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Anandamide elevation in cerebrospinal fluid in initial prodromal states of psychosis

  • Dagmar Koethe (a1), Andrea Giuffrida (a2), Daniela Schreiber (a3), Martin Hellmich (a4), Frauke Schultze-Lutter (a1), Stefan Ruhrmann (a1), Joachim Klosterkötter (a1), Daniele Piomelli (a5) and F. Markus Leweke (a6)...

Summary

Anandamide is a bioactive lipid binding to cannabinoid receptors. A homeostatic role for anandamide has been suggested in schizophrenia. We investigated its role in initial prodromal states of psychosis. We measured the levels of anandamide and its structural analog oleoylethanolamide in cerebrospinal fluid and serum of patients in the initial prodromal state (n=27) alongside healthy volunteers (n=81) using high-performance liquid chromatograph/mass spectrometry. Cerebrospinal anandamide levels in patients were significantly elevated. Patients with lower levels showed a higher risk for transiting to psychosis earlier. This anandamidergic up-regulation in the initial prodromal course may suggest a protective role of the endocannabinoid system in early schizophrenia.

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Copyright

Corresponding author

Correspondence: Dr. F. Markus Leweke, Department of Psychiatry and Psychotherapy, Central Institute of Mental Health, J5, 68159 Mannheim, Germany. Email: leweke@cimh.de

Footnotes

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These authors contributed equally to the work.

The study was funded by the Stanley Medical Research Institute (01-315 and 03-NV-003 to F.M.L.), the Koeln Fortune Program (108-2000 to F.M.L.) and the Federal Ministry of Education and Research (BMBF) (01KN0706 to D.K.).

Declaration of interest

None.

Footnotes

References

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1 Leweke, FM, Giuffrida, A, Wurster, U, Emrich, HM, Piomelli, D. Elevated endogenous cannabinoids in schizophrenia. Neuroreport 1999; 10: 1665–9.
2 Giuffrida, A, Leweke, FM, Gerth, CW, Schreiber, D, Koethe, D, Faulhaber, J, et al. Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptoms. Neuropsychopharmacology 2004; 29: 2108–14.
3 Leweke, FM, Giuffrida, A, Koethe, D, Schreiber, D, Nolden, BM, Neatby, MA, et al. Anandamide levels in cerebrospinal fluid of first-episode schizophrenic patients: impact of cannabis use. Schizophr Res 2007; 94: 2936.
4 Leweke, FM, Koethe, D. Cannabis and psychiatric disorders: it is not only addiction. Addict Biol 2008; 13: 264–75.
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7 Miller, TJ, McGlashan, TH, Woods, SW, Stein, K, Driesen, N, Corcoran, CM, et al. Symptom assessment in schizophrenic prodromal states. Psychiatric Q 1999; 70: 273–87.
8 Andersson, M, Alvarez-Cermeno, J, Bernardi, G, Cogato, I, Fredman, P, Frederiksen, J, et al. Cerebrospinal fluid in the diagnosis of multiple sclerosis: a consensus report. J Neurol Neurosurg Psychiatry 1994; 57: 897902.
9 Schreiber, D, Harlfinger, S, Nolden, BM, Gerth, CW, Schömig, E, Klosterkötter, J, et al. Determination of anandamide and other fatty acylethanolamides in human serum by electrospray tandem mass spectrometry. Anal Biochem 2007; 361: 162–8.
10 Huang, JT, Leweke, FM, Tsang, TM, Koethe, D, Kranaster, L, Gerth, CW, et al. CSF metabolic and proteomic profiles in patients prodromal for psychosis. PLoS ONE 2007; 2: e756.
11 Corcoran, C, Malaspina, D, Hercher, L. Prodromal interventions for schizophrenia vulnerability: the risks of being ‘at risk’. Schizophr Res 2005; 73: 173–84.
12 Leweke, FM, Giuffrida, A, Koethe, D, Schreiber, D, Nolden, BM, Kranaster, L, et al. Anandamide levels in cerebrospinal fluid of first-episode schizophrenic patients: impact of cannabis use. Schizophr Res 2007; 94: 2936.
13 Morgan, CJA, Curran, HV. Effects of cannabidiol on schizophrenia-like symptoms in people who use cannabis. Br J Psychiatry 2008; 192: 306–7.
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Anandamide elevation in cerebrospinal fluid in initial prodromal states of psychosis

  • Dagmar Koethe (a1), Andrea Giuffrida (a2), Daniela Schreiber (a3), Martin Hellmich (a4), Frauke Schultze-Lutter (a1), Stefan Ruhrmann (a1), Joachim Klosterkötter (a1), Daniele Piomelli (a5) and F. Markus Leweke (a6)...

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Anandamide elevation in cerebrospinal fluid in initial prodromal states of psychosis

  • Dagmar Koethe (a1), Andrea Giuffrida (a2), Daniela Schreiber (a3), Martin Hellmich (a4), Frauke Schultze-Lutter (a1), Stefan Ruhrmann (a1), Joachim Klosterkötter (a1), Daniele Piomelli (a5) and F. Markus Leweke (a6)...
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