Not a Perfect Ending but a Better Ending

Still, I have seen a guy last through a month of such storms and then a year later walk out of the hospital.

I guess the point I was getting at is while some may complain that doctors do these things shifting the burden to lawyers and/or politicians is not an improvement. If you don’t want the job don’t go to Med School. If you don’t trust the doctors don’t go to them. Libtards efforts to “fix” things NEVER go well. When will we learn?

Oh, and ANY doctor at my bedside at 0300 is MY doctor!

I have told people for years, “if you want my help with your recreational pharmaceuticals you have come to the wrong place.”. I suppose by extension I would say if you want my help with euthanasia you are mistaken, that is not what I do.

And I will say this, I flunked “Death and Dying” because I started the second of a two question essay on the test with, “Sometimes we treat our pets better than we treat each other”. Having seen my mother die of cancer when I was fifteen made me consider things like euthanasia. The experience of subsequent decades taught me to know better. If there is one profession that demands total integrity it is “physician”. If you can’t commit to that, please, for God’s sake, do something else. Your life will just be hell and so will everyone you interact with.

You need to do a lot more research on Cannabis oil. I am pleased to say that my state of Georgia has just passed legislation that will go into effect in 30-60 days which allows doctors to prescribe Cannabis oil for 8 specific conditions including cancer. Cannabis oil is having very positive results especially in brain cancer and lung cancer.

Prior to l937 Cannabis oil was used in many common medicines in the US and it worked.

You need to do a lot more research on Cannabis oil. I am pleased to say that my state of Georgia has just passed legislation that will go into effect in 30-60 days which allows doctors to prescribe Cannabis oil for 8 specific conditions including cancer. Cannabis oil is having very positive results especially in brain cancer and lung cancer.

I actually have read many medical research articles about cannabis oil (delta-9-tetrahydrocannabinol). There is no evidence beyond rumors that it has a curative effect on anything. It is prescribed (as Dronabinol or Marinol) for appetite induction in cancer patients who have lost their appetite and for whom no other drug is effective. It is also used to treat nausea and vomiting. I am not convinced that it actually is the most effective option for those indications, since the clinical study done on it was so small. It does not cure cancer.

Cannabis oil also activates the same pathway induced by dioxin. Since I got my PhD by studying the molecular mechanisms of dioxin toxicity, this tells me that there are a LOT of things going on when people smoke marijuana. Activation of the dioxin response pathway causes endocrine disruption, birth defects, immune system dysfunction, cancer, and a whole bunch of other things that generally aren't very good for you. Because of my experience studying dioxin, I have a fairly strong desire to stay away from anything that mimics the behavior of dioxin.

When I worked in a hospital, every few months, I would be assigned to do a pharmacy inventory of schedule II, III, and IV drugs. That Army hospital carried marinol (dronabinol) in the inventory. It's been sold as a pharmaceutical for several years now.

“There is no evidence beyond rumors that it has a curative effect on anything.”

Well actually: Studies Showing an Anti-Cancer Effect

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

Caihua Liang,1 Michael D. McClean,3 Carmen Marsit,2 Brock Christensen,1,2 Edward Peters,4 Heather H. Nelson5 and Karl T. Kelsey1,2
Cannabinoids, constituents of marijuana smoke, have been recognized to have potential antitumor properties. However, the epidemiologic evidence addressing the relationship between marijuana use and the induction of head and neck squamous cell carcinoma (HNSCC) is inconsistent and conflicting.

[ PDF ]

GliomaParolaro and Massi. 2008. Cannabinoids as a potential new drug therapy for the treatment of gliomas. Expert Reviews of Neurotherapeutics 8: 37-49
[ PDF ]Galanti et al. 2007. Delta9-Tetrahydrocannabinol inhibits cell cycle progression by downregulation of E2F1 in human glioblastoma multiforme cells. Acta Oncologica 12: 1-9.
AbstractCalatozzolo et al. 2007. Expression of cannabinoid receptors and neurotrophins in human gliomas. Neurological Sciences 28: 304-310.
Abstract

Lung CancerPreet et al. 2008. Delta9-Tetrahydrocannabinol inhibits epithelial growth factor-induced lung cancer cell migration in vitro as well as its growth and metastasis in vivo. Oncogene 10: 339-346.
http://www.nature.com/onc/journal/v27/n3/abs/1210641a.html

Pancreatic Cancer —Michalski et al. 2007. Cannabinoids in pancreatic cancer: correlation with survival and pain. International Journal of Cancer (E-pub ahead of print).

