Cannabis and cancer cachexia

One of the most frightening symptoms of advanced cancer is "cachexia", or severe, unintentional weight-loss and wasting. It's a terrible prognostic sign, and the only truly effective treatment is removal of the cancer. Treatment of this syndrome has the potential to improve quality of life in patients with advanced cancers. Various types of medications, including antidepressants, hormones, and cannabis derivatives have been tried with little effect. Treating the symptoms of incurable cancers is difficult and although we're pretty good at it, we sometimes fail. Cannabis seems a plausible intervention, given the anecdotal and clinical data associating it with increased appetite, although appetite in normal, healthy individuals may be mediated by different pathways than the cachexia in cancer patients. Still, it's worthy of investigation.

(As an aside, what a person with advanced cancer does to find relief is their own business. I hope that we don't fail them so miserably that they have to resort to desperate measures. I once had an elderly patient who was shooting up heroin for his cancer pain because he didn't understand the medical system well enough to seek proper help. He did fine on long-acting oxycodone.)

The Journal of Clinical Oncology published an interesting study in 2006 investigating the possible use of cannabis to treat cancer-related cachexia. Since self-administration of self-procured pot is rather inexact, the investigators compared whole marijuana extracts, purified THC, and placebo. The results were a disappointment for those looking for better treatment of advanced cancer.

While cannabis extract was well-tolerated, there was no difference between the groups, although all groups including placebo had some relief of symptoms. Appetite and quality of life saw similar changes in each group. It may be argued that the dose was insufficient, but the investigators chose the dose based on previous studies that showed too many adverse effects at higher doses.

As already mentioned, the failure could be due to a number of reasons, the most likely being that cannabis does not have a mechanism of action that acts on the same pathways as cachexia---the inflammatory cytokines present in cancer cachexia do not seem to be significantly modulated by cannabis. While cannabis may make some people feel better, there is no consistent evidence that it is any better than placebo in making patients with cancer wasting syndrome feel better.


Strasser, F. (2006). Comparison of Orally Administered Cannabis Extract and Delta-9-Tetrahydrocannabinol in Treating Patients With Cancer-Related Anorexia-Cachexia Syndrome: A Multicenter, Phase III, Randomized, Double-Blind, Placebo-Controlled Clinical Trial From the Cannabi Journal of Clinical Oncology, 24 (21), 3394-3400 DOI: 10.1200/JCO.2005.05.1847


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Out of It: A Cultural History of Intoxication, by Stuart Walton, Walton makes the argument that the stories about how drug and alcohol use inspire creativity are partially rooted in a desire to see those substances legalized. While weed certainly has some beneficial properties, I suspect that the same factor is largely at work here with pot. People want it legalized, so they can smoke it. However, it is viewed as unseemly, immature, and morally wrong to even argue for legalization for recreational view. So, people conjure up medicinal stories, couple them with conspiracy theories, blended that alloy of nonsense with some personal rights arguments to create a more socially acceptable argument for decriminalization.

What is this, "medical marijuana is a crock" week? I'd be very interested if you bothered to dig up any studies that showed positive results in patients using it, but as always, the author's bias determines the information provided.

Hey, the "Pub" in PubMed is for "public". It's all there.

OOOOOOH. Looks like my cure for cancer has been censored. Now, let me see. From that perspective I presume the following:

1) You work for the government, in which case I have less than 24 hours to live before I "commit suicide" and am found dead in my car for offering to cure a disease.

2) Same thing as number 1 except replace government with drug company.

3) You are an advocate for population control and love your perfect imaginary utopia better than human life so you let the sick die to save the earth.

4) You simply want to censor me - like all liberals who love free speech do.

Take your pick.

If anyone is interested in alternative cures to government medicine, let me know. But keep it quiet. We both may end up "committing suicide". At least that's how the FBI defined it.

Let's face it. Everyone who has come up with a supposed cure for a disease in the last 30 years has ended up dead and his work vanished. It is smells like tyranny and looks like tyranny, it must be tyranny.

I guess some people just don't believe in free speech as they claim.

