[Expression of cannabinoid receptor 2 in squamous cell carcinoma].

“The expression of CB2 protein and mRNA levels were detected in normal human skin and squamous cell carcinoma… Both the normal skin and squamous cell carcinoma expressed CB2, which was localized mainly in the basal cell layer and prickle cell layer in human skin with low expressions in the subcutaneous tissue.

 

CONCLUSION:

Squamous cell carcinoma over-expresses CB2 at both the protein and mRNA levels. High expression of CB2 in squamous cell carcinoma suggests an important role of CB2 in the tumorigenesis and development of squamous cell carcinoma.”

http://www.ncbi.nlm.nih.gov/pubmed/20335147

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/

Cannabidiol bioavailability after nasal and transdermal application: effect of permeation enhancers.

“The nonpsychoactive cannabinoid, cannabidiol (CBD), has great potential for the treatment of chronic and ‘breakthrough’ pain that may occur in certain conditions like cancer. To fulfill this goal, suitable noninvasive drug delivery systems need to be developed for CBD. Chronic pain relief can be best achieved through the transdermal route, whereas ‘breakthrough’ pain can be best alleviated with intranasal (IN) delivery. Combining IN and transdermal delivery for CBD may serve to provide patient needs-driven treatment in the form of a nonaddictive nonopioid therapy.

CONCLUSION:

The results of this study indicated that CBD could be successfully delivered through the IN and transdermal routes.”

http://www.ncbi.nlm.nih.gov/pubmed/20545522

The association of N-palmitoylethanolamine with the FAAH inhibitor URB597 impairs melanoma growth through a supra-additive action.

“The incidence of melanoma is considerably increasing worldwide. Frequent failing of classical treatments led to development of novel therapeutic strategies aiming at managing advanced forms of this skin cancer. Additionally, the implication of the endocannabinoid system in malignancy is actively investigated…

CONCLUSIONS:

This study suggests the interest of targeting the endocannabinoid system in the management of skin cancer and underlines the advantage of associating endocannabinoids with enzymatic hydrolysis inhibitors.

This may contribute to the improvement of long-term palliation or cure of melanoma.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3364151/

The antimitogenic effect of the cannabinoid receptor agonist WIN55212-2 on human melanoma cells is mediated by the membrane lipid raft.

“Here are reported the antiproliferative effects of the cannabinoid agonist WIN upon human melanoma cells expressing mRNA and protein for both CB1 and CB2 receptors.

While WIN exerted antimitogenic effects, selective CB1 or CB2 agonists were unable to reproduce such effects and selective CB1 and CB2 antagonists did not inhibit WIN-induced cell death. Cells treated with WIN, preincubated with the lipid raft disruptor methylcyclodestrin, were rescued from death. WIN induced activation of caspases and phosphorylation of ERK that were attenuated in cultures treated with methylcyclodestrin.

 Membrane lipid raft complex-mediated antimitogenic effect of WIN in melanoma could represents a potential targets for a melanoma treatment.”

http://www.ncbi.nlm.nih.gov/pubmed/21807457

Cannabidiol Inhibits Growth and Induces Programmed Cell Death in Kaposi Sarcoma–Associated Herpesvirus-Infected Endothelium

“Kaposi sarcoma is the most common neoplasm caused by Kaposi sarcoma–associated herpesvirus (KSHV). Current treatments for Kaposi sarcoma can inhibit tumor growth but are not able to eliminate KSHV from the host. When the host’s immune system weakens, KSHV begins to replicate again, and active tumor growth ensues. New therapeutic approaches are needed.

Cannabidiol (CBD), a plant-derived cannabinoid, exhibits promising antitumor effects without inducing psychoactive side effects. CBD is emerging as a novel therapeutic for various disorders, including cancer.

In this study, we investigated the effects of CBD both on the infection of endothelial cells (ECs) by KSHV and on the growth and apoptosis of KSHV-infected ECs, an in vitro model for the transformation of normal endothelium to Kaposi sarcoma….

Cannabidiol (CBD) was first isolated in 1940. It is a major component of the plant Cannabis sativa, which is also the source of Δ9-tetrahydrocannabinol (Δ9-THC). Due to its multiple biological activities, CBD has been identified as a potential clinical agent. Moreover, CBD affects these activities without the psychoactive side effects that typify Δ9-THC. Recent studies have documented the potential antitumorigenic properties of CBD in the treatment of various neoplasms, including breast cancer, lung cancer, bladder cancer, glioblastoma,and leukemia.CBD induces these effects through a variety of mechanisms and signaling pathways

CBD has been evaluated clinically for the treatment of various conditions, including anxiety, psychosis, and pain. In contrast to other members of the cannabinoid family, CBD has a strong safety profile and induces no psychotropic effects.Therefore, it has become an attractive agent in the search for new anticancer therapies.Our current study demonstrated that CBD preferentially enhanced apoptosis and inhibited the proliferation of KSHV-infected endothelial cells. This selective targeting of KSHV-induced neoplasia suggests that CBD may have a desirable therapeutic index when used to treat cancer. Moreover, a recent study demonstrated that CBD can be delivered effectively by nasal and transdermal routes, which may be particularly valuable for the treatment of Kaposi sarcoma oral or skin lesions.”

Full text: http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3527984/

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

Kaposi Sarcoma.

“Kaposi sarcoma (KS) is a low-grade vascular tumor associated with Kaposi sarcoma herpesvirus/human herpesvirus 8 (KSHV/HHV8) infection. Kaposi sarcoma lesions predominantly present at mucocutaneous sites, but may involve all organs and anatomic locations. Recognized epidemiologic-clinical forms of KS include classic, African (endemic), AIDS-associated (epidemic), and iatrogenic KS. New clinical manifestations have been described, such as antiretroviral therapy-related KS regression or flares. Kaposi sarcoma lesions evolve from early (patch stage) macules into plaques (plaque stage) that grow into larger nodules (tumor stage). Newer histologic variants include anaplastic, hyperkeratotic, lymphangioma-like, bullous, telangiectatic, ecchymotic, keloidal, pyogenic granuloma-like, micronodular, intravascular, glomeruloid and pigmented KS, as well as KS with sarcoidlike granulomas and KS with myoid nodules. Latency-associated nuclear antigen (HHV8) is the most specific immunohistochemical marker available to help distinguish KS from its mimics. Since KS remains one of the most common AIDS-defining malignancies, it is important that pathologists be able to recognize KS and its contemporary manifestations.”

http://www.ncbi.nlm.nih.gov/pubmed/23368874

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/