Cervical Cancer —Ramer and Hinz. 2008. Inhibition of cancer cell invasion by cannabinoids via increased cell expression of tissue inhibitor of matrix metalloproteinases-1. Journal of the National Cancer Institute 100: 59-69.
http://jnci.oxfordjournals.org/cgi/content/abstract/djm268v1

Breast Cancer —McAllister et al. 2007. Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells. Molecular Cancer Therapeutics 6: 2921-2927.
http://mct.aacrjournals.org/cgi/content/abstract/6/11/2921

Turned-off Cannabinoid Receptor Turns on Colorectal Tumor Growth
New preclinical research shows that cannabinoid cell surface receptor CB1 plays a tumor-suppressing role in human colorectal cancer, scientists report in the Aug. 1 edition of the journal Cancer Research.

CB1 is well-established for relieving pain and nausea, elevating mood and stimulating appetite by serving as a docking station for the cannabinoid group of signaling molecules. It now may serve as a new path for cancer prevention or treatment. “We’ve found that CB1 expression is lost in most colorectal cancers, and when that happens a cancerpromoting protein is free to inhibit cell death,” said senior author Raymond DuBois, M.D., Ph.D., provost and executive vice president of The University of Texas M. D. Anderson Cancer Center.
Read More

Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells. McAllister, S.D. , Christian, R.T., Horowitz, M.P., Garcia, A. and Desprez. P (2007
Molecular Cancer Therapeutics Nov. 6 (11).

Abstract: Invasion and metastasis of aggressive breast cancer cells is the final and fatal step during cancer progression, and is the least understood genetically. Clinically, there are still limited therapeutic interventions for aggressive and metastatic breast cancers available. Clearly, effective and nontoxic therapies are urgently required. Id-1, an inhibitor of basic helix-loop-helix transcription factors, has recently been shown to be a key regulator of the metastatic potential of breast and additional cancers. Using a mouse model, we previously determined that metastatic breast cancer cells became significantly less invasive in vitro and less metastatic in vivo when Id-1 was down-regulated by stable transduction with antisense Id-1. It is not possible at this point, however, to use antisense technology to reduce Id-1 expression in patients with metastatic breast cancer. Here, we report that cannabidiol (CBD), a cannabinoid with a low-toxicity profile, could down-regulate Id-1 expression in aggressive human breast cancer cells. The CBD concentrations effective at inhibiting Id-1 expression correlated with those used to inhibit the proliferative and invasive phenotype of breast cancer cells. CBD was able to inhibit Id-1 expression at the mRNA and protein level in a concentration-dependent fashion. These effects seemed to occur as the result of an inhibition of the Id-1 gene at the promoter level. Importantly, CBD did not inhibit invasiveness in cells that ectopically expressed Id-1. In conclusion, CBD represents the first nontoxic exogenous agent that can significantly decrease Id-1 expression in metastatic breast cancer cells leading to the down-regulation of tumor aggressiveness. [Mol Cancer Ther 2007;6(11):2921-7]
Molecular Cancer Therapeutics 6, 2921-2927, November 1, 2007. doi: 10.1158/1535-7163.MCT-07-0371

British Journal of Cancer (2006) 95, 197-203. doi:10.1038/sj.bjc.6603236 Published online 27 June 2006
A pilot clinical study of Delta9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme

M Guzmán1, M J Duarte2, C Blázquez1, J Ravina2, M C Rosa2, I Galve-Roperh1, C Sánchez1, G Velasco1 and L González-Feria2

