Saturday, March 23, 2013

Cannabis and Cancer Studies

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.

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

Lung Cancer
Preet 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.

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.

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.

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.
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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: or Professor L González-Feria, E-mail:
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.

Inhibition of Glioma Growth in Vivo by Selective Activation of the CB2 Cannabinoid Receptor1
Cristina 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.
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.
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.
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, Tutorial
PMID: 10785541 [PubMed - indexed for MEDLINE]

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]

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 cannabinoid
Munson 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

Effects of delta9-tetrahydrocannabinol in Lewis lung adenocarcinoma cells in tissue culture.
White AC, Munson JA, Munson AE, Carchman RA.
We found a dose-related decrease in DNA synthesis in transformed cell cultures treated with delta9-tetrahydrocannabinol (delta9-THC). The decrease, observed over a 4-hour period, was not accompanied by a change in the radioactive precursor pool as compared to that of control culture. The distribution of labeled products clearly differed from that observed after treatment with cytosine arabinoside. delta9-THC inhibited DNA synthesis at some point beyond the uptake of 3H-thymidine.
PMID: 943561 [PubMed - indexed for MEDLINE]
Prostaglandins Leukot Essent Fatty Acids 2002 Feb;66(2-3):319-32 Related Articles, Books, LinkOut

Endocannabinoids in the immune system and cancer.
Parolaro D, Massi P, Rubino T, Monti E.
Department of Structural and Functional Biology, Pharmacology Unit, University of Insubria, Via A. Da Giussano 10, Busto Arsizio (Varese), 21052, Italy
The present review focuses on the role of the endogenous cannabinoid system in the modulation of immune response and control of cancer cell proliferation. The involvement of cannabinoid receptors, endogenous ligands and enzymes for their biosynthesis and degradation, as well as of cannabinoid receptor-independent events is discussed. The picture arising from the recent literature appears very complex, indicating that the effects elicited by the stimulation of the endocannabinoid system are strictly dependent on the specific compounds and cell types considered. Both the endocannabinoid anandamide and its congener palmitoylethanolamide, exert a negative action in the onset of a variety of parameters of the immune response. However, 2-arachidonoylglycerol appears to be the true endogenous ligand for peripheral cannabinoid receptors, although its action as an immunomodulatory molecule requires further characterization. Modulation of the endocannabinoid system interferes with cancer cell proliferation either by inhibiting mitogenic autocrine/paracrine loops or by directly inducing apoptosis; however, the proapoptotic effect of anandamide is not shared by other endocannabinoids and suggests the involvement of non-cannabinoid receptors, namely the VR1 class of vanilloid receptors. In conclusion, further investigations are needed to elucidate the function of endocannabinoids as immunosuppressant and antiproliferative/cytotoxic agents. The experimental evidence reviewed in this article argues in favor of the therapeutic potential of these compounds in immune disorders and cancer. Copyright 2002 Published by Elsevier Science Ltd.
PMID: 12052046 [PubMed - in process]
J Pharmacol Exp Ther 2001 Dec;299(3):951-9 Related Articles, Books, LinkOut

Inhibition of rat C6 glioma cell proliferation by endogenous and synthetic cannabinoids. Relative involvement of cannabinoid and vanilloid receptors.
Jacobsson SO, Wallin T, Fowler CJ.
Department of Pharmacology and Clinical Neuroscience, Umea University, Umea, Sweden.
The effects of the endocannabinoids anandamide (AEA) and 2-arachidonoylglycerol (2-AG) upon rat C6 glioma cell proliferation were examined and compared with a series of synthetic cannabinoids and related compounds. Cells were treated with the compounds each day and cell proliferation was monitored for up to 5 days of exposure. AEA time- and concentration-dependently inhibited C6 cell proliferation. After 4 days of treatment, AEA and 2-AG inhibited C6 cell proliferation with similar potencies (IC(50) values of 1.6 and 1.8 microM, respectively), whereas palmitoylethanolamide showed no significant antiproliferative effects at concentrations up to 10 microM. The antiproliferative effects of both AEA and 2-AG were blocked completely by a combination of antagonists at cannabinoid receptors (SR141716A and SR144528 or AM251 and AM630) and vanilloid receptors (capsazepine) as well as by alpha-tocopherol (0.1 and 10 microM), and reduced by calpeptin (10 microM) and fumonisin B(1) (10 microM), but not by L-cycloserine (1 and 100 microM). CP 55,940, JW015, olvanil, and arachidonoyl-serotonin were all found to affect C6 glioma cell proliferation (IC(50) values of 5.6, 3.2, 5.5, and 1.6 microM, respectively), but the inhibition could not be blocked by cannabinoid + vanilloid receptor antagonists. It is concluded that the antiproliferative effects of the endocannabinoids upon C6 cells are brought about by a mechanism involving combined activation of both vanilloid receptors and to a lesser extent cannabinoid receptors, and leading to oxidative stress and calpain activation. However, there is at present no obvious universal mechanism whereby plant-derived, synthetic, and endogenous cannabinoids affect cell viability and proliferation.
PMID: 11714882 [PubMed - indexed for MEDLINE]
Proc Natl Acad Sci U S A 1998 Jul 7;95(14):8375-80 Related Articles, Free in PMC, Books, LinkOut

