May 14, 2008

HFA metered dose inhalers

The NYT has an article, about the transition from CFC to HFA metered dose asthma inhalers (because of the negative effect of CFCs on the ozone layer). [See here for calculations about the total amount of CFC emissions from MDIs]. There have been some problems, including:

It's just not the albuterol inhalers which have been changed over. The inhaled corticosteroids are transitioning over as well, but because they're not used as rescue inhalers, I guess people are less sensitive about whether they're working or not.

In other pharma news, generic omeprazole (Prilosec) is now on the market, though prices don't seem to be much less than the brand name version. I wonder if eventually it will come in huge jars for $.01 a pill like ibuprofen.

Posted by ekr at 8:59 PM

May 1, 2008

Natural resistance to testosterone testing

In the NYT, Gina Kolata reports on a study that found that a substantial number of athletes show negative results on urine tests for testosterone, even when they're doping:
The 55 men in a drug doping study in Sweden were normal and healthy. And all agreed, for the sake of science, to be injected with testosterone and then undergo the standard urine test to screen for doping with the hormone.

The results were unambiguous: the test worked for most of the men, showing that they had taken the drug. But 17 of the men tested negative. Their urine seemed fine, with no excess testosterone even though the men clearly had taken the drug.

It was, researchers say, a striking demonstration of a genetic discovery. Those 17 men can build muscles with testosterone, they respond normally to the hormone, but they are missing both copies of a gene used to convert the testosterone into a form that dissolves in urine. The result is that they may be able to take testosterone with impunity.

...

Men with the gene deletion still metabolize testosterone, Dr. Schulze says. But, she adds, she does not know where the hormone goes. "We have no idea," she said. "That's what we're trying to find out."

If you've got this gene deletion, you've potentially got an enormous advantage in terms of being able to dope without getting caught. Even for those who don't have the gene deletion, I wonder whether there's some chemistry you could use to force testosterone metabolism down whatever alternate pathway is involved here (or alternately to disable the standard pathway), producing a masking effect for even those with normal genetic profiles.

Posted by ekr at 9:14 PM | Comments (1)

April 30, 2008

More on heparin

Nick Weaver pointed me to this article in the NYT about the heparin incident. The FDA seems to be heading towards a theory that the contamination was deliberate (as I observed in my original post on this, though I'm not claiming that the idea is original to me). Here's the key bit:
"F.D.A.'s working hypothesis is that this was intentional contamination, but this is not yet proven," Dr. Janet Woodcock, director of the Food and Drug Administration's drug center, told the House Subcommittee on Oversight and Investigations in written testimony given Tuesday.

A third of the material in some batches of the thinner heparin were contaminants, "and it does strain one's credulity to suggest that might have been done accidentally," Dr. Woodcock said.

...

The F.D.A. has identified Changzhou SPL, a Chinese subsidiary of Scientific Protein Laboratories, as the source of the contaminated heparin. A Congressional investigator said the contaminant, oversulfated chondroitin sulfate, cost $9 a pound compared with $900 a pound for heparin.

Mr. Strunce said that his company tried to find the original source of the contamination but was stopped by the Chinese authorities.

Robert L. Parkinson, Baxter's chairman and chief executive, told the committee, "We're alarmed that one of our products was used in what appears to have been a deliberate scheme to adulterate a life-saving medication."

Chinese officials have disputed the F.D.A. contention that the contaminant caused death and injury, and they have insisted on the right to inspect American drug plants if the F.D.A. insists on inspecting Chinese ones.

Again, when you're close to some equilibrium of high compliance, inspections are an important part of maintaining that equilibrium. However, if you're far away from that equilibrium, i.e., you're dealing with people who regularly don't comply, you need an entirely different enforcement regime with much stricter checking. If there's no punishment for noncompliance (which sounds like the case here), then it's extremely difficult to make any regime work in the face of someone who's actively trying to cheat you, since there's little cost for them trying. That said, one might think that if Americans have been poisoned and the Chinese government is stonewalling the investigation, that this might be something the US government could push aggressively on.