Correspondence to: Professor M Guzmán, E-mail: mgp@bbm1.ucm.es or Professor L González-Feria, E-mail: lgferia@yahoo.es
Revised 15 May 2006; accepted 5 June 2006; published online 27 June 2006

Delta9-Tetrahydrocannabinol (THC) and other cannabinoids inhibit tumour growth and angiogenesis in animal models, so their potential application as antitumoral drugs has been suggested. However, the antitumoral effect of cannabinoids has never been tested in humans. Here we report the first clinical study aimed at assessing cannabinoid antitumoral action, specifically a pilot phase I trial in which nine patients with recurrent glioblastoma multiforme were administered THC intratumoraly. The patients had previously failed standard therapy (surgery and radiotherapy) and had clear evidence of tumour progression. The primary end point of the study was to determine the safety of intracranial THC administration. We also evaluated THC action on the length of survival and various tumour-cell parameters. A dose escalation regimen for THC administration was assessed. Cannabinoid delivery was safe and could be achieved without overt psychoactive effects. Median survival of the cohort from the beginning of cannabinoid administration was 24 weeks (95% confidence interval: 15-33). Delta9-Tetrahydrocannabinol inhibited tumour-cell proliferation in vitro and decreased tumour-cell Ki67 immunostaining when administered to two patients. The fair safety profile of THC, together with its possible antiproliferative action on tumour cells reported here and in other studies, may set the basis for future trials aimed at evaluating the potential antitumoral activity of cannabinoids.
http://www.nature.com/bjc/journal/v95/n2/abs/6603236a.html

Inhibition of Glioma Growth in Vivo by Selective Activation of the CB2 Cannabinoid Receptor1Cristina Sánchez2, Maria L. de Ceballos2, Teresa Gómez del Pulgar2, Daniel Rueda, César Corbacho, Guillermo Velasco, Ismael Galve-Roperh, John W. Huffman, Santiago Ramón y Cajal and Manuel Guzmán3
Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, 28040 Madrid, Spain [C. S., T. G. d. P., D. R., G. V., I. G-R., M. G.];
Neurodegeneration Group,
Cajal Institute, CSIC, 28002 Madrid, Spain [M. L. d. C.];
Department of Pathology, Clinica Puerta de Hierro, 28035 Madrid, Spain [C. C., S. R. y C.];
and Department of Chemistry, Clemson University, Clemson, South Carolina 29634-1905 [J. W. H.]

The development of new therapeutic strategies is essential for the management of gliomas, one of the most malignant forms of cancer. We have shown previously that the growth of the rat glioma C6 cell line is inhibited by psychoactive cannabinoids (I. Galve-Roperh et al., Nat. Med., 6: 313-319, 2000). These compounds act on the brain and some other organs through the widely expressed CB1 receptor. By contrast, the other cannabinoid receptor subtype, the CB2 receptor, shows a much more restricted distribution and is absent from normal brain. Here we show that local administration of the selective CB2 agonist JWH-133 at 50 µg/day to Rag-2-/- mice induced a considerable regression of malignant tumors generated by inoculation of C6 glioma cells. The selective involvement of the CB2 receptor in this action was evidenced by: (a) the prevention by the CB2 antagonist SR144528 but not the CB1 antagonist SR141716; (b) the down-regulation of the CB2 receptor but not the CB1 receptor in the tumors; and (c) the absence of typical CB1-mediated psychotropic side effects. Cannabinoid receptor expression was subsequently examined in biopsies from human astrocytomas. A full 70% (26 of 37) of the human astrocytomas analyzed expressed significant levels of cannabinoid receptors. Of interest, the extent of CB2 receptor expression was directly related with tumor malignancy. In addition, the growth of grade IV human astrocytoma cells in Rag-2-/- mice was completely blocked by JWH-133 administration at 50 µg/day. Experiments carried out with C6 glioma cells in culture evidenced the internalization of the CB2 but not the CB1 receptor upon JWH-133 challenge and showed that selective activation of the CB2 receptor signaled apoptosis via enhanced ceramide synthesis de novo. These results support a therapeutic approach for the treatment of malignant gliomas devoid of psychotropic side effects.