By Dr. Smart (not verified) on 24 Nov 2009 #permalink

Oh well. at least I get to post the truth on my own site - until Obama has me assasinated and shut my site down. I am sure my name was sent to the government hit list -

sigh. You try to help some people...

By Dr. Smart (not verified) on 24 Nov 2009 #permalink

I once had an elderly patient who was shooting up heroin for his cancer pain because he didn't understand the medical system well enough to seek proper help.

He didn't understand the medical system well enough to seek proper help, or he knew he was not going to be given enough opiates to keep him comfortable because of fucked up concerns that terminally ill people are going to get "addicted" and thus must not be allowed enough to feel ok and enjoy the last days of their lives?

Look, there may be some people living in Arizona, Utah and Arkansas with a cure for cancer as we speak. However, what they want in return for that cure may scare you enough to want to die anyway. It isn't moeny either. Remember that there are worse things in this world than death. I could get that cure next week if i wanted, but I fear these people. My mott is " I fear no man, I bow to no man", but these people have unspeakable power. They are not normal men. Not even the KGB or the CIA dare screw with these men. They could crash civilization as we know it and not blink an eye. Cushman, Sedona, and Salt Lake is all I can tell you. Don't go there snooping around for these people, or you'll end up in a cage being their pet. There have been few who knew them or met them and then told their tale.

Don't tell me someone is not withholding information about curing diseases. I know better. The little herbal remedies notes I gave you earlier is my own version of a cancer treatment. These people could cure you in minutes, but you would not like what they want in return.

A customer of mine told me of his cancer and I gave him some herbal pointers and some information on alternative medicine for cancer. He hated chemo. I steered him away from it after seeing how it hurts people more than helps in early stage cancer. He took my advice. As far as I know he is still doing okay. My own mother died from breast cancer in 2001. Her chemo shortened her life and the Al Qeada doctor (he was from Pakistan) that treated her was a quak and a freak. I would love to give him some chemo up the ass.

Our HMO ( a wonderful idea) would not pay for her treatments just anywhere. Her doctors were limited. I hate this kind of insurance. I think insurance that takes your money and the dictates to you which doctor you can see should be prosecuted and hanged. Tyranny is not forgiveable.

By Dr. Smart (not verified) on 24 Nov 2009 #permalink

As someone in the arts who doesn't smoke, smoke up or drink alcohol, when these forms of relief are cited by friends -not friends with cancer, to be clear- they often say that it helps them relax, it helps them sleep, it keeps them "even" (whatever that means), it aids creativity.

When I'm stressed, I play video games. I wonder how much a distracting comfort in general helps people when severely ill? I understand cannabis has a chemical effect that gaming does not and this could possibly be shown to have benefits. I agree with you Pal that what advanced cancer patients do is their own business.

I think there may be some truth, some of the time to what History Punk suggests.

"Dr. Smart":

A customer of mine told me of his cancer

You don't have customers, you have a vivid imagination and no ability to read (hint, PalMD wrote about a condition related to cancer).

And if you are delusional enough to think you are a doctor and actually solicit patients, they are not customers, they are victims.

Interesting article. It's good to have real data.

When my friend had cancer, he was throwing up the oral anti-emetics his doctors prescribed, so his father gave him some pot. (My friend was in his 20's at the time and could have gotten his own, but because it is apparently trivial to get a medical marijuana card in our city, his father already had one.) It worked, but eventually the doctors were able to fiddle around with the dosing schedule so that the anti-emetics stayed down, and my friend stopped taking it. Are there other non-oral, non-injectable anti-emetics he could have tried?

Well mr. Chris. let me tell you this.

When the Obama healthcare plan starts to tell people that they are not cost effective (too old) to get treatment for their ailments, I will be right there to help those VICTIMS of government tyranny. If they have cancer, diabetes, etc, I will be there to offer alternatives to government medicine. I have even told people I know to start saving a pill or two of their medicine each month and freeze it so that when rationing comes we can hlep people by giving away this life saving medicine.