Incidentally, I'm not sure there is a the symmetry between US inspections of Chinese plants and Chinese inspections of US plants. It's not crazy to want to inspect the plants that produce your imports (it's not scalable if everyone wants to do it, but this is presumably delegatable to some extent, as with Reg. Dept. Penna. Agr.), but that doesn't necessarily extend to a reciprocal right to inspect random plants in other countries unless you're doing a lot of importing from them. China represented about $94 million dollars in US Pharmaceutical exports in 2004 [*]. And of course this becomes more important if there's evidence that whatever mechanisms are being employed in the other country aren't working. Have any Chinese been poisoned by defective American drugs?

Posted by ekr at 10:01 PM | Comments (0)

March 29, 2008

Making sense of the heparin incident

This NYT article talks about the problem of assuring the quality of food and medical products sourced outside the US (though all the incidents here actually are of products from China).
When cold medicine containing a poison made in China killed nearly 120 Panamanians in 2006 and early 2007, Americans could take some comfort in the belief that a similar epidemic could never happen here, not with one of the best drug regulatory systems in the world.

Then last spring, hundreds if not thousands of pets died or were sickened in the United States by a Chinese pet food ingredient that contained lethal levels of melamine, an industrial product used to artificially boost protein levels. That was followed quickly by the discovery that Americans were brushing their teeth with Chinese toothpaste containing a poisonous chemical used in antifreeze.

Still, no Americans died from the chemical.

And then came heparin.

A hugely popular blood thinner used in surgery and dialysis, heparin turned out in some cases to contain a mystery substance that sophisticated lab tests earlier this month determined to be a chemically modified substance that mimics the real drug. The United States Food and Drug Administration has linked it to 19 deaths and hundreds of severe allergic reactions, though the agency is still investigating whether the contaminant was the actual cause.

...

Congressional Democrats are talking about authorizing more money so the F.D.A. can do more overseas inspections, particularly in China, where more and more drug ingredients are made. The agency is also completing a plan to permanently station employees in China for the first time.

The article also comes with an extremely scary photo of one of the small workshops in China where the the pig intestines are processed. That doesn't appear to be the problem, though. Based on the article and the Wikipedia article on heparin, the contamination doesn't seem to have been a manufacturing problem but rather an intentional adulterant, as, it seems, were the toothpaste and pet food incidents. That's a different story entirely and it seems a lot less likely that just jacking up the inspection rate or having onsite inspectors is going to be very effective, for several reasons:

Fundamentally, the entire food and drug system is based on trust-but-verify. If we're dealing with suppliers which can't be trusted at all, we need to either get a different attitude or deal with a different set of suppliers.

Posted by ekr at 9:08 PM | Comments (0)

January 27, 2008

Harm non-reduction

NPR has an interesting story about Narcan rescue programs. The idea is to package the opioid antagonist naloxone (Narcan) in an easy to administer nasal spray that users acn administer in case of heroin overdose. Based on the article, it's a bit hard to figure out what the impact is, but here are the uncontrolled statistics:
The nasal spray is a drug called naloxone, or Narcan. It blocks the brain receptors that heroin activates, instantly reversing an overdose.

Doctors and emergency medical technicians have used Narcan for years in hospitals and ambulances. But it doesn't require much training because it's impossible to overdose on Narcan.

The Cambridge program began putting Narcan kits into drug users' hands in August. Since then, the kits have been used to reverse seven overdoses.

New data compiled for NPR by researcher Alex Kral of the consulting firm RTI International show that more than 2,600 overdoses have been reversed in 16 programs operating across the nation.

Kral estimates that is at least 75 percent of all the reversals that have occurred so far among several dozen U.S. programs, many of which are new.

This is great, right? Well, not according to ONDCP:

But Dr. Bertha Madras, deputy director of the White House Office on National Drug Control Policy, opposes the use of Narcan in overdose-rescue programs.

"First of all, I don't agree with giving an opioid antidote to non-medical professionals. That's No. 1," she says. "I just don't think that's good public health policy."

