The Endocannabinoid System Differentially Regulates Escape Behavior in Mice.

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“Among the hardwired behaviors, fear or survival responses certainly belong to the most evolutionary conserved ones. However, higher animals possess the ability to adapt to certain environments (e.g., novel foraging grounds), and, therefore, those responses need to be plastic. Previous studies revealed a cell-type specific role of the endocannabinoid system in novelty fear, conditioned fear and active vs. passive avoidance in a shuttle box paradigm.

In this study we aim to investigate, whether knocking-out the cannabinoidreceptor type-1 (CB1) on cortical glutamatergic (Glu-CB1-/-) or GABAergic (GABA-CB1-/-) neurons differentially affects the level of behavioral inhibition, which could ultimately lead to differences in escape behavior.

Taken together, we could show that CB1 on cortical glutamatergic terminals is important for the acquisition of active avoidance, as the absence of CB1 on these neurons creates a bias toward inhibitory avoidance. This is the case in situations without punishment such as electric footshocks. On the contrary CB1 receptors on GABAergic neurons mediate the acquisition of passive avoidance, as the absence of CB1 on those neurons establishes a strong bias toward escape behavior.”

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

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“Brain disorders, including Alzheimer’s disease (AD), often involve specific early alterations in the metabolism of glucose in the brain.

The idea of alleviating symptoms of dementia by boosting cerebral energy metabolism has been toyed with for decades, yet safe pharmacological agents with well characterized mechanism of action are still lacking.

In this sense, we have investigated here the local cerebral glucoregulatory potential of the endocannabinoid system in rodents.

Cannabinoid CB2 receptors (CB2Rs) are emerging as important therapeutic targets in brain disorders that typically involve neurometabolic alterations.

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

In conclusion, the present results provide the first direct pharmacological evidence in vitroand in vivo of a role of CB2R in central glucoregulation.

Additionally, we found that glucoregulation by endogenous CB2R signalling is negatively affected by β-amyloidosis, thought to be the first pathological step in AD.

Therefore, it would be interesting to perform further studies to define how CB2R mediated glucoregulation contributes to the recently discovered therapeutic potential of CB2R agonists in animal models of AD”

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

“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.”

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Cannabis sativa: The Plant of the Thousand and One Molecules.

“Cannabis sativa L. is an important herbaceous species originating from Central Asia, which has been used in folk medicine and as a source of textile fiber since the dawn of times.

This fast-growing plant has recently seen a resurgence of interest because of its multi-purpose applications: it is indeed a treasure trove of phytochemicals and a rich source of both cellulosic and woody fibers.

Equally highly interested in this plant are the pharmaceutical and construction sectors, since its metabolites show potent bioactivities on human health and its outer and inner stem tissues can be used to make bioplastics and concrete-like material, respectively.

In this review, the rich spectrum of hemp phytochemicals is discussed by putting a special emphasis on molecules of industrial interest, including cannabinoids, terpenes and phenolic compounds, and their biosynthetic routes.

Cannabinoids represent the most studied group of compounds, mainly due to their wide range of pharmaceutical effects in humans, including psychotropic activities.

The therapeutic and commercial interests of some terpenes and phenolic compounds, and in particular stilbenoids and lignans, are also highlighted in view of the most recent literature data.

Biotechnological avenues to enhance the production and bioactivity of hemp secondary metabolites are proposed by discussing the power of plant genetic engineering and tissue culture. In particular two systems are reviewed, i.e., cell suspension and hairy root cultures.

Additionally, an entire section is devoted to hemp trichomes, in the light of their importance as phytochemical factories.

Ultimately, prospects on the benefits linked to the use of the -omics technologies, such as metabolomics and transcriptomics to speed up the identification and the large-scale production of lead agents from bioengineered Cannabis cell culture, are presented.”

“Known since the ancient times for its medicinal and textile uses, hemp is currently witnessing a revival, because of its rich repertoire of phytochemicals, its fibers and its agricultural features, namely quite good resistance to drought and pests, well-developed root system preventing soil erosion, lower water requirement with respect to other crops, e.g., cotton.”

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Harvesting the biosynthetic machineries that cultivate a variety of indispensable plant natural products.

“Plants are a sustainable resource for valuable natural chemicals best illustrated by large-scale farming centered on specific products. Here, we review recent discoveries of plant metabolic pathways producing natural products with unconventional biomolecular structures.

Prenylation of polyketides by aromatic prenyltransferases (aPTases) ties together two of the major groups of plant specialized chemicals, terpenoids and polyketides, providing a core modification leading to new bioactivities and downstream metabolic processing. Moreover, PTases that biosynthesize Z-terpenoid precursors for small molecules such as lycosantalene have recently been found in the tomato family.

Gaps in our understanding of how economically important compounds such as cannabinoids are produced are being identified using next-generation ‘omics’ to rapidly advance biochemical breakthroughs at an unprecedented rate. For instance, olivetolic acid cyclase, a polyketide synthase (PKS) co-factor from Cannabis sativa, directs the proper cyclization of a polyketide intermediate.

Elucidations of spatial and temporal arrangements of biosynthetic enzymes into metabolons, such as those used to control the efficient production of natural polymers such as rubber and defensive small molecules such as linamarin and lotaustralin, provide blueprints for engineering streamlined production of plant products.”