Vol. 299, Issue 3, 951-959, December 2001- Pharmacology and Experimental Therapeutics

Anti-tumoral action of cannabinoids: involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation.Galve-Roperh I, Sanchez C, Cortes ML, del Pulgar TG, Izquierdo M, Guzman M.
Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, 28040-Madrid, Spain.

Delta9-Tetrahydrocannabinol, the main active component of marijuana, induces apoptosis of transformed neural cells in culture. Here, we show that intratumoral administration of Delta9-tetrahydrocannabinol and the synthetic cannabinoid agonist WIN-55,212-2 induced a considerable regression of malignant gliomas in Wistar rats and in mice deficient in recombination activating gene 2. Cannabinoid treatment did not produce any substantial neurotoxic effect in the conditions used. Experiments with two subclones of C6 glioma cells in culture showed that cannabinoids signal apoptosis by a pathway involving cannabinoid receptors, sustained ceramide accumulation and Raf1/extracellular signal-regulated kinase activation. These results may provide the basis for a new therapeutic approach for the treatment of malignant gliomas.
PMID: 10700234 [PubMed - indexed for MEDLINE]

1: Biochem Pharmacol 2001 Sep 15;62(6):755-63 Related Articles, Books, LinkOut

Antitumor effects of ajulemic acid (CT3), a synthetic non-psychoactive cannabinoid.Recht LD, Salmonsen R, Rosetti R, Jang T, Pipia G, Kubiatowski T, Karim P, Ross AH, Zurier R, Litofsky NS, Burstein S.

Department of Neurology, University of Massachusetts Medical School, 55 Lake Avenue North, Worcester, MA 01655, USA. RECHTL@ummh.org

One of the endogenous transformation products of tetrahydrocannabinol (THC) is THC-11-oic acid, and ajulemic acid (AJA; dimethylheptyl-THC-11-oic acid) is a side-chain synthetic analog of THC-11-oic acid. In preclinical studies, AJA has been found to be a potent anti-inflammatory agent without psychoactive properties. Based on recent reports suggesting antitumor effects of cannabinoids (CBs), we assessed the potential of AJA as an antitumor agent. AJA proved to be approximately one-half as potent as THC in inhibiting tumor growth in vitro against a variety of neoplastic cell lines. However, its in vitro effects lasted longer. The antitumor effect was stereospecific, suggesting receptor mediation. Unlike THC, however, whose effect was blocked by both CB(1) and CB(2) receptor antagonists, the effect of AJA was inhibited by only the CB(2) antagonist. Additionally, incubation of C6 glioma cells with AJA resulted in the formation of lipid droplets, the number of which increased over time; this effect was noted to a much greater extent after AJA than after THC and was not seen in WI-38 cells, a human normal fibroblast cell line. Analysis of incorporation of radiolabeled fatty acids revealed a marked accumulation of triglycerides in AJA-treated cells at concentrations that produced tumor growth inhibition. Finally, AJA, administered p.o. to nude mice at a dosage several orders of magnitude below that which produces toxicity, inhibited the growth of subcutaneously implanted U87 human glioma cells modestly but significantly. We conclude that AJA acts to produce significant antitumor activity and effects its actions primarily via CB(2) receptors. Its very favorable toxicity profile, including lack of psychoactivity, makes it suitable for chronic usage. Further studies are warranted to determine its optimal role as an antitumor agent.
PMID: 11551521 [PubMed - indexed for MEDLINE]

Biochem J 2001 Aug 15;358(Pt 1):249-55 Related Articles, Books, LinkOut

Palmitoylethanolamide inhibits the expression of fatty acid amide hydrolase and enhances the anti-proliferative effect of anandamide in human breast cancer cells.Di Marzo V, Melck D, Orlando P, Bisogno T, Zagoory O, Bifulco M, Vogel Z, De Petrocellis L.
Istituto per la Chimica di Molecole di Interesse Biologico, Via Toiano 6, 80072, Arco Felice, Napoli, Italy. vdimarzo@icmib.na.cnr.it

