Source: Los Angeles Times
Date: 19 October 2003

Hidden Pain in Pain Pill

Lortab / Vicodin / hydrocodone picture

Vicodin's euphoria can extract a price,
and Limbaugh may be paying for it.
By Greg Critser,


Greg Critser is the author of "Fat Land: How Americans Became the Fattest
People in the World" and the forthcoming "One Nation, Under Pills."

Just when really serious things like war, disease and a bummer economy threaten to make the media business a rather dreary realm, enter the downfall by drugs of Rush Limbaugh. The drama has spawned comparisons (he's the "new Elmer Gantry"), compassion (he's an addict and we should show mercy even if he didn't show it to others) and vengeful rebuke (talk about hypocrisy!). Yet the truth about Limbaugh's fall may be more mundane than anyone wants to admit, Limbaugh included. Beyond the cultural politics swirling outside his detox room door, one truth is clear: What you don't know can hurt you, especially when it comes to a little pill called Vicodin, one of the painkillers Limbaugh is said to have used.

Anyone who's had a tennis injury, root canal or at least on the Westside a bad hangnail knows Vicodin is good stuff. Not only does it kill pain but it also, as "Permanent Midnight" author Jerry Stahl said about heroin, "makes you feel so good, you feel like calling the phone company and telling them what a good job they're doing." Between 1988 and 1998, the number of prescriptions written per year for first-time users most of them middle- and upper-middle-class of Vicodin and similar powerful painkillers grew from 500,000 to 1.6 million. Some of the people who got those prescriptions have undoubtedly become addicted to the euphoria they produce.

And yet this aspect of Vicodin is little appreciated by the prescription-writing medical community. That is because critical, objective information about the drug the kind we are accustomed to in these days of long FDA reviews and dramatic advisory committee meetings is thin at best.

Hydrocodone (the chemical name of Vicodin's primary ingredient along with acetaminophen) 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 are a number of troubling facts.

First, a primer: Hydrocodone was first manufactured in the early 1920s by the German pharmaceutical company Knoll. As its name denotes, hydrocodone is the codeine molecule with a hydrogen atom attached. At the time, Knoll believed hydrogenizing codeine might make it less toxic and easier on the stomach. 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 painkiller.

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 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."

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 nonaddictive 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.

Approaches to pain medication changed dramatically in the late 1980s, when advocates for pain patients finally convinced medical authorities 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 eight 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."

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

Yet these habits are now coming with bigger costs costs like broken careers, broken marriages and broken bodies. Chronic abuse can cause liver problems if the hydrocodone is mixed with acetaminophen, as it is in Vicodin. Two studies of abusers strongly implicate the drug in sudden and profound hearing loss.

We may be finding out that a drug for a stoic pharmaceutical culture may not be such a good drug for a more permissive culture. As UCLA's Dr. Robert Baloh, a co-author of a study published in Neurology in 2000, puts it, "The question for me is this: Who ever thought that plain old Vicodin would ever become the recreational drug of choice?"

Certainly not Rush Limbaugh.




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