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Metabolic fingerprinting of Cannabis sativa L., cannabinoids and terpenoids for chemotaxonomic and drug standardization purposes.

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“Cannabis sativa L. is an important medicinal plant.

In order to develop cannabis plant material as a medicinal product quality control and clear chemotaxonomic discrimination between varieties is a necessity.

Therefore in this study 11 cannabis varieties were grown under the same environmental conditions. Chemical analysis of cannabis plant material used a gas chromatography flame ionization detection method that was validated for quantitative analysis of cannabis monoterpenoids, sesquiterpenoids, and cannabinoids. Quantitative data was analyzed using principal component analysis to determine which compounds are most important in discriminating cannabis varieties.

In total 36 compounds were identified and quantified in the 11 varieties. Using principal component analysis each cannabis variety could be chemically discriminated. This methodology is useful for both chemotaxonomic discrimination of cannabis varieties and quality control of plant material.”

http://www.ncbi.nlm.nih.gov/pubmed/21040939

The effect of phytocannabinoids on airway hyper-responsiveness, airway inflammation, and cough.

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“Cannabis has been demonstrated to have bronchodilator, anti-inflammatory, and antitussive activity in the airways…

We compared the effects of Δ(9)-tetrahydrocannabinol, cannabidiol, cannabigerol, cannabichromene, cannabidiolic acid, and tetrahydrocannabivarin on contractions of the guinea pig-isolated trachea and bronchoconstriction induced by nerve stimulation or methacholine in anesthetized guinea pigs following exposure to saline or the proinflammatory cytokine, tumor necrosis factor α (TNF-α)…

Only Δ(9)-tetrahydrocannabinol inhibited TNF-α-enhanced vagal-induced bronchoconstriction, neutrophil recruitment to the airways, and citric acid-induced cough responses…

The other cannabinoids did not influence cholinergic transmission, and only Δ(9)-THC demonstrated effects on airway hyper-responsiveness, anti-inflammatory activity, and antitussive activity in the airways.”

http://www.ncbi.nlm.nih.gov/pubmed/25655949

Inhibition of human neutrophil chemotaxis by endogenous cannabinoids and phytocannabinoids: evidence for a site distinct from CB1 and CB2.

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“Here, we show a novel pharmacology for inhibition of human neutrophil migration by endocannabinoids, phytocannabinoids, and related compounds.

This study reveals that certain endogenous lipids, phytocannabinoids, and related ligands are potent inhibitors of human neutrophil migration, and it implicates a novel pharmacological target distinct from cannabinoid CB(1) and CB(2) receptors; this target is antagonized by the endogenous compound N-arachidonoyl l-serine.

Furthermore, our findings have implications for the potential pharmacological manipulation of elements of the endocannabinoid system for the treatment of various inflammatory conditions.”

http://www.ncbi.nlm.nih.gov/pubmed/17965195

Turning Over a New Leaf: Cannabinoid and Endocannabinoid Modulation of Immune Function.

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“Cannabis is a complex substance that harbors terpenoid-like compounds referred to as phytocannabinoids.

The major psychoactive phytocannabinoid found in cannabis ∆9-tetrahydrocannabinol (THC) produces the majority of its pharmacological effects through two cannabinoid receptors, termed CB1and CB2. The discovery of these receptors as linked functionally to distinct biological effects of THC, and the subsequent development of syntheticcannabinoids, precipitated discovery of the endogenous cannabinoid (or endocannabinoid) system.

This system consists of the endogenous lipid ligands N- arachidonoylethanolamine (anandamide; AEA) and 2-arachidonylglycerol (2-AG), their biosynthetic and degradative enzymes, and the CB1and CB2 receptors that they activate. Endocannabinoids have been identified in immune cells such as monocytes, macrophages, basophils, lymphocytes, and dendritic cells and are believed to be enzymatically produced and released “on demand” in a similar fashion as the eicosanoids.

It is now recognized that other phytocannabinoids such as cannabidiol (CBD) and cannabinol (CBN) can alter the functional activities of the immune system.

This special edition of the Journal of Neuroimmune Pharmacology (JNIP) presents a collection of cutting edge original research and review articles on the medical implications of phytocannabinoids and the endocannabinoid system.

The goal of this special edition is to provide an unbiased assessment of the state of research related to this topic from leading researchers in the field.

The potential untoward effects as well as beneficial uses of marijuana, its phytocannabinoid composition, and synthesized cannabinoid analogs are discussed.