Palmitoylethanolamide (PEA) has been shown to act in synergy with anandamide (arachidonoylethanolamide; AEA), an endogenous agonist of cannabinoid receptor type 1 (CB(1)). This synergistic effect was reduced by the CB(2) cannabinoid receptor antagonist SR144528, although PEA does not activate either CB(1) or CB(2) receptors. Here we show that PEA potently enhances the anti-proliferative effects of AEA on human breast cancer cells (HBCCs), in part by inhibiting the expression of fatty acid amide hydrolase (FAAH), the major enzyme catalysing AEA degradation. PEA (1-10 microM) enhanced in a dose-related manner the inhibitory effect of AEA on both basal and nerve growth factor (NGF)-induced HBCC proliferation, without inducing any cytostatic effect by itself. PEA (5 microM) decreased the IC(50) values for AEA inhibitory effects by 3-6-fold. This effect was not blocked by the CB(2) receptor antagonist SR144528, and was not mimicked by a selective agonist of CB(2) receptors. PEA enhanced AEA-evoked inhibition of the expression of NGF Trk receptors, which underlies the anti-proliferative effect of the endocannabinoid on NGF-stimulated MCF-7 cells. The effect of PEA was due in part to inhibition of AEA degradation, since treatment of MCF-7 cells with 5 microM PEA caused a approximately 30-40% down-regulation of FAAH expression and activity. However, PEA also enhanced the cytostatic effect of the cannabinoid receptor agonist HU-210, although less potently than with AEA. PEA did not modify the affinity of ligands for CB(1) or CB(2) receptors, and neither did it alter the CB(1)/CB(2)-mediated inhibitory effect of AEA on adenylate cyclase type V, nor the expression of CB(1) and CB(2) receptors in MCF-7 cells. We suggest that long-term PEA treatment of cells may positively affect the pharmacological activity of AEA, in part by inhibiting FAAH expression.
PMID: 11485574 [PubMed - indexed for MEDLINE]

Prostaglandins Other Lipid Mediat 2000 Apr;61(1-2):43-61Related Articles, Books, LinkOut

Cannabimimetic fatty acid derivatives in cancer and inflammation.Di Marzo V, Melck D, De Petrocellis L, Bisogno T.
Istituto per la Chimica di Molecole di Interesse Biologico, Via Toiano 6, 80072, Arco Felice, Napoli, Italy. vdimarzo@icmib.na.cnr.it

Evidence for the role of the cannabimimetic fatty acid derivatives (CFADs), i.e. anandamide (arachidonoylethanolamide, AEA), 2-arachidonoylglycerol (2-AG) and palmitoylethanolamide (PEA), in the control of inflammation and of the proliferation of tumor cells is reviewed here. The biosynthesis of AEA, PEA, or 2-AG can be induced by stimulation with either Ca(2+) ionophores, lipopolysaccharide, or platelet activating factor in macrophages, and by ionomycin or antigen challenge in rat basophilic leukemia (RBL-2H3) cells (a widely used model for mast cells). These cells also inactivate CFADs through re-uptake and/or hydrolysis and/or esterification processes. AEA and PEA modulate cytokine and/or arachidonate release from macrophages in vitro, regulate serotonin secretion from RBL-2H3 cells, and are analgesic in some animal models of inflammatory pain. However, the involvement of endogenous CFADs and cannabinoid CB(1) and CB(2) receptors in these effects is still controversial. In human breast and prostate cancer cells, AEA and 2-AG, but not PEA, potently inhibit prolactin and/or nerve growth factor (NGF)-induced cell proliferation. Vanillyl-derivatives of anandamide, such as olvanil and arvanil, exhibit even higher anti-proliferative activity. These effects are due to suppression of the levels of the 100 kDa prolactin receptor or of the high affinity NGF receptors (trk), are mediated by CB(1)-like cannabinoid receptors, and are enhanced by other CFADs. Inhibition of adenylyl cyclase and activation of mitogen-activated protein kinase underlie the anti-mitogenic actions of AEA. The possibility that CFADs act as local inhibitors of the proliferation of human breast cancer is discussed here.

