Uncommon suffering

Oct 27 2010 Published by under Medicine

(I'm giving you fair warning: this is a long piece, but I've divided it up for you.  Each part will do fine on its own, but of course I'd like you to read both. You'll be a better person for it. --PalMD)

Part I: Uncommon Sense

Everything was OK until Christmas; before that she felt fine.  Then she began to feel tired.  She was having trouble sleeping so, she thought, maybe that was it.  She tried some sleeping pills from the drugstore, but she still didn't feel right.  Just doing a load of laundry wore her out.  She and her husband normally got together with the same set of friends every New Year's Eve, but this year she was too tired.   She hated New Year's Day, because every year she made another set of resolutions, usually about her weight.  When she got on the scale this year, she was up twenty pounds. Twenty pounds!  Impossible!  Her pants fit more or less the same, although her shoes were tight.  In fact, she'd been wearing unlaced shoes around the house and couldn't really fit into most of her socks.  She went to bed disappointed.

That night she woke out of a sound sleep and sat bolt upright---she couldn't breathe.  She ran to the window, threw it open, and gulped in cold air, slowly feeling better.  Her husband called an ambulance.

Heart failure is a condition in which the heart isn't pumping well enough to meet the body's needs.  Fluid can back up into the lungs, making it hard to breathe, the legs can become  swollen; and depending on the severity, heart failure can lead to sudden death.   One of the mainstays for the treatment of heart failure is a class of medications called diruetics which cause patients to urinate more, decreasing swelling and easing breathing.  But diuretics don't really affect the heart itself, they just drain off fluid, alleviating some symptoms.  It seems logical that if a failing pump is responsible for many of the symptoms of heart failure (and it is), then medications that improve the pumping action would be a good thing, and those that decrease it bad.  It's common sense.  It's intuitive.

Medical students and residents often dread discussions about statistics (a characteristic which I'm sure is not unique to these groups).  And who can blame them, really?  Statistical analysis is inherently non-intuitive.  Its purpose is to separate us from our own natural inclinations to identify patterns (our "intuition") in order to systematically study relationships between variables of interest.

A number of years ago, doctors noted that a certain class of drugs ("inotropes") improved the pumping action of the heart.  Patients with heart failure were given these drugs, and their heart function improved.  Common sense, right?  But when the topic was studied systematically, researchers found that these drugs actually increased mortality.  Oops (in this case, "oops" means people dying).

Another group of drugs called beta-blockers can reduce the pumping action of the heart, and for years were assiduously avoided in heart failure---until study after study showed that beta-blockers actually decrease mortality in chronic heart failure.

Common sense can give us a starting point, but until the big questions are examined systematically, we are in danger of intuiting our patients to death.  Beta blockers are now a mainstay of heart failure treatment, and inotropes a rarely-used footnote, a treatment reserved for a specific set of circumstances.  But we didn't figure that out through common sense alone.

Part II: Does smoking pot cause cancer?

Since common sense is such a poor tool, we have to find other tools to hunt down the truth, and there are many ways to ask and answer important medical questions.  Recently, I explored one way to look at risk reduction, in this case, vegetables and cancer, and this got me thinking---what if I wrote something in a bit more detail about how we evaluate the risk or benefit of a behavior?  Would any sane person read it?  Would I be able to make it make sense?  What if I pick a sufficiently controversial topic?  Let's run with it.

Smoking things is bad for the lungs.   Cigarette smoking causes chronic obstructive lung disease and lung cancer.  We can't predict exactly who will be affected, but we do know that the more you smoke, the higher the risk.  Given that smoking cannabis is also popular, and that eventually it is likely to become legal, it is reasonable to ask if smoking cannabis causes cancer as well.  Common sense would suggest it.

Tobacco contributes to the development of several types of cancer.  When it is smoked it causes lung cancer.  When it is chewed, it causes oral cancers.   Both types of ingestion can contribute to head and neck cancers.  Since tobacco can cause so many different kinds of cancer, it seems plausible that there may be something about tobacco itself, rather than just the smoke, that leads to lung cancer.   Since pot is most often smoked without tobacco, maybe it's not as high-risk.

