THC found to cure Gliomas cancer

Gliomas (tumors in the brain) are especially aggressive malignant forms of cancer, often resulting in the death of affected patients within one to two years following diagnosis. There is no cure for gliomas and most available treatments provide only minor symptomatic relief.

A review of the modern scientific literature reveals numerous preclinical studies and one pilot clinical study demonstrating cannabinoids’ ability to act as antineoplastic agents, particularly on glioma cell lines.

Writing in the September 1998 issue of the journal FEBS Letters, investigators at Madrid’s Complutense University, School of Biology, first reported that delta-9-THC induced apoptosis (programmed cell death) in glioma cells in culture.[1] Investigators followed up their initial findings in 2000, reporting that the administration of both THC and the synthetic cannabinoid agonist WIN 55,212-2 “induced a considerable regression of malignant gliomas” in animals.[2] Researchers again confirmed cannabinoids’ ability to inhibit tumor growth in animals in 2003.[3]

That same year, Italian investigators at the University of Milan, Department of Pharmacology, Chemotherapy and Toxicology, reported that the non-psychoactive cannabinoid, cannabidiol (CBD), inhibited the growth of various human glioma cell lines in vivo and in vitro in a dose dependent manner. Writing in the November 2003 issue of the Journal of Pharmacology and Experimental Therapeutics Fast Forward, researchers concluded, “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.”[4]

In 2004, Guzman and colleagues reported that cannabinoids inhibited glioma tumor growth in animals and in human glioblastoma multiforme (GBM) tumor samples by altering blood vessel morphology (e.g., VEGF pathways). Writing in the August 2004 issue of Cancer Research, investigators concluded, “The present laboratory and clinical findings provide a novel pharmacological target for cannabinoid-based therapies.”[5]

More recently, investigators at the California Pacific Medical Center Research Institute reported that the administration of THC on human glioblastoma multiforme cell lines decreased the proliferation of malignant cells and induced cell death more rapidly than did the administration of WIN 55,212-2. Researchers also noted that THC selectively targeted malignant cells while ignoring healthy ones in a more profound manner than the synthetic alternative.[6]

Most recently, Guzman and colleagues reported that THC administration decreases recurrent glioblastoma multiforme tumor growth in patients diagnosed with recurrent GBM. In the first ever pilot clinical trial assessing the use of cannabinoids and GBM, investigators found that the intratumoral administration of THC was associated with reduced tumor cell proliferation in two of nine subjects. "The fair safety profile of THC, together with its possible anti-proliferative action on tumor cells reported here and in other studies, may set the basis for future trials aimed at evaluating the potential antitumoral activity of cannabinoids," investigators concluded.[7] Several additional investigators have also recently called for further exploration of cannabis-based therapies for the treatment of glioma.[8-10]

In addition to cannabinoids’ ability to moderate glioma cells, separate studies demonstrate that cannabinoids and endocannabinoids can also inhibit the proliferation of other various cancer cell lines, including breast carcinoma,[11-14] prostate carcinoma,[15-17] colorectal carcinoma,[18] gastric adenocarcinoma,[19] skin carcinoma,[20] leukemia cells,[21-22] nueroblastoma,[23] lung carcinoma,[24-25] uterus carcinoma,[26] thyroid epithelioma,[27] pancreatic adenocarcinoma,[28-29], cervical carcinoma[30] and lymphoma.[31]

Many experts now believe that cannabinoids “may represent a new class of anticancer drugs that retard cancer growth, inhibit angiogenesis and the metastatic spreading of cancer cells,”[32] and have recommended that at least one cannabinoid, cannabidiol, now be utilized in cancer therapy.[33]

REFERENCES

[1] Guzman et al. 1998. Delta-9-tetrahydrocannabinol induces apoptosis in C6 glioma cells. FEBS Letters 436: 6-10.

[2] Guzman et al. 2000. Anti-tumoral action of cannabinoids: involvement of sustained ceramide accumulation and extracellular signal-regulated kinase activation. Nature Medicine 6: 313-319.

[3] Guzman et al. 2003. Inhibition of tumor angiogenesis by cannabinoids. The FASEB Journal 17: 529-531.

[4] Massi et al. 2004. Antitumor effects of cannabidiol, a non-psychotropic cannabinoid, on human glioma cell lines. Journal of Pharmacology and Experimental Therapeutics Fast Forward 308: 838-845.

[5] Guzman et al. 2004. Cannabinoids inhibit the vascular endothelial growth factor pathways in gliomas (PDF). Cancer Research 64: 5617-5623.

[6] Allister et al. 2005. Cannabinoids selectively inhibit proliferation and induce death of cultured human glioblastoma multiforme cells. Journal of Neurooncology 74: 31-40.

[7] Guzman et al. 2006. A pilot clinical study of delta-9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme. British Journal of Cancer (E-pub ahead of print).

[8] Parolaro and Massi. 2008. Cannabinoids as a potential new drug therapy for the treatment of gliomas. Expert Reviews of Neurotherapeutics 8: 37-49

[9] Galanti et al. 2007. Delta9-Tetrahydrocannabinol inhibits cell cycle progression by downregulation of E2F1 in human glioblastoma multiforme cells. Acta Oncologica 12: 1-9.

[10 Calatozzolo et al. 2007. Expression of cannabinoid receptors and neurotrophins in human gliomas. Neurological Sciences 28: 304-310.

[11] Cafferal et al. 2006. Delta-9-Tetrahydrocannabinol inhibits cell cycle progression in human breast cancer cells through Cdc2 regulation. Cancer Research 66: 6615-6621.

[12] Di Marzo et al. 2006. Anti-tumor activity of plant cannabinoids with emphasis on the effect of cannabidiol on human breast carcinoma. Journal of Pharmacology and Experimental Therapeutics Fast Forward (E-pub ahead of print).