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Hempseed as a nutritional resource: An overview

“The seed of Cannabis sativa L. has been an important source of nutrition for thousands of years in Old World cultures. Technically a nut, hempseed typically contains over 30% oil and about 25% protein, with considerable amounts of dietary fiber, vitamins and minerals. Hempseed oil is over 80% in polyunsaturated fatty acids (PUFAs), and is an exceptionally rich source of the two essential fatty acids (EFAs) linoleic acid (18:2 omega-6) and alpha-linolenic acid (18:3 omega-3). The omega-6 to omega-3 ratio (n6/n3) in hempseed oil is normally between 2:1 and 3:1, which is considered to be optimal for human health. Hempseed has been used to treat various disorders for thousands of years in traditional oriental medicine.”

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The cardiac and haemostatic effects of dietary hempseed

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“Cannabis sativa L. is an annual plant in the Cannabaceae family. It has been an important source of food, fiber, medicine and psychoactive/religious drug since prehistoric times. Hemp has a botanical relationship to drug/medicinal varieties of Cannabis. However, hempseed no longer contains psychotropic action and instead may provide significant health benefits. Hempseed has an excellent content of omega-3 and omega-6 fatty acids. These compounds have beneficial effects on our cardiovascular health.”

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[Cardiovascular effects of cannabinoids].

“The psychoactive properties of cannabinoids, the biologically active constituents of the marijuana plant, have long been recognized. Recent research has revealed that cannabinoids elicit not only neurobehavioral, and immunological, but also profound cardiovascular effects.

Similar effects can be elicited by the endogenous ligand arachidonyl ethanolamine (anandamide) and 2-arachidonoyl-glycerol.

The biological effects of cannabinoids are mediated by specific receptors.

Two cannabinoid receptors have been identified so far: CB1-receptors are expressed by different cells of the brain and in peripheral tissues, while CB2-receptors were found almost exclusively in immune cells.

Through the use of a selective CB1 receptor antagonist and CB1 receptor-knockout mice the hypotensive and bradycardic effects of cannabinoids in rodents could be attributed to activation of peripheral CB1 receptors. In hemodynamic studies using the radioactive microsphere technique in anesthetized rats, cannabinoids were found to be potent CB1-receptor dependent vasodilators in the coronary and cerebrovascular beds.

Recent findings implicate the endogenous cannabinoid system in the pathomechanism of haemorrhagic, endotoxic and cardiogenic shock.

Finally, there is evidence that the extreme mesenteric vasodilation, portal hypertension and systemic hypotension present in advanced liver cirrhosis are also mediated by the endocannabinoid system.

These exciting, recent research developments indicate that the endogenous cannabinoid system plays an important role in cardiovascular regulation, and pharmacological manipulation of this system may offer novel therapeutic approaches in a variety of pathological conditions.”

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Photosynthetic response of Cannabis sativa L., an important medicinal plant, to elevated levels of CO2

“Cannabis sativa L. (Cannabaceae) is a widely distributed plant around the world. It has a long history of medicinal use as far back as the 6th century B.C. Cannabis sativa is the natural source of the cannabinoids, a unique group of terpeno-phenolic compounds that accumulate in the glandular trichomes of the plant.

Δ9-Tetrahydrocannabinolic acid (Δ9-THCA) is the major cannabinoid which upon decarboxylation with age or heating gives rise to Δ9-THC, the primary psychoactive agent. The pharmacologic and therapeutic potency of Cannabis preparations and Δ9-THC have been extensively reviewed.

Despite of its medicinal importance and widespread occurrence, to the best of our knowledge, no information is available on the consequences of rising atmospheric CO2 concentration on its photosynthesis and growth performance.

This study describes the short term effect of elevated CO2 on photosynthetic characteristics and stomatal response in four different high Δ9-THC yielding varieties of Cannabis sativa.

The higher water use efficiency (WUE) under elevated CO2 conditions in Cannabis sativa, primarily because of decreased stomatal conductance and subsequently the transpiration rate, may enable this species to survive under expected harsh greenhouse effects including elevated CO2 concentration and drought conditions.”

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The effect of endocannabinoid system in ischemia-reperfusion injury: a friend or a foe?

“In recent years, the endocannabinoid system has emerged as a new therapeutic target in variety of disorders associated with inflammation and tissue injury, including those of the neuronal, liver, renal and cardiovascular system.

The aim of the present review is to elucidate the effect of endocannabinoid system on ischemia reperfusion injury (IRI) in different organs and systems.

Expert opinion: CB2 receptors may play an important compensatory role in controlling tissue inflammation and injury in cells of the neuronal, cardiovascular, liver and renal systems, as well as in infiltrating monocytes/macrophages and leukocytes during various pathological conditions of the systems (atherosclerosis, restenosis, stroke, myocardial infarction, heart, liver and renal failure).

These receptors limit inflammation and associated tissue injury.

On the basis of preclinical results, pharmacological modulation of CB2 receptors may hold a unique therapeutic potential in stroke, myocardial infarction, atherosclerosis, IRI and liver disease.”

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