Tag Archives: marijuana

Cannabinoid receptor 2: potential role in immunomodulation and neuroinflammation.

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Figure 2

“The cannabinoids are a group of terpenophenolic compounds present in the marijuana plant, Cannabis sativa. At present, three general types of cannabinoids have been identified: phytocannabinoids present uniquely in the cannabis plant, endogenous cannabinoids produced in humans and animals, and synthetic cannabinoids generated in a laboratory. It is worth noting that Cannabis sativa produces over 80 cannabinoids…

An accumulating body of evidence suggests that endocannabinoids and cannabinoid receptors type 1 and 2 (CB(1), CB(2)) play a significant role in physiologic and pathologic processes, including cognitive and immune functions.

…there is growing appreciation of the therapeutic potential of cannabinoids in multiple pathologic conditions involving chronic inflammation (inflammatory bowel disease, arthritis, autoimmune disorders, multiple sclerosis, HIV-1 infection, stroke, Alzheimer’sdisease to name a few), mainly mediated by CB(2) activation.

This review attempts to summarize recent advances in studies of CB(2) activation in the setting of neuroinflammation, immunomodulation and HIV-1 infection.

The full potential of CB2 agonists as therapeutic agents remains to be realized.

Despite some inadequacies of preclinical models to predict clinical efficacy in humans and differences between the signaling of human and rodent CB2 receptors, the development of selective CB2 agonists may open new avenues in therapeutic intervention.

Such interventions would aim at reducing the release of pro-inflammatory mediators particularly in chronic neuropathologic conditions such as HAND or MS.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3663904/

 

Attenuation of experimental autoimmune hepatitis by exogenous and endogenous cannabinoids: involvement of regulatory T cells.

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“Immune-mediated liver diseases including autoimmune and viral hepatitis are a major health problem worldwide. Natural cannabinoids such as Delta(9)-tetrahydrocannabinol (THC) effectively modulate immune cell function, and they have shown therapeutic potential in treating inflammatory diseases.

We investigated the effects of THC in a murine model of concanavalin A (ConA)-induced hepatitis…

Our data demonstrate that targeting cannabinoid receptors using exogenous or endogenous cannabinoids and use of FAAH inhibitors may constitute novel therapeutic modalities to treat immune-mediated liver inflammation.

δ-9-Tetrahydrocannabinol (THC), the major psychoactive component of marijuana (Cannabis sativa), has wide-ranging pharmacological properties. The cannabinoid compounds possess significant immunosuppressive and anti-inflammatory properties. THC and cannabinoid receptor agonists have shown promise in several models of inflammation.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2828293/

Role of Myeloid-Derived Suppressor Cells in Amelioration of Experimental Autoimmune Hepatitis Following Activation of TRPV1 Receptors by Cannabidiol

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“Myeloid-derived suppressor cells (MDSCs) are getting increased attention as one of the main regulatory cells of the immune system. They are induced at sites of inflammation and can potently suppress T cell functions. In the current study, we demonstrate how activation of TRPV1 vanilloid receptors can trigger MDSCs, which in turn, can inhibit inflammation and hepatitis…

This study demonstrates for the first time that MDSCs play a critical role in attenuating acute inflammation in the liver, and that agents such as CBD, which trigger MDSCs through activation of TRPV1 vanilloid receptors may constitute a novel therapeutic modality to treat inflammatory diseases.

Cannabidiol (CBD) is a major non-psychoactive cannabinoid component of marijuana.

Together, these studies not only demonstrate that CBD can protect the host from acute liver injury but also provide evidence for the first time that MDSCs may play a critical role in protecting the liver from acute inflammation.

Non-psychoactive cannabinoids such as CBD possess great therapeutic potential in treating various inflammatory liver diseases, including autoimmune hepatitis.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069975/

Immunoactive effects of cannabinoids: considerations for the therapeutic use of cannabinoid receptor agonists and antagonists

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“The active constituents of Cannabis sativa have been used for centuries as recreational drugs and medicinal agents. Today, marijuana is the most prevalent drug of abuse in the United States and, conversely, therapeutic use of marijuana constituents are gaining mainstream clinical and political acceptance.

Given the documented contributions of endocannabinoid signaling to a range of physiological systems, including cognitive function, and the control of eating behaviors, it is unsurprising that cannabinoid receptor agonists and antagonists are showing significant clinical potential.

In addition to the neuroactive effects of cannabinoids, an emerging body of data suggests that both endogenous and exogenous cannabinoids are potently immunoactive.

The central premise of this review article is that the immunological effects of cannabinoids should be considered in the context of each prescribing decision.

