Continuous Intrathecal Infusion of Cannabinoid Receptor Agonists Attenuates Nerve Ligation-Induced Pain in Rats.

 

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“Cannabinoid receptors (CB1R/CB2R) are known to play important roles in pain transmission.

In this study, we investigated the effects of continuous intrathecal infusion of CB1/2R agonists in the L5/6 spinal nerve ligation pain model.

Continuous intrathecal infusion of CB1/2R agonists elicits antinociception in the pain model.

The mechanisms might involve their actions on neurons and glial cells. CB2R, but not CB1R, seems to play an important role in the regulation of nerve injury-induced neuroinflammation.”

https://www.ncbi.nlm.nih.gov/pubmed/28492437

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Evaluation of Cannabidiol in Animal Seizure Models by the Epilepsy Therapy Screening Program (ETSP).

Neurochemical Research

“Cannabidiol (CBD) is a cannabinoid component of marijuana that has no significant activity at cannabinoid receptors or psychoactive effects. There is considerable interest in CBD as a therapy for epilepsy.

Almost a third of epilepsy patients are not adequately controlled by clinically available anti-seizure drugs (ASDs). Initial studies appear to demonstrate that CBD preparations may be a useful treatment for pharmacoresistant epilepsy.

The National Institute of Neurological Disorders and Stroke (NINDS) funded Epilepsy Therapy Screening Program (ETSP) investigated CBD in a battery of seizure models using a refocused screening protocol aimed at identifying pharmacotherapies to address the unmet need in pharmacoresistant epilepsy. Applying this new screening workflow, CBD was investigated in mouse 6 Hz 44 mA, maximal electroshock (MES), corneal kindling models and rat MES and lamotrigine-resistant amygdala kindling models.

Following intraperitoneal (i.p.) pretreatment, CBD produced dose-dependent protection in the acute seizure models; mouse 6 Hz 44 mA (ED50 164 mg/kg), mouse MES (ED50 83.5 mg/kg) and rat MES (ED50 88.9 mg/kg). In chronic models, CBD produced dose-dependent protection in the corneal kindled mouse (ED50 119 mg/kg) but CBD (up to 300 mg/kg) was not protective in the lamotrigine-resistant amygdala kindled rat. Motor impairment assessed in conjunction with the acute seizure models showed that CBD exerted seizure protection at non-impairing doses.

The ETSP investigation demonstrates that CBD exhibits anti-seizure properties in acute seizure models and the corneal kindled mouse. However, further preclinical and clinical studies are needed to determine the potential for CBD to address the unmet needs in pharmacoresistant epilepsy.”  https://www.ncbi.nlm.nih.gov/pubmed/28478594

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A chronic low dose of Δ9-tetrahydrocannabinol (THC) restores cognitive function in old mice

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“The balance between detrimental, pro-aging, often stochastic processes and counteracting homeostatic mechanisms largely determines the progression of aging. There is substantial evidence suggesting that the endocannabinoid system (ECS) is part of the latter system because it modulates the physiological processes underlying aging.

The activity of the ECS declines during aging, as CB1 receptor expression and coupling to G proteins are reduced in the brain tissues of older animals and the levels of the major endocannabinoid 2-arachidonoylglycerol (2-AG) are lower. However, a direct link between endocannabinoid tone and aging symptoms has not been demonstrated.

Here we show that a low dose of Δ9-tetrahydrocannabinol (THC) reversed the age-related decline in cognitive performance of mice aged 12 and 18 months. This behavioral effect was accompanied by enhanced expression of synaptic marker proteins and increased hippocampal spine density.

THC treatment restored hippocampal gene transcription patterns such that the expression profiles of THC-treated mice aged 12 months closely resembled those of THC-free animals aged 2 months. The transcriptional effects of THC were critically dependent on glutamatergic CB1 receptors and histone acetylation, as their inhibition blocked the beneficial effects of THC.

