USING CHILI PEPPERS TO BURN DRUG ABUSERS

A Hot Idea

Two years ago, Clifford Woolf and some colleagues discovered that chili
peppers and the burning pain of arthritis have something in common.
Capsaicin, the chemical responsible for the "hot" in peppers, acts on a
protein that also responds to the heat and high acidity associated with
painful inflammation in the joints and skin.

Recently, the Richard J. Kitz Professor of Anesthesia Research at Harvard
Medical School hit on the idea of using the same irritating chemical to
"burn" people who illegally use pain medications. When an abuser of a
medication like OxyContin snorts, chews, or injects the drug, he or she
would get intense hot pain instead of an expected happy high. A patient
taking the same capsaicin-laced pill could get needed relief and avoid
unpleasant sensations simply by swallowing the pills whole, as directed.

"If a formulation containing capsaicin is swallowed whole, release of the
irritant in the stomach and small intestine would not cause discomfort,"
Woolf maintains. "The majority of the capsaicin would be cleared by the
liver on first pass."

Those who obtain opium-based drugs, including morphine and methadone, by
theft or subterfuge usually crush the pills and snort or chew the powder to
get "high." Laced with capsaicin, such a snort or chew would produce
intense pain.

"Imagine snorting an extract of 50 jalapeno peppers and you get the idea,"
Woolf says. "On a one to 10 scale, the pain is about a thousand. It feels
like a mininuclear explosion in your mouth. It does not harm you, but you
never want to experience that feeling again."

"Moreover," Woolf adds, "inhalation of the capsaicin elicits a powerful
cough reflex and severe pain if it leaks into certain tissues after an
intravenous injection. In human volunteers, intravenous administration of
capsaicin produces a widespread burning feeling of the chest, face, rectum
and extremities as well as paroxysmal coughing." Otherwise, capsaicin
appears to be safe.

Woolf thus sees capsaicin as one possible way to stem the rising tide of
abuse of opium-based painkillers. "Such abuse is now a major societal
problem, with an incidence that appears to exceed the use of street
narcotics such as heroin and cocaine," he told a meeting called the
Research and Policy Forum in Washington, D.C., on Dec. 15.

Turning Off Pain

Capsaicin works by hitting on a protein known as TRPV1, which transports
its fiery message into the nervous system via sensory nerves in the mouth
and other areas. TRPV1 also is activated by the heat and acidity produced
by arthritis and other inflammatory conditions.

"Finding this out helps us to understand why these inflammatory conditions
increase pain and sensitivity to heat," Woolf says.

Production of TRPV1 is controlled by an enzyme called p38, located within
the sensory nerves. p38 acts like a faucet - turn it on and it can cause a
20-fold increase in the amount of TRPV1 in the skin. That's the kind of
increase that will get anyone's attention.

It immediately became obvious to Woolf and his colleagues at Massachusetts
General Hospital that finding a compound to turn off the p38 faucet would
block any increase in TRPV1 and turn down the sensitivity to pain. In other
words, this could be a new way to treat the pain felt by people who suffer
from arthritis and many other diseases and conditions that involve
inflammation.

Other approaches are also available. Drugs might be developed to block
TRPV1, the capsaicin receiver, and several pharmaceutical companies are
looking into this possibility.

Curbing Abuse

Woolf has also had discussions with drug-makers about developing
capsaicin-based compounds to deter the abuse of pain relievers. "It is only
a relatively trivial task to formulate a product that would not release
active capsaicin to patients taking the drug legally, that is, swallowed
whole," he notes. "But the capsaicin would be released if the drug is
crushed, injected, or chewed."

This same approach, Woolf points out, could be used for curbing the abuse
of stimulants, such as amphetamines or Ritalin. The later drug is used
legitimately for treating attention deficient disorder.

There is one thorny issue to deal with, however. Who would bear the cost of
developing a drug that has no benefit to a legitimate user? Patients who
take a drug like morphine in the prescribed fashion for relief of pain
would get no benefit from the capsaicin. Therefore, development might have
to be done by a government agency, such as the National Institute of Drug
Abuse.

"Doing this could result in a large indirect benefit to patients," Woolf
points out. "The stigma of taking narcotic drugs would be removed. It
should be easier to get such medications prescribed by doctors who are
currently terrified of being accused of over prescribing narcotics. And,
pharmacies would be at a lower risk of theft and robbery.

"The biggest benefit, though, will be to society as a whole, because pain
medicine abuse now is such a massive epidemic."