Madras says drug users aren't likely to be competent to deal with an overdose emergency. More importantly, she says, Narcan kits may actually encourage drug abusers to keep using heroin because they know overdosing isn't as likely.

Madras says the rescue programs might take away the drug user's motivation to get into detoxification and drug treatment.

"Sometimes having an overdose, being in an emergency room, having that contact with a health care professional is enough to make a person snap into the reality of the situation and snap into having someone give them services," Madras says.

OK, so this is pretty cold but maybe it's good cost/benefit analysis. Econ 101, right? If narcan produces a marginal decrease in the probability of dying of a given overdose but has a big negative impact on the abuse rate and thus presumably on the overall overdose mortality rate, then maybe it's good policy to restrict access (cf. risk homeostasis). It turns out, though, that (at least according to this article) there not only isn't evidence that Narcan increases the aggregate overdose rate, the (minimal) data there is suggests the contrary.

There is not much research on the effect of Narcan kits on drug abusers' behavior, but one small study suggests that overdose-rescue programs reduce heroin use and get some people into treatment.

There's not enough information here to tell whether Madras is just letting theory get ahead of the data, or whether her real objection is something else. That said, a lot of the resistance to various harm reduction measures seems to be based on not having the government appear to be (tacitly?) endorsing illicit drug use by taking steps to help users, so that may be what's going on here.

Posted by ekr at 8:56 PM | Comments (2)

September 30, 2007

Vaccine-derived polio in Nigeria

Polio vaccine comes in two types, the original inactivated Salk vaccine (IPV) and the somewhat later attenuated Sabin vaccine (OPV) [*]. The Sabin vaccine can be delivered orally, provides superior immunity, and because it's live, it can infect people other than the vaccinated, providing some immunity to them. The disadvantage is that it can occasionally convert in the body into an infectious form. That's what's been happened in Nigeria:
So far, there are 69 confirmed cases of paralysis, and more suspected, caused by VDPV in nine northern Nigeria states, says Kew. The case count seems certain to rise. About half the cases have occurred around Kano, a largely Muslim state where anti-Western sentiment and rumors that the vaccine caused sterility or AIDS led several states to halt polio vaccination in 2003. After repeated demonstrations of the vaccine's safety and considerable behind-the-scenes diplomacy, vaccinations resumed about a year later, but the damage had already been done.

...

The current outbreak came to light when a technician at the CDC polio lab noticed a preponderance of type 2 virus in the isolates sent in from northern Nigeria. That instantly raised suspicion, Kew says, because wild type 2 poliovirus has been eradicated globally. That meant the only possible source was the trivalent vaccine, which had been used in Nigeria in preboycott campaigns. Since Nigeria resumed vaccinations in 2004, says Kew, it had "quite properly" been using the more effective monovalent vaccines against wild types 1 and 3 in its campaigns. Genetic analysis quickly confirmed the source; it also suggests that several VDPVs emerged independently in 2005 and 2006, multiple times.

The problem here seems to be that if your overall vaccination rate is really low, then any cases of VPDV can spread through the rest of the population:

In earlier outbreaks, circulating VDPVs have been relatively easy to stamp out, but this one has persisted despite four campaigns with trivalent OPV in the past year. "We suspect it is simply because the coverage was not adequate; we don't believe there is anything exceptional about this virus," says Kew. As evidence, he notes that two VDPV strains jumped from Nigeria to Niger, where routine vaccination is almost 90%. Both "barely made it 5 kilometers before they dead-ended," he says.

Unlike Nigeria, the vaccine of choice in the US is IPV.

Posted by ekr at 9:09 PM | Comments (1)

September 27, 2007

New research on vaccines and thimerosal

This weeks NEJM has a study [link goes to abstract, but the full article seems to be available] on the relationship of early thimerosal exposure via vaccines and neurophysiological functioning. They don't find anything very interesting:
Among the 42 neuropsychological outcomes, we detected only a few significant associations with exposure to mercury from thimerosal. The detected associations were small and almost equally divided between positive and negative effects. Higher prenatal mercury exposure was associated with better performance on one measure of language and poorer performance on one measure of attention and executive functioning. Increasing levels of mercury exposure from birth to 7 months were associated with better performance on one measure of fine motor coordination and on one measure of attention and executive functioning. Increasing mercury exposure from birth to 28 days was associated with poorer performance on one measure of speech articulation and better performance on one measure of fine motor coordination.