Still, lung cancer is pretty dreadful, and if we anticipate cannabis use increasing, it would be good to know if it also leads to cancer.  There are a number of ways we can ask this question.  There are also a number of difficulties.  Lung cancer is relatively rare, so large numbers of people need to be studies.  It also takes a long time to develop, so we need a lot of "person-years" or data.

The strongest way to look for an association would be a randomized controlled trial (RCT).  In an RCT, a group of people are randomly selected and divided into groups.  In this case, one would be given pot to smoke, and another group given something to smoke that is known not to cause cancer as a control.  The two groups could be followed over time, and then at a certain point, cancer cases could be compared between the two groups.

But we aren't going to do this, even though this is the most robust way to study the question.  For one thing, we don't have access to a good control substance, something that people could smoke, is enough like pot to fool them, but is known not to cause cancer.  We also can't ethically subject subjects to something we think is reasonably likely to cause grave harm.  An RCT is pretty much out.

Another way to go about asking the question is a cohort study.  In a cohort study, we could gather a group of pot smokers, and identify a similar group of non-pot-smokers and follow them for a specified period of time (or until a particular outcome happens).  We can then look at lung cancer rates in in each group too see if there is a significantly larger number of cases in the pot-smoking group.    This isn't a terrible way to look at the question, but probably would require a lot of patients over a long period of time.

An easier choice would be a case-control study.  In a case-control study, we don't have to wait for enough people to develop lung cancer---we start off by picking a group of lung cancer patients, and then pick out a group of patient similar to them but without lung cancer.  We can then look at all sorts of variables and compare the groups.  This is how the first large study of lung cancer and smoking was done.  But there are a lot of limitations to this sort of study, not the least of which is having to obtain accurate historical information. There will inevitably be some element of recall bias, in which subjects recall their histories in ways that systematically differ from what actually happened.  It's easy to believe that someone just diagnosed with lung cancer might be hyper-attuned to possible past risky behaviors.  Still for rare diseases that take a long time to develop, this is often the only design that is practical.   And while this sort of study can identify correlations, case-control studies are not great for identifying causation.  But they can lead to further studies with different designs, studies that would not seem worthwhile without initial favorable evidence.

And this was the approach taken by researchers in New Zealand.  They identified a group of patients with lung cancer, and compared them with a similar group of people taken from a voter registry.  The then divided them into "pot smokers" and "pot non-smokers" (which included some light pot-smokers), and further divided the pot group by how much they recalled smoking.  The results were fairly striking.  When comparing non-pot-smokers to the heaviest smokers (more than 10.5 "joint-years", with a joint-year being one joint per day for a year) the odds of developing lung cancer were 19 times higher in the heavy smoking group (these relationships held even when controlled for tobacco smoking).  Depending on what estimates you use, you would only have to have a few people become heavy pot smokers to cause an extra case of lung cancer.

These data are similar to those found for cigarette smoking: the more you smoke, the higher your risk.  This case-control study cannot establish cause beyond doubt, but the evidence is pretty strong.   It is biologically plausible that smoked cannabis causes lung cancer, and this case-control studies and others support the association.  Perhaps future cohort studies will give us more information, but at this point, people smoking significant amounts of pot who would otherwise have normal life-expectancies might want to reconsider.

Part 3: Synthesis

My grandfather was, by all accounts, an exceptional man.  I never had the chance to know him; he died of lung cancer when I was very young.  I remember my dad sitting me down on the bed and telling me that Papa had died.  I also remember going to a strange, spooky building to return his oxygen tanks when he no longer needed them.  But that's pretty much it. The rest of my memories belong to others.  Many years later, not long ago in fact, I was up north with my family for a week.  It's been a family tradition for generations, and that particular year, the family was large.  My aunt (Papa's daughter) was there, despite her advancing lung cancer.   I said goodbye to her on the front porch the evening before leaving, and said, "I'm really glad you came."  She said, "Me too," and we both knew exactly what we meant.  That was the last time I saw her before her death.

