Tag Archives: cannabinoid receptors

Delta–9 Tetrahydrocannabinol inhibits growth and metastasis of lung cancer – Harvard University

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“Lung cancer is the major cause of cancer-related mortality worldwide.Many of these over-express epidermal growth factor receptor(EGFR), and are usually highly aggressive and resistant to chemotherapy.

Recent studies have shown that {Delta}-9 Tetrahydrocannabinol (THC),the major component of Cannabis sativa, possess anti-tumor propertiesagainst various types of cancers.

 However, not much is knownabout its effect on lung cancer. In this study, we sought tocharacterize the effect of THC on EGF-induced growth and metastasisof human non small lung cancer cell (NSCLC) lines A549 and SW-1573.

We demonstrate that these cell lines and primary tumor samplesderived from lung cancer patients express cannabinoids receptorsCB1 and CB2, the known targets for THC action. We further showthat THC inhibits EGF-induced growth in these cell lines. Inaddition THC attenuated EGF-stimulated chemotaxis and chemoinvasion.Next we characterized the effect of THC on in vivo lung cancergrowth and metastasis in a murine model. A549 cells were implantedin SCID mice (n=6 per group) through subcutaneous and intravenousinjections to generate subcutaneous and lung metastatic cancer,respectively. THC (5mg/kg body wt.) was administered once dailythrough intraperitoneal injections for 21 days. The mice wereanalyzed for tumor growth and lung metastasis.

 A significantreduction (~50%) in tumor weight and volume were observed inTHC treated animals compared to the vehicle treated animals.THC treated animals also showed a significant (~60%) reductionin macroscopic lesions on the lung surface in comparison tovehicle treated control. Immunohistochemical analysis of thetumor samples from THC treated animals revealed anti-proliferativeand anti-angiogenic effects of THC with significant reductionin staining for Ki67, a proliferative marker and CD31, an endothelialmarker indicative of vascularization. Investigation into thesignaling events associated with reduced EGF-induced functionaleffects revealed that THC also inhibits EGF-induced Akt phosphorylation.Akt is a central signaling molecule of EGFR-mediated signalingpathways and it regulates a diverse array of cellular functions,including proliferation, angiogenesis, invasion and apoptosis.

Cumulatively, these studies indicate that THC has anti-tumorigenic and anti-metastatic effects against lung cancer. Novel therapies against EGFR overexpressing, aggressive and chemotherapy resistant lung cancers may include targeting the cannabinoids receptors.”

http://www.aacrmeetingabstracts.org/cgi/content/meeting_abstract/2007/1_Annual_Meeting/4749%20?maxtoshow&hits=80&RESULTFORMAT&fulltext=cannabinoid&searchid=1&FIRSTINDEX=1760&resourcetype=HWCIT

Marijuana Derivative May Offer Hope in Cocaine Addiction – TIME

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“A new study in mice has found that activating a receptor affected by marijuana can dramatically reduce cocaine consumption. The research suggests that new anti-addiction drugs might be developed using synthetic versions of cannabidiol (CBD), the marijuana component that activates the receptor—or even by using the purified natural compound itself.

Researchers formerly believed that the receptor, known as CB2, was not found in the brain and that therefore CBD had no psychoactive effects. But a growing body of research suggests otherwise. After THC, CBD is the second most prevalent active compound in marijuana.”

More: http://healthland.time.com/2011/07/26/marijuana-derivative-may-offer-hope-in-cocaine-addiction/

Marijuana tied to better blood sugar control – NBC

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“People who had used marijuana in the past month had smaller waists and lower levels of insulin resistance – a diabetes precursor – than those who never tried the drug, in a new study.

The findings, based on surveys and blood tests of about 4,700 U.S. adults, aren’t enough to prove marijuana keeps users thin or wards off disease. And among current pot smokers, higher amounts of marijuana use weren’t linked to any added health benefits, researchers reported in The American Journal of Medicine.

“These are preliminary findings,” said Dr. Murray Mittleman, who worked on the study at Beth Israel Deaconess Medical Center in Boston.

