Cancer and Marijuana

Since I’ve not managed to make a grand unified Marijuana posting, I’ve decided to “move on” and do it in chunks. Some things are amenable to the “one full story”, others more to “bits and pieces”.

So the latest news is just that the National Institutes of Health have decided to throw in the towel on PC and admit that it kills cancer cells. Details to elaborate over many years, no doubt.

http://www.whiteoutpress.com/articles/2014/q3/marijuana-destroys-cancer-tumors-says-nih-and-new-study/

July 25, 2014
Marijuana destroys Cancer Tumors says NIH and new Study
By Mark Wachtler

July 25, 2014. Norwich, England. (ONN) The US federal government and the National Institutes of Health (NIH) have quietly confirmed what some of us have known for years – that marijuana somehow fights cancer cells without harming healthy cells. Now, Cancer.gov and the NIH have actually published that fact, reversing four decades of disinformation and propaganda against the natural remedy on behalf of multi-national pharmaceutical corporations. And to top it off, the results of a just-released study demonstrates how it happens.

Now I cite this 2014 article because this story was just now reaching the ‘regular news’. I saw it on some “cable” TV news channel just about a week ago. Clearly some news travels faster than other to your TV set…

Study discovers how marijuana shrinks tumors

Cancer is big business and big money. Many have long suspected that the cure for cancer has always been held hostage by the powers that be so Wall Street corporations can continue to rake in $125 billion a year fighting the disease with radiation, pills and endless surgeries. The National Cancer Institute alone has taken in and spent an estimated $90 billion allegedly trying to find a cure for cancer. Image, all they had to do was ask a teenager or just test a documented 3,000-year-old medical treatment. Marijuana is the first known medical treatment used by humans, literally dating back to roughly 1,000 BC.

So what’s some of the “story behind the story”? You know, that technical stuff most reports glaze at…

Note this is from 2002. Not exactly “new news”.

http://www.ncbi.nlm.nih.gov/pubmed/12091357

Blood. 2002 Jul 15;100(2):627-34.

Targeting CB2 cannabinoid receptors as a novel therapy to treat malignant lymphoblastic disease.

McKallip RJ1, Lombard C, Fisher M, Martin BR, Ryu S, Grant S, Nagarkatti PS, Nagarkatti M.

Abstract
In the current study, we examined whether ligation of CB2 receptors would lead to induction of apoptosis in tumors of immune origin and whether CB2 agonist could be used to treat such cancers. Exposure of murine tumors EL-4, LSA, and P815 to delta-9-tetrahydrocannabinol (THC) in vitro led to a significant reduction in cell viability and an increase in apoptosis. Exposure of EL-4 tumor cells to the synthetic cannabinoid HU-210 and the endogenous cannabinoid anandamide led to significant induction of apoptosis, whereas exposure to WIN55212 was not effective. Treatment of EL-4 tumor-bearing mice with THC in vivo led to a significant reduction in tumor load, increase in tumor-cell apoptosis, and increase in survival of tumor-bearing mice. Examination of a number of human leukemia and lymphoma cell lines, including Jurkat, Molt-4, and Sup-T1, revealed that they expressed CB2 receptors but not CB1. These human tumor cells were also susceptible to apoptosis induced by THC, HU-210, anandamide, and the CB2-selective agonist JWH-015. This effect was mediated at least in part through the CB2 receptors because pretreatment with the CB2 antagonist SR144528 partially reversed the THC-induced apoptosis. Culture of primary acute lymphoblastic leukemia cells with THC in vitro reduced cell viability and induced apoptosis. Together, the current data demonstrate that CB2 cannabinoid receptors expressed on malignancies of the immune system may serve as potential targets for the induction of apoptosis. Also, because CB2 agonists lack psychotropic effects, they may serve as novel anticancer agents to selectively target and kill tumors of immune origin.

Key takaway here being that it is both THC and Cannabinoids that have activities, just in different parts of the biochemistry. The argument for “the whole package” instead of drug extracts has some merit.

When we get to 2012, things are continuing to develop.

http://www.ncbi.nlm.nih.gov/pubmed/22198381

FASEB J. 2012 Apr;26(4):1535-48. doi: 10.1096/fj.11-198184. Epub 2011 Dec 23.

Cannabidiol inhibits lung cancer cell invasion and metastasis via intercellular adhesion molecule-1.

Ramer R1, Bublitz K, Freimuth N, Merkord J, Rohde H, Haustein M, Borchert P, Schmuhl E, Linnebacher M, Hinz B.

