Tag Archives: CB(1) and CB(2) receptors

Anticancer activity of anandamide in human cutaneous melanoma cells.

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“Cannabinoids are implicated in the control of cell proliferation, but little is known about the role of the endocannabinoid system in human malignant melanoma. This study was aimed at characterizing the in vitro antitumor activity of anandamide (AEA) in A375 melanoma cells…

 Overall, these findings demonstrate that AEA induces cytotoxicity against human melanoma cells in the micromolar range of concentrations through a complex mechanism, which involve COX-2 and LOX-derived product synthesis and CB1 activation. Lipid raft modulation, probably linked to GPR55 activation, might also have a role.”

http://www.ncbi.nlm.nih.gov/pubmed/24041928

Towards a better Cannabis drug.

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“Opium smoking has been mostly replaced by i.v. injection of morphine and heroin and we see cocaine sniffing rather than chewing of coca leaves. Cannabis use – be it of marijuana, hashish or bhang – differs.

Any cannabis cognoscente will insist that the crude material is ‘much better’ than pure Δ9 – tetrahydrocannabinol (THC), the only major psychoactive constituent of cannabis (Mechoulam et al., 1970).

Indeed, although pure THC is available as a drug (named Dronabinol) it is apparently not used illicitly.

The pharmacological/biochemical basis for this difference is not clear and is presumably due to several factors. A major reason seems to be the pharmacokinetic difference between cannabis smoking and the oral administration of THC.

 On smoking, the cannabis effects are noted almost immediately, while a 1.5 – 2 hour delay is observed on oral administration.

A further factor may be conditioning to the smell, although there are no published data along these lines. A further factor may be the presence of the terpenoid CB2 agonist beta-caryophyllene in cannabis (Gertsch et al., 2008).

CB2 agonists are well known to cause numerous effects (mostly of a protective nature) which may counteract some of the effects of THC (Pacher & Mechoulam, 2011).”

http://www.ncbi.nlm.nih.gov/pubmed/24024867

Cannabinoid receptors as a target for therapy of ovarian cancer

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“Ovarian cancer represents one of the leading cause of cancer-relateddeaths for women and is the most common gynecologic malignancy.In spite of relative low morbidity, ovarian cancer has a highfatality ratio, with overall 5-year survival of less than 30%.At present, there are inadequate treatment options for the managementof advanced ovarian cancer, and therefore development of novelapproaches for treatment of this disease are needed.

Cannabinoids,the active components of Cannabis sativa linnaeous and their derivatives have received considerable attention in recent yearsdue to their diverse pharmacological activities such as cell growth inhibition and tumor regression. To date, two differentcannabinoid receptors have been characterized and cloned frommammalian tissues: the “central” CB1 receptor and the “peripheral”CB2 receptor…

These results support a new therapeutic approach for the treatmentof ovarian cancer. It is also conceivable that with available cannabinoids as lead compounds, non-habit forming agents that have higher biological effects could be developed.”

http://www.aacrmeetingabstracts.org/cgi/content/abstract/2006/1/1084

http://cancerres.aacrjournals.org/content/66/8_Supplement/1084.1

Active Chemicals in Cannabis Inhibits Prostate Cancer Cell Growth

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“According to researchers, active chemicals in cannabis inhibits prostate cancer cell growth…

cannabis

Professor Ines Diaz-Laviada, study author said: “Our research shows that there are areas on prostate cancer cells which can recognize and talk to chemicals found in cannabis called cannabinoids. These chemicals can stop the division and growth of prostate cancer cells and could become a target for new research into potential drugs to treat prostate cancer.””  http://www.elements4health.com/active-chemicals-in-cannabis-inhibits-prostate-cancer-cell-growth.html

“Inhibition of human tumour prostate PC-3 cell growth by cannabinoids R(+)-Methanandamide and JWH-015: Involvement of CB2″ http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2743360/

“Delta9-tetrahydrocannabinol induces apoptosis in human prostate PC-3 cells via a receptor-independent mechanism.” http://www.ncbi.nlm.nih.gov/pubmed/10570948

The endocannabinoid system in advanced liver cirrhosis: pathophysiological implication and future perspectives.

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“Endogenous cannabinoids (EC) are ubiquitous lipid signalling molecules providing different central and peripheral effects that are mediated mostly by the specific receptors CB1 and CB2. The EC system is highly upregulated during chronic liver disease and consistent experimental and clinical findings indicate that it plays a role in the pathogenesis of liver fibrosis and fatty liver disease associated with obesity, alcohol abuse and hepatitis C.

Furthermore, a considerable number of studies have shown that EC and their receptors contribute to the pathogenesis of the cardio-circulatory disturbances occurring in advanced cirrhosis, such as portal hypertension, hyperdynamic circulatory syndrome and cirrhotic cardiomyopathy.

More recently, the EC system has been implicated in the development of ascites, hepatic encephalopathy and the inflammatory response related to bacterial infection. Rimonabant, a selective CB1 antagonist, was the first drug acting on the EC system approved for the treatment of obesity. Unfortunately, it has been withdrawn from the market because of its neuropsychiatric side effects.

