Tag Archives: Cannabinoids

The role of CB1 in immune modulation by cannabinoids.

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“There is clear evidence that CB(2), historically referred to as the peripheral cannabinoid receptor, mediates many of the immune modulatory effects of cannabinoids.

 However, cannabinoid receptors cannot be classified simply as central or peripheral since CB(2) has been shown to play a role in the central nervous system (CNS) and CB(1) mediates many immune system effects. Although Cnr1 mRNA and CB(1) protein expression is lower than Cnr2 mRNA or CB(2) protein expression in cells of the immune system, several studies have shown direct modulation of immune function via CB(1) by endogenous and exogenous cannabinoids in T cells, innate cells, and to a lesser extent, B cells.

In addition, indirect, but CB(1)-dependent, mechanisms of immune modulation exist. In fact, the mechanism by which cannabinoids attenuate neuroinflammation via CB(1) is likely a combination of immune suppression and neuroprotection.

 Although many studies demonstrate that agonists for CB(1) are immune suppressive and anti-inflammatory, CB(1) antagonists also exhibit anti-inflammatory properties. Overall, the data demonstrate that many of the immune modulatory effects of cannabinoids are mediated via CB(1).”

http://www.ncbi.nlm.nih.gov/pubmed/23261520

Activation of cannabinoid receptor 2 attenuates leukocyte-endothelial cell interactions and blood-brain barrier dysfunction under inflammatory conditions.

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“Previous studies have shown that modulation of the receptor-mediated cannabinoid system during neuroinflammation can produce potent neuroprotective and anti-inflammatory effects

…Together, these results suggest that pharmacological CB2R ligands offer a new strategy for BBB protection during neuroinflammation.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3325902/

Emerging role of the cannabinoid receptor CB2 in immune regulation: therapeutic prospects for neuroinflammation.

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“There is now a large body of data indicating that the cannabinoid receptor type 2 (CB2) is linked to a variety of immune events. This functional relevance appears to be most salient in the course of inflammation, a process during which there is an increased number of receptors that are available for activation. Studies aimed at elucidating signal transduction events resulting from CB2 interaction with its native ligands, and of the role of exogenous cannabinoids in modulating this process, are providing novel insights into the role of CB2 in maintaining a homeostatic immune balance within the host. Furthermore, these studies suggest that the CB2 may serve as a selective molecular target for therapeutic manipulation of untoward immune responses, including those associated with a variety of neuropathies that exhibit a hyperinflammatory component.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2768535/

Immunomodulatory properties of kappa opioids and synthetic cannabinoids in HIV-1 neuropathogenesis.

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“Anti-retroviral therapy (ART) has had a tremendous impact on the clinical outcomes of HIV-1 infected individuals. While ART has produced many tangible benefits, chronic, long-term consequences of HIV infection have grown in importance. HIV-1-associated neurocognitive disorder (HAND) represents a collection of neurological syndromes that have a wide range of functional cognitive impairments. HAND remains a serious threat to AIDS patients, and there currently remains no specific therapy for the neurological manifestations of HIV-1.

Based upon work in other models of neuroinflammation, kappa opioid receptors (KOR) and synthetic cannabinoids have emerged as having neuroprotective properties and the ability to dampen pro-inflammatory responses of glial cells; properties that may have a positive influence in HIV-1 neuropathogenesis. The ability of KOR ligands to inhibit HIV-1 production in human microglial cells and CD4 T lymphocytes, demonstrate neuroprotection, and dampen chemokine production in astrocytes provides encouraging data to suggest that KOR ligands may emerge as potential therapeutic agents in HIV neuropathogenesis.

 Based upon findings that synthetic cannabinoids inhibit HIV-1 expression in human microglia and suppress production of inflammatory mediators such as nitric oxide (NO) in human astrocytes, as well as a substantial literature demonstrating neuroprotective properties of cannabinoids in other systems, synthetic cannabinoids have also emerged as potential therapeutic agents in HIV neuropathogenesis.

