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Closing in on a better treatment for schizophrenia

February 24, 2008
AFP

PARIS - Scientists looking at the effects of LSD in the brain have made an unexpected discovery that could lead to improved treatments for schizophrenia, according to a study published Sunday.

While investigating how hallucinogens change brain chemistry, a team of researchers led by Stuart Sealfon at the Mount Sinai School of Medicine in New York noticed that the neural pathways affected, as well as key symptoms, were very similar to those in schizophrenia patients.

Schizophrenics often hear voices, and may believe that other people are reading their minds or controlling their thoughts. These frightening experiences can cause social withdrawal and extreme agitation.

There is no known cure for the chronic disorder, which affects approximately one in 200 people, emerging in men in their late teens and early 20s, and a decade later in women, according to the World Health Organisation.

Created by a Swiss chemist in the late 1930s as a possible treatment for neural and respiratory troubles, lysergic acid diethylamide (LSD) emerged the 1950s and 1960s as a popular recreational drug.

LSD influences the same serotonin receptors that are imbalanced in schizophrenics, and both the drug and the disease result in delusions and hallucinations.

In experiments on mice, Sealfon also found that LSD -- in order to produce the effects sought after -- must simultaneously act on a receptor regulating glutamate, the principal excitatory neurotransmitter.

"While the LSD is binding to the serotonin part of this complex, it takes glutamate and serotonin together to create the unique changes in the cell that occur with LSD," Sealfon told AFP.

When mice under the influence of LSD were given a second drug targetting only the glutamate receptor, it neutralised the hallucinogenic effect of the LSD, said the study, published in the British journal Nature.

This is significant, explained Sealfon, in light of a recent breakthrough treatment for schizophrenia that -- unlike any previous drugs -- acts only on the glutamate receptors.

A study published last fall on successful clinical trials "was international news because it was the first completely new approach to schizophrenia in decades," he said.

An older class of so-called atypical anti-psychotic drug acts exclusively on serotonin levels, but Sealfon's findings suggest that -- like LSD -- the abnormal brain chemistry in schizophrenics may require medicines that regulate both at once.

Autopsies of schizophrenic patients who had been treated with any of the atypical anti-psychotic medications show normal serotonin levels, but low glutamate, he pointed out.

"This could lead to identifying new kinds of drugs to treat schizophrenia that act on this serotonin-glutamate complex," said Sealfon, adding that his research was not originally designed to investigate the disease.

His study also helps settle a decades-long debate, providing further evidence that LSD does, in fact, mirror the symptoms and chemical activity found in the brains of schizophrenics.

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