(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? Continue Reading »

When I lived in Northern California, I would often hear stories about people scouring the back country for psychedelic toads.  In popular imagination, these toad wranglers would then gather around bonfires and with great ceremony and earnestness, they would lick hapless bufoids until they (the humans) fell into ecstatic trances---and then vomited profusely. These stories, often parroted by local media, would end with the news that toad licking had finally been outlawed by the state.   The truth, as usual, is quite a bit more complicated.

Bufotenin, one of many molecules secreted by the skin and parotid glands of some toads of the genus Bufo, is classified by the DEA as a Schedule I drug.  This is the same class as heroin, mescaline, cannabis, and other drugs the DEA feels have a high potential for abuse and little or no therapeutic value.  Bufotenin is also present in certain mushrooms, so I wouldn't swear that is was outlawed because of a pandemic of toad licking.

But many toads are toxic.  While there are few reports in the literature about poisoning due to toad licking, there are plenty of reports of accidental toad poisoning.  Toads are a food product in parts of Southeast Asia.  There have been many reports of accidental toad poisoning in rural Laos, especially when toad skin and toad eggs are part of a meal.

But there's more than one way to get killed by a toad. A traditional Chinese herbal medicine called ch'an su *, which has been sold as an aphrodisiac, topical anesthetic, and a heart medicine, has been responsible for poisonings both in Asia and the U.S. (one of the versions sold in the U.S. was "marketed" as a topical medication, but was taken internally, perhaps for the hallucinogentic affects).  
Some of the chemicals present in toad venom are closely related to cardiac glycosides such as digoxin, a potent naturally-derived heart medication, and intoxication with toad venom closely resembles digoxin poisoning.  In fact, blood tests in victims are often positive for digoxin.  Given the similarities to digoxing poisoning, investigators have tried treating toad poisoning in a clever way. Digoxin (and toad) poisoning requires intensive medical care.  Even with close care, a patient can die of fatal heart arrhythmias.  But a couple of decades ago, an antidote was developed for digoxin poisoning.  Sheep are injected with digoxin and anti-digoxin antibodies are then isolated from their blood.  These antibodies are then chopped up so that only the "Fab" portion is present.  When given to a patient with digoxin toxicity, the Fab binds to circulating digoxin, preventing it from binding to other receptors in the body, and allowing it to be harmlessly excreted by the kidney.

Given how closely toad poisoning and digoxin poisoning resemble each other, and that toad toxins are similar enough to digoxin that they show up as digoxin in toxicology tests, it seems reasonable to think that the same antidote may work for both poisons.  This has been tested in several cases, with apparently good results (there data are limited by the small number of patients).

Cardiac glycoside poisoning is very dangerous.  It would appear that poisoning by sources other than regular medications has a high fatality rate.  Given this, it would seem reasonable to treat suspected toxicity with digoxin immune Fab.  The only catch is cost and availability.  If a kid in New York eats some Chinese toad venom, any hospital can administer the antidote.  If a woman in a small Laotian village eats a bad batch of toad soup, the cure may not be available.  The cost may also be prohibitive.  Each vial costs around $700, and it wouldn't be unusual to give 10 vials.

It may be hard to prevent toad poisoning among rural Laotians without solving societal problems of poverty and hunger.  But in this country we can easily avoid consuming potentially deadly herbal remedies.

*(a special shout-out to my buddy David Kroll who may be interested in this bit of history, if he doesn't already know it).

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Human beings are fundamentally narcissistic, and this narcissism can be antithetical to good science and good medicine. We place far too much confidence in our individual abilities to understand what happens to us, and we place far too much importance on our own experiences, inappropriately generalizing them. That's why science is so important in medicine---to avoid basing life-or-death decisions on something some guy thinks he might have heard once.
In my recent piece on medical marijuana in Forbes, commenters took me to task for what they perceived to be a host of errors in my reasoning. Some of these deserve to be specifically addressed, but not before a summary of the topic.
Marijuana's legal status is a political issue, not a scientific one. I will leave the politics to those cursed with such things. But I'm responsible for medical decisions, and as much as is possible, I have to look at data dispassionately. I have no doubt the individuals find marijuana beneficial for a wide range of problems---this may be a basis for study, but is not adequate data to prescribe a powerful pharmacologic agent.
In 2000, the University of California established the Center for Medicinal Cannabis Research. This month, they released a summary of results to date.

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In November, the citizens of my home state approved a medical marijuana law. The very next day, I started getting calls from patients (often not may own) asking how they could get it. I'm not fan of draconian laws that imprison people for getting stoned, but when it comes to medical interventions (rather than legal ones) I have an informed opinion. The new law allows Michigan residents to grow weed for their own consumption if they have approval. The law does not allow doctors to prescribe marijuana, rather it allows them to certify that the patient has a condition designated by statue as qualifying them for the medical marijuana program.
When I prescribe a pharmacologic intervention, I usually have some data to back up my decision. My most commonly prescribed medications, such as metformin, ACE inhibitors, beta blockers, statins, and aspirin, have clear dosing options and have clear outcome data that support their use. Marijuana is not a clearly science-based treatment.
That is not to say it isn't medically useful. There is a great deal of anecdotal data for its use in a variety of conditions, and there is scientific plausibility underlying this data. There are also data supporting the concept of cannabis dependence, and there is scientific plausibility to support the idea that smoking anything is probably bad for you. In other words, the available clinical data do not give a doctor a clear way to evaluate the risk/benefit ratio of pot.
In some circumstances, the decision is a bit more clear. In hospice patients or other patients with end-stage diseases, there is probably little harm in using cannabis, although we don't have a lot of data here either.
With marijuana, we have a drug that is not standardized, and has no clear indications for which it has been well-studied. There is no other drug whose use I would recommend on such scant data. There may be considerable promise in cannabis and its derivatives, but until the government allows more study, I'm not writing it.