Heart failure can be a miserable disease, but the last couple of decades have seen a revolution in its treatment.  Some of our biggest gains against heart disease have been due to identifying its cause and helping people avoid risks.  Lung cancer, though less common, is a dreadful disease, one where we've made some gains, but not enough.  Eighty-ninety percent of lung cancer deaths are due to smoking.  This makes these deaths preventable.

Everyone has to die of something, but modern medicine has given us tools to help prevent suffering and death.  Morally, I've got nothing against marijuana.  But if it really is as potent a risk factor as suggested by this study, people might want to think twice before sparking up.

References

Packer M, Carver JR, Rodeheffer RJ, Ivanhoe RJ, DiBianco R, Zeldis SM, Hendrix GH, Bommer WJ, Elkayam U, & Kukin ML (1991). Effect of oral milrinone on mortality in severe chronic heart failure. The PROMISE Study Research Group. The New England Journal of Medicine, 325 (21), 1468-75 PMID: 1944425

Fonarow, G., Abraham, W., Albert, N., Stough, W., Gheorghiade, M., Greenberg, B., O'Connor, C., Sun, J., Yancy, C., & Young, J. (2008). Influence of Beta-Blocker Continuation or Withdrawal on Outcomes in Patients Hospitalized With Heart FailureFindings From the OPTIMIZE-HF Program Journal of the American College of Cardiology, 52 (3), 190-199 DOI: 10.1016/j.jacc.2008.03.048

DOLL R, & HILL AB (1950). Smoking and carcinoma of the lung; preliminary report. British medical journal, 2 (4682), 739-48 PMID: 14772469

Aldington, S., Harwood, M., Cox, B., Weatherall, M., Beckert, L., Hansell, A., Pritchard, A., Robinson, G., Beasley, R., & , . (2008). Cannabis use and risk of lung cancer: a case-control study European Respiratory Journal, 31 (2), 280-286 DOI: 10.1183/09031936.00065707

18 responses so far

  • Isabel says:

    "This case-control study cannot establish cause beyond doubt, but the evidence is pretty strong. "

    Right we don't want to depend on the results of one study. Here is an even larger case-control study which found no connection.

    http://www.scientificamerican.com/article.cfm?id=large-study-finds-no-link&ref=rss

    Most studies (and despite the impression Pal gives, many have been done to try and resolve this issue) agree with the California study.

    In other words pot is magical and completely harmless;)

  • El Picador says:

    "in Los Angeles".

    Call me crazy but isn't it possible that the smoggiest city in the US may not be the best place to look at lung cancer rates?

    Can you point us to some studies from clean-air environments, Isabel?

    • PalMD says:

      I heard LA is all lotus blossoms and happiness.

    • Isabel says:

      El Picador you're crazy! Anyway, give me a break. If they are *all* living in the smog what difference would it make? Anyway I think they cleaned it all up in the 70's. The reality is, tobacco raises the risk of many more cancers than can be explained by the smoke itself. Perhaps our magical bodies can deal with smoke better than we realize. Especially when we combine smoking with the cancer-fighting effects of cannabis.

      • DaveH says:

        If the incidence of cancer is already higher due to another factor (in this case smog), then the extra incidences of cancer due to the marijuana represent a smaller proportion of the variance, and has the potential to become lost in the noise of the other signal.

        Without knowing the mathematical specifics, it's hard to say if that is the case. But... as the majority of people do live in cities, the relative risk of smog v. pot might be interesting.

  • El Picador says:

    Oh, I'm with you on the coffin nails, Isabel. Those suckers'll kill you!

  • PalMD says:

    I'm assuming the "cancer fighting effects of cannabis" was tongue in cheek.

    Lest anyone think I'm entirely insane, I'm not terribly fond of prohibition (it's making a wreck out of steve buscemi, right?), but ignoring complex evidence will not help people make smart decisions.

  • Isabel says:

    Well, just think of the benefits of more research into safer delivery methods if it becomes legal.