Thus, restoration of CB1 signaling in old individuals could be an effective strategy to treat age-related cognitive impairments.”

https://www.nature.com/nm/journal/vaop/ncurrent/full/nm.4311.html

“CAN MARIJUANA RESTORE MEMORY? NEW STUDY SHOWS CANNABIS CAN REVERSE COGNITIVE DECLINE IN MICE” http://www.newsweek.com/cannabis-marijuana-restores-memory-learning-cognitive-decline-596160

“A little cannabis every day might keep brain ageing at bay” https://www.newscientist.com/article/2130257-a-little-cannabis-every-day-might-keep-brain-ageing-at-bay/

“Low-dose cannabinoid THC restores memory and learning in old mice”  http://www.medicalnewstoday.com/articles/317342.php

“Daily Dose Of Cannabis May Protect And Heal The Brain From Effects Of Aging”  https://www.forbes.com/sites/janetwburns/2017/05/08/daily-dose-of-cannabis-may-protect-and-heal-the-brain-from-effects-of-aging/#70ef658f2e44

“Cannabis reverses aging processes in the brain”  https://medicalxpress.com/news/2017-05-cannabis-reverses-aging-brain.html

“Future dementia cure – Chemical in cannabis could REVERSE the ageing process” http://www.express.co.uk/life-style/health/801827/dementia-cure-cannabis-THC-chemical-memory

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Δ9-Tetrahydrocannabinol (THC) and AM 404 protect against cerebral ischaemia in gerbils through a mechanism involving cannabinoid and opioid receptors

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“It has been suggested that the endocannabinoid system elicits neuroprotection against excitotoxic brain damage.

In the present study the therapeutic potential of AM 404 on ischaemia-induced neuronal injury was investigated in vivo and compared with that of the classical cannabinoid receptor type 1 (CB1) agonist, Δ9-tetraydrocannabinol (THC), using a model of transient global cerebral ischaemia in the gerbil.

Our findings demonstrate that AM 404 and THC reduce neuronal damage caused by bilateral carotid occlusion in gerbils and that this protection is mediated through an interaction with CB1 and opioid receptors.

Endocannabinoids might form the basis for the development of new neuroprotective drugs useful for the treatment of stroke and other neurodegenerative pathologies.

There is some evidence from experiments with mice that increasing anandamide or 2-arachidonoyl glycerol content may lead to neuroprotection.

Collectively, our data demonstrate that AM 404 and THC protect against neuronal ischaemia-induced injury through a mechanism involving cannabinoid and opioid receptors but not vanilloid receptors.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2189998/

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GPR55 and the regulation of glucose homeostasis.

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“Pathophysiological conditions such as obesity and type 2 diabetes (T2D) are reportedly associated to over-activation of the endocannabinoid system (ECS). Therefore, modulation of the ECS offers potential therapeutic benefits on those diseases. GPR55, the receptor for L-α-lysophosphatidylinositol (LPI) that has also affinity for various cannabinoid ligands, is distributed at the central and peripheral level and it is involved in several physiological processes. This review summarizes the localization and role of GPR55 in tissues that are crucial for the regulation of glucose metabolism, and provides an update on its contribution in obesity and insulin resistance. The therapeutic potential of targeting the GPR55 receptor is also discussed.”

https://www.ncbi.nlm.nih.gov/pubmed/28457969

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Cannabis in Inflammatory Bowel Diseases: from Anecdotal Use to Medicalization?

“Inflammatory bowel diseases (IBD) are disorders of chronic intestinal inflammation of unknown etiology. The basic pathophysiological process is that of immune mediated inflammation affecting the intestinal tract. This process is dependent on and governed by both genetic and environmental factors. There are two distinct forms of IBD – ulcerative colitis and Crohn’s disease.

There is no curative medical treatment. Furthermore, over 30% of patients, and over 70% with Crohn’s disease, will need surgical intervention for their disease. Thus, it comes as no surprise that many patients will turn to complementary or alternative medicine at some stage of their disease. Recent information reveals that between 16% and 50% of patients admit to having tried marijuana for their symptoms.

There is a long list of gastrointestinal symptoms that have been reported to be relieved by cannabis. These include anorexia, nausea, abdominal pain, diarrhea, gastroparesis – all of which can be part of IBD. These effects are related to the fact that the gastrointestinal tract is rich in cannabinoid (CB) receptors and their endogenous ligands, comprising together the endocannabinoid system (ECS).