The endogenous cannabinoid anandamide inhibits human breast cancer cell proliferation.
De Petrocellis L, Melck D, Palmisano A, Bisogno T, Laezza C, Bifulco M, Di Marzo V.
Istituto di Cibernetica, Consiglio Nazionale delle Ricerche), Consiglio Nazionale delle Ricerche, Via Toiano 6, 80072 Arco Felice, Naples, Italy.
Anandamide was the first brain metabolite shown to act as a ligand of "central" CB1 cannabinoid receptors. Here we report that the endogenous cannabinoid potently and selectively inhibits the proliferation of human breast cancer cells in vitro. Anandamide dose-dependently inhibited the proliferation of MCF-7 and EFM-19 cells with IC50 values between 0.5 and 1.5 microM and 83-92% maximal inhibition at 5-10 microM. The proliferation of several other nonmammary tumoral cell lines was not affected by 10 microM anandamide. The anti-proliferative effect of anandamide was not due to toxicity or to apoptosis of cells but was accompanied by a reduction of cells in the S phase of the cell cycle. A stable analogue of anandamide (R)-methanandamide, another endogenous cannabinoid, 2-arachidonoylglycerol, and the synthetic cannabinoid HU-210 also inhibited EFM-19 cell proliferation, whereas arachidonic acid was much less effective. These cannabimimetic substances displaced the binding of the selective cannabinoid agonist [3H]CP 55, 940 to EFM-19 membranes with an order of potency identical to that observed for the inhibition of EFM-19 cell proliferation. Moreover, anandamide cytostatic effect was inhibited by the selective CB1 receptor antagonist SR 141716A. Cell proliferation was arrested by a prolactin mAb and enhanced by exogenous human prolactin, whose mitogenic action was reverted by very low (0.1-0.5 microM) doses of anandamide. Anandamide suppressed the levels of the long form of the prolactin receptor in both EFM-19 and MCF-7 cells, as well as a typical prolactin-induced response, i.e., the expression of the breast cancer cell susceptibility gene brca1. These data suggest that anandamide blocks human breast cancer cell proliferation through CB1-like receptor-mediated inhibition of endogenous prolactin action at the level of prolactin receptor.
PMID: 9653194 [PubMed - indexed for MEDLINE]
: Chem Phys Lipids 2000 Nov;108(1-2):191-209 Related Articles, Books, LinkOut

Endocannabinoids and fatty acid amides in cancer, inflammation and related disorders.
De Petrocellis L, Melck D, Bisogno T, Di Marzo V.
Istituto di Cibernetica, Consiglio Nazionale delle Ricerche, Via Toiano 6, 80072 Arco Felice, Napoli, Italy.
The long history of the medicinal use of Cannabis sativa and, more recently, of its chemical constituents, the cannabinoids, suggests that also the endogenous ligands of cannabinoid receptors, the endocannabinoids, and, particularly, their derivatives may be used as therapeutic agents. Studies aimed at correlating the tissue and body fluid levels of endogenous cannabinoid-like molecules with pathological conditions have been started and may lead to identify those diseases that can be alleviated by drugs that either mimic or antagonize the action of these substances, or modulate their biosynthesis and degradation. Hints for the therapeutic applications of endocannabinoids, however, can be obtained also from our previous knowledge of marijuana medicinal properties. In this article, we discuss the anti-tumor and anti-inflammatory activity of: (1) the endocannabinoids anandamide (arachidonoylethanolamide) and 2-arachidonoyl glycerol; (2) the bioactive fatty acid amides palmitoylethanolamide and oleamide; and (3) some synthetic derivatives of these compounds, such as the N-acyl-vanillyl-amines. Furthermore, the possible role of cannabimimetic fatty acid derivatives in the pathological consequences of cancer and inflammation, such as cachexia, wasting syndrome, chronic pain and local vasodilation, will be examined
Publication Types:
Review, Academic
PMID: 11106791 [PubMed - indexed for MEDLINE]
Endocrinology 2000 Jan;141(1):118-26 Related Articles, Books, LinkOut

