LSD Study Probes Hallucinogen's Effect on Brain

Experiments with mice may lead to new psychiatric drugs, researchers say.

By Steven Reinberg
HealthDay Reporter
Wednesday, January 31, 2007; 12:00 AM

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WEDNESDAY, Jan. 31 (HealthDay News) -- Scientists are examining the responses of mice to learn more about how psychedelic drugs such as LSD, mescaline and "magic mushrooms" work on the brain.

Besides providing new insights into hallucinogens, the study opens a door to understanding how drugs used to treat psychiatric disorders may work, too. It may even point the way to new and better medications for mental illness, the team said.

"We were trying to find out why hallucinogens have their unique effects when very closely related drugs don't have similar effects on behavior and perception," explained co-researcher Dr. Stuart C. Sealfon, a professor of neurology, neuroscience, pharmacology and biological chemistry at Mount Sinai School of Medicine, in New York City.

The findings are published in the Feb. 1 issue of Neuron.

The researchers found that hallucinogens act on specific serotonin receptors in the brain called 5-HT2A receptors (2ARs). Hallucinogens act somewhat differently from other drugs that also target that receptor, Sealfon said.

"It's as if the receptor was a switch that can get turned on in one position for drugs that are not hallucinogens, and it turns on in another position for drugs that are hallucinogens," he explained.

In the study, the researchers closely observed mice to compare differences between the effects of LSD and lisuride, a non-hallucinogenic chemical that also activates 2AR receptors on brain cells.

"Of course, we don't know what the mice experience when they are treated with these drugs," Sealfon said. "But we do know that there is a head twitch response in the mice that provides a good correlation with drugs that are known to be hallucinogenic in humans."

Sealfon's group looked at whether 2AR receptors were essential to the hallucinogenic effect of LSD. In mice genetically engineered to lack the receptors, the researchers observed no hallucinogenic response to LSD. However, restoring the receptors did produce indications of LSD hallucinations in the animals.