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Reciprocal alterations in cortical cannabinoid receptor 1 binding relative to protein immunoreactivity and transcript levels in schizophrenia.

David W Volk, Stephen M Eggan, Andrew G Horti, Dean F. Wong, David A Lewis

Schizophrenia Research October 2014 DOI: 10.1016/j.schres.2014.07.017 (opens in new tab)

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Characteristics Case-control postmortem receptor autoradiography study Peer reviewed
Sample size 21
Population Postmortem prefrontal cortex tissue from subjects with schizophrenia, compared with matched healthy comparison subjects
Measures [3H]-OMAR receptor autoradiography, in situ hybridization for CB1R mRNA, radioimmunocytochemistry for CB1R protein
Topics Cannabis
Keywords Cb1r Cannabinoid PET Prefrontal cortex Radioligand Rimonabant Schizophrenia
Key findings Higher [3H]-OMAR binding to CB1 receptors was found in the prefrontal cortex of schizophrenia subjects despite their previously documented lower CB1R mRNA and protein levels. The authors suggest this discrepancy may reflect altered receptor trafficking or higher CB1R affinity, and propose that greater CB1R availability may contribute to increased susceptibility to cannabis effects in schizophrenia.

Abstract

The deleterious effects of cannabis use in schizophrenia have been linked, in part, to underlying disturbances in endogenous cannabinoid signaling in the prefrontal cortex. However, while receptor autoradiography studies of the primary cannabinoid receptor (CB1R) have consistently found higher CB1R binding in the prefrontal cortex in schizophrenia, deficits in CB1R mRNA levels and protein immunoreactivity have also been reported in the illness. To investigate this apparent discrepancy, we quantified CB1R binding using receptor autoradiography with the selective CB1R ligand [(3)H]-OMAR in the prefrontal cortex of 21 subjects with schizophrenia who were previously found to have lower levels of both CB1R mRNA using in situ hybridization and CB1R protein using radioimmunocytochemistry relative to matched healthy comparison subjects. We observed higher levels of [(3)H]-OMAR binding in the prefrontal cortex of schizophrenia subjects that did not appear to be attributable to psychotropic medications or substance abuse. The combination of lower levels of CB1R mRNA and immunoreactivity with higher CB1R receptor binding may reflect 1) altered trafficking of the receptor resulting in higher levels of membrane-bound CB1R or 2) higher CB1R affinity. In either case, greater CB1R receptor availability may contribute to the increased susceptibility of schizophrenia subjects to the deleterious effects of cannabis use.

Comparable studies

Other observational and cohort studies on cannabis, most cited first.

Study Year Design Participants
High-potency cannabis and the risk of psychosis People with first episode of psychosis and healthy controls from the local population 2009 Case-control study n = 454
Ayahuasca-Assisted Therapy for Addiction: Results from a Preliminary Observational Study in Canada Rural aboriginal population 2013 Observational study
Impaired cognitive performance in drug free users of recreational ecstasy (MDMA) Otherwise healthy young people 2000 Observational
Continued cannabis use and risk of incidence and persistence of psychotic symptoms: 10 year follow-up cohort study Individuals from the general population in Germany aged 14-24 at baseline 2011 Observational cohort n = 1,923
Cannabis-induced psychosis and subsequent schizophrenia-spectrum disorders: follow-up study of 535 incident cases Patients treated for cannabis-induced psychotic symptoms in Denmark between 1994 and... 2005 Observational cohort n = 535

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