Suppression of nerve growth factor Trk receptors and prolactin receptors by endocannabinoids leads to inhibition of human breast and prostate cancer cell proliferation.
Melck D, De Petrocellis L, Orlando P, Bisogno T, Laezza C, Bifulco M, Di Marzo V.
Istituto per la Chimica di Molecole di Interesse Biologico, Consiglio Nazionale delle Ricerche, Arco Felice (NA), Italy.
Anandamide and 2-arachidonoylglycerol (2-AG), two endogenous ligands of the CB1 and CB2 cannabinoid receptor subtypes, inhibit the proliferation of PRL-responsive human breast cancer cells (HBCCs) through down-regulation of the long form of the PRL receptor (PRLr). Here we report that 1) anandamide and 2-AG inhibit the nerve growth factor (NGF)-induced proliferation of HBCCs through suppression of the levels of NGF Trk receptors; 2) inhibition of PRLr levels results in inhibition of the proliferation of other PRL-responsive cells, the prostate cancer DU-145 cell line; and 3) CB1-like cannabinoid receptors are expressed in HBCCs and DU-145 cells and mediate the inhibition of cell proliferation and Trk/PRLr expression. Beta-NGF-induced HBCC proliferation was potently inhibited (IC50 = 50-600 nM) by the synthetic cannabinoid HU-210, 2-AG, anandamide, and its metabolically stable analogs, but not by the anandamide congener, palmitoylethanolamide, or the selective agonist of CB2 cannabinoid receptors, BML-190. The effect of anandamide was blocked by the CB1 receptor antagonist, SR141716A, but not by the CB2 receptor antagonist, SR144528. Anandamide and HU-210 exerted a strong inhibition of the levels of NGF Trk receptors as detected by Western immunoblotting; this effect was reversed by SR141716A. When induced by exogenous PRL, the proliferation of prostate DU-145 cells was potently inhibited (IC50 = 100-300 nM) by anandamide, 2-AG, and HU-210. Anandamide also down-regulated the levels of PRLr in DU-145 cells. SR141716A attenuated these two effects of anandamide. HBCCs and DU-145 cells were shown to contain 1) transcripts for CB1 and, to a lesser extent, CB2 cannabinoid receptors, 2) specific binding sites for [3H]SR141716A that could be displaced by anandamide, and 3) a CB1 receptor-immunoreactive protein. These findings suggest that endogenous cannabinoids and CB1 receptor agonists are potential negative effectors of PRL- and NGF-induced biological responses, at least in some cancer cells.
PMID: 10614630 [PubMed - indexed for MEDLINE]
Eur J Biochem 1998 Jun 15;254(3):634-42 Related Articles, Books, LinkOut

Biosynthesis and degradation of bioactive fatty acid amides in human breast cancer and rat pheochromocytoma cells--implications for cell proliferation and differentiation.
Bisogno T, Katayama K, Melck D, Ueda N, De Petrocellis L, Yamamoto S, Di Marzo V.
Istituto per la Chimica di Molecole di Interesse Biologico, CNR, Napoli, Italy.
The endogenous cannabinoid, anandamide (arachidonoylethanolamide), and the sleep-inducing factor, oleamide (cis-9-octadecenoamide), represent two classes of long-chain fatty acid amides with several neuronal actions and metabolic pathways in common. Here we report that these two compounds are present in human breast carcinoma EFM-19 cells and rat adrenal pheochromocytoma PC-12 cells, together with the enzyme responsible for their degradation, fatty acid amide hydrolase, and the proposed biosynthetic precursors for arachidonoylethanolamide and related acylethanolamides, the N-acyl-phosphatidylethanolamines. Lipids extracted from cells labelled with [14C]ethanolamine contained radioactive compounds with the same chromatographic behaviour as arachidonoylethanolamide and acyl-PtdEtns. The levels of these compounds were not influenced by either stimulation with ionomycin in EFM-19 cells or two-week treatment with the nerve growth factor in PC-12 cells. The chemical nature of arachidonoylethanolamide, related acylethanolamides and the corresponding acyl-PtdEtns was confirmed by gas chromatographic/mass spectrometric analyses of the purified compounds, which also showed the presence of higher levels of oleamide. The latter compound, which does not activate the central CB1 cannabinoid receptor, exhibited an anti-proliferative action on EFM-19 cells at higher concentrations than arachidonoylethanolamide (IC50 = 11.3 microM for oleamide and 2.1 microM for arachidonoylethanolamide), while at a low, inactive dose it potentiated an arachidonoylethanolamide cytostatic effect. The CB1 receptor selective antagonist SR 141716A (0.5 microM) reversed the effect of both arachidonoylethanolamide and oleamide. EFM-19 cells and PC-12 cells were found to contain a membrane-bound [14C]arachidonoylethanolamide-hydrolysing activity with pH dependency and sensitivity to inhibitors similar to those previously reported for fatty acid amide hydrolase. This enzyme was inhibited by oleamide in both intact cells and cell-free preparations. The presence of transcripts of fatty acid amide hydrolase in these cells was shown by northern blot analyses of their total RNA. The rate of [14C]arachidonoylethanolamide hydrolysis by intact cells, the kinetic parameters of arachidonoylethanolamide enzymatic hydrolysis and the amounts of the fatty acid amide hydrolase transcript, were not significantly influenced by a two-week treatment with nerve growth factor and subsequent transformation of PC-12 cells into neuron-like cells. These data show for the first time that: (a) induction by nerve growth factor of a sympathetic neuronal phenotype in PC-12 cells has no effect on arachidonoylethanolamide/oleamide metabolism, (b) arachidonoylethanolamide and oleamide are autacoid suppressors of human breast cancer cell proliferation. Moreover these data lend conclusive support to the previous hypothesis that oleamide may act as an enhancer of arachidonoylethanolamide actions through competitive inhibition of its degradation.
PMID: 9688276 [PubMed - indexed for MEDLINE]
Fundam Appl Toxicol 1996 Mar;30(1):109-17 Related Articles, Books, LinkOut

