The plant cannabinoid Delta9-tetrahydrocannabivarin can decrease signs of inflammation and inflammatory pain in mice.

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“The phytocannabinoid, Delta(9)-tetrahydrocannabivarin (THCV), can block cannabinoid CB(1) receptors… THCV can activate CB(2) receptors… THCV can activate CB2 receptors and decrease signs of inflammation and inflammatory pain in mice partly via CB1 and/or CB2 receptor activation…

Because there is evidence that THCV can behave as a CB1 receptor antagonist in vivo, it would also be of interest to explore the possibility that this compound can suppress unwanted symptoms in animal models of disorders in which symptoms can be ameliorated by a combination of CB2 receptor activation and CB1 receptor blockade…”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2931567/

Cannabidiol: Pharmacology and potential therapeutic role in epilepsy and other neuropsychiatric disorders.

“Cannabis has been used to treat disease since ancient times. Δ9 -Tetrahydrocannabinol (Δ9 -THC) is the major psychoactive ingredient and CBD is the major nonpsychoactive ingredient in cannabis.

Cannabis and Δ9 -THC are anticonvulsant in most animal models but can be proconvulsant in some healthy animals. The psychotropic effects of Δ9 -THC limit tolerability.

CBD is anticonvulsant in many acute animal models, but there are limited data in chronic models.

The antiepileptic mechanisms of CBD are not known, but may include effects on the equilibrative nucleoside transporter; the orphan G-protein-coupled receptor GPR55; the transient receptor potential of vanilloid type-1 channel; the 5-HT1a receptor; and the α3 and α1 glycine receptors.

CBD has neuroprotective and antiinflammatory effects, and it appears to be well tolerated in humans, but small and methodologically limited studies of CBD in human epilepsy have been inconclusive.

More recent anecdotal reports of high-ratio CBD:Δ9 -THC medical marijuana have claimed efficacy, but studies were not controlled.

CBD bears investigation in epilepsy and other neuropsychiatric disorders, including anxiety, schizophrenia, addiction, and neonatal hypoxic-ischemic encephalopathy.”

http://www.ncbi.nlm.nih.gov/pubmed/24854329

Cannabis Proves Effective In Treating Crohn’s Disease According To New Study

cannibis crohn's disease drug

“A new clinical study published in the journal Pharmacology and by the National Institute of Health has found that cannabis is effective in treating Crohn’s disease, which is a form of inflammatory bowel disease (IBD)…

The study, entitled: “Cannabis Finds Its Way into Treatment of Crohn’s Disease”  is co-authored by Rudolf Schicho, PhD and M. Storr, both of the Institute of Experimental and Clinical Pharmacology, Medical University of Graz in Graz, Austria.

In the study abstract, Schicho and Storr note that In ancient medicine, cannabis was widely used to treat and cure bowel disturbances and inflammation, and a recent clinical study now shows that the medicinal herb Cannabis sativa lived up to expectations and proved to be highly efficient in cases of inflammatory bowel diseases.”

http://bionews-tx.com/news/2014/01/29/cannabis-proves-effective-treating-crohns-disease-according-new-study/

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

The influence of cannabinoids on generic traits of neurodegeneration

“In an increasingly ageing population, the incidence of neurodegenerative disorders such as Alzheimer’s disease, Parkinson’s disease and Huntington’s disease are rising. While the aetiologies of these disorders are different, a number of common mechanisms that underlie their neurodegenerative components have been elucidated; namely neuroinflammation, excitotoxicity, mitochondrial dysfunction and reduced trophic support. Current therapies focus on treatment of the symptoms and attempt to delay the progression of these diseases but there is currently no cure.

Modulation of the endogenous cannabinoid system is emerging as a potentially viable option in the treatment of neurodegeneration. Endocannabinoid signalling has been found to be altered in many neurodegenerative disorders. To this end, pharmacological manipulation of the endogenous cannabinoid system, as well as application of phytocannabinoids and synthetic cannabinoids have been investigated. Signalling from the CB1 and CB2 receptors are known to be involved in the regulation of Ca2+ homeostasis, mitochondrial function, trophic support and inflammatory status, respectively, while other receptors gated by cannabinoids such as PPARγ, are gaining interest in their anti-inflammatory properties.

Through multiple lines of evidence, this evolutionarily conserved neurosignalling system has shown neuroprotective capabilities and is therefore a potential target for neurodegenerative disorders. This review details the mechanisms of neurodegeneration and highlights the beneficial effects of cannabinoid treatment.”

http://onlinelibrary.wiley.com/doi/10.1111/bph.12492/full

Cannabinoid-induced autophagy regulates suppressor of cytokine signaling (SOCS)-3 in intestinal epithelium.