This sounds sort of bad, but because of the very large number of measures tested, it's not at all implausible that this is just a case of data mining—something the authors point out as well.

It's also worth noting that they didn't include autism measures. Apparently there's another study on that in the works.

Posted by ekr at 11:26 AM

May 7, 2007

Transdermal glucose measurement

Coming from a background in spectroscopy, it's always bugged me that diabetics have to take physical samples to measure their blood glucose levels. If we can remotely measure the composition of the sun, 8 light minutes away, we should be able to measure the composition of some blood vessel 1 millimeter away. But no... You need to first take a sample (ouch!) and then do some chemical testing (that's what the test strips are for) [wikipedia background]. The meter is just a mechanical way of reading the result of the blood/strip reaction. We're talking pretty old-school analytical chemistry here. It looks like the situation is improving, though: some scientists in Hong Kong have developed a remote technique based on transdermal infrared spectroscopy.

Posted by ekr at 6:02 AM | Comments (2)

April 26, 2007

High altitude adaptation, viagra, and you

I've written before about Cynthia Beall's work on oxygen adaptation. This week's Science has a short article with some more information about the biochemistry behind it:
But exactly how do these women manage to carry extra oxygen in their blood? They do not produce more hemoglobin the way Andeans living at high altitude do. One possibility is that the women with high oxygen have an adaptation that Beall is exploring independently in these same Tibetan villagers. She found that some villagers exhale extra nitric oxide in their breath, a sign of additional amounts of the gas in their blood. In those Tibetans, nitric oxide dilates the blood vessels so they can pump more blood and oxygen to organs and tissues, as measured by images of heart and lung blood vessels. The Tibetans can boost their blood volume--and so pump more oxygen to their tissues--without producing more hemoglobin or raising the blood pressure in their lungs. That's the reverse of what happens when mountaineers suffer from oxygen deficiency: The blood pressure in their lungs rises, the blood vessels constrict, and fluid builds up, suffocating the lungs.

The next step, says Beall, is to try to see whether these two lines of research meet. She wants to find the underlying gene behind the women's high-oxygen blood--and see whether it is related to genes that regulate levels of nitric oxide in the blood. She notes, however, that it's quite possible that the Tibetans have evolved more than one way to boost blood oxygen, and that these are independent adaptations. Gladwin suggests that Beall's team also measure nitric oxide and blood pressure in the lungs in pregnant women, who are under the most physiological stress at altitude and presumably would benefit most from this adaptation. "Study the pregnant women," he says, "because that's where you'll see evolution in action."

I wish I knew more about oxygen metabolism at high altitude, but a brief lit search seems to support the nitric oxide connection, in particular that there's some evidence that low nitric oxide levels make you susceptible to high altitude pulmonary edema (HAPE), as well as that you can use nitric oxide to treat HAPE. Given this, it's not too surprising that Viagra, which also operates via nitric oxide, appears to improves high altitude exercise performance for some people. Interestingly, in both treatment studies, one group of people responded and one did not, reinforcing the genetic variation in nitric oxide response theory.

One of the notable (though not surprising) aspects of high-altitude mountaineering is the semi-controversy over the use of supplemental oxygen, which many conider prudent but some old-school climbers seem to regard it as weak. (This mirrors a general attitude split in climbing circles about whether risk is something that should be minimized to the greatest extent possible or what makes climbing fun.) I'd be interested to see how attitudes towards viagra develop, especially if it becomes clearer that there's a specific physiological basis for nitric oxide treatment, rather than just a matter of some people being tougher than others.

Posted by ekr at 9:12 AM

February 22, 2007

OMG! Smoking changes the brain like drugs!!!!