This review focuses on these two classes of compounds and describes the immunomodulatory and neuroprotective properties attributed to each in the context of HIV neuropathogenesis.”

http://www.ncbi.nlm.nih.gov/pubmed/21850403

Researchers Have Discovered Synthetic Agents Used To Treat HIV Inflammation – Medical News Today

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“HIV can cause serious inflammation, regardless of drug therapy, as it develops slowly in immune cells called macrophages. However, new research conducted at the Temple University School of Medicine’s Department of Pathology and Laboratory Medicine and Center for Substance Abuse Research (CSAR) has just found that there are synthetic agents with anti-inflammatory properties, related to the active ingredient in cannabis, THC (tetrahydrocannabinol) which could limit and treat the chronic inflammation.

These findings suggest that CB2 agonists could be used along with antiretroviral drugs which could lead to a new form of therapy for HIV/AIDS.

It also suggests that the human immune system itself could be used to fight off the HIV infection.

According to Persidsky: “Our study suggests that the body’s own natural defenses can be made more powerful to fight some of the worst symptoms of HIV.”

Stimulating CB2 receptors could also be applied for treating other infections.”

More: http://www.medicalnewstoday.com/articles/260152.php

Cannabis Compounds Reduce Multi-Drug Resistant Infections

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“Cannabis Science, Inc. Dr. Robert Melamede, PhD., Director and Chief Science Officer, reported to the Board on the current state of research into the use of natural plant cannabinoids to reduce the spread of drug-resistant bacteria, including methicillin-resistant Staphyloccus aureus (MRSA), and the prospects for development of topical whole-cannabis treatments.

According to studies published in the Journal of the American Medical Association and by the Center for Disease Control in 2007, MRSA is responsible for more than 18,500 hospital-stay related deaths each year, and increased direct healthcare costs of as much as $9.7 billion.

Dr. Melamede stated, “Research into use of whole cannabis extracts and multi-cannabinoid compounds has provided the scientific rationale for medical marijuana’s efficacy in treating some of the most troubling diseases mankind now faces, including infectious diseases such as the flu and HIV, autoimmune diseases such as ALS (Lou Gehrig’s Disease), multiple sclerosis, arthritis, and diabetes, neurological conditions such as Alzheimer’s, stroke and brain injury, as well as numerous forms of cancer. One common element of these diseases is that patients often suffer extended hospital stays, risking development of various Staphyloccus infections including MRSA. A topical, whole-cannabis treatment for these infections is a functional complement to our cannabis extract-based lozenge.””

More: http://www.drugs.com/clinical_trials/cannabis-compounds-reduce-multi-resistant-infections-7080.html

Marijuana Ingredients Show Promise In Battling Superbugs

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“Substances in marijuana show promise for fighting deadly drug-resistant bacterial infections, including so-called “superbugs,” without causing the drug’s mood-altering effects, scientists in Italy and the United Kingdom are reporting.

Besides serving as infection-fighting drugs, the substances also could provide a more environmentally-friendly alternative to synthetic antibacterial substances now widely used in personal care items, including soaps and cosmetics, they say.

In the new study, Giovanni Appendino and colleagues point out that scientists have known for years that marijuana contains antibacterial substances. However, little research has been done on those ingredients, including studies on their ability to fight antibiotic resistant infections, the scientists say.

To close that gap, researchers tested five major marijuana ingredients termed cannabinoids on different strains of methicillin-resistant Staphylococcus aureus (MRSA), a “superbug” increasingly resistant to antibiotics.

All five substances showed potent germ-killing activity against these drug-resistant strains, as did some synthetic non-natural cannabinoids, they say. The scientists also showed that these substances appear to kill bacteria by different mechanisms than conventional antibiotics, making them more likely to avoid bacterial resistance, the scientists note. At least two of the substances have no known mood-altering effects, suggesting that they could be developed into marijuana-based drugs without causing a “high.””

http://www.sciencedaily.com/releases/2008/09/080908103045.htm

Biologically active cannabinoids from high-potency Cannabis sativa.