Publication Types:
Review
Review, Tutorial
PMID: 10785541 [PubMed - indexed for MEDLINE]

Eur J Pharmacol 2000 Jan 17;387(3):343-7 Related Articles, Books, LinkOut

Relative involvement of cannabinoid CB(1) and CB(2) receptors in the Delta(9)-tetrahydrocannabinol-induced inhibition of natural killer activity. Massi P, Fuzio D, Vigano D, Sacerdote P, Parolaro D. Department of Pharmacology, Chemotherapy and Toxicology, University of Milan, Via Vanvitelli 32/A, 20129, Milan, Italy.

We demonstrated that in vivo administration of Delta(9)-tetrahydrocannabinol in mice (15 mg/kg s.c.) significantly inhibited natural killer cell (NK) cytolytic activity without affecting Concanavalin A (ConA)-induced splenocyte proliferation. Moreover, we investigated the effect of in vivo pretreatment with cannabinoid receptor antagonists, namely, the selective cannabinoid CB(1) receptor antagonist SR 141716 [N-piperidin-5-(4-chlorophenyl)-1-(2, 4-dichlorophenyl)-4-methyl-3-pyrazolecarboxamide] and the selective cannabinoid CB(2) receptor antagonist SR 144528 inverted question markN-[(1S)-endo-1,3, 3-trimethyl bicyclo [2.2.1] heptan-2-yl]-5-(4-chloro-3-methylphenyl)-1-(4-methylbenzyl)-pyrazo le- 3-carboxamide inverted question mark, on Delta(9)-tetrahydrocannabinol-induced inhibition of NK cytolytic activity. Both antagonists partially reversed the Delta(9)-tetrahydrocannabinol inhibition of NK cytolytic activity, although the cannabinoid CB(1) receptor antagonist was more effective than the cannabinoid CB(2) receptor antagonist. The parallel measurement of interferon gamma and interleukin 2 levels revealed that Delta(9)-tetrahydrocannabinol significantly reduced (about 70%) the former cytokine without affecting the latter. Cannabinoid CB(1) and CB(2) receptor antagonists completely reversed the interferon gamma reduction induced by Delta(9)-tetrahydrocannabinol. Our results indicate that both types of cannabinoid receptors are involved in the complex network mediating NK cytolytic activity.
PMID: 10650181 [PubMed - indexed for MEDLINE]

Arch Pharm Res 1998 Jun;21(3):353-6 Related Articles, Books, LinkOut

Boron trifluoride etherate on silica-A modified Lewis acid reagent (VII). Antitumor activity of cannabigerol against human oral epitheloid carcinoma cells.Baek SH, Kim YO, Kwag JS, Choi KE, Jung WY, Han DS.
Department of Chemistry, Wonkwang University, Iksan, Korea.

Geraniol (1), olivetol (2), cannabinoids (3 and 4) and 5-fluorouracil (5) were tested for their growth inhibitory effects against human oral epitheloid carcinoma cell lines (KB) and NIH 3T3 fibroblasts using two different 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay and sulforhodamine B protein (SRB) assay. Cannabigerol (3) exhibited the highest growth-inhibitory activity against the cancer cell lines.
PMID: 9875457 [PubMed - indexed for MEDLINE]

Proc Soc Exp Biol Med 1995 Oct;210(1):64-76 Related Articles, Books, LinkOut

Differential inhibition of RAW264.7 macrophage tumoricidal activity by delta 9tetrahydrocannabinol.