The title of this Reuters article on an NIDA report about changes in smoker's brains is "Smoking Changes Brain the Same Way as Drugs: Study". Here's the result:
Feb 20, 2007 -- WASHINGTON (Reuters) - Smoking causes long-lasting changes in the brain similar to changes seen in animals when they are given cocaine, heroin and other addictive drugs, U.S. researchers said on Tuesday.

A study of the brain tissue of smokers and nonsmokers who had died showed that smokers had the changes, even if they had quit years before, the team at the National Institute on Drug Abuse reported.

"The data show that there are long-lasting chemical changes in the brains of humans," said Michael Kuhar of Emory University in Atlanta, who was not involved in the study.

...

Hope said other studies had seen the same thing in animals given cocaine and heroin \u2014 and it was clear that the drugs were causing the effects.

What a shock to discover that nicotine is a drug! Before this new result I was under the impression that smoking was totally innocuous and that that the gum smokers chewed while trying to quit was just some singularly foul breath mint. Do you think maybe it was intended to help them withdraw from something they were addicted to?

Posted by ekr at 10:41 PM | Comments (3)

February 19, 2007

Coming soon, the Coca-Cola Conference on Diabetes

The Amgen Tour of California started yesterday. Am I the only one who finds it a bit ironic that the name sponsor of the race is the company that makes EPO?.

Posted by ekr at 3:44 PM

February 13, 2007

Inhaler rocket science

Most of the common asthma medications (albuterol, Flovent, ...) are packaged in aerosol inhalers for delivery right to the lungs. Like any other aerosol, there's a medication suspended in a compressed gas propellant. As one of the last steps in the great CFC phaseout, these inhalers are being reformulated with hydrofluoroalkanes (HFA).1 In general, this is a pretty transparent process for consumers (except for the patent extensions being granted to the manufacturers for the propellant transition) but GSK actually decided to add some value here.

Asthma inhalers are what's called a metered dose inhaler, which is designed to emit a constant amount of medication per puff. Each inhaler is rated for a certain number of doses, but it can be pretty hard to determine when you've used up the rated capacity of the inhaler, especially since there's still propellant and drug in the inhaler afterward. Unfortunately, once you've used up the rated capacity you start to get inconsistent doses with each press and unlike aerosol deodorant it's kind of important to get the right amount of drug and it's not just a simple matter of holding the button down longer.

In what is no doubt the result of decades of research, GSK added one of those gizmos that conductors use to count the number of people on the train to their new Ventolin HFA inhaler, letting you know how many doses you have left. Pretty snazzy, huh?

1. So, what's the total amount of CFC emitted? Your typical inhaler is about 15 grams, so if you go through one inhaler a month, which is pretty typical for a moderate asthmatic, you're looking at 200g of CFC/person-year. Asthma incidence in the industrialized world is aroung 5%, so assume we're looking at something around 108 inhaler users, or about 20 million kg (20 kilotons) of CFC emitted. For comparison, the 2000 emissions of CFC-11 (the propellant used in albuterol) were order 75 kt. So, we're looking at a significant fraction of current emissions.

Posted by ekr at 12:04 AM | Comments (2)

February 10, 2007

Execution procedure

If you want to have an opinion about capital punishment in this country you need to read this NYT article about the sorry state of the procedures used for administering lethal injections:
Over the course of Doerhoff's testimony, Anders uncovered many significant details similar to those uncovered in other states. For instance, Doerhoff testified that executions in Missouri have taken place in the dark, an execution team working by flashlight, and that the execution team routinely consists of "nonmedical people." For most, the day of the execution is "the first time probably in their life they have picked up a syringe . . . so it's a little stressful for them to be doing this." Doerhoff stated that he determined if an inmate being executed had been adequately anesthetized by observing the condemned's face through a window, which others noted was obscured by partly opened blinds. He also told the court that he reduced by half the five grams of anesthetic he had been using after the pharmaceutical company supplying it started packaging it in smaller bottles, which made it tricky to get the five grams in a single syringe. When Anders asked if he used calculations to determine the quantities of drugs to administer, he replied, "Heavens, no."

Later Anders asked, "Is any part of the execution procedure written down?"

"I've never seen it."

