Category Archives: Uncategorized

Selective Cannabinoid Receptor-1 Agonists Regulate Mast Cell Activation in an Oxazolone-Induced Atopic Dermatitis Model.

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“Many inflammatory mediators, including various cytokines (e.g. interleukins and tumor necrosis factor [TNF]), inflammatory proteases, and histamine are released following mast cell activation.

Endogenous cannabinoids such as palmitoylethanolamide (PEA) and N-arachidonoylethanolamine (anandamide or AEA), were found in peripheral tissues and have been proposed to possess autacoid activity, implying that cannabinoids may downregulate mast cell activation and local inflammation.

Our results indicate that CB1R agonists down-regulate mast cell activation and may be used for relieving inflammatory symptoms mediated by mast cell activation, such as atopic dermatitis, psoriasis, and contact dermatitis.”

http://www.ncbi.nlm.nih.gov/pubmed/26848215

Cannabinoid receptor 2 augments eosinophil responsiveness and aggravates allergen-induced pulmonary inflammation in mice.

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“Accumulation of activated eosinophils in tissue is a hallmark of allergic inflammation.

The endocannabinoid 2-arachidonoylglycerol (2-AG) has been proposed to elicit eosinophil migration in a CB2 receptor/Gi/o -dependent manner.

Here we explored the direct contribution of specific CB2 receptor activation to human and mouse eosinophil effector function in vitro and in vivo.

Our data indicate that CB2 may directly contribute to the pathogenesis of eosinophil-driven diseases. Moreover, we provide new insights into the molecular mechanisms underlying the CB2 -mediated priming of eosinophils. Hence, antagonism of CB2 receptors may represent a novel pharmacological approach for the treatment of allergic inflammation and other eosinophilic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/26850094

Medical cannabis: considerations for the anesthesiologist and pain physician.

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“New regulations are in place at the federal and provincial levels in Canada regarding the way medical cannabis is to be controlled. We present them together with guidance for the safe use of medical cannabis and recent clinical trials on cannabis and pain.

Health Canada has approved a new regulation on medical marijuana/cannabis, the Marihuana for Medical Purposes Regulations: The production of medical cannabis by individuals is illegal. Health Canada, however, has licensed authorized producers across the country, limiting the production to specific licenses of certain cannabis products. There are currently 26 authorized licensed producers from seven Canadian provinces offering more than 200 strains of marijuana.

We provide guidance for the safe use of medical cannabis.

The recent literature indicates that currently available cannabinoids are modestly effective analgesics that provide a safe, reasonable therapeutic option for managing chronic non-cancer-related pain.

The science of medical cannabis and the need for education of healthcare professionals and patients require continued effort. Although cannabinoids work to decrease pain, there is still a need to confirm these beneficial effects clinically and to exploit them with acceptable benefit-to-risk ratios.”

http://www.ncbi.nlm.nih.gov/pubmed/26850063

Medical marijuana programs – Why might they matter for public health and why should we better understand their impacts?

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“Although cannabis is an illegal drug, ‘medical marijuana programs’ (MMPs) have proliferated (e.g., in Canada and several US states), allowing for legal cannabis use for therapeutic purposes.

While both health risks and potential therapeutic  for cannabis use have been documented, potential public health impacts of MMPs – also vis-à-vis other psychoactive substance use – remain under-explored.

We briefly reviewed the emerging evidence on MMP participants’ health status, and specifically other psychoactive substance use behaviors and outcomes.

MMP participants report improvements in overall health status, and specifically reductions in levels of risky alcohol, prescription drug and – to some extent – tobacco or other illicit drug use…”

http://www.ncbi.nlm.nih.gov/pubmed/26844050

The Cannabinoid CB1/CB2 Agonist WIN55212.2 Promotes Oligodendrocyte Differentiation In Vitro and Neuroprotection During the Cuprizone-Induced Central Nervous System Demyelination.

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“Different types of insults to the CNS lead to axon demyelination. Remyelination occurs when the CNS attempts to recover from myelin loss and requires the activation of oligodendrocyte precursor cells.

With the rationale that CB1 receptor is expressed in oligodendrocytes and marijuana consumption alters CNS myelination, we study the effects of the cannabinoid agonist WIN55212.2 in (1) an in vitro model of oligodendrocyte differentiation and (2) the cuprizone model for demyelination.

The cannabinoid agonist WIN55212.2 promotes oligodendrocyte differentiation in vitro.

Moreover, 0.5 mg/kg of the drug confers neuroprotection during cuprizone-induced demyelination, while 1 mg/kg aggravates the demyelination process.”

http://www.ncbi.nlm.nih.gov/pubmed/26842941

Metabolomics of Δ9-tetrahydrocannabinol: implications in toxicity.

