Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptoms

The endocannabinoids are a family of bioactive lipids that activate CB ₁ cannabinoid receptors in the brain and exert intense emotional and cognitive effects. Here, we have examined the role of endocannabinoid signaling in psychotic states by measuring levels of the endocannabinoid anandamide in cerebrospinal fluid (CSF) of acute paranoid-type schizophrenic patients. We found that CSF anandamide levels are eight-fold higher in antipsychotic- naïve first-episode paranoid schizophrenics (n = 47) than healthy controls (n = 84), dementia patients (n = 13) or affective disorder patients (n = 11). Such an alteration is absent in schizophrenics treated with 'typical' antipsychotics (n = 37), which antagonize dopamine D₂-like receptors, but not in those treated with 'atypical' antipsychotics (n = 34), which preferentially antagonize 5HT_2A receptors. Furthermore, we found that, in nonmedicated acute schizophrenics, CSF anandamide is negatively correlated with psychotic symptoms (r_s = -0.452, P = 0.001). The results suggest that anandamide elevation in acute paranoid schizophrenia may reflect a compensatory adaptation to the disease state.