“Autophagy is a catabolic process involved in homeostatic and regulated cellular protein recycling and degradation via the lysosomal degradation pathway. Emerging data associates impaired autophagy, increased activity in the endocannabinoid system and upregulation of suppressor of cytokine signaling (SOCS)-3 protein expression during intestinal inflammatory states. We have investigated whether these three processes are linked. By assessing the impact of phyto-cannabinoid cannabidiol (CBD), synthetic cannabinoid (ACEA) and endocannabinoid (AEA) on autophagosome formation, we explored whether these actions were responsible for cyclic SOCS3 protein levels. Our findings show that all three cannabinoids induce autophagy in a dose-dependent manner in fully differentiated CaCo2 cells, a model of mature intestinal epithelium. ACEA and AEA induced canonical autophagy, which was cannabinoid receptor (CB)-1 mediated. In contrast, CBD was able to bypass both the CB1 receptor and the canonical pathway to induce autophagy, albeit to a lesser extent. Functionally, all three cannabinoids reduced SOCS3 protein expression, which was reversed by blocking both early and late autophagy. In conclusion, the regulatory protein, SOCS3, is itself regulated by autophagy and cannabinoids play a role in this process, which could be important when considering therapeutic applications for the cannabinoids in inflammatory conditions.”

http://www.ncbi.nlm.nih.gov/pubmed/24833710

Functionalization of β-Caryophyllene Generates Novel Polypharmacology in the Endocannabinoid System.

“The widespread dietary plant sesquiterpene hydrocarbon β-caryophyllene is a CB2 cannabinoid receptor-specific agonist showing anti-inflammatory and analgesic effects in vivo…

Our study shows that by removing the conformational constraints induced by the medium-sized ring and by introducing functional groups in the sesquiterpene hydrocarbon 1, a new scaffold with pronounced polypharmacological features within the endocannabinoid system could be generated.

The structural and functional repertoire of cannabimimetics and their yet poorly understood intrinsic promiscuity may be exploited to generate novel probes and ultimately more effective drugs.”

http://www.ncbi.nlm.nih.gov/pubmed/24831513

“Involvement of peripheral cannabinoid and opioid receptors in β-caryophyllene-induced antinociception…β-caryophyllene (BCP) is a common constitute of the essential oils of numerous spice, food plants and major component in Cannabis… The combined injection of morphine and BCP may be an alternative in treating chemogenic pain.” http://www.ncbi.nlm.nih.gov/pubmed/23138934

Cannabinoid receptor 1 inhibition improves the intestinal microcirculation.

“The data supports the involvement of the CB1R signaling in leukocyte activation during sepsis. Drugs targeting the CB1R may have therapeutic potential in systemic inflammation, such as sepsis.”

http://www.ncbi.nlm.nih.gov/pubmed/23334604

“Cannabinoid receptor 1 inhibition causes seizures during anesthesia induction in experimental sepsis… The data suggest that CB1R inhibition in combination with pentobarbital may increase the incidence of anesthetic-induced seizures in the case of sepsis.”

http://www.ncbi.nlm.nih.gov/pubmed/22504215

 

The cannabinoid 2 receptor as a potential therapeutic target for sepsis.

“The sepsis syndrome represents an improper immune response to pathogens and is associated with an unacceptably high rate of mortality. Although supportive care is of benefit to the septic patient, there are no viable therapeutics available that target the immune system suitable for the whole septic population. Recently, using a physiologically relevant murine mouse model, the cannabiniod 2 receptor has been shown to play a critical role in the host response to sepsis. Here, the structure, expression, signaling, and function of the CB2 receptor on leukocytes will be reviewed. Further, the effects mediated by the CB2 receptor during sepsis will be reviewed. Altogether, alterations in inflammation and the host response during sepsis by the CB2 receptor support its use as a possible therapeutic agent.”

http://www.ncbi.nlm.nih.gov/pubmed/20509835

http://www.thctotalhealthcare.com/category/sepsis-2/

Cannabinoid receptor 2 counteracts interleukin-17-induced immune and fibrogenic responses in mouse liver.

“Interleukin (IL)-17 is a proinflammatory and fibrogenic cytokine mainly produced by T-helper (Th)17 lymphocytes, together with the hepatoprotective and antifibrogenic cytokine, IL-22.

Cannabinoid receptor 2 (CB2) is predominantly expressed in immune cells and displays anti-inflammatory and antifibrogenic effects.

In the present study, we further investigated the mechanism underlying antifibrogenic properties of CB2 receptor and explored its effect on the profibrogenic properties of IL-17.

These data demonstrate that CB2 receptor activation decreases liver fibrosis by selectively reducing IL-17 production by Th17 lymphocytes via a STAT5-dependent pathway, and by blunting the proinflammatory effects of IL-17 on its target cells, while preserving IL-22 production.”

http://www.ncbi.nlm.nih.gov/pubmed/23813495

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