Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors

“Cannabinoids inhibit skin tumor growth in vivo. Here we show that the CB1 and the CB2 receptor are expressed in normal skin and skin tumors of mice and humans. In cell culture experiments pharmacological activation of cannabinoid receptors induced the apoptotic death of tumorigenic epidermal cells, whereas the viability of nontransformed epidermal cells remained unaffected. Local administration of the mixed CB1/CB2 agonist WIN-55,212-2 or the selective CB2 agonist JWH-133 induced a considerable growth inhibition of malignant tumors generated by inoculation of epidermal tumor cells into nude mice. Cannabinoid-treated tumors showed an increased number of apoptotic cells.

 

Cannabinoids, the active components of Cannabis sativa linnaeus (marijuana)…

Marijuana and its derivatives have been used in medicine for many centuries, and currently there is a renaissance in the study of the therapeutic effects of cannabinoids… cannabinoids may be potential antitumoral agents owing to their ability to induce the regression of various types of tumors, including lung adenocarcinoma, glioma, and thyroid epithelioma in animal models.

This background prompted us to explore whether (a) the skin and skin tumors express cannabinoid receptors; (b) cannabinoid receptor activation exerts a growth-inhibiting action on skin tumors in vivo; and (c) inhibition of angiogenesis is implicated in the anti-tumoral effect of cannabinoids.

Our data show that (a) CB1 and CB2 receptors are present in the skin and skin tumors; (b) local cannabinoid receptor activation induces the regression of skin tumors in vivo; and (c) at least two mechanisms may be involved in this action: direct apoptosis of tumor cells and inhibition of tumor angiogenesis.

These results support a new therapeutic approach for the treatment of skin tumors.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC151833/

Revisiting CB1 receptor as drug target in human melanoma.

“Previous studies have indicated the antitumoral effect of human melanocytes, human melanoma cell lines expressing CB1 receptor (CB1), and of the peritumoral administration of endocannabinoids. In the present study, we systematically screened several human melanoma cell lines for the expression of CNR1 and demonstrated transcription of the authentic gene. The product of CNR1, the CB1 protein, was found localized to the cell membrane as well as to the cytoskeleton. Further, the studied human melanoma cell lines expressed functional CB1 since physiological and synthetic ligands, anandamide (AEA), Met-F-AEA, ACEA and AM251 showed a wide range of biological effects in vitro, for example anti-proliferative, proapoptotic and anti-migratory. More importantly, our studies revealed that systemic administration of a stable CB1 agonist, ACEA, into SCID mice specifically inhibited liver colonization of human melanoma cells.

Since therapeutic options for melanoma patients are still very limited, the endocannabinoid-CB1 receptor system may offer a novel target.”

http://www.ncbi.nlm.nih.gov/pubmed/22447182

A Population-based Case-Control Study of Marijuana Use and Head and Neck Squamous Cell Carcinoma

Logo of nihpa

“Marijuana (Cannabis sativa) contains more than 60 unique compounds known as cannabinoids. Cannabinoids, constituents of marijuana smoke, have been recognized to have potential antitumor properties. However, the epidemiological evidence addressing the relationship between marijuana use and the induction of head and neck cancer (HNSCC) is inconsistent and conflicting. An early epidemiological study reported that marijuana use was associated with an elevated risk for head and neck cancer.  However, more recent studies have failed to confirm the association of marijuana use with an increased head and neck cancer risk.

 In fact, many of these studies reported non-significant protective estimates of effect, consistent with a possible anticarcinogenic action of cannabinoids.

A recent epidemiologic review raised the need for additional, well conducted, large studies to clarify the nature of the association of marijuana use with the risk of cancer, especially head and neck cancer. In order to further elucidate the association between marijuana use and head neck cancer risk, we assessed marijuana use in detail in a population-based case-control study.

After adjusting for potential confounders (including smoking and alcohol drinking), 10 to 20 years of marijuana use was associated with a significantly reduced risk of HNSCC.

Our study suggests that moderate marijuana use is associated with reduced risk of HNSCC.”

