The study, published in the Archives of General Psychiatry, said heavy marijuana use, particularly in adolescence, appears to be associated with an increased risk for the later development of schizophrenia.

Dr. David A. Lewis of the Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine said expression of the cannabinoid 1 receptor, or CB1R, the site of action of the main chemical ingredient of marijuana, is significantly reduced in the brains of individuals with schizophrenia.

Activation of CB1R impairs signaling by gamma-aminobutyric acid, an important neurotransmitter essential for core cognitive processes such as working memory. The use of marijuana in individuals with schizophrenia appears to worsen this deficit in gamma-aminobutyric acid synthesis.

Lewis and his colleagues examined specimens of brain tissue collected after death from 23 people with schizophrenia and 23 normal comparison subjects matched for a number of factors, including age and sex.

"CB1R levels were significantly 15 percent lower in the subjects with schizophrenia," Lewis said said in a statement. "We measured these biochemical messengers using three techniques, and each time got the same answer -- less CB1R in people with schizophrenia."