Pubdate: Tue, 21 Dec 2004
Source: Harvard University Gazette (MA Edu)
Copyright: 2004, the President and Fellows of Harvard College
Contact: (617) 495-0754
Website: http://www.news.harvard.edu/gazette/
Details: http://www.mapinc.org/media/2841
Author: William J. Cromie, Harvard News Office

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."