Cannabidiol Modulates the Immunophenotype and Inhibits the Activation of the Inflammasome in Human Gingival Mesenchymal Stem Cells.

Posted on December 12, 2016 by David

“Human Gingival Mesenchymal Stem Cells (hGMSCs) are multipotential cells that can expand and differentiate in culture under specific and standardized conditions.

In the present study, we have investigated whether in vitro pre-treatment of hGMSCs with Cannabidiol(CBD) can influence their expression profile, improving the therapeutic potential of this cell culture.

In conclusion, the present study will provide a new simple and reproducible method for preconditioning hGMSCs with CBD, before transplantation, as an interesting strategy for improving the hGMSCs molecular phenotype, reducing the risk of immune or inflammatory reactions in the host, and in parallel, for increasing their survival and thus, their long-term therapeutic efficacy.”

https://www.ncbi.nlm.nih.gov/pubmed/27932991

Cannabidiol Activates Neuronal Precursor Genes in Human Gingival Mesenchymal Stromal Cells.

Posted on December 7, 2016 by David

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“In the last years, mesenchymal stromal cells (MSCs) from oral tissues have received considerable interest in regenerative medicine since they can be obtained with minimal invasive procedure and exhibit immunomodulatory properties.

This study was aimed to investigate whether in vitro pre-treatment of MSCs obtained from human gingiva (hGMSCs) with Cannabidiol (CBD), a cannabinoid component produced by the plant Cannabis sativa, may promote human gingiva derived MSCs to differentiate towards neuronal precursor cells.

From our results we hypothesize that human gingiva-derived MSCs conditioned with CBD could represent a valid method for improving the hGMSCs phenotype and thus might be a potential therapeutic tool in the treatment of neurodegenerative diseases.”

https://www.ncbi.nlm.nih.gov/pubmed/27918106

Plant cannabinoids: a neglected pharmacological treasure trove.

Posted on December 7, 2016 by David

“Most of the cannabinoids in Cannabis sativa L. have not been fully evaluated for their pharmacological activity.

A publication in this issue presents evidence that a plant cannabinoid, Δ⁹-tetrahydrocannabivarin is a potent antagonist of anandamide, a major endogenous cannabinoid.

It seems possible that many of the non-psychoactive constituents of this plant will be of biological interest.

I sincerely believe that the plant cannabinoids are a neglected pharmacological treasure trove.”

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1751232/

Targeted proteomics of cannabinoid receptor CB1 and the CB1b isoform.

Posted on December 5, 2016 by David

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“Cannabinoid receptors (CBR), including CB1 and CB2 have been therapeutic targets for a number of conditions.

Recently, splice variants of the CB1R have been identified in humans.

The isoforms differ in their N-terminus sequence and pharmacological activity relative to the CB1R, as a result, the differentiation between the CB1 receptor and its isoform is required.

As a result, a selected reaction monitoring mass spectrometry (SRM-MS) method was developed for the quantitation of CB1 and the CB1b isoform in CHO cells transduced with CB1 and CB1b.

The SRM-MS protocol was assessed with isotopically labeled peptide standards and had high reproducibility of intra-day assay (CVs from 1.9 to 4.3% for CB1 and 0.5 to 5.9% for CB1b) and inter-day assay (CVs from 1.2 to 5.2% for CB1 and 1.2 to 6.1% for CB1b).”

https://www.ncbi.nlm.nih.gov/pubmed/27914737

What is THC?

Posted on December 4, 2016 by David

“THC, or tetrahydrocannabinol, is the chemical responsible for most of marijuana’s psychological effects. It acts much like the cannabinoid chemicals made naturally by the body, according to the National Institute on Drug Abuse (NIDA).

Cannabinoid receptors are concentrated in certain areas of the brain associated with thinking, memory, pleasure, coordination and time perception. THC attaches to these receptors and activates them and affects a person’s memory, pleasure, movements, thinking, concentration, coordination, and sensory and time perception, according to NIDA.

THC is one of many compounds found in the resin secreted by glands of the marijuana plant. More of these glands are found around the reproductive organs of the plant than on any other area of the plant. Other compounds unique to marijuana, called cannabinoids, are present in this resin.

One cannabinoid, CBD is nonpsychoactive, according to the National Center for Biotechnology Information, and actually blocks the high associated with THC.”

http://www.livescience.com/24553-what-is-thc.html

http://www.thctotalhealthcare.com/category/thc-delta-9-tetrahydrocannabinol/

Δ9-THC-Caused Synaptic and Memory Impairments Are Mediated through COX-2 Signaling

Posted on December 4, 2016 by David

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“Marijuana has been used for thousands of years as a treatment for medical conditions.

However, untoward side effects limit its medical value. Here, we show that synaptic and cognitive impairments following repeated exposure to Δ⁹-tetrahydrocannabinol (Δ⁹-THC) are associated with the induction of cyclooxygenase-2 (COX-2), an inducible enzyme that converts arachidonic acid to prostanoids in the brain. COX-2 induction by Δ⁹-THC is mediated via CB1 receptor-coupled G protein βγ subunits.

Pharmacological or genetic inhibition of COX-2 blocks downregulation and internalization of glutamate receptor subunits and alterations of the dendritic spine density of hippocampal neurons induced by repeated Δ⁹-THC exposures. Ablation of COX-2 also eliminates Δ⁹-THC-impaired hippocampal long-term synaptic plasticity, spatial, and fear memories.

Importantly, the beneficial effects of decreasing β-amyloid plaques and neurodegeneration by Δ⁹-THC in Alzheimer’s disease animals are retained in the presence of COX-2 inhibition.

