Category Archives: Uncategorized

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

Comprehensive Review of Medicinal Marijuana, Cannabinoids, and Therapeutic Implications in Medicine and Headache: What a Long Strange Trip It’s Been ….

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“The use of cannabis, or marijuana, for medicinal purposes is deeply rooted though history, dating back to ancient times. It once held a prominent position in the history of medicine, recommended by many eminent physicians for numerous diseases, particularly headache and migraine.

Through the decades, this plant has taken a fascinating journey from a legal and frequently prescribed status to illegal, driven by political and social factors rather than by science.

However, with an abundance of growing support for its multitude of medicinal uses, the misguided stigma of cannabis is fading, and there has been a dramatic push for legalizing medicinal cannabis and research.

Almost half of the United States has now legalized medicinal cannabis, several states have legalized recreational use, and others have legalized cannabidiol-only use, which is one of many therapeutic cannabinoids extracted from cannabis.

Physicians need to be educated on the history, pharmacology, clinical indications, and proper clinical use of cannabis, as patients will inevitably inquire about it for many diseases, including chronic pain and headache disorders for which there is some intriguing supportive evidence…

The literature suggests that the medicinal use of cannabis may have a therapeutic role for a multitude of diseases, particularly chronic pain disorders including headache.

Supporting literature suggests a role for medicinal cannabis and cannabinoids in several types of headache disorders including migraine and cluster headache, although it is primarily limited to case based, anecdotal, or laboratory-based scientific research.

Cannabis contains an extensive number of pharmacological and biochemical compounds, of which only a minority are understood, so many potential therapeutic uses likely remain undiscovered.

Cannabinoids appear to modulate and interact at many pathways inherent to migraine, triptan mechanisms ofaction, and opiate pathways, suggesting potential synergistic or similar benefits.

Modulation of the endocannabinoid system through agonism or antagonism of its receptors, targeting its metabolic pathways, or combining cannabinoids with other analgesics for synergistic effects, may provide the foundation for many new classes of medications.”

http://www.ncbi.nlm.nih.gov/pubmed/26015168

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

(+/-)9,10-Dihydroxy-delta6a(10a)-tetrahydrocannabinol and (+/-)8,9-dihydroxy-delta6a(10a)-tetrahydrocannabinol: 2 new cannabinoids from Cannabis sativa L.

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“The structures of 2 new polyhydroxylated cannabinoids, (+/-)9,10-dihydroxy-delta6a(10a)-tetrahydrocannabinol and (+/-)8,9-dihydroxy-delta6a(10a)-tetrahydrocannabinol, obtained from a hexane extract of an Indian Cannabis variant were determined by spectral means and correlation with cannabinol.”

http://www.ncbi.nlm.nih.gov/pubmed/720501