Tag Archives: cancer

Inhibition of cancer cell invasion by cannabinoids via increased expression of tissue inhibitor of matrix metalloproteinases-1.

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JNCI: Journal of the National Cancer Institute

“Cannabinoids, in addition to having palliative benefits in cancer therapy, have been associated with anticarcinogenic effects. Although the antiproliferative activities of cannabinoids have been intensively investigated, little is known about their effects on tumor invasion.”

“Increased expression of TIMP-1 mediates an anti-invasive effect of cannabinoids. Cannabinoids may therefore offer a therapeutic option in the treatment of highly invasive cancers.”

“There is considerable evidence to suggest an important role for cannabinoids in conferring anticarcinogenic activities. In this study, we identified TIMP-1 as a mediator of the anti-invasive actions of MA, a hydrolysis-stable analog of the endocannabinoid anandamide, and THC, a plant-derived cannabinoid.”

“In conclusion, our results suggest that there exists a signaling pathway by which the binding of cannabinoids to specific receptors leads via intracellular MAPK activation to induction of TIMP-1 expression and subsequent inhibition of tumor cell invasion. To our knowledge, this is the first report of TIMP-1–dependent anti-invasive effects of cannabinoids.”

http://jnci.oxfordjournals.org/content/100/1/59.long

Antiangiogenic activity of the endocannabinoid anandamide: correlation to its tumor-suppressor efficacy.

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  “Endocannabinoids are now emerging as suppressors of key cell-signaling pathways involved in cancer cell growth, invasion, and metastasis. We have previously observed that the metabolically stable anandamide analog, 2-methyl-2′-F-anandamide (Met-F-AEA) can inhibit the growth of thyroid cancer in vivo. Our hypothesis was that the anti-tumor effect observed could be at least in part ascribed to inhibition of neo-angiogenesis… our results suggest that anandamide could be involved in the control of cancer growth targeting both tumor cell proliferation and the angiogenic stimulation of the vasculature.”

http://www.ncbi.nlm.nih.gov/pubmed/17192847

Nabilone: an effective antiemetic in patients receiving cancer chemotherapy.

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Abstract

“Eighty evaluable patients receiving chemotherapy were entered on a random prospective double-blind study to evaluate the effectiveness of nabilone, a synthetic cannabinoid, compared to prochlorperazine. Most of these patients received cisplatin, a drug that universally produces severe nausea and vomiting, as part of a combination chemotherapy regimen. The patients served as their own controls, receiving either nabilone or prochlorperazine during two consecutive treatment courses with the identical chemotherapy. Side effects consisting of hypotension and lethargy were more pronounced with nabilone. Toxicity, in general, did not preclude antiemetic treatment and in no way interfered with chemotherapy. Sixty patients (75 per cent) reported nabilone to be more effective than prochlorperazine for relief of nausea and vomiting. Of these 60 patients, 46 required further chemotherapy and continued taking nabilone as the antiemetic of choice.”

http://www.ncbi.nlm.nih.gov/pubmed/6271844

Recent advantages in cannabinoid research.

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Abstract

“Although the active component of cannabis Delta9-THC was isolated by our group 35 years ago, until recently its mode of action remained obscure. In the last decade it was established that Delta9-THC acts through specific receptors – CB1 and CB2 – and mimics the physiological activity of endogenous cannabinoids of two types, the best known representatives being arachidonoylethanolamide (anandamide) and 2-arachidonoylglycerol (2-AG). THC is officially used against vomiting caused by cancer chemotherapy and for enhancing appetite, particularly in AIDS patients. Illegally, usually by smoking marijuana, it is used for ameliorating the symptoms of multiple sclerosis, against pain, and in a variety of other diseases. A synthetic cannabinoid, HU-211, is in advanced clinical tests against brain damage caused by closed head injury. It may prove to be valuable against stroke and other neurological diseases.”

http://www.ncbi.nlm.nih.gov/pubmed/10575284

Marijuana as antiemetic medicine: a survey of oncologists’ experiences and attitudes.

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Abstract

“A random-sample, anonymous survey of the members of the American Society of Clinical Oncology (ASCO) was conducted in spring 1990 measuring the attitudes and experiences of American oncologists concerning the antiemetic use of marijuana in cancer chemotherapy patients. The survey was mailed to about one third (N = 2,430) of all United States-based ASCO members and yielded a response rate of 43% (1,035). More than 44% of the respondents report recommending the (illegal) use of marijuana for the control of emesis to at least one cancer chemotherapy patient. Almost one half (48%) would prescribe marijuana to some of their patients if it were legal. As a group, respondents considered smoked marijuana to be somewhat more effective than the legally available oral synthetic dronabinol ([THC] Marinol; Unimed, Somerville, NJ) and roughly as safe. Of the respondents who expressed an opinion, a majority (54%) thought marijuana should be available by prescription. These results bear on the question of whether marijuana has a “currently accepted medical use,” at issue in an ongoing administrative and legal dispute concerning whether marijuana in smoked form should be available by prescription along with synthetic THC in oral form. This survey demonstrates that oncologists’ experience with the medical use of marijuana is more extensive, and their opinions of it are more favorable, than the regulatory authorities appear to have believed.”

http://www.ncbi.nlm.nih.gov/pubmed/2045870

Delta-9-tetrahydrocannabinol in cancer chemotherapy: research problems and issues.

