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.