Dronabinol for supportive therapy in patients with malignant melanoma and liver metastases.

“Loss of appetite and nausea can reduce the quality of life of patients with malignant melanoma and liver metastases. Often established antiemetic drugs fail to bring relief. Tetrahydrocannabinol (THC, Marinol), which is the active agent of Indian hemp, has been used successfully in this situation for other malignant tumors.

PATIENTS AND METHODS:

We treated 7 patients with hematogenous metastatic melanoma and liver metastases suffering from extensive loss of appetite and nausea supportively with dronabinol (Marinol. All of these patients had previously received standard antiemetic therapy without adequate relief. Dronabinol is a synthetic Delta-tetrahydrocannabinol. The drug was administered in capsule form. We evaluated the palliative effects of dronabinol with a special patient evaluation form, which was filled out at the beginning of the therapy and again after 4 weeks.

RESULTS:

The majority of patients described a significant increase in appetite and decrease in nausea. These effects remained for some weeks, but then decreased as metastases progressed and the general condition worsened. All of the patients experienced slight to moderate dizziness, but it was not sufficiently troubling to cause interruption or termination of therapy.

CONCLUSION:

Loss of appetite and nausea due to liver metastases of malignant melanoma can be treated in individual cases supportively with Dronabinol.”

http://www.ncbi.nlm.nih.gov/pubmed/16408219

Peripheral Cannabinoids Attenuate Carcinoma Induced Nociception in Mice

“Cancer pain remains poorly understood and there are no effective therapies…

 We tested whether a local CBr2 agonist produces antinociception. Our findings suggest that a peripheral CBr2 agonist could provide relief for cancer patients. Cannabinoids also potentiate the analgesic effects of morphine and prevent tolerance.

These desirable effects of cannabinoids show promise for management of cancer pain and may lead to improved analgesic therapy.

These findings support the suggestion that cannabinoids are capable of producing antinociception in carcinoma-induced pain.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2771220/

Inhibition of basal and ultraviolet B-induced melanogenesis by cannabinoid CB(1) receptors: a keratinocyte-dependent effect.

“Ultraviolet radiation is the major environmental insult to the skin and stimulates the synthesis of melanin in melanocytes, which then distribute it to the neighboring keratinocytes where it confers photo-protection. Skin color results from the paracrine interaction between these two cell types. Recent studies suggest that endocannabinoids are potential mediators in the skin. Here, we investigated whether cannabinoid drugs play a role in melanogenesis and if ultraviolet radiation modifies the cutaneous endocannabinoid system.

We provide evidence that human melanoma cells (SK-mel-1) express CB(1) receptors… 

Furthermore, ultraviolet-B radiation increased endocannabinoids levels only in keratinocytes, whereas CB(1) cannabinoid receptor expression was up-regulated only in melanoma cells.

Our results collectively suggest that ultraviolet radiation activates paracrine CB(1)-mediated endocannabinoid signaling to negatively regulate melanin synthesis.

The endocannabinoid system in the skin may be a possible target for future therapies in pigmentary disorders.”

http://www.ncbi.nlm.nih.gov/pubmed/21298280

The CB1/CB2 receptor agonist WIN-55,212-2 reduces viability of human Kaposi’s sarcoma cells in vitro.

“Kaposi’s sarcoma is a highly vascularized mesenchymal neoplasm arising with multiple lesions of the skin. Endogenous cannabinoids have been shown to inhibit proliferation of a wide spectrum of tumor cells. We studied the effects of cannabinoids on human Kaposi’s sarcoma cell proliferation in vitro.