Toxicity and carcinogenicity of delta 9-tetrahydrocannabinol in Fischer rats and B6C3F1 mice.
Chan PC, Sills RC, Braun AG, Haseman JK, Bucher JR.
National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina 27709, USA.
delta 9-Tetrahydrocannabinol (delta 9-THC) was studied for potential carcinogenicity in rodents because it is the principal psychoactive ingredient in marihuana and it has potential medicinal uses. delta 9-THC in corn oil was administered by gavage to groups of male and female Fischer rats and B6C3F1 mice at 0, 5, 15, 50, 150, or 500 mg/kg, 5 days a week for 13 weeks and for 13-week plus a 9-week recovery period, and to groups of rats at 0, 12.5, or 50 mg/kg and mice at 0, 125, 250, or 500 mg/kg, 5 times a week for 2 years. In all studies, mean body weights of dosed male and female rats and mice were lower than controls but feed consumptions were similar. Convulsions and hyperactivity were observed in dosed rats and mice; the onset and frequency were dose related. Serum FSH and LH levels in all dosed male rats and corticosterone levels in 25 mg/kg female rats were significantly higher than controls at 15 months in the 2-year studies. delta 9-THC administration for 13 weeks induced testicular atrophy and uterine and ovarian hypoplasia; the lesions persisted in a 9-week recovery period. In the 2-year studies, survival of dosed rats was higher than controls; that of mice was similar to controls. Incidences of testicular interstitial cell, pancreas and pituitary gland adenomas in male rats, mammary gland fibroadenoma and uterus stromal polyp in female rats, and hepatocellular adenoma/carcinoma in male and female mice were reduced in a dose-related manner. Decreased tumor incidences may be at least in part due to reduced body weights of dosed animals. Incidences of thyroid gland follicular cell hyperplasia were increased in all dosed groups of male and female mice, and follicular cell adenomas were significantly increased in the 125 mg/kg group of males, but there was no evidence of a dose-related trend in proliferative lesions of the thyroid. There was no evidence that delta 9-THC was carcinogenic in rats or mice.
PMID: 8812248 [PubMed - indexed for MEDLINE]
J Mol Med 2001;78(11):613-25Related Articles, Books, LinkOut

Control of the cell survival/death decision by cannabinoids.
Guzman M, Sanchez C, Galve-Roperh I.
Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid, Spain.
Cannabinoids, the active components of Cannabis sativa (marijuana), and their derivatives produce a wide spectrum of central and peripheral effects, some of which may have clinical application. The discovery of specific cannabinoid receptors and a family of endogenous ligands of those receptors has attracted much attention to cannabinoids in recent years. One of the most exciting and promising areas of current cannabinoid research is the ability of these compounds to control the cell survival/death decision. Thus cannabinoids may induce proliferation, growth arrest, or apoptosis in a number of cells, including neurons, lymphocytes, and various transformed neural and nonneural cells. The variation in drug effects may depend on experimental factors such as drug concentration, timing of drug delivery, and type of cell examined. Regarding the central nervous system, most of the experimental evidence indicates that cannabinoids may protect neurons from toxic insults such as glutamaergic overstimulation, ischemia and oxidative damage. In contrast, cannabinoids induce apoptosis of glioma cells in culture and regression of malignant gliomas in vivo. Breast and prostate cancer cells are also sensitive to cannabinoid-induced antiproliferation. Regarding the immune system, low doses of cannabinoids may enhance cell proliferation, whereas high doses of cannabinoids usually induce growth arrest or apoptosis. The neuroprotective effect of cannabinoids may have potential clinical relevance for the treatment of neurodegenerative disorders such as multiple sclerosis, Parkinson's disease, and ischemia/stroke, whereas their growth-inhibiting action on transformed cells might be useful for the management of malignant brain tumors. Ongoing investigation is in search for cannabinoid-based therapeutic strategies devoid of nondesired psychotropic effects.
Publication Types:
Review, Academic
PMID: 11269508 [PubMed - indexed for MEDLINE]
1: Cancer Causes Control 1997 Sep;8(5):722-8 Related Articles, Books, LinkOut

Cannabinoids Halt Pancreatic Cancer, Breast Cancer Growth, Studies Say.
Madrid, Spain: Compounds in cannabis inhibit cancer cell growth in human breast cancer cell lines and in pancreatic tumor cell lines, according to a pair of preclinical trials published in the July issue of the journal of the American Association for Cancer Research.
In one trial, investigators at Complutense University in Spain and the Institut National de la Sante et de la Recherche Medicale (INSERM) in France assessed the anti-cancer activity of cannabinoids in pancreatic cancer cell lines and in animals. Cannabinoid administration selectively increased apoptosis (programmed cell death) in pancreatic tumor cells while ignoring healthy cells, researchers found. In addition, "cannabinoid treatment inhibited the spreading of pancreatic tumor cells ... and reduced the growth of tumor cells" in animals.
"These findings may contribute to ... a new therapeutic approach for the treatment of pancreatic cancer," authors concluded.
In the second trial, investigators at Spain's Complutense University reported that THC administration "reduces human breast cancer cell proliferation [in vitro] by blocking the progression of the cell cycle and by inducing apoptosis." Authors concluded that their findings "may set the bases for a cannabinoid therapy for the management of breast cancer."
Previous preclinical data published in May in the Journal of Pharmacological and Experimental Therapeutics reported that non-psychoactive cannabinoids, particularly cannabidiol (CBD), dramatically halt the spread of breast cancer cells and recommended their use in cancer therapy.
Separate trials have also shown cannabinoids to reduce the size and halt the spread of glioma (brain tumor) cells in animals and humans in a dose dependent manner. Additional preclinical studies have demonstrated cannabinoids to inhibit cancer cell growth and selectively trigger malignant cell death in skin_cancer_cells, leukemic_cells, lung cancer cells, and prostate_carcinoma_cells, among other cancerous cell lines.
For more information, please contact Paul Armentano, NORML Senior Policy Analyst, at (202) 483-5500. Full text of both studies, "Cannabinoids induce apoptosis of pancreatic tumor cells via endoplasmic reticulum stress-related genes" and "Delta-9-tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation" are available in the July 1, 2006 issue of Cancer Research, available online at:
Additional information on cannabinoids' anti-cancer properties is available in NORML's report, "Cannabinoids as Cancer Hope," online at:

