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An Alternative to Medicinal Marijuana

Nerve agents stimulated cannabinoid receptors in mice, offering pain relief without side effects

SUNDAY, April 27 (HealthDay News) -- Scientists think they may have found a way to harness marijuana's medicinal powers without unleashing the plant's memory-robbing properties.

But a new and improved dope-based medication is unlikely to hit doctors' offices near you soon.

"This has great potential but it's years away from human application," said one expert, Dr. Dennis J. Patin, associate professor of clinical anesthesiology at the University of Miami Miller School of Medicine. "I expect that some drug company will research further," he said.

And John Casida, senior author of the paper in the April 27 issue of Nature Chemical Biology, stressed that his team "report new fundamental mechanistic discoveries on the cannabinoid system, rather than proposing a medicine or treatment."

Tetrahydrocannabinol (THC), the psychoactive ingredient in marijuana, can relieve both pain and anxiety but, unfortunately, also results in cognitive problems such as memory loss.

In fact, one recent study found that multiple sclerosis patients who smoke marijuana in search of symptom relief are more likely to suffer cognitive shortfalls and mood disorders, such as depression and anxiety.

Casida and his colleagues at the University of California, Berkeley, and the Scripps Research Institute in La Jolla, Calif., found that organophosphorus (OP) nerve agents blocked the breakdown of certain enzymes, which has the end result of stimulating the cannabinoid receptors in the brain.

OP nerve agents work like OP pesticides, leading to an excess of the neurotransmitter acetylcholine in the central and peripheral nervous system.

In this experiment, using mice, the OP compounds had the therapeutic effects of THC (pain relief, lower body temperatures) without the cognitive drawbacks.

"We find that that a single organophosphorus compound is capable of eliciting full-blown cannabinoid effects that mirror those of direct cannabinoid receptor stimulators such as THC," said Casida, who is director of the Environmental Chemistry and Toxicology Laboratory at Berkeley. "We believe our compound does not act directly on the cannabinoid receptors, but instead elicits its effects by blocking the enzymes that degrade the endogenous cannabinoids . . . which in turn stimulate the cannabinoid receptors in the brain."

"Blocking these enzymes not only raises endogenous cannabinoid signaling power but also lowers arachidonic acid levels, which may be relevant for pain relief," Casida added. The arachidonic acid pathway is involved in pain and inflammation.

This raises the tantalizing possibility that, one day, a drug might be developed which has medical value but does not get the patient stoned.

More information

The Drug Policy Alliance has more on medical marijuana.

SOURCES: John Casida, Ph.D., professor, entomology and toxicology, and director, Environmental Chemistry and Toxicology Laboratory, University of California, Berkeley; Dennis J. Patin, M.D., associate professor of clinical anesthesiology, University of Miami Miller School of Medicine; April 27, 2008, Nature Chemical Biology

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