Endocannabinoid metabolism in the prefrontal cortex in schizophrenia.

Adolescent cannabis use is associated with greater relative risk, increased symptom severity, and earlier age of onset of schizophrenia. We investigated whether this interaction may be partly attributable to disease-related disturbances in metabolism of the major cortical endocannabinoid 2-arachidonoylglycerol (2-AG). Transcript levels for the recently discovered 2-AG metabolizing enzyme, α-β-hydrolase domain 6 (ABHD6), were assessed using quantitative PCR in the prefrontal cortex of schizophrenia and healthy subjects (n=84) and antipsychotic- or tetrahydrocannabinol-exposed monkeys. ABHD6 mRNA levels were elevated in schizophrenia subjects who were younger and had a shorter illness duration but not in antipsychotic- or tetrahydrocannabinol-exposed monkeys. Higher ABHD6 mRNA levels may increase 2-AG metabolism which may influence susceptibility to cannabis in the earlier stages of schizophrenia.