Further Reading

Tuesday, March 19, 2013


From Brave Mykala FB Page:
 October 6, 2012
"Why is Mykayla still on chemotherapy despite the fact that she is in remission?  

Why is Mykayla on chemotherapy if cannabis cures cancer?

These are two questions we frequently encounter … so I am going to do the best that I can to help explain the answers to these two questions.


Mykayla Comstock was diagnosed with intermediate risk T-Cell acute lymphoblastic leukemia on July 14th, 2012, at 7 years old. She is also Oregon's youngest Medical Cannabis Patient. This is where her journey is chronicled for all to see.
Brave Mykayla Comstock wants to help change how childhood cancer is approached. Mykayla uses Cannabis as medicine. She began using Whole Extract Cannabis Oil to help her leukemia go into remission. Now she continues to use cannabis to help mitigate the debilitating effects of her required chemotherapy protocol, successfully. Mykayla and her family want to speak out, spread the word, raise awareness and let everyone know that Cancer Doesn't Have to be So Scary! #peaceloveCURE
From the Family-

Mykayla has received stunning benefits from her cannabis therapy; from the very beginning there has been a very minimal need for pharmaceutical medications. We have not experienced excessive nausea. We have been fortunate to not have to experience consistent infections. Her blood cell and immune cell counts have been spectacular all through and through; her doctors have admitted to being "baffled."
Some of her oncologists and nurses have not been accepting of our choices, some have; We as parent do not particularly care. We have seen what has worked. This powerfully medicinal plant has been a blessing to Mykayla on her journey.
Children who are fighting cancer of any sort should be allowed access to the positive benefits of cannabis; Parents need to become aware of the alternatives to pharmaceuticals.
We are sharing Mykayla's story with the hopes that you will become aware and see for yourselves. Thank you for following Mykayla's journey. Help us spread the word.

- Brave Mykayla does not inhale the smoke or vapors of the cannabis flowers-

These are the Ways Mykayla Uses Cannabis---
Full Extract Cannabis Oil
Raw Organic Cannabis Juice - non-psychoactive
Infused Agave Nectar
Lotions, soaps and salves


From Peter Garmain:

Peter Garmain = diabetes gone: "this is a b4 +after pic of me. last year my blood sugar was 12%@8 pills a day after a fast tests. 215lbs. 7 weeks of digesting the oil ,rick simpsons cure level.
my blood sugar was 4.5% "no pills" that was last nov.still the same. my diabetes  is gone. i kept doing a small dose of the oil.
today the scale said 162.5lbs. i did not change my diet, but the oil did for me ;p"

digesting cannabis oil has no medicinal benefits at all, lol..

video here=

Saturday, March 16, 2013


Spain Study Confirms Hemp Oil Cures Cancer without Side Effects

The International Medical Veritas Association (IMVA) is putting hemp oil on its cancer protocol. It is a prioritized protocol list whose top five items are magnesium chloride, iodine, selenium, Alpha Lipoic Acid and sodium bicarbonate. It makes perfect sense to drop hemp oil right into the middle of this nutritional crossfire of anti cancer medicines, which are all available without prescription.
Hemp oil has long been recognised as one of the most versatile and beneficial substances known to man. Derived from hemp seeds (a member of the achene family of fruits) it has been regarded as a superfood due to its high essential fatty acid content and the unique ratio of omega3 to omega6 and gamma linolenic acid (GLA) – 2:5:1. Hemp oil, is known to contain up to 5% of pure GLA, a much higher concentration than any other plant, even higher than spirulina. For thousands of years, the hemp plant has been used in elixirs and medicinal teas because of its healing properties and now medical science is zeroing in on the properties of its active substances.
Both the commercial legal type of hemp oil and the illegal THC laden hemp oil are one of the most power-packed protein sources available in the plant kingdom. Its oil can be used in many nutritional and transdermal applications. In other chapters in my Winning the War on Cancer book we will discuss in-depth about GLA and cancer and also the interesting work of Dr. Johanna Budwig. She uses flax seed oil instead of hemp oil to cure cancer – through effecting changes in cell walls – using these omega3 and omega6 laden medicinal oils.
Actually there is another way to use medical marijuana without smoking the leaf. According to Dr. Tod H. Mikuriya, “The usual irritating and toxic breakdown products of burning utilized with smoking are totally avoided with vaporization. Extraction and inhaling cannabinoid essential oils below ignition temperature of both crude and refined cannabis products affords significant mitigation of irritation to the oral cavity, and tracheobronchial tree from pyrollytic breakdown products.[iii]