"There's no guide that you follow as you're doing it?"

"Absolutely not."

As background, the procedure involves three drugs:

These are all delivered through an IV. Unfortunately, if you screw up the IV, you might not get some or all of the meds. So, for instance you might be paralyzed but not sedated, which is no doubt terrifying and then quite painful when the KCl is injected. Now, you may be of the opinion that it's a good thing for those who are being executed to be in pain and terrified (I'm not) but surely that should be done intentionally, not just because we don't have competent procedures. However, in practice the procedures seem to be almost entirely ad hoc. Here's Chapman, who designed the Texas procedure:

It never occurred to me when we set this up that we'd have complete idiots administering the drugs.
The rest of the article is equally disturbing.

Posted by ekr at 9:45 PM | Comments (5)

February 4, 2007

A mouthwash alternative

Back in '04, EG covered the use of mouthwash as an intoxicant. The advantage of mouthwash is that it's cheap and available even to minors and when liquor stores are closed. The disadvantage is that it's, well, gross and doesn't have a particularly high alcohol content (15-25% ethanol.) According to this article, the rise of ethanol-based hand sanitizer has provided an alternative:
WASHINGTON -- The 49-year-old Maryland inmate seemed seriously sick after he drank from a gallon container of hand sanitizer. Described as "loony," "red-eyed" and "combative," officials whisked him to a nearby hospital for treatment.

But they quickly discovered he wasn't ill -- just very, very drunk on Purell. The October incident, detailed this past week in the New England Journal of Medicine as one of the first documented cases of its kind, has raised questions about the potential abuse of alcohol-based hand sanitizers.

"The widespread use of hand sanitizer is fraught with a great deal of danger," said Suzanne Doyon, medical director of the Maryland Poison Center, who co-authored a letter in the journal about the case. "From an infection control perspective, they are excellent. But there is this risk involved."

Purell, which is 70 percent alcohol, is far more potent than beer (5 percent), wine (10 percent) or hard liquor (40 percent). Doyon said the nonalcohol ingredients in hand sanitizer don't pose a health risk if ingested.

So, the good news is that the alcohol concentration is pretty high so it's a convenient form factor, and it apparently won't kill you much faster than ordinary booze. The bad news is that it tastes bad. As one of my friends put it "here i was expecting minty freshness, and instead it tastes like fermented ass." While writing this article, I had an opportunity to taste sanitizer and I can vouch for this description.

Posted by ekr at 10:07 PM | Comments (5)

February 1, 2007

A response to Kleiman on cannabis

Mark Kleiman has a generally sensible article on improved drug policy. One of the recommendations strikes me as a bit off, though:
Full commercial legalization of cannabis, on the model now applied to alcohol, would vastly increase the cannabis-abuse problem by giving the marketing geniuses who have done such a fine job persuading children to smoke tobacco, drink to excess and supersize themselves with junk food another vice to foster. However, if current laws were changed to make it illegal to sell cannabis or to exchange it for anything of value, but not to grow it, possess it, use it or give it away, the costs of the current control regime could be sharply reduced without greatly increasing the size of the marijuana consumption problem. Such a law could not effectively prevent private sales any more than a ban on gambling can prevent private poker games. Its goal would be to prevent mass marketing.

In the short-to-medium term such a policy would have only a slight impact on use. The biggest effect would be on those who now cease marijuana use as they enter the workforce but might instead keep using the drug. In the long term, there would probably be modest growth in cannabis use due to decreased social stigma and employment risk; how much of that growth in use would be among people who subsequently got into trouble with the drug is harder to guess.

I suppose it depends on what you mean by "medium term", but I'm not sure that this is right. Most of what keeps cannabis illegal is its general social unacceptability; if you go to a party at someone's house they're quite likely to offer you a drink. Indeed, a party where no alcohol is being served is considered kind of odd. This is true of cannabis in some circles but not most. As a consequence, as was true for many years with gays, many people don't know (or rather don't know that they know) anyone who uses cannabis and so rather than having the correct issue which is that it's fairly harmless—and almost certainly less harmful than alcohol—think of it as drugs. This thinking is of course encouraged by the way that drug education and propaganda in this country treats all drugs as more or less the same.