 To do so, we first investigated the presence of the cannabinoid receptors CB(1) and CB(2) mRNAs in the human Kaposi’s sarcoma cell line KS-IMM by RT-PCR and, subsequently, the effects of the mixed CB(1)/CB(2) agonist WIN-55,212-2 (WIN) on cell proliferation in vitro. WIN showed antimitogenic effects on Kaposi’s sarcoma cells…

  In view of the antiproliferative effects of cannabinoids on KS-IMM cells, one could envision the cannabinoid system as a potential target for pharmacological treatment of Kaposi’s sarcoma”

http://www.ncbi.nlm.nih.gov/pubmed/19539619

How to Make a Glycerin-Based Medical Marijuana Tincture

" Making your own medical marijuana tincture is a fairly easy process. "

How to Make a Glycerin-Based Medical Marijuana Tincture

“Medical marijuana can come in many forms. A patient can choose his or her preferred method of consumption. Glycerin-based tinctures are very versatile and a great alternative to smoking, vaporizing, or strong-tasting alcohol-based tinctures.

A quality glycerin cannabis tincture can be mixed with any food or beverage and allows patients who need fast relief to place the tincture directly under their tongue. Not only does this method bring fast relief, it also allows patients to control their dosage in a similar manner to smoking their medicine. Although it takes a little time, making your own medical marijuana tincture is a fairly easy process.

Here’s what you will need to get started:
– A crock pot with a “low” and “warm” setting
– Cheesecloth
– Large bowl
– Latex gloves
– Wooden spoon
– 1 gallon of food-grade vegetable glycerin
– 1/4 -1/2 lb of medical marijuana or high quality trim material
– Glass storage container (not pictured)”

Read more: http://bigbudsmag.com/grow/how/article/how-make-glycerin-based-medical-marijuana-tincture-january-2013

Marijuana Compound May Beat Antipsychotics at Treating Schizophrenia

“A certain marijuana compound known as cannabidiol (CBD) can treat schizophrenia as well as antipsychotic drugs, with far fewer side effects, according to a preliminary clinical trial.”

Read more: http://psychcentral.com/news/2012/06/07/marijuana-compound-may-beat-antipsychotics-at-treating-schizophrenia/39803.html

Doctors utilise marijuana as pain relief

“A pair of scientists at California Pacific Medical Center in San Francisco has found that a compound derived from marijuana could stop metastasis in many kinds of aggressive cancer, potentially altering the fatality of the disease forever.

“It took us about 20 years of research to figure this out, but we are very excited,” said Pierre Desprez, one of the scientists behind the discovery. The finding, which has already undergone both laboratory and animal testing, and is awaiting permission for clinical trials in humans.

Desprez, a molecular biologist, spent decades studying ID-1, the gene that causes cancer to spread. Fellow researcher  Sean McAllister was studying the effects of Cannabidiol, or CBD, a non-toxic, non-psychoactive chemical compound found in the cannabis plant. Finally, the pair collaborated, combining CBD and cells containing high levels of ID-1 in a petri dish.

“What we found was that his Cannabidiol could essentially ‘turn off’ the ID-1,” Desprez told HuffPost. The cells stopped spreading and returned to normal.

“We likely would not have found this on our own,” he added. “That’s why collaboration is so essential to scientific discovery.”

Desprez and McAllister’s findings was first published in 2007. Since then, their team has found that CBD works both in the lab and in animals. And now, they’ve found even more good news.

“We started by researching breast cancer. But now we’ve found that Cannabidiol works with many kinds of aggressive cancers–brain, prostate–any kind in which these high levels of ID-1 are present.”

“We’ve found no toxicity in the animals we’ve tested, and Cannabidiol is already used in humans for a variety of other ailments,” he said. Indeed, the compound is used to relieve anxiety and nausea, and, since it is non-psychoactive, does not cause the “high” associated with THC.

While marijuana advocates will surely praise the discovery, Desprez explained that it’s not so easy as just lighting up. “We used injections in the animal testing and are also testing pills. But you could never get enough Cannabidiol for it to be effective just from smoking.”

Furthermore, the team has started synthesizing the compound in the lab instead of using the plant in an effort to make it more potent.”It’s a common practice. But hopefully it will also keep us clear of any obstacles while seeking approval.””

By Sola Ogundipe

http://www.vanguardngr.com/2013/01/doctors-utilise-marijuana-as-pain-relief/