Cannabidiol disrupts the reconsolidation of contextual drug-associated memories in Wistar rats.

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“In addicts, craving and relapse are frequently induced by the recall of memories related to a drug experience. Several studies have demonstrated that drug-related memories are reactivated after exposure to environmental cues and may undergo reconsolidation, a process that can strengthen memories. Thus, reactivation of mnemonic traces provides an opportunity for disrupting memories that contribute to the pathological cycle of addiction.

Here we used drug-induced conditioned place preference (CPP) to investigate whether cannabidiol (CBD), a phytocannabinoid, given just after reactivation sessions, would affect reconsolidation of drug-reward memory, reinstatement of morphine-CPP, or conditioned place aversion precipitated by naltrexone in Wistar rats.

We found that CBD impaired the reconsolidation of preference for the environment previously paired with both morphine and cocaine. This disruption seems to be persistent, as the preference did not return after further reinstatement induced by priming drug and stress reinstatement.

Moreover, in an established morphine-CPP, an injection of CBD after the exposure to a conditioning session led to a significant reduction of both morphine-CPP and subsequent conditioned place aversion precipitated by naltrexone in the same context.

Thus, established memories induced by a drug of abuse can be blocked after reactivation of the drug experience.

Taken together, these results provide evidence for the disruptive effect of CBD on reconsolidation of contextual drug-related memories and highlight its therapeutic potential to attenuate contextual memories associated with drugs of abuse and consequently to reduce the risk of relapse.”

http://www.ncbi.nlm.nih.gov/pubmed/26833888

The molecular mechanism and effect of cannabinoid-2 receptor agonist on the blood-spinal cord barrier permeability induced by ischemia-reperfusion injury.

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“Previous studies have shown that modulation of the receptor-mediated endocannabinoid system during ischemia injury can induce potent neuroprotective effects.

However, little is known about whether cannabinoid-2 (CB2) receptor agonist would produce a protective effect on blood-spinal cord barrier (BSCB) during ischemia.

Taken together, all of these results suggested that JWH-015 might regulate the BSCB permeability and this effect could be related to paracellular and transcellular pathway.

And pharmacological CB2R ligands offer a new strategy for BSCB protection during ischemic injury.”

http://www.ncbi.nlm.nih.gov/pubmed/26835555

Cannabinoids for pediatric epilepsy? Up in smoke or real science?

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“Public interest in the use of “medical marijuana” for the treatment of childhood epilepsy has burgeoned in the last few years. This has occurred in parallel with a growing interest in “medical marijuana” in general. Physicians and pediatricians must balance their patients’ desire for immediate access to these products with the tenets of evidence-based medicine. This review discusses the biochemistry of cannabis products (the phytocannabinoids) setting this in the context of the endogenous endocannabinoid system. The differing and potentially modulating effects of delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD) are reviewed. The evidence-base supporting or not the use of cannabis products for the treatment of neurological disease and specifically epilepsy is explored. The potential for adverse effects and particularly of neurotoxicity is addressed. Finally, public health and sociocultural implications are touched upon. Specific recommendations for interested physicians are provided including advocacy for patients and for a change in the “scheduling” of cannabis in order to better foster much-needed high-quality scientific research in this important area.”

http://www.ncbi.nlm.nih.gov/pubmed/26835389

[Efficacy, tolerability and safety of cannabinoids for chronic neuropathic pain : A systematic review of randomized controlled studies].

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“Recently published systematic reviews came to different conclusions with respect to the efficacy, tolerability and safety of cannabinoids for treatment of chronic neuropathic pain.

Cannabinoids were marginally superior to placebo in terms of efficacy and inferior in terms of tolerability.

Cannabinoids and placebo did not differ in terms of safety during the study period.

Short-term and intermediate-term therapy with cannabinoids can be considered in selected patients with chronic neuropathic pain after failure of first-line and second-line therapies.”

http://www.ncbi.nlm.nih.gov/pubmed/26830780

http://www.thctotalhealthcare.com/category/neuropathic-pain/

β-Caryophyllene potently inhibits solid tumor growth and lymph node metastasis of B16F10 melanoma cells in high-fat diet-induced obese C57BL/6N mice.

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“…high-fat diet (HFD) feeding stimulated solid tumor growth and lymph node (LN) metastasis… β-caryophyllene (BCP) is a natural bicyclic sesquiterpene found in many essential oils and has been shown to exert anti-inflammatory activities….

BCP inhibits HFD-induced melanoma progression…

β-Caryophyllene potently inhibits solid tumor growth and lymph node metastasis of B16F10 melanoma cells in high-fat diet-induced obese C57BL/6N mice.” http://www.ncbi.nlm.nih.gov/pubmed/26025912

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”  http://www.ncbi.nlm.nih.gov/pubmed/23138934

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

Anticonvulsant activity of β-caryophyllene against pentylenetetrazol-induced seizures.

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“Increasing evidence suggests that plant-derived extracts and their isolated components are useful for treatment of seizures and, hence, constitute a valuable source of new antiepileptic drugs with improved efficacy and better adverse effect profile.

β-Caryophyllene is a natural bicyclic sesquiterpene that occurs in a wide range of plant species and displays a number of biological actions, including neuroprotective activity.

In the present study, we tested the hypothesis that β-caryophyllene displays anticonvulsant effects.