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Abstract

“A critical review of the literature assessing the antiemetic efficacy of delta-9-tetrahydrocannabinol (THC) in patients receiving cancer chemotherapy showed considerable inconsistency in results. The equivocal nature of these results partly reflects the difficulty of doing research on antiemetic therapies, but also can be attributed to differences in the adequacy and nature of the research designs, procedures, and assessment instruments that have been used. Several factors were also identified that are seldom studied but may be important in determining whether THC will be effective: patient variables, such as chemotherapy regimen and age; pharmacologic variables, such as drug tolerance, dose, schedule, toxicity, route of administration, and drug interactions; and environmental variables associated with administration setting. The need to differentiate pharmacologically induced from conditioned nausea and vomiting was also pointed out. We believe that THC does have antiemetic efficacy, but the lack of controlled research does not allow precise knowledge of its true effectiveness and toxicity. Well-controlled trials are needed to help answer some of these questions.”

http://www.ncbi.nlm.nih.gov/pubmed/6305249

Amelioration of cancer chemotherapy-induced nausea and vomiting by delta-9-tetrahydrocannabinol.

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Abstract

“The antinausea and antivomiting effects of delta-9-tetrahydrocannabinol (THC) in children receiving cancer chemotherapy were compared with those of metoclopramide syrup and prochlorperazine tablets in two double-blind studies. THC was found to be a significantly better antinausea and antivomiting agent… In some patients, THC enhanced appetite during a course of chemotherapy. In two patients, a “high” associated with THC administrationwas reported. Drowsiness was reported significantly more frequently with THC.”

http://www.ncbi.nlm.nih.gov/pubmed/231736

An efficient new cannabinoid antiemetic in pediatric oncology.

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Abstract

“Delta-8-tetrahydrocannabinol (delta-8-THC), a cannabinoid with lower psychotropic potency than the main Cannabis constituent, delta-9-tetrahydrocannabinol (delta-9-THC), was administered (18 mg/m2 in edible oil, p.o.) to eight children, aged 3-13 years with various hematologic cancers, treated with different antineoplastic drugs for up to 8 months. The total number of treatments with delta-8-THC so far is 480. The THC treatment started two hours before each antineoplastic treatment and was continued every 6 hrs for 24 hours. Vomiting was completely prevented. The side effects observed were negligible.”

http://www.ncbi.nlm.nih.gov/pubmed/7776837

Therapeutic use of Cannabis sativa on chemotherapy-induced nausea and vomiting among cancer patients: systematic review and meta-analysis.

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Abstract

“This paper aims to evaluate the anti-emetic efficacy of cannabinoids in cancer patients receiving chemotherapy using a systematic review of literature searched within electronic databases such as PUBMED, EMBASE, PSYCINFO, LILACS, and ‘The Cochrane Collaboration Controlled Trials Register’. Studies chosen were randomized clinical trials comprising all publications of each database until December 2006. From 12 749 initially identified papers, 30 fulfilled the inclusion criteria for this review, with demonstration of superiority of the anti-emetic efficacy of cannabinoids compared with conventional drugs and placebo. The adverse effects were more intense and occurred more often among patients who used cannabinoids. Five meta-analyses were carried out: (1) dronabinol versus placebo [n=185; relative risk (RR)=0.47; confidence interval (CI)=0.19-1.16]; (2) Dronabinol versus neuroleptics [n=325; RR=0.67; CI=0.47-0.96; number needed to treat (NNT)=3.4]; (3) nabilone versus neuroleptics (n=277; RR=0.88; CI=0.72-1.08); (4) levonantradol versus neuroleptics (n=194; RR=0.94; CI=0.75-1.18); and (5) patients’ preference for cannabis or other drugs (n=1138; RR=0.33; CI=0.24-0.44; NNT=1.8). The superiority of the anti-emetic efficacy of cannabinoids was demonstrated through meta-analysis.”

http://www.ncbi.nlm.nih.gov/pubmed/18625004

Cannabinoids in the treatment of chemotherapy-induced nausea and vomiting: beyond prevention of acute emesis.

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Abstract

“Chemotherapy-induced nausea and vomiting (CINV) remains a significant problem in the care of cancer patients. Although the use of serotonin (5-HT3) receptor antagonists, as well as neurokinin-1 inhibitors, has reduced rates of acute emesis, many patients still experience acute vomiting; moreover, these agents have reduced efficacy in preventing nausea, delayed CINV, and breakthrough CINV. Nausea, in particular, continues to have a major–and often overlooked–impact on patients’ quality of life. Optimizing the treatment for CINV likely will involve combinations of agents that inhibit the numerous neurotransmitter systems involved in nausea and vomiting reflexes. Cannabinoids are active in many of these systems, and two oral formulations, dronabinol (Marinol) and nabilone (Cesamet), are approved by the US Food and Drug Administration for use in CINV refractory to conventional antiemetic therapy. Agents in this class have shown superiority to dopamine receptor antagonists in preventing CINV, and there is some evidence that the combination of a dopamine antagonist and cannabinoid is superior to either alone and is particularly effective in preventing nausea. The presence of side effects from the cannabinoids may have slowed their adoption into clinical practice, but in a number of comparative clinical trials, patients have expressed a clear preference for the cannabinoid, choosing its efficacy over any undesired effects. Improvement in antiemetic therapy across the entire spectrum of CINV will involve the use of agents with different mechanisms of action in concurrent or sequential combinations, and the best such combinations should be identified. In this effort, the utility of the cannabinoids should not be overlooked.”

http://www.ncbi.nlm.nih.gov/pubmed/17566383