Cannabinoids

In a magazine article, I encountered a report on the medical use of certain extracts of cannabis (cannabinoids) that promote apoptosis (cell suicide) in certain tumor cells such as those occurring in the brain. This, at least, happens in vitro and also in lab animals. The clinical evidence is marginal but seems encouraging. Here is the abstract of a good review

Cannabinoids as potential new therapy for the treatment of gliomas
Expert Rev. Neurotherapeutics 8(1), 37-49 (2008)
Daniela Parolaro and Paola Massi
Via A da Giussano 10, Busto Arsizio (VA), Italy
Tel.: +39 033 133 9417 Fax: +39 033 133 9459 daniela.parolaro@uninsubria.

Gliomas constitute the most frequent and malignant primary brain tumors. Current standard therapeutic strategies (surgery, radiotherapy and chemotherapeutics, e.g., temozolomide, carmustin or carboplatin) for their treatment are only palliative and survival diagnosis is normally 6-12 months. The development of new therapeutic strategies for the management of gliomas is therefore essential. Interestingly, cannabinoids have been shown to exert antiproliferative effects on a wide spectrum of cells in culture. Of interest, cannabinoids have displayed a great potency in reducing glioma tumor growth either in vitro or in animal experimental models, curbing the growth of xenografts generated by subcutaneous or intratecal injection of glioma cells in immune-deficient mice. Moreover, cannabinoids appear to be selective antitumoral agents as they kill glioma cells without affecting the viability of nontransformed counterparts. A pilot clinical trial on patients with glioblastoma multiforme demonstrated their good safety profile together and remarkable antitumor effects, and may set the basis for further studies aimed at better evaluating the potential anticancer activity of cannabinoids.

The idea is clear from the abstract. The materials come in the form of pills and sprays for use in the mouth. They appear to be helpful and seem to have no negative side effects.

The doctors we have been talking to do not seem ready to try this on Barbara but, even if they could, it would be illegal in New York State. However, the medical use of these extracts is legal in New Jersey where MSKCC does have an outpost. There does seem to be a problem with getting these products even in NJ, but I presume that this will be solved.

Engelbert's son Michael tells me that there are now synthetic versions of cannabis that reach the same receptors as the natural stuff. Several of these are legal. Is this a reasonable thing to try? I must learn more.

Sara adds: this review also seems interesting. It is from 2003, does not seems to have been followed up.

Predrag adds: I have been skeptical about cannabinoids, as I have so far found only one clinical trial (Guzmán, Madrid 2006 with no follow-up clinical trials), and Barbara needs a full-fledged clinical trail very soon, accepted by her doctors, and coordinated with the planned radiation/chemo combo. Pot is controversial, and websites have to be sifted with care. Wiki says "the mechanisms which promote THC's tumor cell–killing action are unknown." In US there do not seem to be major ongoing efforts in this direction; I found Sean D. McAllister in San Francisco. There's no sign yet that the approach works in laboratory animals, let alone people. Dr. Paul Graham Fisher, chief of the Division of Child Neurology at Stanford University and Lucile Packard Children's Hospital says "you're seeing a lot more thinking outside the box about trying to treat glioblastoma. I think in the next 10 to 15 years we're going to start seeing progress forward." For now, he says, there's no evidence that marijuana is good or bad for glioblastoma tumors (HealthDay News - Monday, January 11 2010). Georgetown Lombardi Cancer Center is currently only preparing a clinical trial. Maybe US government is conspiring to prevent a cure for cancer, but I doubt it. The review that Sara cites has 268 Google Scholar cites, and some of that reading is interesting.

this article (not public access, need to get it thorough GaTech Library):

Cannabinoids as Potential Antitumoral Agents in Pancreatic Cancer G. Velasco, A. Carracedo, M. Lorente and M. Guzmán

Pancreatology 2009, 39-49

says

On the basis of these preclinical findings, a pilot clinical study of ▵9-tetrahydrocannabinol (THC) in patients with recurrent glioblastoma multiforme has recently been run,

see

A pilot clinical study of Δ9-tetrahydrocannabinol in patients with recurrent glioblastoma multiforme, Guzman M, Duarte MJ, Blazquez C, Ravina J, Rosa MC, Galve- Roperh I, Sanchez C, Velasco G, Gonzalez-Feria L, Br J Cancer 95 197–2003 (2006)

Targeting Cannabinoid Receptors in Brain Tumors, Guillermo Velasco, Arkaitz Carracedo, Cristina Blázquez, Mar Lorente, Tania Aguado, Cristina Sánchez, Ismael Galve-Roperh and Manuel Guzmán, in Cannabinoids and the Brain 2008, II, 361-374.

This literature is immense (my estimate is over 5000 articles in last 5 years), beyond what layman can comprehend, and we need a native guide for this. Maybe we could get Engelbert's son Michael to join the blog and have look at it?

Predrag to Ed: How about trying to pull your Columbia professor rank, calling up the authors of the Columbia University clinical trial (2007) "showing that HIV/AIDS patients who inhaled cannabis four times daily experienced substantial increases in food intake with little evidence of discomfort and no impairment of cognitive performance." Not the problem at hand, but they should know what clinical trials are in progress? The director of these studies is Margaret Haney, try calling her? Please please introduce yourself as the Columbia Ratherferd Chair Professor in Astronomy, and not as Ed, medical people respect hierarchy.

Even it it does not slow down the tumor, it might be a palliative, and that cannot hurt.