We present evidence that the immunological effects of cannabinoid receptor agonists and antagonists are highly relevant to the spectrum of disorders for which cannabinoid therapeutics are currently offered.

Therapeutically relevant cannabinoid receptor ligands include tetra-hydrocannabinol itself, its synthetic forms, and its closely related compounds.

As a final point, the application of CB1 antagonists may be immunostimulative…”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3804300/

Targeting the CB2 receptor for immune modulation.

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“Early work on the biology of the components of Cannabis sativa showed evidence for a potential influence on immune regulation.

With the discovery of a peripheral cannabinoid receptor associated with immune cells, many laboratories have sought to link the immunoregulatory activities of cannabinoid compounds with this receptor, hoping that such compounds would lack the psychoactive effects of marijuana and other nonspecific cannabinoid agonists.

In this report, the authors investigate the role of the cannabinoid CB2 receptor in immune regulation, with particular emphasis on compounds shown to regulate immune cell recruitment.

The authors conclude by using the immune cell recruitment model to rationalise cannabinoidCB2 receptor-specific effects in modulating immune disease, particularly the increasing evidence for its role in experimental autoimmuneencephalomyelitis and in influencing bone density.”

http://www.ncbi.nlm.nih.gov/pubmed/16981823

Cannabinoid Modulation of Neuroinflammatory Disorders

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Table 1.

“Cannabis sativa is a herb belonging to the Cannabaceae family, characterized by palmate leaves and numerous fibers. Its first record as a medicine dates back to 5000 years ago and it was found in China, where cannabis was used for a myriad of purposes and diseases, including malaria, neuropathic pain, nausea, sexual dysfunction and constipation.

The use of cannabis spread from Central Asia and deeply influenced Indian folk medicine. However, sedative and psychotropic effects of cannabis turned it into a recreational drug. This fact resulted in discrimination against the consumption of the cannabis plant and its derivatives, which delayed the scientific findings in this field…

In recent years, a growing interest has been dedicated to the study of the endocannabinoid system. The isolation of Cannabis sativa main psychotropic compound, Δ(9)-tetrahydrocannabinol (THC), has led to the discovery of an atypical neurotransmission system that modulates the release of other neurotransmitters and participates in many biological processes, including the cascade of inflammatory responses.

In this context, cannabinoids have been studied for their possible therapeutic properties in neuroinflammatory diseases. In this review, historic and biochemical aspects of cannabinoids are discussed, as well as their function as modulators of inflammatory processes and therapeutic perspectives for neurodegenerative disorders, particularly, multiple sclerosis.

Cannabinoid compounds may be extracted from the plant (phytocannabinoids) or be artificially obtained (synthetic cannabinoids)…

To date, it is still impossible to prove or rule out all benefits of cannabis described empirically by ancient herbal practitioners. For now, science aims to understand how cannabinoid compounds are associated with neuroinflammation and how cannabis-based medicine can help millions of patients worldwide.”

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3386505/

Activation through cannabinoid receptors 1 and 2 on dendritic cells triggers NF-kappaB-dependent apoptosis: novel role for endogenous and exogenous cannabinoids in immunoregulation.

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<br /> FIGURE 1.<br />

“Cannabinoids are compounds derived from the Cannabis sativa (marijuana) plant, as well as produced endogenously in the brain and by immune cells. Cannabinoids mediate their effect through cannabinoid receptors (CB), designated CB1 and CB2, which belong to a superfamily of G-protein-coupled receptors.

CB1 receptors are expressed at high levels in CNS, where they regulate psychoactivity. CB1 receptors are also expressed on immune cells. In contrast, the CB2 receptors are primarily expressed on immune cells and do not contribute to the psychoactivity. The presence of endogenous CB-ligand systems in immune cells suggests that they may play a critical physiological role, the precise nature of which remains to be characterized.

Cannabinoids can decrease the immune response… Cannabinoids have also been widely used in the treatment of pain and inflammation.

Moreover, preliminary studies have shown the possible use of cannabinoids in the treatment of autoimmune diseases such as multiple sclerosis.

Recent studies from our lab demonstrated that Δ9-tetrahydrocannabinol (THC) can trigger apoptosis in vivo in thymocytes and splenocytes, which may account for immunosuppression.

 We demonstrate for the first time that THC and endocannabinoids such as anandamide can induce apoptosis in DCs through activation of CB1 and CB2 receptors.

These studies provide the basis for understanding the mechanism by which THC triggers immunosuppression and mediates anti-inflammatory properties.

Many studies have suggested the use of THC or related cannabinoids in the treatment of autoimmune diseases.”

http://www.jimmunol.org/content/173/4/2373.long

CB2 cannabinoid receptor agonist, JWH-015, triggers apoptosis in immune cells: potential role for CB2-selective ligands as immunosuppressive agents.