I do have customers. Sorry to disappoint you. My customers seemt o like me too. So far I had no complaints. As a matter of fact one of my co-workers with diabetes is considereing quitting his high priced medicine and going with herbal and supplemental alternatives like Chromium, etc. I asked not to do it uless he lost at least 35 pounds and got his sugar a little more balanced. Then I would help him get rid of his medicince and cure his diabetes. Type II diabetes is curable. Doctors say it isn't. I don't blame them. If I could keep someone fat and coming back making me money, I would too. I get no money from anyone. My services are completely profit free and voluntary. Thank you.

People complain how greedy insurance companies are (and it's true), but never complain how greedy the doctor is.

By Dr. Smart (not verified) on 24 Nov 2009 #permalink

Type II diabetes is managed through diet and exercise, not cured.

You are either an idiot troll or a Poe troll.

Chris, you are completely deluded.

Type II diabetes CAN be cured, but only with colloidal silver in a homeopathic solution. Dr. Smart has more details, I'm sure.

Dr. Smart posted a whole list of substances which may have some degree of anticancer properties in various model systems, but have no proven effect in human anti-cancer trials.

eg. Selenium, while a very old trial suggested a protective effect, recent comprehensive trials and meta-analyses could find no significant effect of selenium on cancer mortality.
Lippman SM, Klein EA, Goodman PJ, et al. Effect of selenium and vitamin E on risk of prostate cancer and other cancers: the Selenium and Vitamin E Cancer Prevention Trial (SELECT). JAMA (2009) 301(1):39â51
see also Cochrane Database Syst Rev. 2008 Jul 16;(3):CD004183.

Curcuminin: Works a treat in tissue culture and animal models where it can be injected. There's lots of failed cancer therapies where that is true. Lousy bioavailability, it's very hard to get any real amount of curcuminin into the body. Currently no clinical trial data to suggest it is at all efficacious in cancer.

Green Tea: I work on this stuff. Some of the chemicals that are in green tea can kill cells in dishes and in certain animal models, but again getting a meaningful amount of this stuff into the body is really, really hard. Prospective studies suggest a reduction in cancer risk of between 10% to 20%, depending on how much your drink. Prospective studies can be misleading misleading, and controlled trials will need to be done to evaluate Green teas effect properly. Nonetheless, even at the most optimistic, cancer incidence reduction will not be large.

It's quite easy to show chemicals kill cancer cells in petrie dishes (we're working on some of these things in the lab right now), but there are lots of reasons why these things, which may or may not work in animal models, will not work in humans (whether you can get enough of the chemical into the body to have an effect, how the body breaks down the chemical, how the blood supply is delivered to the tumor etc. etc. etc. Just because something has an antioxidant effect doesn't mean it will have any anticancer effect.


Type II diabetes CAN be cured, but only with colloidal silver in a homeopathic solution.

LOL... :-p

Dr. Smarts original submission was removed, my comment was aimed at credulous claims for products as anti-cancer therapies.

Dr. Smart now says:

As a matter of fact one of my co-workers with diabetes is considereing quitting his high priced medicine and going with herbal and supplemental alternatives like Chromium, etc.

Probably a really bad idea, while chromium picolate can improve insulin sensitivity, and may help reduce the amount of anti-diabetic drugs needed, there is yet no evidence that it can replace anti-diabetic medicines in type II diabetes (indeed, in all the trials I looked at, type II diabetics added chromium to their existing medications).

Diet and exercise can certainly improve insulin responsiveness, and reduce medication needs in type II diabetes, but even with good compliance anti-diabetic medication is still needed. Suggesting to someone that they can go off their diabetic medications with chromium supplementation is very dangerous.

Can Fam Physician. 2009 Jun;55(6):591-6.
Ophthalmic Physiol Opt. 2008 Nov;28(6):503-23.
But see Metab Syndr Relat Disord. 2009 Summer;7(2):143-50. Where a range of problems are not normalised by chromium

Blah blah Obama healthcare plan blah blah blah blah blah blah blah blah blah blah (blah blah) blah blah blah blah blah blah, I will be right there to help those VICTIMS of government tyranny.

At the risk of feeding a troll:

Where were the teabaggers during the eight years that george w. bush was in the White House?

