Alterations in a molecular brain pathway that are activated by marijuana may give rise to the cognitive symptoms of schizophrenia, scientists at the University of Pittsburgh School of Medicine have said.
The researchers say that activation of the cannabinoid 1 receptor (CB1R), the site of action of the main chemical ingredient of marijuana, impairs signalling by gamma-aminobutyric acid (GABA), an important neurotransmitter essential for core cognitive processes such as working memory.
AdvertisementWriting about their observations in the Archives of General Psychiatry, the researchers have revealed that the use of marijuana in individuals with schizophrenia appears to worsen this deficit in GABA synthesis.
The researchers say that their suggest possible new drug targets that could help to improve function in people with the mental illness, given that reduced GABA is known to be present in schizophrenia.
"Heavy marijuana use, particularly in adolescence, appears to be associated with an increased risk for the later development of schizophrenia, and the course of illness is worse for people with schizophrenia who use marijuana," said Dr. David A. Lewis, corresponding author of the study and UPMC Endowed Professor in Translational Neuroscience, Western Psychiatric Institute and Clinic, University of Pittsburgh School of Medicine.
"We wanted to understand the biological mechanisms that could explain these observations, and with this study, I believe that we can narrow down at least part of the 'why' to CB1R, the receptor for both tetrahydrocannabinol (THC), the main psychoactive ingredient in marijuana, and the brains own cannabinoid chemical messengers," he added.
For their study, the researchers examined specimens of brain tissue collected after death from 23 people with schizophrenia, and 23 normal comparison subjects.
The team evaluated levels of CB1R messenger RNA and protein.
The levels of glutamic acid decarboxylase (GAD-67), an enzyme that makes GABA, and cholecystokinin (CCK), a neuropeptide released from GABA neurons that regulates the production of the brain's own cannabinoids, were also measured.
"CB1R levels were significantly 15 percent lower in the subjects with schizophrenia. We measured these biochemical messengers using three techniques, and each time got the same answer - less CB1R in people with schizophrenia," Dr. Lewis said.
According to him, this reduction appears to be the brain's way of compensating for lower levels of GABA, and the use of marijuana defeats this compensation.
"These findings may provide insight into the biological basis of why cannabis use worsens schizophrenia, and, as a result, identify a novel target for new drug development that could improve treatments available for schizophrenia," said Dr. Lewis.