[13] De Petrocellis et al. 1998. The endogenous cannabinoid anandamide inhibits human breast cancer cell proliferation. Proceedings of the National Academy of Sciences of the United States of America 95: 8375-8380.

[14] 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.

[15] Sarfaraz et al. 2005. Cannabinoid receptors as a novel target for the treatment of prostate cancer. Cancer Research 65: 1635-1641.

[16] Mimeault et al. 2003. Anti-proliferative and apoptotic effects of anandamide in human prostatic cancer cell lines. Prostate 56: 1-12.

[17] Ruiz et al. 1999. Delta-9-tetrahydrocannabinol induces apoptosis in human prostate PC-3 cells via a receptor-independent mechanism. FEBS Letters 458: 400-404.

[18] Pastos et al. 2005. The endogenous cannabinoid, anandamide, induces cell death in colorectal carcinoma cells: a possible role for cyclooxygenase-2. Gut 54: 1741-1750.

[19] Di Marzo et al. 2006. op. cit

[20] Casanova et al. Inhibition of skin tumor growth and angiogenesis in vivo by activation of cannabinoid receptors. 2003. Journal of Clinical Investigation 111: 43-50.

[21] Powles et al. 2005. Cannabis-induced cytotoxicity in leukemic cell lines. Blood 105: 1214-1221

[22] Jia et al 2006. Delta-9-tetrahydrocannabinol-induced apoptosis is jurkat leukemic T cells in regulated by translocation of Bad to mitochondria. Molecular Cancer Research 4: 549-562.

[23] Manuel Guzman. 2003. Cannabinoids: potential anticancer agents (PDF). Nature Reviews Cancer 3: 745-755.

[24] Ibid.

[25] 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.

[26] Manuel Guzman. 2003. Cannabinoids: potential anticancer agents (PDF). Nature Reviews Cancer 3: 745-755.

[27] Baek et al. 1998. Antitumor activity of cannabigerol against human oral epitheloid carcinoma cells. Archives of Pharmacal Research: 21: 353-356.

[28] Carracedo et al. 2006. Cannabinoids induce apoptosis of pancreatic tumor cells via endoplasmic reticulum stress-related genes. Cancer Research 66: 6748-6755.

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

[30] 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.

[31] Gustafsson et al. 2006. Cannabinoid receptor-mediated apoptosis induced by R(+)-methanandamide and Win55,212 is associated with ceramide accumulation and p38 activation in Mantle Cell Lymphoma. Molecular Pharmacology (E-pub ahead of print).

[32] Natalya Kogan. 2005. Cannabinoids and cancer. Mini-Reviews in Medicinal Chemistry 5: 941-952.

[33] Di Marzo et al. 2006. op. cit.

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Can Pot Extend Ted Kennedy's Life? Too Bad It's Illegal

By Paul Armentano, NORML. Posted May 23, 2008.

Scientific studies indicate that marijuana can halt the spread of numerous cancer cells, including the type that Kennedy suffers from.
In the 14 years I've worked in marijuana law reform, few events have struck me as so needlessly tragic as the federal government's consistent and deliberate stifling of medical cannabis research. Nowhere is the Fed's refusal to allow this science more overt and inhumane than as it pertains to the investigation of cannabinoids as anti-cancer agents, particularly in the treatment of gliomas.

As noted in today's wire stories regarding Sen. Edward Kennedy's diagnosis, glioma is an aggressive form of cancer that affects an estimated 10,000 Americans annually. Standard treatments for the cancer include radiation and chemotherapy, though neither procedure has proven particularly effective -- the disease kills approximately half its victims within one year and all within three years.

But what if there was an alternative treatment for gliomas that could selectively target the cancer while leaving healthy cells intact? And what if federal bureaucrats were aware of this treatment, but deliberately withheld this information from the public?

Sadly, the above questions are not hypothetical. As I originally wrote in a 2004 essay for Alternet.org, titled Pot Shows Promise as a Cancer Cure":

In fact, 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."

Despite these favorable preliminary findings, U.S. government officials banished the study and refused to fund any follow-up research until conducting a similar -- though secret -- clinical trial in the mid-1990s. That study, conducted by the U.S. National Toxicology Program to the tune of $2 million, concluded that mice and rats administered high doses of THC over long periods had greater protection against malignant tumors than untreated controls.

However, rather than publicize their findings, government researchers shelved the results, which only became public after a draft copy of its findings were leaked in 1997 to a medical journal which in turn forwarded the story to the national media.

In the years since the completion of the National Toxicology trial, the U.S. government has yet to fund a single additional study examining the drug's potential anti-cancer properties. Is this a case of federal bureaucrats putting politics over the health and safety of patients? You be the judge.

Fortunately, in the past 10 years scientists overseas have generously picked up where U.S. researchers so abruptly left off, reporting that cannabinoids can halt the spread of numerous cancer cells -- including prostate cancer, breast cancer, lung cancer, pancreatic cancer, and in one human clinical trial, brain cancer.

Writing earlier this year in the journal Expert Review of Neurotherapeutics, Italian researchers reiterated, "(C)annabinoids have displayed a great potency in reducing glioma tumor growth either in vitro or in animal experimental models. (They) appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of nontransformed counterparts." Not one mainstream media outlet reported their findings. Perhaps now they'll pay better attention.

What possible advancements in the treatment of cancer may have been achieved over the past 34 years had U.S. government officials chosen to advance -- rather than suppress -- clinical research into the anti-cancer effects of cannabis? It's a shame we have to speculate; it's even more tragic that the families of Senator Kennedy and thousands of others must suffer while we do.