    I do try to keep up with the research, and use it in moderation. The thing is, there is a hyperfocus on cannabis. We can make anything look bad by doing a million studies. We hold Cannabis to a higher standard, both legally and morally. This is the focus of my fascination with the subject.

    The stronger pot available today means less leaf material smoked and is positive thing.

    • PalMD says:

      "We can make anything look bad by doing a million studies" is cynical and wrong. We can make anything look good or bad depending on how we manipulate the truth, but as data accumulate, the truth tends to precipitate.

      As far as "pot stronger=can smoke less", i don't buy that one.

      • Vicki says:

        For at least some people, stronger -> smoke less is valid, because the aim is to reach a certain mental state, and if it takes 1/3 (arbitrary number) as much pot to reach that state, they'll smoke about 1/3 as much. "About" because none of this is precise; it's not neatly labeled the way I can get a drink with a known ethanol percentage, and if I want measure out a specific quantity with various handy tools like measuring cups.

        I think the alcohol analogy is valid: someone who drinks beer sometimes and Scotch sometimes might regularly have three drinks on an evening out, but the quantity of liquid involved will not be the same: even if there's a mixer, the cocktails will likely be smaller than the beers.

        The question is, in part, how much of the risk is from smoke qua smoke, and how much is from chemicals specific to cannabis? The smoke risk should be less if people are using a smaller quantity of pot to get the effect; any risks from THC or other cannabinoids might be equal or even greater.

  • snoey says:

    >I’m assuming the “cancer fighting effects of cannabis” was tongue in cheek.

    No idea if this has held up, but:

    http://www.sciencedaily.com/releases/2007/04/070417193338.htm

  • P4 says:

    The conclusion of this was terribly disappointing, as I was expecting the obvious question to arise: does PO marijuana cause cancer? Does dronabinol cause cancer? If not...well, there's your solution, duh. Nobody has to smoke marijuana to obtain the benefits, and nobody who seriously studies its medicinal use has suggested doing so.

    • PalMD says:

      There is also vaporisation...

      But there are many, many people who argue that smoking is far superior to other methods of cannabanoid delivery.

    • Isabel says:

      What is PO?

      "Nobody has to smoke marijuana to obtain the benefits, and nobody who seriously studies its medicinal use has suggested doing so."

      There are many advantages to smoking, the main one being precise dosage control (controlled by the user). The second immediate effects, which is related to reason#1. Third is different effects-eating it is different.

      Surprisingly, last time I researched it anyway, vaporizing had not been shown to have a clear health advantage.

  • daedalus2u says:

    I was at a talk that Thomas Insel gave a couple of weeks ago, and he made the statement that something like 38% of all cigarettes smoked in the US are smoked by people with schizophrenia.

    Nicotine is not the only physiologically active substance in tobacco smoke. I suspect that it is the carbon monoxide that schizophrenics are using to self-medicate. Of course they can get addicted to nicotine too but I don't think that improves their schizophrenia.

    CO has cross-talk with many NO pathways that involve hemes. CO binds to heme a few orders of magnitude weaker than does NO, so it takes ppm of CO to mimic ppb of NO.

  • Rune C. Olwen says:

    @ daedalus2u: interesting idea.
    (Perhaps I will have a chance to ask a very intense smoker with a schizophrenics diagnose in a few weeks, for him it is definitely self-medication)

    "The question is, in part, how much of the risk is from smoke qua smoke"
    Is there any data about smoking sage?
    Or, comparing the outcome of longterm "cleansing rituals" with sage to passive smoking?

    I have taken part in some new age rituals some years ago, but I did never get used to any stink = my name for smoking of plants AND room scents. And the chance of trying THC or several cannabinoids in solution as a muscle relaxing medicine never arose.

  • You should google Tashkin et Al for cannabis and lung cancer.

    Dude, any update on this: http://scienceblogs.com/whitecoatunderground/2009/11/kids_got_autism_get_em_high.php

    You didn't answer the last few replies. How do you feel about it now?