Tag Archives: CB2

The cannabinoid CB₂ receptor-selective phytocannabinoid beta-caryophyllene exerts analgesic effects in mouse models of inflammatory and neuropathic pain.

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European Neuropsychopharmacology Home

“The widespread plant volatile beta-caryophyllene (BCP) was recently identified as a natural selective agonist of the peripherally expressedcannabinoid receptor 2 (CB₂).

…the natural plant product BCP may be highly effective in the treatment of long lasting, debilitating pain states. Our results have important implications for the role of dietary factors in the development and modulation of chronic pain conditions.

Cannabis preparations, which have been used since thousands of years for the treatment of pain have recently come again into the focus as potential therapeutics for inflammatory and neuropathic pain conditions. Currently, cannabis extracts and synthetic preparations of the psychoactive cannabis compound Δ9-tetrahydrocannabinol (THC) have been approved in many countries for clinical pain management at doses and formulations that show on only minor central side effects…

A natural selective agonist for CB2 receptors is the plant volatile BCP, which represents a dietary phytocannabinoid. BCP is found in large amounts in the essential oils of many common spices and food plants… Several health effects have been attributed to BCP or medicinal plants containing BCP, including anti-inflammatory, local anesthetic, anti-carcinogenic, anti-fibrotic and anxiolytic-like activity.

In the present study, we investigated the analgesic effects of BCP in formalin-induced inflammation model and in a model of neuropathic pain, which involves the partial ligation of the sciatic nerve… BCP is the first natural CB2 receptor agonist, which could orally reduce inflammatory responses in different animal models of pain.

Thus, it is likely that BCP belongs to a group of common plant natural products with major potential impact on human health.

The oral intake of this dietary cannabinoid with vegetable food could be advantageous in the daily routine clinical practice over synthetic cannabinoid agonists.”

http://www.europeanneuropsychopharmacology.com/article/S0924-977X(13)00302-7/fulltext

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

The type 2 cannabinoid receptor regulates susceptibility to osteoarthritis in mice.

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“The aim of this study was to evaluate the role of the type 2 cannabinoid receptor (Cnr2) in regulating susceptibility to osteoarthritis in mice.

These studies demonstrate that the Cnr2 pathway plays a role in the pathophysiology of osteoarthritis in mice and shows that pharmacological activation of CB2 has a protective effect.

Further studies of the role of cannabinoid receptors in the pathogenesis of osteoarthritis in man are warranted.”

http://www.ncbi.nlm.nih.gov/pubmed/25937028

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

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

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“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.”

http://www.ncbi.nlm.nih.gov/pubmed/25936364

New quinolone- and 1,8-naphthyridine-3-carboxamides as selective CB2 receptor agonists with anticancer and immuno-modulatory activity.

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“Several recent studies suggest that selective CB2 receptor agonists may represent a valid pharmacological approach in the treatment of various diseases due to the absence of relevant psychoactive side effect…

Two compounds showing the best binding and selectivity profile behaved as a full agonist and a partial agonist at the CB2 receptor and induced a concentration-dependent decrease of cell viability on LNCaP, a prostatic cancer cell line expressing CB2 receptor.

Moreover considering that the CB2 receptor is mainly expressed in cells and organs of the immune system, the same compounds were studied for their potential immune-modulatory and anti-inflammatory effects in activated lymphocytes isolated from healthy controls and multiple sclerosis (MS) patients.”

http://www.ncbi.nlm.nih.gov/pubmed/25935384

Cannabinoid Receptor-2 Regulates Embryonic Hematopoietic Stem Cell Development via PGE2 and P-selectin Activity.

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“Cannabinoids (CB) modulate adult hematopoietic stem and progenitor cell (HSPCs) function, however, impact on the production, expansion or migration of embryonic HSCs is currently uncharacterized.

Here, using chemical and genetic approaches targeting CB-signaling in zebrafish, we show that CB receptor (CNR) 2, but not CNR1, regulates embryonic HSC development…

Together, these data suggest CNR2-signaling optimizes the production, expansion and migration of embryonic HSCs by modulating multiple downstream signaling pathways.”

http://www.ncbi.nlm.nih.gov/pubmed/25931248

Role of CB2 receptors in social and aggressive behavior in male mice.

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“This study was designed to examine the role of cannabinoid CB2r in social and aggressive behavior…

Our results suggest that CB2r is implicated in social interaction and aggressive behavior and deserves further consideration as a potential new target for the management of aggression.”

http://www.ncbi.nlm.nih.gov/pubmed/25921034

The Antitumor Activity of Plant-Derived Non-Psychoactive Cannabinoids.