Where was the concern for government tyranny when the "Patriot" Act was before Congress?

Where was the worry about government spending when the neocon artists were lying about Iraq to gin up a war over nonexistent WMDs? (Oh, yeah, I just remembered, it isn't zOMG SOOOOOOOOCIALISM! when Publican fatcats get the money.)

Um, Ray C., the bit you picked out is about the sanest thing Dr. Smart has said in the entire thread. Look at the first two paragraphs of post #7 - either this guy is a troll/Poe who should be working as a script writer for the X-Files, or he's completely lost touch with reality, and then some.

History Punk is right -- people wanna smoke dope. And because that's true, when the government makes it illegal, it's only available illegally, but people still wanna smoke dope.

The best outcome of federal legalization of marijuana would be that it would eventually eliminate the criminal violence associated with providing it to those who wanna smoke dope. The way it's semi-legalized in California and a few other states can't accomplish this goal without a federal OK.

I once had an elderly patient who was shooting up heroin for his cancer pain because he didn't understand the medical system well enough to seek proper help.

I have a youngish patient who was shooting up heroin because he couldn't afford to buy the prescription medications. Once he admitted the problem, got social work help, and had the proper meds he was no longer in pain and as a bonus could think clearly. This same patient, a guy with sacral mets and severe pain on weight bearing, was walking to the hospital every day to get radiation because he couldn't afford the bus. Had to try several programs before finally finding one that could help him with that. Sometimes it's not just the health care costs per se that prevent care.

This article isn't about anti-marijuana bias. This is about separating our personal political views and looking at the evidence. Personally, I think that marijuana should be legal for everyone, with similar restrictions to alcohol and tobacco. However, I still don't think that we should push marijuana for medical uses if the evidence just doesn't support it. This isn't about bias; it's about evidence. If the evidence shows that it is safe and effective, then I'll fully support it, just as I'm sure PalMD will.

I have no real opinion about this but I am curious who funded the study and if there was special interest by any group lobbying or otherwise. Any chance of special interest or bias?

hmm there actually has been some interesting and legitimate research on diet and managing diabetes. I would like to see more studies with a larger population.

Original Human 'Stone Age' Diet Is Good For People With Diabetes, Study Finds

ScienceDaily (June 28, 2007) â Foods of the kind that were consumed during human evolution may be the best choice to control diabetes type 2. A study from Lund University, Sweden, found markedly improved capacity to handle carbohydrate after eating such foods for three months.

During 2.5 million years of human evolution, before the advent of agriculture, our ancestors were consuming fruit, vegetables, nuts, lean meat and fish. In contrast, cereals, dairy products, refined fat and sugar, which now provide most of the calories for modern humans, have been staple foods for a relatively short time.

Staffan Lindeberg at the Department of Medicine, Lund University, has been studying health effects of the original human diet for many years. In earlier studies his research team have noted a remarkable absence of cardiovascular disease and diabetes among the traditional population of Kitava, Trobriand Islands, Papua New Guinea, where modern agrarian-based food is unavailable.

In a clinical study in Sweden, the research group has now compared 14 patients who were advised to consume an âancientâ (Paleolithic, âOld stone Ageâ) diet for three months with 15 patients who were recommended to follow a Mediterranean-like prudent diet with whole-grain cereals, low-fat dairy products, fruit, vegetables and refined fats generally considered healthy. All patients had increased blood sugar after carbohydrate intake (glucose intolerance), and most of them had overt diabetes type 2. In addition, all had been diagnosed with coronary heart disease. Patients in the Paleolithic group were recommended to eat lean meat, fish, fruit, vegetables, root vegetables and nuts, and to avoid grains, dairy foods and salt.

The main result was that the blood sugar rise in response to carbohydrate intake was markedly lower after 12 weeks in the Paleolithic group (â26%), while it barely changed in the Mediterranean group (â7%). At the end of the study, all patients in the Paleolithic group had normal blood glucose.

