SHRINKING MORPHINE DOSE COULD REDUCE ADDICTION RISK

NEW YORK (Reuters Health) - A New York researcher has demonstrated that
morphine and other opiates are effective in tiny doses when given in
combination with drugs that block their effects.

Currently, patients often receive very high doses of opiates for pain
treatment, in part because small doses can actually cause pain. And when a
standard dose wears off and a person's opiate level reaches a certain low
level, pain is again enhanced.

``The patient may experience more pain than they would have if there was no
morphine present,'' Dr. Stanley M. Crain, a professor of neuroscience at
Albert Einstein College of Medicine, Bronx, New York, told Reuters Health.
``That's why the clinician will give another dose of morphine before that
happens.''

Crain has been studying opiates and opiate blockers such as naltrexone and
naloxone for 10 years. While opiate drugs work by blocking receptors in the
nerves that produce the sensation of pain, he has shown in laboratory
studies that these drugs also stimulate a small subset of receptors that
increase pain. ''It does explain a lot of paradoxes in the clinical
literature about morphine's inability to control pain effectively,'' he noted.

The painkilling effect of opiates can be enhanced, Crain proposes, by
giving a small dose of naltrexone that will block the pain receptors
stimulated by opiates. This would allow morphine, codeine, and other opiate
painkillers to be used in much smaller doses, reducing the risk of side
effects and decreasing the chance that a person will develop tolerance to
the drug.

The study, published in the January issue of the journal Brain Research,
supports this hypothesis. The investigators found that a dose of morphine
1,000 times smaller than the normally effective dose blocked pain in mice
when given along with a tiny dose of naltrexone. Crain and his colleagues
measured the painkilling effects of the drug by dipping the animals' tails
in hot water and timing how long it took each mouse to flick its tail.

The study has major implications for pain treatment in humans, Crain
explained. ``When you use a high dose of morphine, you have all those
noxious side effects--nausea, vomiting, itching, tolerance, addiction,'' he
said.

Also, the pain-producing effects of morphine are enhanced in people who
become dependent upon or addicted to the drug, further increasing the need
for high doses in pain treatment. ''We think this is one of the major
causes of tolerance and dependence,'' he added.

The findings could point the way toward making opiates effective in
patients who have become tolerant to them, Crain suggested, and could even
have implications for treating heroin addicts. He is now investigating the
effects of low-dose opiates with naltrexone in mice that have developed
tolerance to the drug.

Pain Therapeutics Inc. in California, a company that has licensed Crain's
patents, is currently testing his hypotheses in clinical trials.