HIDDEN PAIN IN PAIN PILL

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.