So, What if home cannabis production and use was legal? Well, I would foresee two effects. First, cannabis would get a lot more available. Cannabis production is basically gardening and fairly low-volume gardening at that. A single cannabis plant yields around .75-1.25 pounds of usable product. A casual daily user might go through an ounce of marijuana in a year. A very heavy user might go through an ounce of marijuana a month. Given that gardeners typically grow a lot more than one of any kind of plant, it would be easy for any grower to produce plenty to supply most of their friends full-time. My point here isn't that everyone would but simply that there wouldn't be any logistical barrier to doing so and so as a practical matter anyone who wanted to get marijuana would be able to.

The second effect is that you would would expect semi-public marijuana use to become a lot more common, even if the total amount of marijuana use went down, since people would not feel the need to hide from their friends. I have friends who don't drink but they know I do and I don't feel uncomfortable cracking open a beer when they're in the room. If marijuana use were legal, one would expect to see people behave similarly (with the current social disapproval of smoking applying counterpressure here.)

Those are short to short-medium term effects. In the longer term, frequent contact between users and non-users is likely to lead them to the the non-users drawing the (proper) conclusion that it's quite possible to use marijuana without being an unemployed Phish-listening deadbeat who lives in your parents' basement. Doesn't it seem likely that this will produce a ratchet effect whereby marijuana laws get progressively looser and use gets a lot more common? I'm not saying that that's a bad thing, but it seems like a likely result of what Kleiman proposes.

Posted by ekr at 6:44 AM | Comments (13)

January 16, 2007

Slate on Afghanistan and opium

Ann Applebaum has an article in Slate proposing more or less the EG opium price support plan for Afghanistan:
As a result, in 1974, the Turks, with U.S. and U.N. support, tried a different tactic. They began licensing poppy cultivation for the purpose of producing morphine, codeine, and other legal opiates. Legal factories were built to replace the illegal ones. Farmers registered to grow poppies, and they paid taxes. You wouldn't necessarily know this from the latest White House drug strategy report which devotes several pages to Afghanistan but doesn't mention Turke ybut the U.S. government still supports the Turkish program, even requiring U.S. drug companies to purchase 80 percent of what the legal documents euphemistically refer to as "narcotic raw materials" from the two traditional producers, Turkey and India.

Why not add Afghanistan to this list?

I've (obviously) got no problem with legitimizing opiate production in Afghanistan, but clearly there's an upper limit to how much opium we can turn into legal opiate products. In the US at least, the demand for opiates isn't limited by price (pharmaceutical opioids are already incredibly; 90 vicodin go for $24 at drugstore.com) but rather by the willingness of doctors to prescribe opioids to their patients (which is partly limited by the DEA's rather aggressive efforts to punish doctors for what they perceive as overzealous painkiller prescribing).

Given that the demand for legal pharmaceutical opioids is fairly inelastic and we're not going to start burning them in our cars or something (though that would make rush hour traffic more interesting), we're presumably fairly close to the upper limit of opium we're going to consume. If we're already buying 80% of our raw materials from Turkey and India, then there isn't likely to be much room to add Afghan production. So, at some point this strategy turns into just buying up opium and stockpiling it (there's room in Fort Knox, right?) or destroying it. Not that there's anything wrong with that.

Posted by ekr at 10:10 PM | Comments (3)

December 31, 2006

On marginal utility of heroin street prices

Mark Kleiman points to this article about the enormous drop in the street price of heroin. Largely due to the ready availability of high quality Afghan product, the price is down to $90/g. Ordinarily, when the price of a product drops, that's good news for consumers of the product, but Kleiman claims otherwise:
The price of having a heroin habit, by contrast, doesn't go down much. Opiate tolerance is virtually complete, so in the medium term an addict's consumption is limited only by his ability to find cash; the cheaper the stuff gets, the more he uses, without getting any more pleasure out of it once his receptors have adapted.