In addition, the role of the endocannabinoid system and approaches to its manipulation to treat select human disease processes are addressed.”

http://www.ncbi.nlm.nih.gov/pubmed/26054900

“A variety of cannabinoids was examined in these studies, including the FDA-approved synthetic cannabinoid receptor agonist nabilone, an oral mucosal cannabis spray, the FAAH inhibitor PF-04457845, oral or inhaled cannabis extract, and smoked cannabis. The majority of these studies revealed modest analgesic effects of these formulations without serious side effects, lending credence to the idea that cannabinoid-based medications ultimately may be a reasonable treatment option for chronic non-cancer pain.”  http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4469415/

Cannabidiol for the Prevention of Graft-Versus-Host-Disease after Allogeneic Hematopoietic Cell Transplantation: Results of a Phase II Study.

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“Graft-versus-host-disease (GVHD) is a major obstacle to successful allogeneic hematopoietic cell transplantation (alloHCT).

Cannabidiol (CBD), a non-psychotropic ingredient of Cannabis sativa possesses potent anti-inflammatory and immunosuppressive properties. We hypothesized that CBD may decrease GVHD incidence and severity after alloHCT…

The combination of CBD with standard GVHD prophylaxis is a safe and promising strategy to reduce the incidence of acute GVHD. A randomized double blind controlled study is warranted.”

http://www.ncbi.nlm.nih.gov/pubmed/26033282

Δ9-Tetrahydrocannabinol attenuates allogeneic host-versus-graft response and delays skin graft rejection through activation of cannabinoid receptor 1 and induction of myeloid-derived suppressor cells.

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“Immune cells have been shown to express cannabinoid receptors and to produce endogenous ligands. Moreover, activation of cannabinoid receptors on immune cells has been shown to trigger potent immunosuppression.

Despite such studies, the role of cannabinoids in transplantation, specifically to prevent allograft rejection, has not, to our knowledge, been investigated previously. In the current study, we tested the effect of THC on the suppression of HvGD as well as rejection of skin allografts…

Together, our research shows, for the first time to our knowledge, that targeting cannabinoid receptors may provide a novel treatment modality to attenuate HvGD and prevent allograft rejection.”

http://www.ncbi.nlm.nih.gov/pubmed/26034207

Primary Macrophage Chemotaxis Induced by Cannabinoid Receptor 2 Agonists Occurs Independently of the CB2 Receptor.

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“Activation of CB2 has been demonstrated to induce directed immune cell migration. However, the ability of CB2 to act as a chemoattractant receptor in macrophages remains largely unexplored…

Taken together our results conclusively demonstrate that CB2 is not a chemoattractant receptor for murine macrophages. Furthermore we show for the first time that JWH133, HU308, L-759,656 and L-759,633 have off-target effects of functional consequence in primary cells and we believe that our findings have wide ranging implications for the entire cannabinoid field.”

http://www.ncbi.nlm.nih.gov/pubmed/26033291

High prevalence of cannabis use among Aka foragers of the Congo Basin and its possible relationship to helminthiasis

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Cover image for Vol. 27 Issue 3

“Little is known about cannabis use in hunter-gatherers. Therefore, we investigated cannabis use in the Aka, a population of foragers of the Congo Basin.

Because cannabis contains anthelminthic compounds,” http://medical-dictionary.thefreedictionary.com/anthelmintic ” and the Aka have a high prevalence of helminthiasis, we also tested the hypothesis that cannabis use might be an unconscious form of self-medication against helminths.

THCA levels were negatively correlated with parasite infection and reinfection, supporting the self-medication hypothesis.

This, to our knowledge, is the first biomarker-validated study of cannabis use in a hunting-gathering population, and also the first to explore the relationship between the use of cannabis, which is toxic to helminths, and intestinal helminth infection.

Although the conventional view is that drug abuse impairs immunity, thus increasing susceptibility to infection, if recreational drug use is explained by the drugs’ antiparasitic properties, this would suggest that the immune system plays a key role in regulating drug use.”  

http://onlinelibrary.wiley.com/doi/10.1002/ajhb.22740/full

“Medical Marijuana Smoking Linked to Parasite Prevention. Scientists from Washington State University have suggested that smoking cannabis may have a beneficial effect with regard to the avoidance of intestinal parasite infections, which could explain why the drug has such a long history of recreational use… those who smoked cannabis had a lower rate of infection.” http://www.newhistorian.com/medical-marijuana-smoking-linked-to-parasite-prevention/3936/

Maternal marijuana use and neonatal morbidity.

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“Marijuana use is becoming increasingly common in the obstetric population, however it is unknown whether it is associated with poor neonatal outcomes. We sought to determine the prevalence and risk factors for marijuana use in pregnancy, and to evaluate whether marijuana use is independently associated with poor neonatal outcomes.

CONCLUSION:

Marijuana use is common in pregnancy, but may not be an independent risk factor for poor neonatal outcomes in term pregnancies.”

http://www.ncbi.nlm.nih.gov/pubmed/26026918