Abstract
Cannabinoids inhibit cancer cell invasion via increasing tissue inhibitor of matrix metalloproteinases-1 (TIMP-1). This study investigates the role of intercellular adhesion molecule-1 (ICAM-1) within this action. In the lung cancer cell lines A549, H358, and H460, cannabidiol (CBD; 0.001-3 μM) elicited concentration-dependent ICAM-1 up-regulation compared to vehicle via cannabinoid receptors, transient receptor potential vanilloid 1, and p42/44 mitogen-activated protein kinase. Up-regulation of ICAM-1 mRNA by CBD in A549 was 4-fold at 3 μM, with significant effects already evident at 0.01 μM. ICAM-1 induction became significant after 2 h, whereas significant TIMP-1 mRNA increases were observed only after 48 h. Inhibition of ICAM-1 by antibody or siRNA approaches reversed the anti-invasive and TIMP-1-upregulating action of CBD and the likewise ICAM-1-inducing cannabinoids Δ(9)-tetrahydrocannabinol and R(+)-methanandamide when compared to isotype or nonsilencing siRNA controls. ICAM-1-dependent anti-invasive cannabinoid effects were confirmed in primary tumor cells from a lung cancer patient. In athymic nude mice, CBD elicited a 2.6- and 3.0-fold increase of ICAM-1 and TIMP-1 protein in A549 xenografts, as compared to vehicle-treated animals, and an antimetastatic effect that was fully reversed by a neutralizing antibody against ICAM-1 [% metastatic lung nodules vs. isotype control (100%): 47.7% for CBD + isotype antibody and 106.6% for CBD + ICAM-1 antibody]. Overall, our data indicate that cannabinoids induce ICAM-1, thereby conferring TIMP-1 induction and subsequent decreased cancer cell invasiveness.

So the cannabinoids also slow the spread and inhibit invasiveness.

Then there are the other things it does that can make pain and inflammation less. (Frankly, if they come out with a THC reduced high CBD variety that reduces arthritic inflammation a whole load of folks will be lining up, me included.)

http://www.cancer.gov/about-cancer/treatment/cam/patient/cannabis-pdq/#link/_13

Have any preclinical (laboratory or animal) studies been conducted using Cannabis or cannabinoids?

Preclinical studies of cannabinoids have investigated the following:

Antitumor activity

Studies in mice and rats have shown that cannabinoids may inhibit tumor growth by causing cell death, blocking cell growth, and blocking the development of blood vessels needed by tumors to grow. Laboratory and animal studies have shown that cannabinoids may be able to kill cancer cells while protecting normal cells.

A study in mice showed that cannabinoids may protect against inflammation of the colon and may have potential in reducing the risk of colon cancer, and possibly in its treatment.

A laboratory study of delta-9-THC in hepatocellular carcinoma (liver cancer) cells showed that it damaged or killed the cancer cells. The same study of delta-9-THC in mouse models of liver cancer showed that it had antitumor effects. Delta-9-THC has been shown to cause these effects by acting on molecules that may also be found in non-small cell lung cancer cells and breast cancer cells.

A laboratory study of cannabidiol (CBD) in estrogen receptor positive and estrogen receptor negative breast cancer cells showed that it caused cancer cell death while having little effect on normal breast cells. Studies in mouse models of metastatic breast cancer showed that cannabinoids may lessen the growth, number, and spread of tumors.

A laboratory study of cannabidiol (CBD) in human glioma cells showed that when given along with chemotherapy, CBD may make chemotherapy more effective and increase cancer cell death without harming normal cells. Studies in mouse models of cancer showed that CBD together with delta-9-THC may make chemotherapy such as temozolomide more effective.

Stimulating appetite

Many animal studies have shown that delta-9-THC and other cannabinoids stimulate appetite and can increase food intake.

Pain relief

Cannabinoid receptors (molecules that bind cannabinoids) have been studied in the brain, spinal cord, and nerve endings throughout the body to understand their roles in pain relief.

Cannabinoids have been studied for anti-inflammatory effects that may play a role in pain relief.

Animal studies have shown that cannabinoids may prevent nerve problems (pain, numbness, tingling, swelling, and muscle weakness) caused by some types of chemotherapy.

Nausea and vomiting

Cannabinoid receptors found in brain cells may have a role in controlling nausea and vomiting. Animal studies have shown that delta-9-THC and other cannabinoids may act on cannabinoid receptors to prevent vomiting caused by certain types of chemotherapy.

Anxiety and sleep

Cannabinoid receptors found in the brain and other parts of the nervous system may be involved in controlling mood and anxiety.
Anti-anxiety effects of cannabidiol (CBD) have been shown in several animal models.

Here’s an older study (2006) that is interesting as it specifically calls out angiogenisis. Typically a tumor starts growth without much blood supply. Later, blood vessels form to feed it (angiogenisis) and if that step doesn’t happen, it has a more limited future growth. In any case, these were folks with recurrent and essentially untreatable cancers who were given an experimental dose of THC mostly to see if it had horrid bad effects or if it was OK to test it on less terminal folks… Yeah, medicine is like that…

http://www.nature.com/bjc/journal/v95/n2/abs/6603236a.html

Translational Therapeutics
BJC Open article

British Journal of Cancer (2006) 95, 197–203. doi:10.1038/sj.bjc.6603236 http://www.bjcancer.com
Published online 27 June 2006

A pilot clinical study of Δ9-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

1Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, Madrid 28040, Spain
2Department of Neurosurgery, Hospital Universitario de Canarias, La Laguna, Tenerife 38320, Spain
Correspondence: Professor M Guzmán, E-mail: mgp@bbm1.ucm.es; Professor L González-Feria, E-mail: lgferia@yahoo.es

Revised 15 May 2006; Accepted 5 June 2006
Advance online publication 27 June 2006

Abstract
Δ9-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). Δ9-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.

