Category Archives: Autoimmune Disease

Cannabidiol arrests onset of autoimmune diabetes in NOD mice.

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Figure 2

“Cannabidiol (CBD) is a potent anti-inflammatory agent. It is effective in supressing IFN-γ and TNF-α production and progression of autoimmune Th1-mediated rheumatoid arthritis by inhibition of T cell proliferation. This observation led us to investigate the possible effects of CBD on additional autoimmune diseases.

We have previously reported that cannabidiol (CBD) lowers the incidence of diabetes in young non-obese diabetes-prone (NOD) female mice.

In the present study we show that administration of CBD to 11-14 week old female NOD mice… ameliorates the manifestations of the disease…

CBD was extracted from Cannabis resin (hashish)…

Our data strengthen our previous assumption that CBD, known to be safe in man, can possibly be used as a therapeutic agent for treatment of type 1 diabetes.

CBD is not psychoactive and has anti-inflammatory and anti autoimmune properties.

Based on the above presented results, on the previously documented anti-inflammatory effects of CBD and on its clinical safety, it seems reasonable to consider the use of CBD for controlling type 1 diabetes at an early stage of the disease.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2270485/

A biosynthetic pathway for anandamide

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“The endocannabinoid arachidonoyl ethanolamine (anandamide) is a lipid transmitter synthesized and released “on demand” by neurons in the brain. Anandamide is also generated by macrophages where its endotoxin (LPS)-induced synthesis has been implicated in the hypotension of septic shock and advanced liver cirrhosis. Anandamide can be generated from its membrane precursor, N-arachidonoyl phosphatidylethanolamine (NAPE) through cleavage by a phospholipase D (NAPE-PLD).

Here we document a biosynthetic pathway for anandamide in mouse brain…

Both PTPN22 and endocannabinoids have been implicated in autoimmune diseases, suggesting that the PLC/phosphatase pathway of anandamide synthesis may be a pharmacotherapeutic target.

The observed exclusive role of the PLC/phosphatase pathway in LPS-induced AEA synthesis may offer therapeutic targets for the treatment of these conditions.

Furthermore, cannabinoids have immunosuppressive effects in autoimmune models of multiple sclerosis and diabetes, and mice deficient in CB1 receptors show increased susceptibility to neuronal damage found in autoimmune encephalitis…”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1557387/#!po=23.3333

Multiple sclerosis may disrupt endocannabinoid brain protection mechanism

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“Since the discovery of the endocannabinoids [eCB; anandamide and 2-arachidonoylglycerol (2-AG), various pathological conditions were shown to increase the eCB tone and to inhibit molecular mechanisms that are involved in the production, release, and diffusion of harmful mediators such as proinflammatory cytokines or excess glutamate.

In this issue of PNAS, Witting et al.  demonstrate that, unexpectedly and contrary to the effects of other brain diseases, cell damage induced by experimental autoimmune encephalomyelitis (EAE), an immune-mediated disease widely used as a laboratory model of multiple sclerosis (MS), does not lead to enhancement of eCB levels, although the cannabinoid receptors remain functional.

Nearly two decades ago, Lyman et al.  reported that Δ9-THC, the psychoactive component of marijuana, suppresses the symptoms of EAE. A few years later, Wirguin et al. reported the same effect by Δ8-THC, a more stable and less psychotropic analogue of Δ9-THC.

Thus, THC was shown to inhibit both clinical and histological signs of EAE even before the endocannabinoids were described.

THC was also shown to control spasticity and tremor in chronic relapsing EAE, a further autoimmune model of MS , and to inhibit glutamate release via activation of the CB1-cannabinoid receptor in EAE. Moreover, mice deficient in the cannabinoid receptor CB1 tolerate inflammatory and excitotoxic insults poorly and develop substantial neurodegeneration after immune attack in EAE.

Thus, the brain loses some of its endogenous neuroprotective capacity, but it may still respond to exogenous treatment with 2-AG or other CB1 agonists. Assuming that the biochemical changes taking place in the EAE model of MS are similar to those in MS itself, these results represent a biochemical-based support to the positive outcome noted with cannabinoid therapy in MS.