These results suggest that the applicability of medical marijuana would be broadened by concurrent inhibition of COX-2.”

http://www.cell.com/cell/abstract/S0092-8674(13)01360-3

“Cannabidiolic acid as a selective cyclooxygenase-2 inhibitory component in cannabis.” https://www.ncbi.nlm.nih.gov/pubmed/18556441

Cannabis-induced Moto-Cognitive Dysfunction in Wistar Rats: Ameliorative Efficacy of Nigella Sativa.

Posted on December 3, 2016 by David

“Cannabis is a widely used illicit drug with various threats of personality syndrome, and Nigella sativa has been widely implicated as having therapeutic efficacy in many neurological diseases.

The present study investigates the ameliorative efficacy of Nigella sativa oil (NSO) on cannabis-induced moto-cognitive defects.

CONCLUSIONS:

The observed ameliorative effects of NSO make it a promising agent against moto-cognitive dysfunction and cerebelo-hippocampal alterations induced by cannabis.”

https://www.ncbi.nlm.nih.gov/pubmed/27904421

Are adolescents more vulnerable to the harmful effects of cannabis than adults? A placebo-controlled study in human males.

Posted on December 3, 2016 by David

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“Preclinical research demonstrates that cannabinoids have differing effects in adolescent and adult animals. Whether these findings translate to humans has not yet been investigated. Here we believe we conducted the first study to compare the acute effects of cannabis in human adolescent (n=20; 16-17 years old) and adult (n=20; 24-28 years old) male cannabis users, in a placebo-controlled, double-blind cross-over design.

After inhaling vaporized active or placebo cannabis, participants completed tasks assessing spatial working memory, episodic memory and response inhibition, alongside measures of blood pressure and heart rate, psychotomimetic symptoms and subjective drug effects (for example, ‘stoned’, ‘want to have cannabis’).

Results showed that on active cannabis, adolescents felt less stoned and reported fewer psychotomimetic symptoms than adults. Further, adults but not adolescents were more anxious and less alert during the active cannabis session (both pre- and post-drug administration). Following cannabis, cognitive impairment (reaction time on spatial working memory and prose recall following a delay) was greater in adults than adolescents. By contrast, cannabis impaired response inhibition accuracy in adolescents but not in adults.

Moreover, following drug administration, the adolescents did not show satiety; instead they wanted more cannabis regardless of whether they had taken active or placebo cannabis, while the opposite was seen for adults. These contrasting profiles of adolescent resilience (blunted subjective, memory, physiological and psychotomimetic effects) and vulnerability (lack of satiety, impaired inhibitory processes) show some degree of translation from preclinical findings, and may contribute to escalated cannabis use by human adolescents.” https://www.ncbi.nlm.nih.gov/pubmed/27898071

“Developmental observations suggest further that CB1 receptors develop only gradually during the postnatal period, which correlates with an insensitivity to the psychoactive effects of cannabinoid treatment in the young organism. Therefore, it is suggested that children may respond positively to medicinal applications of cannabinoids without undesirable central effects.” https://www.ncbi.nlm.nih.gov/pubmed/15159678

Cannabimimetic phytochemicals in the diet – an evolutionary link to food selection and metabolic stress adaptation?

Posted on November 29, 2016 by David

“The endocannabinoid system (ECS) is a major lipid signaling network that plays important pro-homeostatic (allostatic) roles not only in the nervous system but in peripheral organs.

Increasing evidence points towards a dietary component in the modulation of the ECS.

Cannabinoid receptors in hominids co-evolved with diet and the ECS constitutes a feedback loop for food selection and energy metabolism.

Here it is postulated that the mismatch of ancient lipid genes of hunter-gatheres and pastoralists with the high carbohydrate diet introduced by agriculture could be compensated via dietary modulation of the ECS.

In addition to the fatty acid precursors of endocannabinoids the potential role of dietary cannabimimetic phytochemicals in agriculturist nutrition is discussed.

Dietary secondary metabolites from vegetables and spices able to enhance the activity of cannabinoid-type 2 (CB2) receptors may provide adaptive metabolic advantages and counteract inflammation.

Food able to modulate the CB1/CB2 receptor activation ratio may thus play a role in the nutrition transition of Western high calorie diets. In this review the interplay between diet and the ECS is highlighted from an evolutionary perspective.

The emerging potential of cannabimimetic food as nutraceutical strategy is critically discussed.”

https://www.ncbi.nlm.nih.gov/pubmed/27891602

Cannabidiol reduces neuroinflammation and promotes neuroplasticity and functional recovery after brain ischemia.

Posted on November 28, 2016 by David

Image result for Prog Neuropsychopharmacol Biol Psychiatry.

“This study investigated the effects of cannabidiol (CBD), a non-psychotomimetic phytochemical present in Cannabis sativa, on the cognitive and emotional impairments induced by bilateral common carotid artery occlusion (BCCAO) in mice.

Using a multi-tiered behavioral testing battery during 21days, we found that BCCAO mice exhibited long-lasting functional deficits reflected by increase in anxiety-like behavior (day 9), memory impairments (days 12-18) and despair-like behavior (day 21).

Short-term CBD 10mg/kg treatment prevented the cognitive and emotional impairments, attenuated hippocampal neurodegeneration and white matter (WM) injury, and reduced glial response that were induced by BCCAO.

In addition, ischemic mice treated with CBD exhibited an increase in the hippocampal brain derived neurotrophic factor (BDNF) protein levels.

CBD also stimulated neurogenesis and promoted dendritic restructuring in the hippocampus of BCCAO animals.

Collectively, the present results demonstrate that short-term CBD treatment results in global functional recovery in ischemic mice and impacts multiple and distinct targets involved in the pathophysiology of brain ischemic injury.”

https://www.ncbi.nlm.nih.gov/pubmed/27889412