Rick Simpson, the man in the documentary below, has been making hemp oil and sharing it with friends and neighbors without charging for it. In small doses, he says, it makes you well without getting you high. “Well you can’t deny your own eyes can you?” Simpson asks. “Here’s someone dying of cancer and they’re not dying anymore. I don’t care if the medicine comes from a tomato plant, potato plant or a hemp plant, if the medicine is safe and helps and works, why not use it?” he asks.
When a person has cancer and is dying this question reaches a critical point. The bravery of Rick Simpson from Canada in showing us how to make hemp oil for ourselves offers many people a hope that should be increasingly appreciated as money dries up for expensive cancer treatments. We are going to need inexpensive medicines in the future and there is nothing better than the ones we can make reasonably cheaply ourselves.

For most people in the world it is illegal so the choice could come down to breaking the law or dying. There is no research to indicate what advantages oral use of hemp oil vs. vaporization but we can assume that advantage would be nutritional with oral intake. Dr. Budwig work would sustain this point of view especially for cancer patients.

The Science

According to Dr. Robert Ramer and Dr. Burkhard Hinz of the University of Rostock in Germany medical marijuana can be an effective treatment for cancer.[v] Their research was published in the Journal of the National Cancer Institute Advance Access on December 25th of 2007 in a paper entitled Inhibition of Cancer Cell Invasion by Cannabinoids via Increased Expression of Tissue Inhibitor of Matrix Metalloproteinases-1.
The biggest contribution of this breakthrough discovery, is that the expression of TIMP-1 was shown to be stimulated by cannabinoid receptor activation and to mediate the anti-invasive effect of cannabinoids. Prior to now the cellular mechanisms underlying this effect were unclear and the relevance of the findings to the behavior of tumor cells in vivo remains to be determined.

Marijuana cuts lung cancer tumor growth in half, a 2007 Harvard Medical School study shows.[vi] The active ingredient in marijuana cuts tumor growth in lung cancer in half and significantly reduces the ability of the cancer to spread, say researchers at Harvard University who tested the chemical in both lab and mouse studies.
This is the first set of experiments to show that the compound, Delta-tetrahydrocannabinol (THC), inhibits EGF-induced growth and migration in epidermal growth factor receptor (EGFR) expressing non-small cell lung cancer cell lines. Lung cancers that over-express EGFR are usually highly aggressive and resistant to chemotherapy. THC that targets cannabinoid receptors CB1 and CB2 is similar in function to endocannabinoids, which are cannabinoids that are naturally produced in the body and activate these receptors.
“The beauty of this study is that we are showing that a substance of abuse, if used prudently, may offer a new road to therapy against lung cancer,” said Anju Preet, Ph.D., a researcher in the Division of Experimental Medicine. Acting through cannabinoid receptors CB1 and CB2, endocannabinoids (as well as THC) are thought to play a role in variety of biological functions, including pain and anxiety control, and inflammation.
Researchers reported in the August 15, 2004 issue of Cancer Research, the journal of the American Association for Cancer Research, that marijuana’s constituents inhibited the spread of brain cancer in human tumor biopsies.[vii]

In a related development, a research team from the University of South Florida further noted that THC can also selectively inhibit the activation and replication of gamma herpes viruses. The viruses, which can lie dormant for years within white blood cells before becoming active and spreading to other cells, are thought to increase one’s chances of developing cancers such as Kaposi’s Sarcoma, Burkitt’s lymphoma and Hodgkin’s disease.[viii]

In 1998, a research team at Madrid’s Complutense University discovered that THC can selectively induce programmed cell death in brain tumor cells without negatively impacting surrounding healthy cells. Then in 2000, they reported in the journal Nature Medicine that injections of synthetic THC eradicated malignant gliomas (brain tumors) in one-third of treated rats, and prolonged life in another third by six weeks.[ix]

Led by Dr. Manuel Guzman the Spanish team announced they had destroyed incurable brain cancer tumors in rats by injecting them with THC. They reported in the March 2002 issue of “Nature Medicine” that they injected the brains of 45 rats with cancer cells, producing tumors whose presence they confirmed through magnetic resonance imaging (MRI). On the 12th day they injected 15 of the rats with THC and 15 with Win-55,212-2 a synthetic compound similar to THC.[x]

Researchers at the University of Milan in Naples, Italy, reported in the Journal of Pharmacology and Experimental Therapeutics that non-psychoactive compounds in marijuana inhibited the growth of glioma cells in a dose-dependent manner, and selectively targeted and killed malignant cells through apoptosis. “Non-psychoactive CBD produce[s] a significant anti-tumor activity both in vitro and in vivo, thus suggesting a possible application of CBD as an antineoplastic agent.”[xi]

The first experiment documenting pot’s anti-tumor effects took place in 1974 at the Medical College of Virginia at the behest of the U.S. government. The results of that study, reported in an Aug. 18, 1974, Washington Post newspaper feature, were that marijuana’s psychoactive component, THC, “slowed the growth of lung cancers, breast cancers and a virus-induced leukemia in laboratory mice, and prolonged their lives by as much as 36 percent.”[xii]