These data suggest that the high level of IFN-γ in the CNS, noted in mice with EAE, disrupts eCB-mediated neuroprotection, while maintaining functional cannabinoid receptors, thus providing additional support for the use of cannabinoid-based medicine to treat MS.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1458835/

Experimental autoimmune encephalomyelitis disrupts endocannabinoid-mediated neuroprotection

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“Focal cerebral ischemia and traumatic brain injury induce an escalating amount of cell death because of harmful mediators diffusing from the original lesion site.

Evidence suggests that healthy cells surrounding these lesions attempt to protect themselves by producing endocannabinoids (eCBs) and activating cannabinoid receptors, the molecular target for marijuana-derived compounds.

Indeed, activation of cannabinoid receptors reduces the production and diffusion of harmful mediators.

Here, we provide evidence that an exception to this pattern is found in experimental autoimmuneencephalomyelitis (EAE), a mouse model of multiple sclerosis…

Our data suggest that the high level of CNS IFN-gamma associated with EAE disrupts eCB-mediated neuroprotection while maintaining functional cannabinoid receptors, thus providing additional support for the use of cannabinoid-based medicine to treat multiple sclerosis.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC1458883/

Anandamide Attenuates Th-17 Cell-Mediated Delayed-Type Hypersensitivity Response by Triggering IL-10 Production and Consequent microRNA Induction

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“Endogenous cannabinoids [endocannabinoids] are lipid signaling molecules that have been shown to modulate immune functions..

Cannabinoids are compounds derived from the Cannabis sativa plant and exert many effects on the immune system. Cannabinoids have potential as therapeutic agents in several different disease conditions, including experimental autoimmune hepatitis, Multiple Sclerosis, and Graft vs. Host Disease…

This report suggested a role of the endogenous cannabinoid system in regulation of allergic inflammation.

These studies also suggest that endogenous cannabinoid system is one of the homeostatic mechanisms that the body employs to down-regulate immune response to foreign antigens as well as combat autoimmunity.

Targeting of this system could yield valuable therapeutics in the future.”

http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0093954

Brain Innate Immunity In The Regulation Of Neuroinflammation: Therapeutic Strategies By Modulating Cd200-Cd200r Interaction Involve The Cannabinoid System.

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“The central nervous system (CNS) innate immune response includes an arsenal of molecules and receptors expressed by professional phagocytes, glial cells and neurons that is involved in host defence and clearance of toxic and dangerous cell debris. However, any uncontrolled innate immune responses within the CNS are widely recognized as playing a major role in the development of autoimmune disorders and neurodegeneration, with multiple sclerosis (MS) and Alzheimer’s disease (AD) being primary examples. Hence, it is important to identify the key regulatory mechanisms involved in the control of CNS innate immunity and which could be harnessed to explore novel therapeutic avenues. Neuroimmune regulatory proteins (NIReg) such as CD95L, CD200, CD47, sialic acid, complement regulatory proteins (CD55, CD46, fH, C3a), HMGB1, may control the adverse immune responses in health and diseases. In the absence of these regulators, when neurons die by apoptosis, become infected or damaged, microglia and infiltrating immune cells are free to cause injury as well as an adverse inflammatory response in acute and chronic settings. We will herein provide new emphasis on the role of the pair CD200-CD200R in MS and its experimental models: experimental autoimmune encephalomyelitis (EAE) and Theiler’s virus induced demyelinating disease (TMEV-IDD). The interest of the cannabinoid system as inhibitor of inflammation prompt us to introduce our findings about the role of endocannabinoids (eCBs) in promoting CD200-CD200 receptor (CD200R) interaction and the benefits caused in TMEV-IDD. Finally, we also review the current data on CD200-CD200R interaction in AD, as well as, in the aging brain.”

http://www.ncbi.nlm.nih.gov/pubmed/24588829

Marijuana treatments for autoimmune disorders

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“Researchers from the University of South Carolina say that tetrahydrocannabinol, the principal constituent of marijuana, may have another medical use – treating those with autoimmune disorders.

Tetrahydrocannabinol (THC) is known to have analgesic effects so can be used to treat pain. It also aids relaxation and can reduce feelings of nausea and stimulate appetite…

Now, a new study, published in the Journal of Biological Chemistry, explores how analgesicmicroRNAs are influenced by THC.