“It looks like there may be some favorable effects on blood sugar control, however a lot more needs to be done to have definitive answers on the risks and potential benefits of marijuana usage.”

Although pot smoking is a well-known cause of “the munchies,” some previous studies have found marijuana users tend to weigh less than other people, and one suggested they have a lower rate of diabetes. Trials in mice and rats hint that cannabis and cannabinoid receptors may influence metabolism.”

More: http://www.nbcnews.com/id/51981899

New study suggests marijuana prevents diabetes

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“A provocative study comes right as Massachusetts begins a new medical marijuana law. The theory? Using pot could lower your risk of diabetes.

We’ve all heard about “the munchies,” that urge to eat more when under the influence of marijuana.

But a new study published by the American Journal of Medicine finds despite the habit among recreational pot users to take in more calories, it doesn’t lead to weight gain. And the benefits of marijuana don’t end there.

“What we saw was that people who were current users of marijuana had improved sensitivity to insulin compared to non-users, they had better good cholesterol, and reduced waist circumference,” said Dr. Murray Mittleman, lead author and researcher at Harvard Medical School.

The research included more than 4,600 men and women participating in a national nutrition survey in the last decade. Marijuana users maintained more normal blood sugar levels compared to non-users, which meant their bodies were regulating insulin well. That puts them at a lower diabetes risk.

“When somebody smokes marijuana there are a variety of compounds that are present in marijuana, some of which may partially block some of the receptors as well as stimulate others, which is why people use it presumably,” said Mittleman.

Blocking certain receptors could be what’s behind the health benefits found in the study. Researchers say the findings point to the importance of more marijuana research.

“We just had the medical marijuana passed here in Massachusetts. But two states now have recreational use approved and we really are opening up the doors to the use of this drug. Yet we don’t have the information that we need to make sensible recommendations,” said Mittleman.

As for the latest findings, could marijuana be the next diabetes drug?”

http://www.wcvb.com/news/investigative/new-study-suggests-marijuana-prevents-diabetes/-/12520878/20364894/-/bu6cmu/-/index.html

Is marijuana good for your health? New study shows benefits

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“People who had used marijuana in the past month had smaller waists and lower levels of insulin resistance – a diabetes precursor – than those who never tried the drug, in a new study.

“These are preliminary findings,” said Dr. Murray Mittleman, who worked on the study at Beth Israel Deaconess Medical Center in Boston. 

“It looks like there may be some favorable effects on blood sugar control, however a lot more needs to be done to have definitive answers on the risks and potential benefits of marijuana usage.”

Although pot smoking is a well-known cause of “the munchies,” some previous studies have found marijuana users tend to weigh less than other people, and one suggested they have a lower rate of diabetes. Trials in mice and rats hint that cannabis and cannabinoid receptors may influence metabolism.”
 

Cannabidiol (CBD): Fighting Inflammation & Aggressive Forms of Cancer

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“Marijuana contains at least 60 known chemicals called cannabinoids, which activate cannabinoid receptors in your body. Tetrahydrocannabinol, or THC, is the main component responsible for the psychoactive effects, or “high,” marijuana is known for. While THC is known to have some medicinal value, there has been recent investigation into a new cannabinoid that is rumored to have more medicinal benefits than any single pharmaceutical drug on the market.”

“What is Cannabidiol (CBD)?

This cannabinoid is known as Cannabidiol (CBD), and is the second most abundant cannabinoid in cannabis. Research done by G.W. Pharmaceuticals suggests that CBD could be used for treating symptoms of rheumatoid arthritis and other autoimmune diseases, diabetes, nausea, bowel disorders, and many other hard-to-control side effects. According to an article from Projectcbd.com, CBD has even demonstrated neuroprotective effects, and its anti-cancer potential is currently being explored.