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“Marijuana has been used for recreational and medicinal purposes for centuries. Its medicinal use can be traced back to ancient Chinese and Egyptian civilizations…

Cannabinoids are known to interact with CB1 and CB2 receptors expressed in the nervous and immune system, respectively, and mediate a wide range of effects, including anti-inflammatory properties…

The current study suggests that targeting CB2 receptors may constitute a unique treatment modality against inflammatory diseases…

Together, this study suggests that CB2-selective agonists, devoid of psychotropic effect, may serve as novel anti-inflammatory/immunosuppressive agents.”

 http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1864948/

Cannabinoid-induced apoptosis in immune cells as a pathway to immunosuppression.

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Fig. 1

“Cannabinoids are a group of compounds found in the marijuana plant (Cannabis sativaL.). Marijuana has been used both for recreational and medicinal purposes for several centuries.

Cannabinoids have been shown to be effective in the treatment of nausea and vomiting associated with cancer chemotherapy, anorexia and cachexia seen in HIV/AIDS patients, as well as neuropathic pain, and spasticity in multiple sclerosis.

More recently, the anti-inflammatory properties of cannabinoids are drawing significant attention. In the last 15 years, studies with marijuana cannabinoids led to the discovery of cannabinoid receptors (CB1 and CB2) and their endogenous ligands, which make up what is known as the endocannabinoid system.

Cannabinoids are a group of compounds present in Cannabis plant (Cannabis sativa L.). They mediate their physiological and behavioral effects by activating specific cannabinoid receptors. With the recent discovery of the cannabinoid receptors (CB1 and CB2) and the endocannabinoid system, research in this field has expanded exponentially.

Cannabinoids have been shown to act as potent immunosuppressive and anti-inflammatory agents and have been shown to mediate beneficial effects in a wide range of immune-mediated diseases such as multiple sclerosis, diabetes, septic shock, rheumatoid arthritis, and allergic asthma.

Cannabinoid receptor 1 (CB1) is mainly expressed on the cells of the central nervous system as well as in the periphery. In contrast, cannabinoid receptor 2 (CB2) is predominantly expressed on immune cells. The precise mechanisms through which cannabinoids mediate immunosuppression is only now beginning to be understood…

In this review, we will focus on apoptotic mechanisms of immunosuppression mediated by cannabinoids on different immune cell populations and discuss how activation of CB2 provides a novel therapeutic modality against inflammatory and autoimmune diseases as well as malignancies of the immune system, without exerting the untoward psychotropic effects…

…cannabinoids do induce apoptosis in immune cells, alleviating inflammatory responses and protecting the host from acute and chronic inflammation.

The cumulative effect of cannabinoids on all cell populations of the immune system can be beneficial, when there is a need for immune suppression.

For example, in patients with autoimmune diseases such as multiple sclerosis, arthritis and lupus, or in those with septic shock, where the disease is caused by activated immune cells, targeting the immune cells via CB2 agonists may trigger apoptosis and act as anti-inflammatory therapy.

CB2 select agonists are not psychoactive and because CB2 is expressed primarily in immune cells, use of CB2 agonists could provide a novel therapeutic modality against autoimmune and inflammatory diseases.

In addition to the use of exogenous cannabinoids, in vivo manipulation of endocannabinoids may also offer novel treatment opportunities against cancer and autoimmune diseases.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3005548/

Direct suppression of autoreactive lymphocytes in the central nervous system via the CB2 receptor.

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The cannabinoid system is evolutionally conserved and is present in invertebrates and vertebrates. One of the best-studied cannabinoids is Δ9-tetrahydrocannabinol (THC), the predominant active component of Cannabis sativa or marijuana.

The marijuana plant has been exploited by humans since their early history and was used for centuries in Asian medicine to reduce the severity of pain, inflammation and asthma. However, only recently have the mechanisms of the medicinal properties of THC begun to be understood. This understanding is largely due to the identification and cloning of two cannabinoid receptors.

The cannabinoid system is now recognized as a regulator of both the nervous and immune systems.

Although marijuana has been used for centuries for the treatment of a variety of disorders, its therapeutic mechanisms are only now being understood.

The best-studied plant cannabinoid, delta9-tetrahydrocannabinol (THC), produced by Cannabis sativa and found in marijuana, has shown evidence of being immunosuppressive in both in vivo and in vitro.

These studies are theoretically in agreement with the suggestions of others that cannabinoid receptor agonists would be beneficial for the treatment of MS in humans.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2219523/