The improved glucose tolerance in the Paleolithic group was unrelated to changes in weight or waist circumference, although waist decreased slightly more in that group. Hence, the research group concludes that something more than caloric intake and weight loss was responsible for the improved handling of dietary carbohydrate. The main difference between the groups was a much lower intake of grains and dairy products and a higher fruit intake in the Paleolithic group. Substances in grains and dairy products have been shown to interfere with the metabolism of carbohydrates and fat in various studies.

"If you want to prevent or treat diabetes type 2, it may be more efficient to avoid some of our modern foods than to count calories or carbohydrate," says Staffan Lindeberg.

This is the first controlled study of a Paleolithic diet in humans.

Story Source:
> Adapted from materials provided by Lund University .

Lund University (2007, June 28). Original Human 'Stone Age' Diet Is Good For People With Diabetes, Study Finds. ScienceDaily. Retrieved November 23, 2009, from /releases/2007/06/070627225459.htm

I'm with catgirl on this (what a weird thing to say - not the type of sentence that crops up in my daily life).

I figure legalization of pot and government control, as with alcohol and tobacco would be fine. I am also interested in the evidence for cannabis as medicine; in Canada we have Sativex for MS pain, and the clinical trials did suggest that it was helpful. I don't doubt that there will be other uses for cannainoids in medicine, but evidence of effectiveness and safety are essential.

By Epinephrine (not verified) on 25 Nov 2009 #permalink

That's disappointing... I would have thought that appetite stimulation would be one area where MM would be a slam dunk. Of course, this is just one study, so who knows...

The bottom line, as others have said, is that the political insanity around marijuana in general makes it almost impossible to evaluate the medical potential of cannibinoids. It's really unfortunate, because either a) patients are unable to receive a potentially effective treatment because of lack of research, or b) people are forgoing more effective conventional approaches in favor of self-medication with a bogus treatment. Or both. Any way you slice it, the uncertainty is bad for the public.

I think that the fundamental problem is that cancer cachexia is not caused by "lack of appetite" and pot seems to stimulate appetite. Cachexia is mediated by a variety of proinflammatory cytokines, none of which cannabis affects significantly.

I remember when that study came out. It was surprising and disappointing, because that was the thing I'd always been hoping for with marijuana. It seemed so promising. (Side-note: my grandfather recently passed away, and we believe that cancer cachexia was the immediate cause. Long story; he specifically refused to get it diagnosed, because, as an old surgeon, he was pretty sure it was pancreatic cancer, knew what would be needed in order to diagnose it, felt that his 91 years were sufficient, and definitely didn't want a lot of medical interventions to prolong his life. He actually welcomed the cachexia, figuring it would be a relatively dignified way to go. And in the end, go he did. He hastened the process by also refusing all liquids apart from liquid morphine, highballs, and the occasional bottle of Dos Equis.)

But if marijuana acts on different pathways than cachexia, I guess that explains it. Too bad. But hopefully it can help with some other cases of lost appetite.

By Calli Arcale (not verified) on 25 Nov 2009 #permalink

James, the problem of cancer cachexia (and most other types of cachexia) is (mostly) not a problem of insufficient appetite. People can be fed intravenously at rates sufficient to make them calorie-neutral, i.e. they receive as many calories as oxidizable substrates as they are metabolizing. When this is done with people with cachexia, they continue to lose lean body mass (i.e. skeletal muscle) and gain fat.

The idea that cachexia is a problem of insufficient calorie intake is wrong, but many in the field do not appreciate that it is wrong.

I see cachexia as a derangement mostly in liver metabolism and in peripheral tissue metabolism. Most diet energy goes into making glucose by the liver. Cells then use that glucose to make ATP. If a cell has enough mitochondria, it makes that ATP by oxidative phosphorylation. If the cell does not have enough mitochondria, then it makes ATP via an alternative pathway, via glycolysis. It takes 19 times more glucose to make the same ATP via glycolysis as via oxidative phosphorylation. It the supply of ATP from mitochondria is reduced by 5%, then the cell needs twice as much glucose to support equivalent ATP production. Can the liver supply twice as much glucose? Can the vasculature supply twice as much glucose? Usually it takes hyperglycemia to supply more glucose. Many states that lead to cachexia produce hyperglycemia naturally, sepsis for example.