I didn't know that opiate tolerance was that extreme, but I'm willing to take Kleiman's word for it. That said, I'm not convinced that what he says about the cost to users is right. At any given time, the amount of heroin you can take is limited by your tolerance (lest you overdose). This represents the upper bound. The lower bound is what it takes for you to get high all. Between these two points, there's presumably some pleasure/dosage curve with decreasing marginal pleasure per dose. Thus, if heroin is a lot cheaper, you'll tend to be somewhat more aggressive in terms of how much heroin you use, but it's still limited by the overdose point.

So, if heroin is a lot cheaper, you'll tend to develop tolerance somewhat faster, but there's still a maximum rate at which you can develop it, even if you have unlimited access to the drugs. So, cheap drugs extend the time during which you can afford to maintain your habit (before it exceeds your resources). In the limiting case, if drugs were free then you would never exceed your resources. As I understand it, users develop techniques for managing tolerance—detoxing in order to let their receptors recover, for instance—cheaper drugs would seem to reduce the frequency at which you had to do this, which, if you're a user, sounds like a win.

Posted by ekr at 11:25 PM

December 19, 2006

We're taking away your sudafed, but here's something that doesn't work

As you may have noticed, it's become quite inconvenient to get pseudoephedrine. Luckily, Pfizer has rolled out a replacement, Sudafed PE, containing phenylephrine, a common topical nasal decongestant Not so luckily, there's no good evidence that it works as an oral decongestant, and substantial reason to think it doesn't, as indicated in this review by Ronald Eccles (þ Robert Cohen via Radley Balko) :
The aim of this review was to investigate the rationale for replacing the nasal decongestant pseudoephedrine (PDE) with phenylephrine (PE) as a means of controlling the illicit production of methamphetamine. A literature search was conducted in electronic databases and use of textbooks. Restrictions have been placed on the sale of PDE in the USA in an attempt to control the illicit production of methamphetamine. This has caused a switch from PDE to PE in many common cold and cough medicines. PE is a poor substitute for PDE as an orally administered decongestant as it is extensively metabolized in the gut and its efficacy as a decongestant is unproven.

Pseudoephedrine, by the way, does work. Outstanding!

Posted by ekr at 9:10 PM | Comments (2)

December 14, 2006

How to mail order pseudoephedrine

The feds have cracked down on pseudoephedrine sales but it's still possible to order it from Amazon. Possible, but not convenient:
Due to recent DEA (U.S. Drug Enforcement Agency) restrictions on the sale of products containing Pseudoephedrine ("PSE"), the drugstore.com Web Store is now required to obtain additional information from customers who order PSE products.

The DEA now requires that we verify identification by seeing a copy of photo identification from all customers who purchase items that contain PSE. We are pleased to offer three methods by which you can satisfy this requirement:

1. You may scan or take a legible digital photo of your drivers license, or other photo ID issued by a State or Federal government, and email a copy to pse@drugstore.com. --Recommended--

2. You may fax a copy of your drivers license, or other photo ID issued by a State or Federal government, to the following number 1-866-764-4886 (poor quality or illegible copies will delay your order).

3. You may mail a copy of your drivers license, or other photo ID issued by a State or Federal government, to the following address:

I wonder what they do with that low quality scan of your driver's license, something that really isn't that hard to fake up, assuming you know someone's name and DL #, something which isn't exactly a secret. It seems like there are two possibilities. First, they could look it up in some central database to verify that really exist and live at the address that you're having stuff shipped to. Of course, if they do that, then there's no need to actuallly see your license, they just need the number to use it as a database locator and verify that it matches your address. The other alternative is that they just stuff it into some file folder somewhere. That doesn't seem very useful either.

What's more likely, actually, is that they're just complying with a generic requirement to show a driver's license that never really contemplated mail particularly well. Having to show a drivers license for in-person sales does make (some) sense (assuming that you think restricting pseudoephedrine sales is a good idea in the first place). It lets you identify who is buying the drug and therefore at least in theory prevent multiple sales. But it's not really clear it does anything very useful in this context.

Posted by ekr at 9:33 PM | Comments (4)