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“Cannabis sativa is the most commonly used recreational drug, Δ9-tetrahydrocannabinol (Δ9-THC) being the main addictive compound.

Biotransformation of cannabinoids is an important field of xenobiochemistry and toxicology and the study of the metabolism can lead to the discovery of new compounds, unknown metabolites with unique structures and new therapeutic effects.

The pharmacokinetics of Δ9-THC is dependent on multiple factors such as physical/chemical form, route of administration, genetics, and concurrent consumption of alcohol.

This review aims to discuss metabolomics of Δ9-THC, namely by presenting all known metabolites of Δ9-THC described both in vitro and in vivo, and their roles in the Δ9-THC-mediated toxic effects.

Since medicinal use is increasing, metabolomics of Δ9-THC will also be discussed in order to uncover potential active metabolites that can be made available for this purpose.”

http://www.ncbi.nlm.nih.gov/pubmed/26828228

CB2 Cannabinoid Receptor Knockout in Mice Impairs Contextual Long-Term Memory and Enhances Spatial Working Memory.

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“Neurocognitive effects of cannabinoids have been extensively studied with a focus on CB1 cannabinoid receptors because CB1 receptors have been considered the major cannabinoid receptor in the nervous system. However, recent discoveries of CB2 cannabinoid receptors in the brain demand accurate determination of whether and how CB2 receptors are involved in the cognitive effects of cannabinoids.

CB2 cannabinoid receptors are primarily involved in immune functions, but also implicated in psychiatric disorders such as schizophrenia and depression. Here, we examined the effects of CB2 receptor knockout in mice on memory to determine the roles of CB2 receptors in modulating cognitive function.

Our results suggest that CB2 cannabinoid receptors play diverse roles in regulating memory depending on memory types and/or brain areas.”

http://www.ncbi.nlm.nih.gov/pubmed/26819779

Clinical/Therapeutic Approaches for Cannabinoid Ligands in Central and Peripheral Nervous System Diseases: Mini Review.

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“Cannabinoids, the components of Cannabis sativa Linnaeus, interact with CB1 and CB2 receptors, which are located both in the central nervous system and in the periphery and thus may exert a widespread biological activity in the body.

The main medicinal properties of cannabinoids include analgesic, anti-inflammatory, antitumor, appetite stimulation, antiemesis, and muscle relaxation effects.

This mini review aims to explore existing clinical trials that investigated the use of cannabinoids in diseases affecting the nervous system.

There is evidence that cannabinoid-based drugs may effectively control some symptoms associated with nervous system dysfunction, especially various types of pain and neurologic disorders, although studies are limited.

The efficacy of cannabinoid drugs in the treatment of nervous system diseases should be verified in future large-scale randomized clinical trials.”

http://www.ncbi.nlm.nih.gov/pubmed/26818043

Social defeat leads to changes in the endocannabinoid system; an overexpression of calreticulin and motor impairment in mice.

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“Social defeat leads to changes in the endocannabinoid system; an overexpression of calreticulin and motor impairment in mice… the aim of this study was to investigate the long-lasting effects of chronic psychosocial stress on motor coordination and motor learning, CB1 receptor expression, endogenous cannabinoid ligands and gene expression in the cerebellum. After chronic psychosocial stress, motor coordination and motor learning were impaired… The present study provides evidence that chronic stress activates calreticulin and might be one of the pathological mechanisms underlying the motor coordination and motor learning dysfunctions seen in social defeat mice.” http://www.ncbi.nlm.nih.gov/pubmed/26815100

Impact of adolescent marijuana use on intelligence: Results from two longitudinal twin studies.

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“The purpose of the present study was to examine the associations of marijuana use with changes in intellectual performance in two longitudinal studies of adolescent twins.

There was no evidence of a dose-response relationship between frequency of use and intelligence quotient (IQ) change. Furthermore, marijuana-using twins failed to show significantly greater IQ decline relative to their abstinent siblings.

Evidence from these two samples suggests that observed declines in measured IQ may not be a direct result of marijuana exposure but rather attributable to familial factors that underlie both marijuana initiation and low intellectual attainment.”

http://www.ncbi.nlm.nih.gov/pubmed/26787878
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4747759/
http://www.pnas.org/content/113/5/E500.long
“Short-term cannabis use in adolescence does not appear to cause IQ decline or impair executive functions, even when cannabis use reaches the level of dependence. Family background factors explain why adolescent cannabis users perform worse on IQ and executive function tests.”
https://www.ncbi.nlm.nih.gov/pubmed/28734078