In conclusion, use of cannabis is common in IBD, and it seems to be mostly safe. Accumulating preliminary data from human studies support a beneficial role of cannabinoids in IBD.”

https://www.ima.org.il/FilesUpload/IMAJ/0/228/114217.pdf

https://www.ima.org.il/imaj/ViewArticle.aspx?aId=4045

https://www.ncbi.nlm.nih.gov/pubmed/28457058

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Marijuana compounds show promise in treatment of cardiac disease

Marijuana compounds show promise in treatment of cardiac disease

“A Nevada company is hoping to develop new medicines for heart failure using compounds in marijuana and a novel therapy identified by a University of Hawaiʻi at Mānoa researcher. Dr. Alexander Stokes, assistant research professor in the Department of Cell and Molecular Biology at the UH John A. Burns School of Medicine, obtained a U.S. patent for his novel therapy in 2015. The patent claims the cannabinoid receptor TRPV1 can be regulated therapeutically by plant-based cannabinoids.”  https://medicalxpress.com/news/2017-01-marijuana-compounds-treatment-cardiac-disease.html

“Marijuana compounds show promise in treatment of cardiac disease”  http://manoa.hawaii.edu/news/article.php?aId=8355

“Marijuana compounds show promise in treatment of cardiac disease”  http://www.hawaii.edu/news/2017/01/12/marijuana-compounds-show-promise-in-treatment-of-cardiac-disease/

 

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Cannabinoid CB2 receptor ligand profiling reveals biased signalling and off-target activity

“The cannabinoid CB2 receptor (CB2R) represents a promising therapeutic target for various forms of tissue injury and inflammatory diseases. There is a great interest in the development of selective type-2 cannabinoid receptor (CB2R) agonists as potential drug candidates for various pathophysiological conditions, which include chronic and inflammatory pain, pruritus, diabetic neuropathy and nephropathy, liver cirrhosis, and protective effects after ischaemic-reperfusion injury.” https://www.nature.com/articles/ncomms13958

“Pain relief without the high. Researchers at Leiden University led by Mario van der Stelt (Leiden Institute for Chemistry) have set ‘gold standards’ for developing new painkillers based on the medicinal effects of cannabis.”  https://www.sciencedaily.com/releases/2017/01/170104103916.htm

ScienceDaily
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Endocannabinoid system acts as a regulator of immune homeostasis in the gut

PNAS, Proceedings of the National Academy of Sciences

“Exogenous cannabinoids such as marijuana exert their influence through cannabinoid receptors. Endogenous cannabinoids such as anandamide (AEA) function through the same receptors, and their physiological roles are a subject of intense study. Here, we show that AEA plays a pivotal role in maintaining immunological health in the gut. The immune system in the gut actively tolerates the foreign antigens present in the gut through mechanisms that are only partially understood. We show that AEA contributes to this critical process by promoting the presence of CX3CR1hi macrophages, which are immunosuppressive. These results uncover a major conversation between the immune and nervous systems. In addition, with the increasing prevalence of ingestion of exogenous marijuana, our study has significant implications for public health.”  http://www.pnas.org/content/early/2017/04/18/1612177114.full

“Our study unveils a role for the endocannabinoid system in maintaining immune homeostasis in the gut/pancreas and reveals a conversation between the nervous and immune systems using distinct receptors.”  https://www.ncbi.nlm.nih.gov/pubmed/28439004

“Active ingredients in both hot peppers and cannabis calm the gut’s immune system” https://medicalxpress.com/news/2017-04-ingredients-hot-peppers-cannabis-calm.html

 

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Editorial: The CB2 Cannabinoid System: A New Strategy in Neurodegenerative Disorder and Neuroinflammation

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“The cannabinoid receptors subtype 2 (CB2R) are emerging as novel targets for the development of new therapeutic approaches and PET probes useful to early diagnose neuroinflammation as first step in several neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson disease (PD).

This Research Topic is mainly focused on the involvment of CB2R in neurodegenerative disorders and on the usefulness of CB2R ligands in the therapy and early diagnosis of neuroinflammation as onset of neurodegeneration.

In the reviews of Aso and Ferrer and Cassano et al. an interesting and exaustive overview of the endogenous cannabinoid signaling and its role in neuroinflammation and neurogenesis is reported. The potential of CB2R as therapeutic target in AD is argued by several evidences derived by robust experimental models and the effects modulated by CB2R agonists on different pathways involved in the pathogenesis of AD are discussed; indeed, these ligands are able to reduce inflammation, Aβ production and deposition, tau protein hyper-phosphorylation and oxidative stress damage caused by Aβ peptides. CB2R agonists are also able to induce Aβ clearance leading to cognitive improvement in AD models.

In conclusion, considering that neuroinflammation has been widely reported as indicator and modulator of neurodegeneration, the reduction of the neuroinflammatory responses could be considered as a new therapeutic strategy in these diseases. Moreover, the selective CB2R overexpression on the activated-microglial cells provides also a highly specialized target useful to an early diagnosis of the neurodegenerative diseases.”

http://journal.frontiersin.org/article/10.3389/fnins.2017.00196/full

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