Pharmacopsychiatry 2005; 38 - A143
DOI: 10.1055/s-2005-918765

The role of the endogenous cannabinoid system in schizophrenia

FM Leweke 1, A Giuffrida 2, D Koethe 1, BM Nolden 1, CW Gerth 1, D Schreiber 1, S Gross 1, A Juelicher 1, J Klosterkötter 1, D Piomelli 3
  • 1Klinik und Poliklinik für Psychiatrie und Psychotherapie, Universität zu Köln
  • 2Department of Pharmacology, University of Texas Health Science Center San Antonio, San Antonio, USA
  • 3Department of Pharmacology, University of California, Irvine, Irvine, USA

Aims: Cannabis use is considered a risk factor for schizophrenia. However, the underlying neurobiological mechanisms remain conjectural. This study investigates the centrally acting endocannabinoid anandamide (AEA) in acute schizophrenia and the influence of cannabis use hereon. Methods: Concentrations of AEA were measured by HPLC/ MS in cerebrospinal fluid (CSF) and serum of acute antipsychotic-naïve schizophrenics (S-N; n=47), D2- (S- CT; n=37) and 5HT2A/D2-antagonistically (S-AT; n=34) treated acute schizophrenics, and healthy volunteers (HV; n=81). Psychopathology, patterns of cannabis use, and urine drug screenings were assessed independently. Results: AEA in CSF is significantly elevated in S-N. This is reversed in S-CT, but not in S-AT. Furthermore, CSF AEA is negatively correlated with psychotic symptoms in S-N. S-N with less than 5x of cannabis use lifetime and no acute use (n=25) show significantly higher AEA in CSF than HV (n=55; P=.000). They also differ significantly from patients with a history of more than 20x but no recent use of cannabis (n=9; P=.001). Conclusions: The elevation of AEA in schizophrenia may reflect a compensatory adaptation to dopaminergic hyperactivity. The history of cannabis use in S-N yields a significant association to AEA in CSF. The adaptive and counterbalancing role of AEA in S-N seems to be disrupted by the chronic use of cannabis.