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Inhibition of cerebral type 1 cannabinoid receptors is associated with impaired auditory mismatch negativity generation in the ketamine model of schizophrenia

Patrik Roser, IS Haussleiter, HJ Chong, C Maier, Wolfram Kawohl, Christine Norra, Georg Juckel

Pharmacopsychiatry September 1, 2011 DOI: 10.1055/s-0031-1292535 (opens in new tab)

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Study at a glance

AI-extracted from the abstract
Characteristics Randomized, double-blind, placebo-controlled cross-over study Peer reviewed
Sample size 20
Population Healthy male subjects
Interventions Ketamine Rimonabant
Dose subanesthetic doses of intravenous ketamine
Measures Mismatch negativity (MMN) amplitudes to frequency and duration deviants
Topics Esketamine Ketamine
Citations 2
Key points Ketamine infusion had no significant effect on MMN amplitudes in either deviance condition. Co-administration of rimonabant produced significant deficits in MMN amplitudes to duration deviants at electrode position Fz, suggesting CB1 receptor antagonism may impair auditory sensory memory via disturbed endocannabinoid-glutamatergic interaction.

Abstract

Preclinical and clinical research suggests that the endogenous cannabinoid system is involved in cognitive impairments related to schizophrenia. In particular, deficient generation of mismatch negativity (MMN) indicating auditory sensory memory is a characteristic finding in schizophrenic patients. Experimental studies implicate deficient N-methyl-D-aspartate (NMDA) receptor functioning in such abnormalities. The primary aim of this study was to investigate the effects of the cannabinoid CB1 receptor antagonist rimonabant on MMN deficits in the NMDA receptor antagonist model of schizophrenia by using ketamine. Twenty healthy male subjects participated in a randomized, double-blind, placebo-controlled cross-over study with subanesthetic doses of intravenous ketamine. The MMNs to frequency and duration deviants were elicited within an auditory oddball paradigm and recorded by 32 channel EEG. Ketamine infusion had no significant effect on MMN amplitudes in both deviance conditions. In contrast to placebo, co-administration of rimonabant produced significant deficits in MMN amplitudes to duration deviants at electrode position Fz. The results point to the involvement of the endogenous cannabinoid system in auditory sensory memory as a cognitive key feature in schizophrenia. They particularly suggest that CB1 receptor antagonism may impair cognitive performance by disturbed interaction between endocannabinergic activity and glutamatergic neurotransmission implied in schizophrenia.

Comparable studies

Other randomized controlled trials on ketamine, most cited first.

Study Year Design Participants
Subanesthetic Effects of the Noncompetitive NMDA Antagonist, Ketamine, in Humans Healthy human subjects recruited from the community 1994 Randomized controlled trial n = 19
Antidepressant Efficacy of Ketamine in Treatment-Resistant Major Depression: A Two-Site Randomized Controlled Trial Patients with treatment-resistant major depression experiencing a major depressive episode 2013 Randomized controlled trial n = 73
Remifentanil-induced Postoperative Hyperalgesia and Its Prevention with Small-dose Ketamine Patients undergoing major abdominal surgery 2005 Randomized controlled trial n = 75
Efficacy of Intravenous Ketamine for Treatment of Chronic Posttraumatic Stress Disorder Patients with chronic PTSD related to a range of trauma exposures 2014 Randomized controlled trial n = 41
Ketamine-Induced Deficits in Auditory and Visual Context-Dependent Processing in Healthy Volunteers Healthy volunteers 2000 Single-blind placebo-controlled study n = 20

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