Keywords: cannabinoid; glioblastoma multiforme; pilot clinical study; antitumoral drug

So it didn’t cure the incurable, but did slow it down. At least in this trial. One wonders what a mixed THC / Cannabinoids would do…

Here’s a study from 2015 finding a cannabinoid component useful in breast cancer treatment:

http://www.moloncol.org/article/S1574-7891(14)00295-6/fulltext

Modulation of the tumor microenvironment and inhibition of EGF/EGFR pathway: Novel anti-tumor mechanisms of Cannabidiol in breast cancer

Mohamad Elbazemail, Mohd W. Nasseremail, Janani Raviemail, Nissar A. Waniemail, Dinesh K. Ahirwaremail, Helong Zhaoemail, Steve Oghumuemail, Abhay R. Satoskaremail, Konstantin Shiloemail, William E. Carson IIIemail, Ramesh K. Ganjucorrespondenceemail

Highlights
•CBD inhibits TNBC proliferation, migration and invasion.
•CBD inhibits EGF/EGFR signaling pathway and its downstream targets.
•CBD inhibits GM-CSF, CCL3 and MIP-2 secretion from cancer cells.
•CBD inhibits breast cancer growth and metastasis in two mouse models.
•CBD inhibit M2 macrophage recruitment to the tumor stroma.

Abstract

The anti-tumor role and mechanisms of Cannabidiol (CBD), a non-psychotropic cannabinoid compound, are not well studied especially in triple-negative breast cancer (TNBC). In the present study, we analyzed CBD’s anti-tumorigenic activity against highly aggressive breast cancer cell lines including TNBC subtype. We show here -for the first time-that .CBD significantly inhibits epidermal growth factor (EGF)-induced proliferation and chemotaxis of breast cancer cells. Further studies revealed that CBD inhibits EGF-induced activation of EGFR, ERK, AKT and NF-kB signaling pathways as well as MMP2 and MMP9 secretion. In addition, we demonstrated that CBD inhibits tumor growth and metastasis in different mouse model systems. Analysis of molecular mechanisms revealed that CBD significantly inhibits the recruitment of tumor-associated macrophages in primary tumor stroma and secondary lung metastases. Similarly, our in vitro studies showed a significant reduction in the number of migrated RAW 264.7 cells towards the conditioned medium of CBD-treated cancer cells. The conditioned medium of CBD-treated cancer cells also showed lower levels of GM-CSF and CCL3 cytokines which are important for macrophage recruitment and activation. In summary, our study shows -for the first time-that CBD inhibits breast cancer growth and metastasis through novel mechanisms by inhibiting EGF/EGFR signaling and modulating the tumor microenvironment. These results also indicate that CBD can be used as a novel therapeutic option to inhibit growth and metastasis of highly aggressive breast cancer subtypes including TNBC, which currently have limited therapeutic options and are associated with poor prognosis and low survival rates.

In Conclusion

There ARE negatives to Marijuana consumption, especially for young boys where it can interfere in the testosterone / estrogen balance results (link in another article later). It also causes some degree of confusion (personal experience …) and it can even cause a minor kind of paranoia if you are sitting in a Denny’s at 1 AM scarfing down pancakes and 2 cops sit down at the counter across from your booth… but I digress…

So for me, it has never held a whole lot of interest. I “tried it” back in the ’70s and largely moved on.

HOWEVER:

It does look to have very definite medical properties in several areas and especially for anyone with terminal cancer, well ‘worth a shot’. I’d not mix it with any other cancer treatment without the M.D. saying “OK”, but once you have that “nothing more we can do” line in your face, it looks like a reasonable “well hell, why not” response.

I’ve found many other such articles, including one specifically about prostate cancer. It does look to be particularly effective in the cancers of the estrogen / testosterone sensitive tissues (my guess). Since just about any guy over 60 to 70 is looking at eventual prostate cancer formation, I expect we’ll be seeing a whole lot more old guys with red eyes in our future ;-)

I’d also expect we’ll be seeing a large number of derivative drugs come out of it as it gets processed through the drug industry.

I’m not going to be headed out to ‘score a baggy’ any time soon since among other things I have a tendency for it to just put me to sleep (part of why that ’70s experiment was a short one… pay a chunk of change to stuff down a whole bag of Chips and Dip and then fall asleep? Why?…) but it is pretty clear a lot of folks don’t react that way. For anyone on chemo, that might be a feature anyway…

So count me on the side of those who endorse legalization of Marijuana (for whatever use… you are an adult and it is your body, not mine and not the government’s and certainly not your employer’s…) even if it isn’t particularly attractive to me. Besides, some day I might need something that shrinks tumors, slows or stops their spread, and inhibits angiogeneses all while making chemo tolerable and getting me to eat even while feeling horrid.

In short, looks to me like it works at least as well as most of the stuff pushed on us by The Medical and Drug Establishment.

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