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Journal of Natural Products

“Nine new cannabinoids (1-9) were isolated from a high-potency variety of Cannabis sativa. Their structures were identified as (+/-)-4-acetoxycannabichromene (1), (+/-)-3”-hydroxy-Delta((4”,5”))-cannabichromene (2), (-)-7-hydroxycannabichromane (3), (-)-7R-cannabicoumarononic acid A (4), 5-acetyl-4-hydroxycannabigerol (5), 4-acetoxy-2-geranyl-5-hydroxy-3-n-pentylphenol (6), 8-hydroxycannabinol (7), 8-hydroxycannabinolic acid A (8), and 2-geranyl-5-hydroxy-3-n-pentyl-1,4-benzoquinone (9) through 1D and 2D NMR spectroscopy, GC-MS, and HRESIMS. The known sterol beta-sitosterol-3-O-beta-d-glucopyranosyl-6′-acetate was isolated for the first time from cannabis. Compounds 6 and 7 displayed significant antibacterial and antifungal activities, respectively, while 5 displayed strong antileishmanial activity.” http://www.ncbi.nlm.nih.gov/pubmed/19344127

“Biologically Active Cannabinoids from High-Potency Cannabis sativa”  http://pubs.acs.org/doi/abs/10.1021/np900067k

Antibacterial cannabinoids from Cannabis sativa: a structure-activity study.

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Journal of Natural Products

“Marijuana (Cannabis sativa) has long been known to contain antibacterial cannabinoids, whose potential to address antibiotic resistance has not yet been investigated. All five major cannabinoids (cannabidiol (1b), cannabichromene (2), cannabigerol (3b), Delta (9)-tetrahydrocannabinol (4b), and cannabinol (5)) showed potent activity against a variety of methicillin-resistant Staphylococcus aureus (MRSA) strains of current clinical relevance.

Activity was remarkably tolerant to the nature of the prenyl moiety, to its relative position compared to the n-pentyl moiety (abnormal cannabinoids), and to carboxylation of the resorcinyl moiety (pre-cannabinoids). Conversely, methylation and acetylation of the phenolic hydroxyls, esterification of the carboxylic group of pre-cannabinoids, and introduction of a second prenyl moiety were all detrimental for antibacterial activity.

Taken together, these observations suggest that the prenyl moiety of cannabinoids serves mainly as a modulator of lipid affinity for the olivetol core, a per se poorly active antibacterial pharmacophore, while their high potency definitely suggests a specific, but yet elusive, mechanism of activity.” http://www.ncbi.nlm.nih.gov/pubmed/18681481

“Antibacterial Cannabinoids from Cannabis sativa: A Structure−Activity Study”  http://pubs.acs.org/doi/abs/10.1021/np8002673

Poly-ε-caprolactone microspheres as a drug delivery system for cannabinoid administration: development, characterization and in vitro evaluation of their antitumoral efficacy.

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“Cannabinoids show promise for the treatment of various medical conditions such as emesis, anorexia, pain, cancer, multiple sclerosis, Parkinson’s disease and glaucoma.

The objective of the present work was to assess the feasibility of developing cannabinoid loaded poly-ε-caprolactone (PCL) microparticles prepared by the oil-in-water emulsion-solvent evaporation technique as a suitable dosage form for their administration.

In vitro cell viability studies demonstrated the antitumoral activity of CBD released from microparticles. After 4 and 7 days of incubation, CBD in microspheres significantly inhibited the growth of MDA-MB-231 cells by 60% as compared to the 50% attained with free drug.

The results suggest that PCL microparticles could be an alternative delivery system for long-term cannabinoid administration, showing potential therapeutic advantages over free drug.”

http://www.ncbi.nlm.nih.gov/pubmed/22580111