Chronic Effects of Cannabis Use on the Auditory Mismatch Negativity.

Background: Cannabis use is associated with the development of psychotic symptoms and increased risk for schizophrenia. The mismatch negativity (MMN) is a brain event-related potential marker of change detection thought to index glutamatergic N-methyl-D-aspartate receptor-mediated neurotransmission, which is known to be deficient in schizophrenia. This study examined auditory MMN in otherwise healthy chronic cannabis users compared with nonuser control subjects. Methods: Forty-two chronic cannabis users and 44 nonuser healthy control subjects completed a multi-feature MMN paradigm, which included duration, frequency, and intensity deviants (deviants 6%; standards 82%). The MMN was compared between users and control subjects as well as between long- and short-term users and age- and gender-matched control subjects. Associations between MMN, cannabis use measures, and symptoms were examined. Results: The MMN amplitude was significantly reduced to frequency but not duration or intensity deviants in overall cannabis users relative to control subjects. Frequency MMN was similarly attenuated in short- and long-term users relative to control subjects. Long-term users also exhibited reduced duration MMN relative to control subjects and short-term users and this was correlated with increased duration of exposure to cannabis and increased psychotic-like experiences during intoxication. In short-term users, a younger age of onset of regular cannabis use and greater frequency of use were associated with greater psychotic-like experiences and symptomatic distress. Conclusions: These results suggest impaired sensory memory that might reflect N-methyl-D-aspartate receptor dysfunction in chronic cannabis users. The pattern of MMN alterations in cannabis users differed from that typically observed in patients with schizophrenia, indicating overlapping but distinct underlying pathology. [ABSTRACT FROM AUTHOR]