Funded by the National Institute of Health to find evidence that marijuana damages the immune system, found instead that THC slowed the growth of three kinds of cancer in mice — lung and breast cancer, and a virus-induced leukemia. The DEA quickly shut down the Virginia study and all further cannabis/tumor research even though the researchers “found that THC slowed the growth of lung cancers, breast cancers and a virus-induced leukemia in laboratory mice, and prolonged their lives by as much as 36 percent.”
“Antineoplastic Activity of Cannabinoids,” an article in a 1975 Journal of the National Cancer Institute reports, “Lewis lung adenocarcinoma growth was retarded by the oral administration of tetrahydrocannabinol (THC) and cannabinol (CBN)” — two types of cannabinoids, a family of active components in marijuana. “Mice treated for 20 consecutive days with THC and CBN had reduced primary tumor size.”
Marijuana relieves pain that narcotics like morphine and OxyContin have hardly any effect on, and could help ease suffering from illnesses such as multiple sclerosis, diabetes and cancer.[xiii]

According to Devra Davis in her book Secret History of the War on Cancer, 1.5 million lives have been lost because Americans failed to act on existing knowledge about the environmental causes of cancer. It is impossible to calculate the added deaths from suppressed ‘cancer cures’ but we do know of the terrible suffering of hundreds of thousands of people who have been jailed for marijuana use.

Hemp oil with THC included has the making of a primary cancer treatment, which even alone seems to have a great chance of turning the tide against cancer tumors. It has the added advantage of safety, ease of use, lack of side effects and low cost if one makes it oneself. Surrounded by other medicinal anti-cancer substances in a full protocol it’s hard to imagine anyone failing and falling in their war on cancer.
THC should be included in every cancer protocol.

Sodium bicarbonate is another excellent anti tumor substance that reduces tumors but is much more difficult to administer than THC hemp oil. Cannabinoids are able to pass through all barriers in the body like Alpha Lipoic Acid so simple oral intake is sufficient. With bicarbonate we need intravenous applications and often even this is not sufficient, often we have to use catheters and few doctors in the world are willing to administer this way.

In the end all cancer treatments that are not promoted by mainstream oncology are illegal. No licensed doctor is going to claim that are curing cancer with sodium bicarbonate though they will treat people with cancer explaining they are balancing pH or some other metabolic profile with this common emergency room medicine found also most kitchens of the world. More than several states have passed laws making medical marijuana legal but the federal government will not relax and let people be free to choose their treatments even if their lives depend on it.
Davis notes that the cowardice of research scientists, who publish thoroughly referenced reports but pull their punches at the end, by claiming that more research needs to be done before action can be taken. Statements like these are exploited by industry that buys time to make much more money. It is a deliberate attempt that creates wholesale public doubt from small data gaps and remaining scientific uncertainties.

They have done that with everything right up to and including sunlight. Everything is thought to be dangerous except the pharmaceutical drugs which are the most dangerous substances of all. Stomach wrenching chemotherapy and the death principle of radiation are legal yet safe THC laden hemp oil is not.
It is legal for doctors to attack people with their poisons but you can go to jail for trying to save yourself or a loved one from cancer with the oil of a simple garden weed. Our civilization has put up with this insanity but there is a great price being paid. In a mad medical world people die that need not and this is a terrible sadness that has destroyed the integrity and ethics of modern medicine.

The science for the use of hemp oil is credible, specific fact-based, and is documented in detail.[xiv]

There is absolutely no reason to not legalize medical marijuana and create an immediate production and distribution of THC hemp oil to cancer patients. Unfortunately we live in a world populated with governments and medical henchmen who would rather see people die cruel deaths then have access to a safe and effect cancer drug.

Meanwhile the Food and Drug Administration approved Genentech’s best-selling drug, Avastin, as a treatment for breast cancer, in a decision, according to the New York Times, “that appeared to lower the threshold somewhat for approval of certain cancer drugs. The big question was whether it was enough for a drug temporarily to stop cancer from worsening — as Avastin had done in a clinical trial — or was it necessary for a drug to enable patients to live longer, which Avastin had failed to do. Oncologists and patient advocates were divided, in part because of the drug’s sometimes severe side effects.”[xv]

The differences between Avastin and hemp oil are huge. First Avastin will earn Genentech hundreds of millions where THC hemp oil will earn no one anything. Second there are no severe or even mild side effects to taking hemp oil and lastly it is not a temporary answer but a real solution. Certainly hemp oil will ensure a longer life.


Monday, March 11, 2013


Merits of Cannabis Extract

Last semester, I ran an event through Students for Sensible Drug Policy about cannabis extract medicine. During the presentation, my friend Corrie Yelland discussed how she cured her anal canal cancer with only cannabis oil — no traditional treatments. Two years ago, I held a similar presentation with Dennis Hill, another friend with aggressive prostate cancer who went into remission using only cannabis oil.   

These successes were achieved without chemotherapy, radiation or surgery. Furthermore, these two individuals were confident in this course of treatment because of the hundreds of other people who have eliminated cancer and other serious diseases with cannabis extracts, in the form of oil.

