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Brain may produce its own antipsychotic drug

Brain may produce its own antipsychotic drug

A cannabis-like substance produced by the brain may dampen delusional or psychotic experiences, rather than trigger them.

Heavy cannabis use has been linked to psychosis in the past, leading researchers to look for a connection between the brain's natural cannabinoid system and schizophrenia.

Sure enough, when Markus Leweke of the University of Cologne, Germany, and Andrea Giuffrida and Danielle Piomelli of the University of California, Irvine, looked at levels of the natural cannabis-like substance anandamide, they were higher in people with schizophrenia than in healthy controls.

The team measured levels of anandamide in the cerebrospinal fluid (CSF) of 47 people suffering their first bout of schizophrenia, but who had not yet taken any drugs for it, and 26 people who had symptoms of psychosis and have a high risk of schizophrenia.

Compared with 84 healthy volunteers, levels were six times as high in people with symptoms of psychosis and eight times as high in those with schizophrenia.

"This is a massive increase in anandamide levels," Leweke told the National Cannabis and Mental Illness Conference in Melbourne, Australia, last week. And that is just in the CSF. Levels could be a hundred times higher in the synapses, where nerve signalling is taking place, he says.

Cause or effect

But were the high anandamide levels triggering the psychotic symptoms or a response to them? Leweke and his colleagues found, to their surprise, that the more severe people's schizophrenia was the lower their anandamide levels.

The team's theory is that rather than triggering psychosis, the substance is released in response to psychotic symptoms to help control them. People with the worst symptoms might be unable to produce sufficient anandamide to prevent them.

At some point in their lives, between 5 and 30 per cent of healthy people have had symptoms such as delusions or hallucinations, which can be triggered by something as simple as sleep deprivation. "All of us are potentially psychotic," says David Castle of the University of Melbourne. So for the body to have a system that prevents these experiences getting out of hand makes sense, he says.

Frequent episodes

The new findings suggest antipsychotic drugs could be developed that target the anandamide system, but it will not be simple. The active ingredient in cannabis, THC, binds to anandamide receptors.

But people with schizophrenia who use cannabis actually have more severe and frequent psychotic episodes than those who do not. This may be because THC makes anandamide receptors less sensitive.

Leweke's team also found anandamide levels lowest in people with schizophrenia who used cannabis more frequently, suggesting it may disrupt the system in other ways too. Up to 60 per cent of people with schizophrenia use cannabis.

A study by Castle, also reported at the Melbourne meeting, has found that people use the drug to get rid of unpleasant emotions associated with the disease such as anxiety and depression.

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