MicroRNAs (miRNAs) are small, single-stranded, non-coding RNAs that play a vital role in regulating gene expression. And the authors claim that the ability to alter miRNA expression may be the key to successful treatment for many autoimmune diseases, including multiple sclerosis, arthritis and type 1 diabetes.”

More: http://www.medicalnewstoday.com/articles/269432.php

Control of Spasticity in a Multiple Sclerosis Model is mediated by CB1, not CB2, Cannabinoid Receptors

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“There is increasing evidence to suggest that cannabis can ameliorate muscle-spasticity in multiple sclerosis, as was objectively shown in experimental autoimmune encephalomyelitis models. The purpose of this study was to investigate further the involvement of CB1 and CB2 cannabinoid receptors in the control of experimental spasticity…

Conclusions and Implications:

The CB1 receptor controls spasticity and cross-reactivity to this receptor appears to account for the therapeutic action of some CB2 agonists.

 As cannabinoid-induced psychoactivity is also mediated by the CB1 receptor, it will be difficult to truly dissociate the therapeutic effects from the well-known, adverse effects of cannabinoids when using cannabis as a medicine.

The lack of knowledge on the true diversity of the cannabinoid system coupled with the lack of total specificity of current cannabinoid reagents makes interpretation of in vivo results difficult, if using a purely pharmacological approach.

Gene knockout technology provides an important tool in target validation and indicates that the CB1 receptor is the main cannabinoid target for an anti-spastic effect.”

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2189718/

Therapeutic potential of cannabinoid medicines.

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Drug Testing and Analysis

“Cannabis was extensively used as a medicine throughout the developed world in the nineteenth century but went into decline early in the twentieth century ahead of its emergence as the most widely used illicit recreational drug later that century. Recent advances in cannabinoid pharmacology alongside the discovery of the endocannabinoid system (ECS) have re-ignited interest in cannabis-based medicines.

The ECS has emerged as an important physiological system and plausible target for new medicines. Its receptors and endogenous ligands play a vital modulatory role in diverse functions including immune response, food intake, cognition, emotion, perception, behavioural reinforcement, motor co-ordination, body temperature, wake/sleep cycle, bone formation and resorption, and various aspects of hormonal control. In disease it may act as part of the physiological response or as a component of the underlying pathology.

In the forefront of clinical research are the cannabinoids delta-9-tetrahydrocannabinol and cannabidiol, and their contrasting pharmacology will be briefly outlined. The therapeutic potential and possible risks of drugs that inhibit the ECS will also be considered. This paper will then go on to review clinical research exploring the potential of cannabinoid medicines in the following indications: symptomatic relief in multiple sclerosis, chronic neuropathic pain, intractable nausea and vomiting, loss of appetite and weight in the context of cancer or AIDS, psychosis, epilepsy, addiction, and metabolic disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/24006213

http://onlinelibrary.wiley.com/doi/10.1002/dta.1529/abstract

Cannabinoids Decrease the Th17 Inflammatory Autoimmune Phenotype.

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“Cannabinoids, the Cannabis constituents, are known to possess anti-inflammatory properties but the mechanisms involved are not understood. Here we show that the main psychoactive cannabinoid, Δ-9-tetrahydrocannabinol (THC), and the main nonpsychoactive cannabinoid, cannabidiol (CBD), markedly reduce the Th17 phenotype which is known to be increased in inflammatory autoimmune pathologies such as Multiple Sclerosis…

Pretreatment with CBD also resulted in increased levels of the anti-inflammatory cytokine IL-10. Interestingly, CBD and THC did not affect the levels of TNFα and IFNγ. The downregulation of IL-17 secretion by these cannabinoids does not seem to involve the CB1, CB2, PPARγ, 5-HT1A or TRPV1 receptors…

In conclusion, the results show a unique cannabinoid modulation of the autoimmune cytokine milieu combining suppression of the pathogenic IL-17 and IL-6 cytokines along with boosting the expression of the anti-inflammatory cytokine IL-10.”

http://www.ncbi.nlm.nih.gov/pubmed/23892791