Compounds able to target selectively the peripheral CB1 receptors are under evaluation.

In addition, molecules stimulating CB2 receptor or modulating the activity of enzymes implicated in EC metabolism are promising areas of pharmacological research.

Liver cirrhosis and the related complications represent an important target for the clinical application of these compounds.”

http://www.ncbi.nlm.nih.gov/pubmed/23890208

Anti-inflammatory activity of topical THC in DNFB-mediated mouse allergic contact dermatitis independent of CB1 and CB2 receptors.

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“∆9 -Tetrahydrocannabinol (THC), the active constituent of Cannabis sativa, exerts its biological effects in part through the G-protein-coupled CB1 and CB2 receptors, which were initially discovered in brain and spleen tissue, respectively. However, THC also has CB1/2 receptor-independent effects. Because of its immune-inhibitory potential, THC and related cannabinoids are being considered for the treatment of inflammatory skin diseases.

Here we investigated the mechanism of the anti-inflammatory activity of THC and the role of CB1 and CB2 receptors…

CONCLUSIONS:

Topically applied THC can effectively attenuate contact allergic inflammation by decreasing keratinocyte-derived pro-inflammatory mediators that orchestrate myeloid immune cell infiltration independent of CB1/2 receptors.

This has important implications for the future development of strategies to harness cannabinoids for the treatment of inflammatory skin diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/23889474

Effects of anandamide in migraine: data from an animal model

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“Endocannabinoid system seems to be involved in the modulation of NTG-induced hyperalgesia, and probably, in the pathophysiological mechanisms of migraine…

The study confirms that a dysfunction of the endocannabinoid system may contribute to the development of migraine attacks and that a pharmacological modulation of CB receptors can be useful for the treatment of migraine pain…

By combining our data with the findings available from the literature, we can hypothesize that a dysfunction of the endocannabinoid system may contribute to the development of migraine attacks and that a specific pharmacological modulation of CB1 and CB2 receptors may be useful for the treatment of migraine pain, without deleterious effects, as well as of specific associated symptoms (nausea, in primis).”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3072518/

Marijuana may block Alzheimer’s

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“The active ingredient in marijuana may stall decline from Alzheimer’s disease, research suggests.” 

Brain

 

“Scientists showed a synthetic version of the compound may reduce inflammation associated with Alzheimer’s and thus help to prevent mental decline.

They hope the cannabinoid may be used to develop new drug therapies.”

More: http://news.bbc.co.uk/2/hi/health/4286435.stm

[Marihuana and cannobinoids as medicaments].

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“Biological activity of cannabinoids is caused by binding to two cannabinoid receptors CB1 and CB2. Psychoactive is not only tetrahydrocannabinol (THC) but also: cannabidiol, cannabigerol or cannabichromen.

Formerly, the usefulness of hemp was assessed in the relation to temporary appeasement of the symptoms of some ailments as nausea or vomiting.

Present discoveries indicates that cannabis-based drugs has shown ability to alleviate of autoimmunological disorders such as: Multiple sclerosis (MS), Rheumatoid arthritis (RA) or inflammatory bowel disease.

Another studies indicates that cannabinoids play role in treatment of neurological disorders like Alzheimer disease or Amyotrophic lateral sclerosis (ALS) or even can reduce spreading of tumor cells.

Cannabinoids stand out high safety profile considering acute toxicity, it is low possibility of deadly overdosing and side-effects are comprise in range of tolerated side-effects of other medications.

In some countries marinol and nabilone are used as anti vomiting and nausea drug. First cannabis-based drug containg naturally occurring cannabinoids is Sativex. Sativex is delivered in an mucosal spray for patients suffering from spasticity in MS, pain relevant with cancer and neuropathic pain of various origin.

Cannabis side-effects varies and depend from several factors like administrated dose, rout of administration and present state of mind. After sudden break from long-lasting use, withdrawal symptoms can appear, although they entirely disappear after a week or two.”

http://www.ncbi.nlm.nih.gov/pubmed/23421098

Therapeutic Utility of Cannabinoid Receptor Type 2 (CB2) Selective Agonists.

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“The cannabinoid receptor type 2 (CB2), is a class A GPCR that was cloned in 1993 while looking for an alternate receptor that could explain the pharmacological properties of 9- tetrahydrocannabinol. CB2 was identified among cDNAs based on its similarity in amino-acid sequence to the CB1 receptor and helped provide an explanation for the established effects of cannabinoids on the immune system.

In addition to the immune system, CB2 has widespread tissue expression and has been found in brain, PNS and GI tract. Several “mixed” cannabinoid agonists are currently in clinical use primarily for controlling pain and it is believed that selective CB2 agonism may afford a superior analgesic agent devoid of the centrally mediated CB1 effects.

Thus, selective CB2 receptor agonists represent high value putative therapeutics for treating pain and other disease states. In this perspective, we seek to provide a concise update of progress in the field.”

http://www.ncbi.nlm.nih.gov/pubmed/23865723