Irvine, Calif., May 18, 1999
Brains of people with schizophrenia contain levels of a chemical related to marijuana that are two times higher than those in people who don't have the disease, a team of UC Irvine researchers has found.
The findings could bring scientists closer to learning what causes schizophrenia, a disease that has bewildered researchers for decades and that torments an estimated one percent of the population worldwide. In addition, knowing how the chemical—called anandamide, the Sanskrit word for "bliss"—works could result in new, more effective therapies for schizophrenics, according to the researchers, whose findings appear in the June 3 issue of Neuroreport.
Daniele Piomelli, associate professor of pharmacology at UCI's College of Medicine; Andrea Guiffrida, a postdoctoral researcher at UCI, and F. M. Leweke, professor of neurology at the Medizinische Hochschule Hannover in Germany, said that the high levels of anandamide in the patients they studied may indicate that nerve cells in schizophrenics are not able to use this chemical properly.
The team studied 10 schizophrenic patients ages 18 to 49 for levels of anandamide by measuring their cerebrospinal fluid, a liquid that surrounds the brain and spinal cord. The levels of anandamide did not vary according to age, type of medication the patients were taking, or whether the patients were male or female.
"Treatment of schizophrenia has been hindered because we've never understood how the disease develops, and we don't know how drugs we currently use work on the disease," Piomelli said. "We hope that by understanding how anandamide works in the brain, we can arrive at a better understanding of schizophrenia and develop more effective treatments."
Although the cause of schizophrenia is not known, the disease has long been associated with abnormally high levels of another brain neurotransmitter called dopamine. Dopamine is largely responsible for stimulating movement and other motor behavior in the brain. For years, scientists have linked the uncontrolled production of dopamine to schizophrenia, Tourette's syndrome (which causes severe "nervous tics") and Parkinson's disease. Current therapies for these diseases include drugs that either hinder dopamine production or block its ability to stimulate nerve cells.
In findings published earlier this year, Piomelli's team reported that the effects of dopamine appear to be regulated by a network of marijuana-like anandamide. When anandamide is bound to nerve cell sites called cannabinoid receptors (named because they are targets of cannabinol, the active ingredient of marijuana), the chemical tempers the effects of dopamine. When these cannabinoid receptors were prevented from binding to anandamide in rats, the blocked nerve cells could not inhibit dopamine's effects, and the rats experienced severe uncontrolled motor activity.
Piomelli said the latest findings suggest that anandamide could be playing one of two roles in schizophrenics' brains. One theory is that since dopamine levels are already high in those with the disease, anandamide levels rise in an effort to regulate the rising dopamine levels. Another theory is that schizophrenia induces a higher level of anandamide, indicating that anandamide, not dopamine, may play a key role in causing schizophrenia.
Piomelli's team next will conduct more experiments with a larger group of patients in an attempt to resolve these questions and gain greater understanding of how schizophrenia develops.
"We've known that many schizophrenics smoke marijuana and claim that it eases some of their symptoms," he said. "While that is far from any treatment we'd recommend, this behavior, as well as our findings of high levels of anandamide in these patients, does indicate that anandamide plays an important role in the development of the disease."