Line of Research Could Advance Schizophrenia TX

By Goldman, Erik L. | Clinical Psychiatry News, February 2007 | Go to article overview

Line of Research Could Advance Schizophrenia TX


Goldman, Erik L., Clinical Psychiatry News


NEW YORK -- Overexpression of cannabinoid receptors and hyperactivity of the brain's endogenous endocannabinoid system may be responsible for the delusions and aberrant associations characteristic of schizophrenia, Steven Laviolette, Ph.D., said at the annual meeting of the National Alliance for Research on Schizophrenia and Depression.

The endocannabinoid system, which is acted upon by use of marijuana (Cannabis sativa), is a naturally occurring receptor system within the brain that has become the subject of considerable research in recent years. It is responsible for the processing of the emotional salience connected with direct sensory perceptions. In other words, it is the brain system responsible for assigning and evaluating the emotional significance of what we perceive.

Current research indicates that people with schizophrenia show significant differences in the expression and activity of the endocannabinoid system, said Dr. Laviolette, of the department of anatomy and cell biology, Schulich School of Medicine, University of Western Ontario, London.

"The delusions, psychotic ideation, and distorted associations of schizophrenia are related to aberrant emotional processing of sensory inputs," he said. "Our evidence suggests that a dysregulated cannabinoid system may be involved in the emotional processing disturbances observed in schizophrenia. Increased cannabinoid levels in schizophrenia may pathologically amplify the emotional significance of sensory stimuli, similar to the effect of heavy marijuana exposure."

Emotional salience is the province of the prefrontal cortex, the amygdala, and in particular, the cingulate gyrus. All of these brain regions are normally rich in endocannabinoid receptors. But people with schizophrenia show markedly increased expression of these receptors in the cingulate gyrus, compared with controls who do not have schizophrenia.

The available data suggest that a hyperactive cannabinoid system may be one of the core neurologic abnormalities underlying schizophrenia. Endocannabinoid hyperactivity causes the person to perceive intense emotional significance from an ordinary external signal that would carry no such meaning for an individual with normal endocannabinoid expression.

Thus, an individual with schizophrenia may believe that an ordinary television news broadcast is a message from a demon directed personally at him, said Dr. Laviolette by way of example.

This line of research is interesting, given what is known about the impact of marijuana use on individuals at risk for schizophrenia and schizotypal disorders. "Abuse of marijuana early on in life is associated with higher rates of schizophrenia in males, and it is also linked to increased numbers of psychotic episodes in patients with schizophrenia."

Dr. Laviolette stressed that these findings should not be misconstrued to mean that cannabis smoking causes schizophrenia; the link may not, in fact, be causal. But the data do suggest that for someone with an already overactive endocannabinoid system and a predisposition for developing schizophrenia, abuse of the drug only adds fuel to the fire and may be a triggering factor for frank psychosis.

Research into endocannabinoid function is also opening up new possibilities for treatment of schizophrenia using agents that block cannabinoid signaling. Work in this direction is still at the earliest stages, but it represents an entirely new direction in drug development. …

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