Burnette-Curley D, Cabral GA.
Department of Microbiology and Immunology, Virginia Commonwealth University/Medical College of Virginia, Richmond 23298-0678, USA.

delta 9tetrahydrocannabinol (THC), the major psychoactive component of marijuana, has been shown to inhibit macrophage cell contact-dependent cytolysis of tumor cells. The purpose of this study was to determine whether THC inhibited macrophage cytolytic function by targeting selectively tumor necrosis factor (TNF)-dependent pathways versus L-arginine-dependent reactive nitrogen intermediates. An in vitro system employing RAW264.7 macrophage-like cells as effectors and TNF-sensitive mouse L929 fibroblasts or nitric oxide (NO.)-sensitive P815 mastocytoma cells as targets, was employed to assess the effect of THC on cytolysis. Macrophages were pretreated with THC or vehicle for 48 hr, subjected to multistep activation with 10 U/ml recombinant mouse gamma-interferon (IFN-gamma) plus 100 ng/ml LPS or to direct activation with 1 microgram/ml LPS, and co-cultured with tumor cells in the presence or absence of THC. THC inhibited TNF-dependent killing by macrophages subjected to either multistep or direct activation. Decreased amounts of TNF-alpha were detected in medium of macrophage cultures treated with THC. In contrast, THC inhibited NO.-dependent cell contact killing only for macrophages subjected to direct activation. Decreased levels of NO2-, a stable degradation product of the short-lived and highly toxic effector molecule NO., were produced by these macrophages. In addition, the effect of the enantiomeric pairs (-)CP55,940/(+)CP56,667 or (-)HU-210/(+)HU-211 on macrophage cell contact-dependent killing was assessed. Inhibition of macrophage tumoricidal activity against TNF-sensitive L929 cells was effected by both isomers of THC analogs. In contrast, both of the enantiomeric pairs had an effect on killing of NO.-sensitive P815 mastocytoma cells only for macrophages subjected to direct activation. These data suggest that cannabinoids inhibit macrophage cell contact-dependent killing of tumor cells by a noncannabinoid receptor-mediated mechanism. However, specific cytolytic pathways are inhibited differentially by cannabinoids depending on the activation stimuli to which macrophages are exposed.
PMID: 7675800 [PubMed - indexed for MEDLINE]

: J Natl Cancer Inst 1975 Sep;55(3):597-602 Related Articles, Books, LinkOut

Antineoplastic activity of cannabinoidMunson AE, Harris LS, Friedman MA, Dewey WL, Carchman RA.
Lewis lung adenocarcinoma growth was retarded by the oral administration of delta9-tetrahydrocannabinol (delta9-THC), delta8-tetrahydrocannabinol (delta8-THC), and cannabinol (CBN), but not cannabidiol (CBD). Animals treated for 10 consecutive days with delta9-THC, beginning the day after tumor implantation, demonstrated a dose-dependent action of retarded tumor growth. Mice treated for 20 consecutive days with delta8-THC and CBN had reduced primary tumor size. CBD showed no inhibitory effect on tumor growth at 14, 21, or 28 days. Delta9-THC, delta8-THC, and CBN increased the mean survival time (36% at 100 mg/kg, 25% at 200 mg/kg, and 27% at 50 mg/kg, respectively), whereas CBD did not. Delta9-THC administered orally daily until death in doses of 50, 100, or 200 mg/kg did not increase the life-spans of (C57BL/6 times DBA/2)F1 (BDF1) mice hosting the L1210 murine leukemia. However, delta9-THC administered daily for 10 days significantly inhibited Friend leukemia virus-induced splenomegaly by 71% at 200 mg/kg as compared to 90.2% for actinomycin D. Experiments with bone marrow and isolated Lewis lung cells incubated in vitro with delta9-THC and delta8-THC showed a dose-dependent (10(-4)-10(-7)) inhibition (80-20%, respectively) of tritiated thymidine and 14C-uridine uptake into these cells. CBD was active only in high concentrations (10(-4)).
PMID: 1159836 [PubMed - indexed for MEDLINE]

