Pubdate: Mon, 08 Feb 1999 Source: Milwaukee Journal Sentinel (WI) Contact: Website: Copyright: 1999, Milwaukee Journal Sentinel.


Scientists hope to isolate the pain-killing powers of the natural compounds

Amid the various battles to legalize medical marijuana stands this little-known fact: Our brains and bodies are flooded with a natural form of the drug.

Called cannabinoids, after the euphoria-inducing plant Cannabis sativa, this family of compounds blocks pain, erases memories and triggers hunger. Newer studies show they may also regulate the immune system, enhance reproduction and even protect the brain from stroke and trauma damage.

Discovered in humans just a few years ago and, until recently, virtually unstudied, the compounds have become one of the looming mysteries of the nervous system and a field of exploding scientific interest.

Already, scientists are testing cannabinoids with hopes of harnessing the medical power of marijuana to treat pain without its high, smoke or political baggage. A key challenge is separating the curing power of the compounds from their mind-altering side effects.

"That's the holy grail of this field," said Steven Childers, a pharmacologist at the Wake Forest University School of Medicine in Winston- Salem, N.C.

Because cannabinoids are so numerous in the brain, they also could help explain the workings of some of our body's most complex, and least understood, systems.

"It's obviously important because there's so much of it. And we never knew it existed before," said J. Michael Walker, a Brown University psychologist who has conducted some of the first studies of how cannabinoids block pain. "It could help us understand movement, it could help us understand memory, it could help us understand pain. We don't really know how any of these things work."

There has always been evidence, from the intoxicating effects cannabis evokes in smokers, that it contains powerful compounds.

The sticky, flowering buds of the plant have been harvested as medicine for centuries. Five thousand years ago, Chinese physicians used the plant to treat malaria, absentmindedness and "female disorders." African tribes used it to treat snakebite and the pain of childbirth, while Indian physicians prescribed it for headaches.

Sifting through the plant's chemical stew in the early '60s, Israeli pharmacologist Raphael Mechoulam discovered more than 60 cannabinoids in marijuana, including the famous and psychoactive compound THC. In 1992, a team led by Mechoulam and William Devane trumped that discovery by showing that humans produced their own cannabinoids. They called the substance anandamide, Sanskrit for eternal bliss.

Our brains contain receptors that interact with the anandamide we produce. In an accident of nature and chemistry, compounds in pot are shaped similarly and therefore trigger similar but more potent effects. The same is true of the plant drugs nicotine and cocaine.

Now, scientists are beginning to understand just what natural cannabinoids might be doing in the human body.

"We're opening doors now we couldn't even have predicted existed," said Childers, president of the International Cannabinoid Research Society.

For example:

Herbert Schuel and Lani J. Burkman of the University of Buffalo have reported that cannabinoids help control the exquisite synchrony of timing during reproduction by slowing anxious sperm if they try to approach an egg before it's ready for fertilization. This may also explain why heavy pot users, both men and women, are sometimes infertile.

Cannabinoids have been found to both suppress and enhance the body's defenses against diseases and tumors, a duality that has researchers puzzled. "It's a science clearly in flux," said Thomas W. Klein, an immunologist at the University of South Florida. "The more we learn, the more confused we are."

While pot warnings "This is your brain on drugs" have long spotlighted the drug's damaging effects on the brain, research last summer from the National Institute of Mental Health shows cannabinoids protect brain cells from stroke or trauma damage.

In 1997, scientists at the Neurosciences Institute in San Diego showed that cannabinoids block the formation of new memories in slices of animal brain tissues. This power to forget might keep the brain from filling up or getting overwhelmed with unimportant memories.

Researchers' largest hopes are focused on using a synthetic form of cannabinoids to block pain, including chronic nerve pain that existing drugs block inadequately.

Animal studies show cannabinoids can block other kinds of pain almost before they begin stopping the pain signals before they reach the spinal cord or brain, working as well as morphine. That power suggests they could be substituted for morphine, which is addictive and must be used in increasing doses over time.

Cannabinoids enhance morphine's power; combining the drugs could vastly reduce the dosages needed to kill pain, offsetting problems of addiction and drug tolerance. Cannabinoids also counteract nausea, another plus for patients with cancer and AIDS.

"It might be possible to manipulate levels of the body's own cannabinoids. You could create drugs like Prozac that block the body's reuptake of cannabinoids or inhibit their breakdown so they stay active longer," said Andrea Hohmann, who previously worked with Walker and now researches pain at the National Institute of Dental and Craniofacial Research.

"These kind of manipulations may not have the unwanted side effects of marijuana and aren't going to carry the same kind of political baggage."