The liver makes glucose from 3-carbon substrates. During glycolysis, ATP and lactate are produced. Lactate is a 3-carbon substrate and can be converted back into glucose by the liver, but it takes mitochondria to do so, the mitochondria have to oxidize the NADH that is produced when lactate is converted into pyruvate as part of the glucogenesis pathway. If the liver doesnât have enough mitochondria to turn lactate into glucose, it can turn that lactate into fat (which takes less NADH consumption). In fact every cell can turn lactate into fat. That is what is observed in cachexia, ectopic fat starts to appear in tissue compartments that normally donât have droplets of fat, first visceral fat, next fat in the liver, then fat in skeletal muscle, and ultimately fat in organs such as the heart. When ectopic fat starts to appear in the heart, you are in a world of hurt and are in the terminal stages of what ever is causing the cachexia and killing you.

If (as I think) cachexia is due to derangements in metabolic capacity, increasing food consumption may make it worse. Diverting metabolic capacity to digesting food and generating ectopic lipid may be completely counterproductive and may even hasten death. It is metabolically âeasierâ to catabolize skeletal muscle, using muscle mitochondria to supply ATP for that proteolysis and then the liver converts the liberated amino acids into glucose. A good short term strategy when you need a lot of glucose for a short period (as in sepsis or running from a bear), a bad strategy for the long term.

The nausea that prevents food consumption during cachexia may be protective by reducing the metabolic load on the liver. Understanding and appreciating these fine details of physiology is quite challenging and likely quite idiosyncratic. It likely wonât be figured out by trying to apply a âone-size-fits-allâ approach.

Where in the diet-appetite-nausea-emesis-cachexia pathway MJ has its effects isnât known. If it acts by increasing liver metabolic capacity by fostering mitochondria biogenesis, it would (in my opinion help). If it blocks signals reducing food intake to spare liver metabolic capacity it would hurt. If it does both but to different extents in different people at different times for different causes of cachexia (which I think is most likely), then it is a complicated thing to understand and its current regulation as an illegal substance makes research to figure out complex multi-factorial aspects of it essentially impossible.

The anti-drug mentality has raised the bar for research on MJ to requiring extraordinary evidence before it can be done. Extraordinary evidence canât be obtained without research, research canât be done without extraordinary evidence.

@daedalus2u: Wait, how does NO figure into it? :P

The reviews on marijuana and psychosis that I've read say that there's evidence that marijuana induces psychosis preferentially in people who are already "pre-psychotic." Based on that, giving marijuana to a mentally healthy adult who does not have a history of addiction seems to have quite a low risk. Giving it to somebody with a history of occasional, possibly long-ago recreational use would have an even lower risk. I agree that more studies should be done before cannabis becomes a standard of care. However, in certain situations, doctors often prescribe low-risk drugs to that treat people's symptoms, and cannabis seems to me to fall into that category.

NO is what triggers mitochondria biogenesis and regulates how much ATP can be gotten via oxidative phosphorylation. Low NO reduces the mitochondria number and causes more glycolysis. When that gets bad it causes the metabolic syndrome (which is adaptive to get more glucose to cells that can't get enough).

NO is needed to "balance" the pro-inflammatory cytokines that PalMD mentioned. If there isn't enough NO, then those pro-inflammatory cytokines cause a low NO state which spirals down into eventual organ degeneration. Which organ fails first depends on the idiosyncratic details of that individual's physiology. Usually it is the high metabolic rate organs that fail first, brain, heart, liver, kidneys. Cachexia is a symptom of end stage organ failure in all of them.

if smoking cannabis makes cancer patients feel good then it is reducing stress -> good enough reason for me

also, it's been awhile but I do remember reading about the different kinds of cannabis - sativa and indica. One is more of a body buzz and one is more "heady" or psychoactive buzz but I haven't seen any distinction in any MM articles. that demonstrates to me that the surface has barely been scratched when it comes to medical research.

By Vash the Stampede (not verified) on 08 Jul 2010 #permalink