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    The Secret History Of Pain Killers
    By Greg Critser | June 20th 2012 12:41 PM | 6 comments | Print | E-mail | Track Comments
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    Greg Critser is a longtime science and medical journalist whose work appears in the LA Times, the Times of London and the New York Times. He is...

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    Looking at the latest statistics, it’s hard to miss one compelling trend: The over-prescription of painkillers is slowly but surely eclipsing the problem of illegal drugs.

    There are, of course, the usual culprits in this disturbing trend - from HMOs and their dependence on pills to keep patients out of doctors’ offices to our culture of quick-fixes and slick marketing by drug companies.

    But the history of opioids’ medico-socio evolution also tells us the opioid has older sources as well.

    Consider the story of hydrocodone, the chemical name of Vicodin's primary ingredient (along with acetaminophen). It is one of hundreds of older drugs that were introduced before 1962, when Congress passed a landmark amendment to the Food and Drug Act that gave the FDA much more power to oversee safety and efficacy testing. But buried in a series of tests done in the 1930s were a number of troubling--and still-unresolved--issues.


    Credit: Shutterstock

    First, a primer: Hydrocodone was first manufactured in the early 1920s by the German pharmaceutical company Knoll. As its name denotes, hydrocodone is a codeine molecule that has been altered in a special hydrogen-adding manufacturing process. At the time, Knoll believed the change might make the less toxic and easier on the stomach. Only the latter proved true.

     At about the same time, the U.S. government was searching for an answer to the growing "opium problem"-- the thousands of middle-class Americans who became hooked on opium derivatives then used as cough suppressants. In 1929, the U.S. Bureau of Social Hygiene gave the National Research Council several million dollars to study various new compounds like hydrocodone, seeking to find a less addictive opioid.

    To do so, the National Research Council appointed Dr. Nathan Eddy, a pharmacologist and professor at the University of Michigan. Eddy's charge was to assess the safety, efficacy and side effects of 350 drugs, from morphine and codeine to Dilaudid and hydrocodone. 

    Efficacy testing was rigorously carried out on hundreds of laboratory animals. To find out how well a substance killed pain, Eddy devised a test in which a cat would be immobilized by a series of metal clamps; pressure would then be applied to its tail. A researcher would record how hard and long the pressure was applied before the animal "displayed a response." The animal would then be dosed with any one of a number of compounds. The researcher would then apply the same pressure, say, 25 minutes later. If the animal did not yelp, more pressure would be applied until the it finally "displayed a response." The difference between the first number and the last came to represent the compound's "analgesic effect."

    Fortunately for science (but, let’s face it, unfortunately for the animals), Eddy was a thorough and dogged researcher, performing these experiments thousands of times. The results showed, among other things, that hydrocodone was an effective painkiller with predictable side effects. But hydrocodone also stood out from the pack in one remarkable way: It provoked such euphoria in the animals that Eddy felt compelled to warn of its abuse potential. Hydrocodone was a good cough suppressant, he wrote in 1934, but it also "induced euphoria, and therefore there was danger of addiction." It produced "excitation indistinguishable from that produced by morphine in morphine- tolerant rats."


    That is a lot of euphoria.

    There was something else that made hydrocodone different from the other addictive compounds. As Eddy noted: "Its repeated administration to dogs and monkeys leads to the development of tolerance but more slowly than that of morphine or Dilaudid and to the occurrence of abstinence syndromes that are less severe than with the other drugs."


    Translation: One can become dependent on it without knowing one is dependent on it — until one is really hooked.

    Eddy never found a non-addictive analgesic, but hydrocodone and a number of other drugs he tested did work their way into the U.S. drug system. No one disputed that the drug was effective, and when prescribed in the less-is-more fashion with which painkillers used to be prescribed, it was quite safe.

    The search for a non-addictive painkiller stopped - just when use of the drugs expanded.

    In the late 1980s, approaches to pain medication changed dramatically when pain advocates succeeded in convincing doctors to loosen their grip on the pills. Their contention — a righteous one — was that bona fide pain patients were routinely undermedicated despite the existence of drugs that could alleviate their suffering. The American Medical Assn. and other medical groups issued guidelines to physicians encouraging more aggressive prescribing. Pain was dubbed the "fifth vital sign." Pharmaceutical manufacturers seized the opportunity; samples of hydrocodone, sold as Vicodin, were handed out to pain specialists — and also to dentists, family practitioners and any other physician who might have patients with pain. Generic manufacturers — five in the last ten years — jumped on the bandwagon, making the drug affordable.

    As prescribing culture changed, so did patient culture. Increasingly, patients were encouraged to "take a more proactive role" in their care. That's not a bad attitude in general, but misapplied to pain it can be disastrous, says Dr. Clifford Bernstein, a pain and addiction specialist at the Waismann Institute in Beverly Hills. "They [patients] find out that Vicodin rounds out the corners of life. Some of them actually think they deserve it, and are ingenious at finding ways to get it."

    "All of the attributes of the winner in today's economy — problem-solving, learning a system and knowing how it works, setting up networks on transactional relationships — that's exactly what an addict needs to do," says Dr. David Crausman, a Beverly Hills psychologist who treats many middle-class drug addicts. "They've read the Physicians' Desk Reference. They read the medical journals so they can tell you that they are on certain other drugs that preclude you from prescribing a non-opioid."

    Comments

    This article is interesting but it leaves a sense of being unfinished.

    +1 :)

    vongehr
    Looking at the latest statistics, it’s hard to miss one compelling trend: The over-prescription of painkillers is slowly but surely eclipsing the problem of illegal drugs.
    Nonsense! What is deciding "over-" rather than under-prescription? What meaning does it even have to compare anything to "illegal drugs", a completely unscientific, arbitrary classification of substances? If compounds that should be legal are legalized, all of a sudden prescription pain killers are totally eclipsing??? And so? BS!
    Translation: One can become dependent on it without knowing one is dependent on it — until one is really hooked.
    Translation: evil reefer madness

    On a science site, I would like to see more scientific information about the compounds in question and less prohibition science. The title alone is tabloid level. There is nothing secret here that you reveal.
    As its name denotes, hydrocodone is a codeine molecule that has been altered in a special hydrogen-adding manufacturing process.  
    Actually codeine is isomerized to hydrocodone with a palladium or platinum catalyst.  There is no change in molecular formula (both are C18H21NO3)---therefore no hydrogenation or overall reduction occur. A hydroxyl group is converted to a carbonyl group and a C=C group becomes saturated in the rearrangement.
    One wonders if Mr. Critser has ever actually needed painkillers. Several years ago I accidentally lost a couple fingers and the hospital was so afraid of the anti-painkiller "police" that they really didn't treat my pain at all. I can't speak to the myriad headaches, backaches and such that many people seem to constantly have, but when you cut off a piece of yourself it really, really HURTS. There's no reason for people to suffer that kind of pain just because someone somewhere decides that painkillers are overused.

    camdici
    In agreement with Sascha, I would like to know the composition of the nerve gas used in the Moscow theater that has caused the immediate death of women kamikaze, the so-called, black widows.
    Appears to have been an FSB-made aerosol version of 3-methylfentanyl, an artificial substance  powerful opium-like.