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“As a therapeutic agent, most people are familiar with the palliative effects of the primary psychoactive constituent of Cannabis sativa (CS), Δ9-tetrahydrocannabinol (THC), a molecule active at both the cannabinoid 1 (CB1) and cannabinoid 2 (CB2) receptor subtypes.

Through the activation primarily of CB1 receptors in the central nervous system, THC can reduce nausea, emesis and pain in cancer patients undergoing chemotherapy.

During the last decade, however, several studies have now shown that CB1 and CB2 receptor agonists can act as direct antitumor agents in a variety of aggressive cancers.

In addition to THC, there are many other cannabinoids found in CS, and a majority produces little to no psychoactivity due to the inability to activate cannabinoid receptors.

For example, the second most abundant cannabinoid in CS is the non-psychoactive cannabidiol (CBD). Using animal models, CBD has been shown to inhibit the progression of many types of cancer including glioblastoma (GBM), breast, lung, prostate and colon cancer.

This review will center on mechanisms by which CBD, and other plant-derived cannabinoids inefficient at activating cannabinoid receptors, inhibit tumor cell viability, invasion, metastasis, angiogenesis, and the stem-like potential of cancer cells.

We will also discuss the ability of non-psychoactive cannabinoids to induce autophagy and apoptotic-mediated cancer cell death, and enhance the activity of first-line agents commonly used in cancer treatment.”

Intrathecal Injection of JWH-015 Attenuates Bone Cancer Pain Via Time-Dependent Modification of Pro-inflammatory Cytokines Expression and Astrocytes Activity in Spinal Cord.

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“Cannabinoid receptor type 2 (CB2) agonists display potential analgesic effects in acute and neuropathic pain.

Overall, our results provided evidences for the persistent participation of inflammation reaction in the progression of bone cancer pain, and demonstrated that JWH-015 reduced the expression of IL-1β, IL-6, IL-18, and TNF-α and inhibited astrocytes activation in a time-dependent manner, thereby displaying an analgesic effect.”

Cannabinoids Inhibit T-cells via Cannabinoid Receptor 2 in an in vitro Assay for Graft Rejection, the Mixed Lymphocyte Reaction

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“Cannabinoids are known to have anti-inflammatory and immunomodulatory properties.

Cannabinoid receptor 2 (CB2) is expressed mainly on leukocytes and is the receptor implicated in mediating many of the effects of cannabinoids on immune processes.

This study tested the capacity of Δ9-tetrahydrocannabinol (Δ9-THC) and of two CB2-selective agonists to inhibit the murine Mixed Lymphocyte Reaction (MLR), an in vitro correlate of graft rejection following skin and organ transplantation. Both CB2-selective agonists and Δ9-THC significantly suppressed the MLR in a dose dependent fashion…

Together, these data support the potential of this class of compounds as useful therapies to prolong graft survival in transplant patients.

Cannabinoids were reported to have effects on immune responses as early as the 1970s, but the basis for this activity was not understood until the cannabinoid receptors were cloned

Ideally, the anatomically disparate expression of CB1 and CB2 would allow for the use of compounds selective for CB2, and thus eliminate the unwanted psychoactive effects from CB1 activation, while maintaining the anti-inflammatory and immunosuppressive properties.

CB2-selective cannabinoids have been proposed as possible candidates to block graft rejection.

The results presented in this paper show that Δ9-THC, a mixed CB1/CB2 agonist, and two CB2-selective agonists can inhibit the Mixed Lymphocyte Reaction (MLR), an in vitro correlate of organ and skin graft rejection.”

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3864984/

Effects of Cannabinoids on T-cell Function and Resistance to Infection.

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“This review examines the effects of cannabinoids on immune function, with a focus on effects on T-cells, as well as on resistance to infection. The paper considers the immune modulating capacity of marijuana, of ∆9-THC extracted from the marijuana plant, and synthetic cannabinoids…

The overall conclusion of the studies discussed in this review is that cannabinoids that bind to the CB2 receptor, including ∆9-THC and CB2 selective agonists are immunosuppressive.

The studies provide objective evidence for potentially beneficial effects of marijuana and ∆9-THC on the immune system in conditions where it is desirable to dampen immune responses.

An emerging area of investigation that is reviewed is evidence to support the conclusion that CB2 selective agonists are a new class of immunosuppressive and anti-inflammatory compounds that may have exceptional beneficial effects in a variety of conditions, such as autoimmune diseases and graft rejection, where it is desirable to dampen the immune response without psychoactive effects.”

http://www.ncbi.nlm.nih.gov/pubmed/25876735

http://www.thctotalhealthcare.com/category/autoimmune-disease/