It is important to point out that cannabis oil treatments consist of ingesting massive quantities of the extract over time — at least 60 grams in 3 months — and do not involve smoking, which is the most familiar form of medicinal cannabis use, but is also by far the least effective. Medicine is meant to be ingested, not smoked. Yet millions of people have found that just smoking cannabis is more effective than many vigorously researched pharmaceuticals for pain reduction.

If such patients began to ingest cannabis oil instead of smoking, many would cure their ailments instead of simply managing them.

I would like to address the No. 1 concern people have with this seemingly outrageous claim: If cannabis oil really cures cancer, why isn’t it being used on a widespread basis, or at least being discussed further?

First of all, oil is used on a relatively significant scale — I can provide more than 120 testimonials to anyone who wants them. But compared to those who smoke cannabis or people who don’t use cannabis at all, those rates are extremely low.

Second, many people who use this treatment don’t come forward because they fear social stigmas, law enforcement or simply don’t want to talk about such a personal issue. Those who do come forward to their doctors or the media are usually dismissed. Doctors attribute cannabis-related cures to spontaneous remission or faulty diagnoses, and the media rarely wants to damage its credibility by having a story about cannabis curing cancer, which initially sounds insane.

It takes a lot of research and conversations with patients to truly understand this issue, and most people in power aren’t willing to take the time to do that.

Nonetheless, the cannabis extract movement is growing, and the media is slowly beginning to pay attention. Dr. William Courtney appeared in a video on The Huffington Post on Dec. 1, discussing how he cured an 8-month-old of brain cancer with just oil (once again, no chemotherapy, radiation or surgery), as well as his cure of a different terminal cancer patient by juicing cannabis.

Dr. Robert Melamede has made news with his publicly traded corporation Cannabis Science’s cures of skin cancer. Today, a group of oil producers and patients in Michigan are holding a “Cannabis Cures Cancer” concert — their second concert of this type — to spread the message.

Furthermore, there have been five documentaries made about cannabis oil curing cancer, and several local news affiliates in Canada and the U.S. have actually run stories about individual patients. Over the past five years, I’ve seen this movement grow from being concentrated mainly in Canada to exploding in Colorado, Washington and Oregon (though surprisingly not too much in California).

This phenomenal growth has only one root — the evidence that cannabis oil works, and that, in my experience, it works better than any other medicine humans currently have access to.

I am happy to share any information I have with anyone who wants it, and connect you with real patients who have been cured of cancer with cannabis oil. I guarantee no matter how skeptical you are, if you look into this matter deeply, you will see how profoundly true and important this really is.

Source: DiamondBackOnline
Justin Kander is a senior marketing major. He can be reached at

Friday, March 8, 2013


  New Study: Vaporized Marijuana is a Safe and Effective Pain Treatment

   marijuanaleaf4 265x165 New Study: Vaporized Marijuana is a Safe and Effective Pain TreatmentWhen we talk about the medicinal benefits of marijuana, those who disapprove of its use tend to roll their eyes. But the fact is, this powerful plant has numerous potential applications in healthcare and pain management in particular. A new study has once again demonstrated that the vilified plant can safely and effectively treat general pain along with the painful symptoms of neuropathy.

Neuropathy is damage to the nervous system – particularly the peripheral nervous system (not including the brain and spinal cord). It is characterized by pain and numbness especially in the hands and feet, and is often the result of diabetes. Neuropathy can also be caused by injuries, toxic exposure, infections, and more.

This latest study was conducted by researchers at the University of California Davis Medical Center and was published in The Journal of Pain. It was a double-blind, placebo-controlled, crossover study that looked at the effectiveness of using vaporized, inhaled cannabis in 39 participants. These participants were experiencing neuropathic pain despite having tried traditional treatments (like opiate drugs). All participants continued to take their prescribed medications throughout the 4 week study period.

Researchers gave participants doses of cannabis with moderate THC levels (3.53 percent) or low THC levels (1.29 percent). (THC, or tetrahydrocannabinol, is the plant’s primary psychoactive chemical). Some also received a placebo with no THC. They found both doses of cannabis to be effective in reducing pain significantly.
“Both the low and medium doses proved to be salutary analgesics for the heterogeneous collection of neuropathic pain conditions studied. Both active study medications provided statistically significant 30% reductions in pain intensity when compared to placebo,” stated the researchers.

This is far from the first study to illustrate the pain-relieving benefits of cannabis. In fact, cannabis (even in THC-free form, or free of psychoactive effects) has been identified as a powerful pain reliever in more than 80 peer-reviewed studies. Still, the herb is classified as dangerous by the U.S. government.
Why is marijuana still illegal? Opponents of medicinal marijuana (including the federal government) say the research isn’t enough. It isn’t clear what they would like to see in marijuana studies, but it’s beginning to look like they want the impossible. It seems they would rather Americans continue consuming addictive prescription pain medications than use a plant.

According to AlterNet, sales of opiate pain pills have tripled since 1999. Oxycodone (one of the more popular choices on the legal and illegal market) has increased from 8.3 tons in 1997 to a whopping 105 tons in 2011. Overdose deaths are similarly climbing as is the number of people addicted to these substances. To date, no one has died from a marijuana overdose.


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