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Scientists Isolate Marijuana Target in Brain, May Help Drug Development

August 8, 1990

NEW YORK (AP) _ Scientists say they have isolated and cloned a ″button″ that marijuana pushes in the brain to produce its effects, an advance that may lead to new pain-killers and other medications.

Marijuana’s main active ingredient attaches itself to the protein structure on the surface of brain cells, triggering alterations in mood and thinking, researchers said.

The new work suggests that the brain contains some natural substance that resembles the marijuana ingredient, called a cannabinoid, scientists said.

The work is presented in Thursday’s issue of the British journal Nature by scientists from the National Institute of Mental Health in Bethesda, Md.

Their paper describes details of the brain-cell structure as it appears in rats, but further study showed the human structure is virtually identical, said study co-author Tom Bonner.

Marijuana is best known for producing a calm, mildly euphoric state. Time seems to slow down and users become more sensitive to sights, sounds and touch. Ideas may flow rapidly through the mind while short-term memory is suppressed.

Marijuana ingredients can also relieve pain and ease or prevent high blood pressure, epileptic convulsions, nausea, asthma and the eye disease glaucoma, scientists say.

The new work opens the door to developing derivatives that mimic those therapeutic effects while lacking undesired ones, commented Dr. Solomon Snyder, director of the neuroscience department at Johns Hopkins Medical School in Baltimore.

The newly cloned structure is called a receptor. Many drugs and natural substances bind to particular receptors to exert their effects on the body.

Previous studies suggest that cannabinoids exert a variety of effects because they bind to a variety of receptor variants, called subtypes, Snyder said.

″So if you could get a derivative that works on the therapeutic subtype but not the subtype that makes you high, then you would have an effective drug without the possibility of being a drug of abuse,″ he said in a telephone interview.

″Drug companies have been working on this for years, but have been unsuccessful because they didn’t have any way to look at these receptor subtypes that we think exist.″

Researchers should now be able to use the cloned cannabinoid receptor to search for related subtypes, he said.

″Then a drug company can synthesize lots of chemicals and check them out on receptor A and receptor B, and then gradually sculpt a molecule that fits receptor A and not receptor B, and then you have a super drug,″ he said.

Bonner said the existence of the receptor suggests that the brain naturally contains some sort of cannabinoid-like substance. ″The receptor’s not there just so that people can go out and smoke pot and get high,″ he said.

Finding the brain chemical would shed light on the workings of the central nervous system, and might give clues to developing new medications, he said.

In the Nature paper, scientists said they found genetic material that tells brain cells how to make the receptor. From that they could deduce the chemical makeup of the receptor.

When they inserted the genetic material into hamster ovary cells, the cells produced receptors on their surfaces. The receptors behaved as expected when exposed to cannabinoids.

Bonner’s co-authors were Lisa Matsuda, Stephen Lolait, Dr. Michael Brownstein and Alice Young.

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