Cannabinoid Receptor System Dysregulation in Schizophrenia

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Researchers explored the role of the dysregulated cannabinoid receptor system in patients diagnosed with schizophrenia.
Researchers explored the role of the dysregulated cannabinoid receptor system in patients diagnosed with schizophrenia.

The latest pre-clinical and clinical data indicate a possible role of cannabinoid receptors in the development of neuropsychiatric disorders such as schizophrenia. Investigators affiliated with the University of Illinois at Chicago, University of California San Diego, and the Jesse Brown Veterans Affairs Medical Center recently published their findings that are consistent with this notion. They show that the dysregulation of the endocannabinoid signaling system is present among individuals diagnosed with schizophrenia without a comorbid cannabis-use disorder. These data were reported in Psychiatry Research.

Researchers compared the mRNA expression level of cannabinoid receptors in human peripheral blood mononuclear cells obtained from 35 patients (17 females) diagnosed with schizophrenia with those of 35 (18 females) typical, healthy participants. Participants in both groups did not have current substance-use disorder, including marijuana, alcohol, opiates, cocaine, and methamphetamine use, abuse, or dependence. There was a significant difference with regard to race between the two groups, with Black participants being overrepresented in the schizophrenia group. There were no differences between the groups with regard to age, body mass index, or tobacco use, and these characteristics were not used as covariates in the analyses.

Investigators used the DMS-IV-TR and the Structured Clinical Interview for DSM-IV-TR Axis I Disorder research version, patient edition (SCID) to diagnose the participants. They also used the measures of the MATRICS Consensus Cognitive Battery to evaluate cognitive function including sustained attention (the Continuous performance test), visual scanning, psychomotor processing speed (the Trails A subtest), verbal learning (the HVLT subtest) and visual learning (the BVMT subtest), visual working memory (the WMS spatial span subtest), executive function (the Mazes subtest), and semantic fluency (the Verbal fluency subtest). In their study, special emphasis was on attention, processing speed, and working memory, as individuals diagnosed with schizophrenia are most impaired in these cognitive domains. To examine the clinical symptomatology, they used the Positive and Negative Syndrome Scale (PANSS) in both groups of participants.

Results indicate that peripheral cannabinoid receptor mRNA levels in peripheral blood mononuclear cells were significantly upregulated in patients diagnosed with schizophrenia compared with those of control participants. More specifically, cannabinoid receptor 1 (CB1R) and cannabinoid receptor 2 (CB2R) levels were both elevated in patients with schizophrenia. Investigators reported a significant negative correlation between peripheral cannabinoid receptor mRNA levels and Attention [CB1R (rs=-0.438, P=0.02); and, CB2R (rs=-0.40, P=0.05)] in persons with schizophrenia, and as Attention decreased, levels of CB1R and CB2R increased. They also reported a significant negative correlation between Processing Speed and CB2R (rs=-0.42, P=0.02), as well as a significant negative correlation between Working Memory and CB2R (rs=-0.40, P=0.04), in patients with schizophrenia. There were no such correlations in the control group.

With regard to the PANSS Cognitive, Positive, and Negative factor scores, they reported a significant positive correlation between CB2R and Positive factors scores, as well as a significant positive correlation between both CB1R and CB2R and both Negative and Cognitive factor scores. Thus, the observed PANSS Cognitive factor scores were in line with their results from the MATRICS Cognitive Battery measures.

“PBMCs cannabinoid receptor levels may coordinate with illness severity even in the absence of cannabis use, and, it is possible that the association between CB receptor expression and schizophrenia converges on immune dysfunction in the PBMCs,” investigators concluded.


Chase KA, Feiner B, Rosen C, et al. Characterization of peripheral cannabinoid receptor expression and clinical correlates in schizophrenia. Psychiatry Res. 2016;245:346-353.

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