Cancer Res 1976 Jan;36(1):95-100 Related Articles, Books, LinkOut

The inhibition of DNA synthesis by cannabinoids.Carchman RA, Harris LS, Munson AE.
Several of the cannabinoids found in marihuana have been shown to inhibit tumor growth and increase the life-span of mice bearing the Lewis lung adenocarcinoma. When trypsin-dispersed isolated Lewis lung cells are incubated in vitro, they maintain their capacity to carry out macromolecular synthesis (RNA, DNA, protein). This process can be inhibited by cytosine arabinoside, actinomycin D, or methyl-1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea, whereas cyclophosphamide, an agent that must be bioactivated, was inactive. Inhibition of DNA synthesis as measured by [3H]thymidine uptake into acid-insoluble material was used as an index of cannabinoid activity against isolated Lewis lung cells, L1210 leukemia cells, and bone marrow cells incubated in vitro delta9-, delta8-, 1-hydroxy-3-n pentyl-, and 1-delta8-tetrahydrocannabinol, and cannabinol demonstrated a dose-dependent inhibition of DNA synthesis whereas cannabidiol and 1-hydroxy-3-n-pentylcannabidiol were markedly less inhibitory in our in vitro cell systems. Furthermore, our in vitro observations with these cannabinoids are supported by in vivo tumor inhibition studies. Ring modifications as in cannabichromene or cannabicyclol abolish in vitro activity as does dihydroxylation at the 8beta and 11 positions of 1-delta9-trans-tetrahydrocannabinol. Delta9-trans-tetrahydrocannabinol demonstrated the least toxicity of all inhibitory cannabinoids in vivo; this is supported by its lesser effect on bone marrow DNA synthesis in vitro.
PMID: 1248011 [PubMed - indexed for MEDLINE]

Res Commun Chem Pathol Pharmacol 1977 Aug;17(4):703-14 Related Articles, Books, LinkOut

Effects of cannabinoids on L1210 murine leukemia. 1. Inhibition of DNA synthesis. Tucker AN, Friedman MA.
The effect of cannabinoid derivatives on thymidine-3H uptake in L1210 murine leukemia was determined. In experiments at 200 mg/kg 3 hrs after treatment, the order of activity was delta9-tetrahydrocannabinol less than cannabinol less than cannabidiol less than abnormal cannabidiol less than 11-hydroxy-delta9-tetrahydrocannabinol less than delta8-tetrahydrocannabinol. The inhibitory effect of delta8-tetrahydrocannabinol was 99%. When animals were dosed on consecutive days with delta9-tetrahydrocannabinol and killed on the third day, thymidine-3H incorporation was increased while delta8-tetrahydrocannabinol retained its inhibitory activity under the same conditions. Delta-9-tetrahydrocannabinol and delta8-tetrahydrocannabinol inhibited RNA and protein synthesis in a fashion analagous to the inhibition of DNA synthesis.
PMID: 897352 [PubMed - indexed for MEDLINE]

Cancer Biochem Biophys 1977;2(2):51-4 Related Articles, Books, LinkOut

In vivo effects of cannabinoids on macromolecular biosynthesis in Lewis lung carcinomas.Friedman MA.
Cannabinoids represent a novel class of drugs active in increasing the life span mice carrying Lewis lung tumors and decreasing primary tumor size. In the present studies, the effects of delta9-THC, delta8-THC, and cannabidiol on tumor macromolecular biosynthesis were studied. These drugs inhibit thymidine-3H incorporation into DNA acutely, but did not inhibit leucine uptake into tumor protein. At 24 h after treatment, cannabinoids did not inhibit thymidine-3H incorporation into DNA, leucine-3H uptake into protein or cytidine-3H into RNA.
PMID: 616322 [PubMed - indexed for MEDLINE]

: J Natl Cancer Inst 1976 Mar;56(3):655-8 Related Articles, Books, LinkOut

Well, my neighbor died of lung cancer before he was 40 and was “using” medical Marijuana for his neck problem.

Yeh smoking it will help with nausea and headaches but the cannabis oil is highly highly concentrated. You take like a drop of it on your tongue a couple of times a day or whatever. Its very potent stuff.