Altogether, the present data suggest that β-caryophyllene displays anticonvulsant activity against seizures induced by PTZ in mice.

Since no adverse effects were observed in the same dose range of the anticonvulsant effect, β-caryophyllene should be further evaluated in future development of new anticonvulsant drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/26827298

“β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis.”  http://www.ncbi.nlm.nih.gov/pubmed/23138934

Regulation of Stem Cells by the Endocannabinoid System

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“The endocannabinoids, endogenous lipid mediators of related chemical structure to the prototype exogenous cannabinoid Δ9-THC found in marijuana, have emerged as important mediators that regulate central and peripheral neural functions as well as immune responses.

Endogenous and exogenous cannabinoid ligands bind to cannabinoid receptors: the predominant central cannabinoid receptor type 1 (CB1) and the peripheral cannabinoid receptor type 2 (CB2). CB1 and CB2 are members of the G-protein coupled receptor family.

Cannabinoids were shown to modulate the immune system and to affect the migration of blood cells, such as T-cells, monocytes and myeloid leukemia cells, through CB receptors.

Recent data indicate the potential role of cannabinoid ligands and receptors in the regulation of hematopoiesis and hematopoietic stem cell (HSC) migration and trafficking.

These studies may lead to clinical applications of cannabinoid-based compounds as new HSC-mobilizer agents for therapeutic intervention in bone marrow failure.”

http://link.springer.com/chapter/10.1007/978-94-007-2993-3_30

Cannabinoid receptor signaling in progenitor/stem cell proliferation and differentiation.

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“Cannabinoids, the active components of cannabis (Cannabis sativa) extracts, have attracted the attention of human civilizations for centuries, much earlier than the discovery and characterization of their substrate of action, the endocannabinoid system (ECS).

The latter is an ensemble of endogenous lipids, their receptors [in particular type-1 (CB1) and type-2 (CB2) cannabinoid receptors] and metabolic enzymes.

Cannabinoid signaling regulates cell proliferation, differentiation and survival, with different outcomes depending on the molecular targets and cellular context involved.

Cannabinoid receptors are expressed and functional from the very early developmental stages, when they regulate embryonic and trophoblast stem cell survival and differentiation, and thus may affect the formation of manifold adult specialized tissues derived from the three different germ layers (ectoderm, mesoderm and endoderm).

In the ectoderm-derived nervous system, both CB1 and CB2 receptors are present in neural progenitor/stem cells and control their self-renewal, proliferation and differentiation. CB1 and CB2 show opposite patterns of expression, the former increasing and the latter decreasing along neuronal differentiation.

Recently, endocannabinoid (eCB) signaling has also been shown to regulate proliferation and differentiation of mesoderm-derived hematopoietic and mesenchymal stem cells, with a key role in determining the formation of several cell types in peripheral tissues, including blood cells, adipocytes, osteoblasts/osteoclasts and epithelial cells.

Here, we will review these new findings, which unveil the involvement of eCB signaling in the regulation of progenitor/stem cell fate in the nervous system and in the periphery.

The developmental regulation of cannabinoid receptor expression and cellular/subcellular localization, together with their role in progenitor/stem cell biology, may have important implications in human health and disease.”

http://www.ncbi.nlm.nih.gov/pubmed/24076098

CB2 cannabinoid receptors promote mouse neural stem cell proliferation.

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“Neurospheres are clonal cellular aggregates of neural stem/precursor cells that grow in culture as free-floating clusters. Activation of CB1 cannabinoid receptors, which are expressed by these cells, promotes proliferation.

In the present study we investigated the expression of CB2 cannabinoid receptors and the effect of exogenous cannabinoids on neural stem/precursor cell proliferation.

Neurospheres containing nestin-positive and sn-1 diacylglycerol lipase alpha-positive cells expressed both CB1 and CB2 receptors, which were maintained through several passages…

Together, our results suggest that cannabinoids stimulate proliferation of neural stem/precursor cells acting on both CB1 and CB2 cannabinoid receptors through a phosphoinositide-3 kinase/Akt pathway.”

http://www.ncbi.nlm.nih.gov/pubmed/17328768

Cannabinoid receptor 2 and its agonists mediate hematopoiesis and hematopoietic stem and progenitor cell mobilization.

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“Endocannabinoids are arachidonic acid derivatives and part of a novel bioactive lipid signaling system, along with their G-coupled cannabinoid receptors (CB₁ and CB₂) and the enzymes involved in their biosynthesis and degradation.

However, their roles in hematopoiesis and hematopoietic stem and progenitor cell (HSPC) functions are not well characterized. Here, we show that bone marrow stromal cells express endocannabinoids (anandamide and 2-arachidonylglycerol), whereas CB₂ receptors are expressed in human and murine HSPCs.

On ligand stimulation with CB₂ agonists, CB₂ receptors induced chemotaxis, migration, and enhanced colony formation of bone marrow cells, which were mediated via ERK, PI3-kinase, and Gαi-Rac1 pathways.

Taken together, these results demonstrate that the endocannabinoid system is involved in hematopoiesis and that CB₂/CB₂ agonist axis mediates repopulation of hematopoiesis and mobilization of HSPCs.

Thus, CB₂ agonists may be therapeutically applied in clinical conditions, such as bone marrow transplantation.”

http://www.ncbi.nlm.nih.gov/pubmed/21063029