While it was originally believed that THC is a breakdown product of CBD, it is now known that both THC and CBD are actually metabolites of their decarboxylated acidic forms, THCa and CBDa. These acidic precursors are decarboxylated (essentially dried) by heat or extraction to produce THC and CBD; only then do they become psychoactive. The compound has medicinal benefits without the “high” that some patients do not desire. This makes CBD appealing to patients who are looking for an alternative to their current meds, which often have opiate-like effects.”

More: http://www.medicaljane.com/2012/12/20/cannabidiol-cbd-medicine-of-the-future/

Study: Cannabinoids Offer Likely Therapeutic Option For Patients With Post-Traumatic Stress

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“Future research targeting cannabinoids and their receptors may lead to evidence-based treatments for patients diagnosed with post-traumatic stress disorder (PTSD), according to clinical trial data published in May in the journal Molecular Psychiatry.

Investigators at the New York University School of Medicine reported that subjects diagnosed with PTSD typically possess elevated quantities of endogenous cannabinoid receptors in regions of the brain associated with fear and anxiety. Investigators also determined that many of these subjects experience a decrease in their natural production of anandamide, an endogenous cannabinoid neurotransmitter, resulting in an imbalanced endocannibinoid regulatory system.

Researchers speculated that an increase in the body’s production of cannabinoids would likely restore subjects’ natural brain chemistry and psychological balance. They affirmed, “[Our] findings substantiate, at least in part, emerging evidence that … plant-derived cannabinoids such as marijuana may possess some benefits in individuals with PTSD by helping relieve haunting nightmares and other symptoms of PTSD.”

Authors concluded: “The data reported herein are the first of which we are aware of to demonstrate the critical role of CB1 (cannabinoid) receptors and endocannabinoids in the etiology of PTSD in humans. As such, they provide a foundation upon which to develop and validate informative biomarkers of PTSD vulnerability, as well as to guide the rational development of the next generation of evidence-based treatments for PTSD.”

More: http://norml.org/news/2013/05/30/study-cannabinoids-offer-likely-therapeutic-option-for-patients-with-post-traumatic-trauma

[From cannabis to selective CB2R agonists: molecules with numerous therapeutical virtues].

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“Originally used in Asia for the treatment of pain, spasms, nausea and insomnia, marijuana is the most consumed psychotropic drug worldwide. The interest of medical cannabis has been reconsidered recently, leading to many scientific researches and commercialization of these drugs.

Natural and synthetic cannabinoids display beneficial antiemetic, anti-inflammatory and analgesic effects in numerous diseases, however accompanied with undesirable effects due to the CB1 receptor. Present researches focus on the design of therapeutical molecules targeting the CB2 receptors, and thus avoiding central side effects and therefore psychotropic effects caused by the CB1 receptor.”

http://www.ncbi.nlm.nih.gov/pubmed/23732102

Association between Cannabinoid CB1 Receptor Expression and Akt Signalling in Prostate Cancer

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“In prostate cancer, tumour expression of cannabinoid CB1 receptors is associated with a poor prognosis. One explanation for this association comes from experiments with transfected astrocytoma cells, where a high CB receptor expression recruits the Akt signalling survival pathway. In the present study, we have investigated the association between CB1 receptor expression and the Akt pathway in a well-characterised prostate cancer tissue microarray.

Conclusions/Significance

The present study provides data that is consistent with the hypothesis that at a high CB1 receptor expression, the Akt signalling pathway becomes operative.”

Full Text: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0065798

Transient changes in the endocannabinoid system after acute and chronic ethanol exposure and abstinence in the rat: a combined PET and microdialysis study.

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“Recent biochemical and post-mortem evidence suggests involvement of the endocannabinoid system in alcohol drinking behaviour and dependence…

CONCLUSION:

This study provides in vivo evidence that acute ethanol consumption is associated with enhanced endocannabinoid signalling in the NAcc, indicated by an increased CB1R binding and AEA content. In addition, chronic ethanol exposure leads to regional dysfunctions in CB1R levels, involving the hippocampus and caudate-putamen that are reversible within 2 weeks in this animal model.”

http://www.ncbi.nlm.nih.gov/pubmed/23740372