmission in Prefrontal Cortex Slices.

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“In the era of combined antiretroviral therapy (cART), human immunodeficiency virus type 1 (HIV-1) is now considered a chronic disease that specifically targets the brain and causes HIV-1-associated neurocognitive disorders (HAND).

Endocannabinoids exhibit neuroprotective and anti-inflammatory properties in several central nervous system (CNS) disease models, but their effects in HAND are poorly understood.

Results indicated a Tat-induced decrease in GABAergic neurotransmission, which was occluded by cannabinoids via a CB1R-related mechanism.

Understanding the relationship between Tat toxicity and endocannabinoid signaling has the potential to identify novel therapeutic interventions to benefit individuals suffering from HAND and other cognitive impairments.”

http://www.ncbi.nlm.nih.gov/pubmed/26993829

http://www.thctotalhealthcare.com/category/hivaids/

Overactivity of the intestinal endocannabinoid system in celiac disease and in methotrexate-treated rats.

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“The endocannabinoid system is upregulated in both human inflammatory bowel diseases and experimental models of colitis. In this study, we investigated whether this upregulation is a marker also of celiac disease-induced atrophy. The levels of the cannabinoid CB(1) receptor, of the endocannabinoids, anandamide, and 2-arachidonoyl-glycerol (2-AG), and of the anti-inflammatory mediator palmitoylethanolamide (PEA) were analyzed in bioptic samples from the duodenal mucosa of celiac patients at first diagnosis assessed by the determination of antiendomysial antibodies and histological examination. Samples were analyzed during the active phase of atrophy and after remission and compared to control samples from non-celiac patients. The levels of anandamide and PEA were significantly elevated (approx. 2- and 1.8-fold, respectively) in active celiac patients and so were those of CB(1) receptors. Anandamide levels returned to normal after remission with a gluten-free diet. We also analyzed endocannabinoid and PEA levels in the jejunum of rats 2, 3, and 7 days after treatment with methotrexate, which causes inflammatory features (assessed by histopathological analyses and myeloperoxidase activity) similar to those of celiac patients. In both muscle/serosa and mucosa layers, the levels of anandamide, 2-AG, and PEA peaked 3 days after treatment and returned to basal levels at remission, 7 days after treatment. Thus, intestinal endocannabinoid levels peak with atrophy and regress with remission in both celiac patients and methotrexate-treated rats. The latter might be used as a model to study the role of the endocannabinoid system in celiac disease.”

http://www.ncbi.nlm.nih.gov/pubmed/17396241

Abnormal anandamide metabolism in celiac disease.

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“The endocannabinoid system has been extensively investigated in experimental colitis and inflammatory bowel disease, but not in celiac disease, where only a single study showed increased levels of the major endocannabinoid anandamide in the atrophic mucosa. On this basis, we aimed to investigate anandamide metabolism in celiac disease by analyzing transcript levels (through quantitative real-time reverse transcriptase-polymerase chain reaction), protein concentration (through immunoblotting) and activity (through radioassays) of enzymes responsible for anandamide synthesis (N-acylphosphatidyl-ethanolamine specific phospholipase D, NAPE-PLD) and degradation (fatty acid amide hydrolase, FAAH) in the duodenal mucosa of untreated celiac patients, celiac patients on a gluten-free diet for at least 12 months and control subjects. Also, treated celiac biopsies cultured ex vivo with peptic-tryptic digest of gliadin were investigated. Our in vivo experiments showed that mucosal NAPE-PLD expression and activity are higher in untreated celiac patients than treated celiac patients and controls, with no significant difference between the latter two groups. In keeping with the in vivo data, the ex vivo activity of NAPE-PLD was significantly enhanced by incubation of peptic-tryptic digest of gliadin with treated celiac biopsies. On the contrary, in vivo mucosal FAAH expression and activity did not change in the three groups of patients, and accordingly, mucosal FAAH activity was not influenced by treatment with peptic-tryptic digest of gliadin. In conclusion, our findings provide a possible pathophysiological explanation for the increased anandamide concentration previously shown in active celiac mucosa.”

http://www.ncbi.nlm.nih.gov/pubmed/22209002

Stimulation of brain glucose uptake by cannabinoid CB2 receptors and its therapeutic potential in Alzheimer’s disease.

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“Cannabinoid CB2 receptors (CB2Rs) are emerging as important therapeutic targets in brain disorders that typically involve neurometabolic alterations. We here addressed the possible role of CB2Rs in the regulation of glucose uptake in the mouse brain.

Together, these results reveal a novel general glucoregulatory role for CB2Rs in the brain, raising therapeutic interest in CB2R agonists as nootropic agents.”

http://www.ncbi.nlm.nih.gov/pubmed/26976670

Cannabidiol and epilepsy: rationale and therapeutic potential.

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“Despite the introduction of new antiepileptic drugs (AEDs), the quality of life and therapeutic response for patients with epilepsy remains still poor. Unfortunately, besides several advantages, these new AEDs have not satisfactorily reduced the number of refractory patients. Therefore, the need for different other therapeutic options to manage epilepsy is still a current issue.

To this purpose, emphasis has been given to phytocannabinoids, which have been medicinally used since ancient time in the treatment of neurological disorders including epilepsy.

In particular, the nonpsychoactive compound cannabidiol (CBD) has shown anticonvulsant properties, both in preclinical and clinical studies, with a yet not completely clarified mechanism of action.

However, it should be made clear that most phytocannabinoids do not act on the endocannabinoid system as in the case of CBD.

In in vivo preclinical studies, CBD has shown significant anticonvulsant effects mainly in acute animal models of seizures, whereas restricted data exist in chronic models of epilepsy as well as in animal models of epileptogenesis.

Likewise, clinical evidence seem to indicate that CBD is able to manage epilepsy both in adults and children affected by refractory seizures, with a favourable side effect profile.

However, to date, clinical trials are both qualitatively and numerically limited, thus yet inconsistent. Therefore, further preclinical and clinical studies are undoubtedly needed to better evaluate the potential therapeutic profile of CBD in epilepsy, although the actually available data is promising.”

http://www.ncbi.nlm.nih.gov/pubmed/26976797

Does modulation of the endocannabinoid system have potential therapeutic utility in cerebellar ataxia?

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“Cerebellar ataxias represent a spectrum of disorders which are, however, linked by common symptoms of motor incoordination and are typically associated with deficient in Purkinje cell firing activity and, often, degeneration. Cerebellar ataxias currently lack a curative agent.

The endocannabinoid (eCB) system includes eCB compounds and their associated metabolic enzymes, together with cannabinoid receptors, predominantly the cannabinoid CB1 receptor (CB1 R) in the cerebellum; activation of this system in the cerebellar cortex is associated with deficits in motor coordination characteristic of ataxia, effects which can be prevented by CB1 R antagonists.

Of further interest are various findings that CB1 R deficits may also induce a progressive ataxic phenotype.

Together these studies suggest that motor coordination is reliant on maintaining the correct balance in eCB system signalling.

Recent work also demonstrates deficient cannabinoid signalling in the mouse ‘ducky2J ‘ model of ataxia.

In light of these points, the potential mechanisms whereby cannabinoids may modulate the eCB system to ameliorate dysfunction associated with cerebellar ataxias are considered.”

http://www.ncbi.nlm.nih.gov/pubmed/26970080