Molecular Precision Mental Health

Molecular Precision Mental Health

Endocannabinoid Research

The body’s own endocannabinoid system (ECS) is not yet understood completely in its pysiological and pathophysiological importance. However, it is possible to derive its importance concerning disease processes of mental health disorders from our experimental studies in healthy volunteers and psychiatric patients.

Therefore we have investigated the role of endogenous cannabinoids (eCBs) in psychiatric disorders in recent years. It became apparent that the concentrations of eCBs anandamide are significantly increased in the cerebrospinal fluid of patients with schizophrenic psychoses compared with healthy controls. Anandamide thus represents a natural counter-regulation against other neurotransmitter systems that are particularly activated in diseases of that kind.

This enables us to gain insight in the underlying neurobiological processes of endocannabinoid functions in psychiatric disorders. Moreover it renders possible to develop therapeutic strategies that target the endocannabinoid system.


This research was and is supported by the Stanley Medical Research Institute of the Theodore and Vada Stanley Foundation, USA (Grant IDs 01-315 and 03-NV-003 to FML), the Cologne Fortune Program, the European Commission (GxE Experimental EU FP7 HEALTH-F2-2010-241909), and special grant from the Deputy Vice-Chancler Research of the University of Sydney.


D. Koethe, F. Pahlisch, M. Hellmich, C. Rohleder, C. Hoyer, A. Meyer-Lindenberg, E. F. Torrey, D. Piomelli, F. M. Leweke: Familial abnormalities of endocannabinoid signalling in schizophrenia. World J Biol Psychiatry (2019) 20:117-125

A. R. Reuter, J. M. Bumb, J. K. Mueller, E. Arens, F. M. Leweke, D. Koethe, E. Schwarz: Differential association of anandamide with binocular depth inversion in schizophrenia. World J Biol Psychiatry (2017) 18:483-488

L. Kranaster., C. Hoyer, S. S. Aksay, J. M. Bumb, F. M. Leweke, C. Janke, M. Thiel, B. Lutz, L. Bindila, A. Sartorius: Electroconvulsive therapy enhances endocannabinoids in the cerebrospinal fluid of patients with major depression: a preliminary prospective study. Eur Arch Psychiatry Clin Neurosci (2017) 267:781-786

M. Grosshans, E. Schwarz, J. M. Bumb, C. Schaefer, S. Vollstädt-Klein, H. Tost, A. Meyer-Lindenberg, F. Kiefer, F. M. Leweke: Understanding the role of oleoylethanolamide in obesity: differential association with body mass index and food cue-induced brain activation. JAMA Psychiatry (2014) 71:1254-1261

D. Muhl, M. Kathmann, C. Hoyer, L. Kranaster, M. Hellmich, C. W. Gerth, J. Faulhaber, E. Schlicker, F. M. Leweke: Increased CB2 mRNA and anandamide in human blood after cessa¬tion of cannabis abuse. Naunyn-Schmiedeberg’s Arch Pharmacol (2014) 387:691

C. Schaefer, F. Enning, J. K. Mueller, J. M. Bumb, C. Rohleder, T. M. Odorfer, J. Klosterkötter, M. Hellmich, D. Koethe, C. Schmahl, M. Bohus, F. M. Leweke: Endogenous cannabinoids are altered in complex post traumatic stress and borderline personality disorders. Eur Arch Psychiatry Clin Neurosci (2013) 26:459-463.

J. Ceccarini, M. De Hert, R. Van Winkel, J. Peuskens, G. Bormans, L. Kranaster, D. Koethe, F. M. Leweke, K. Van Laere: Increased ventral striatal CB1 receptor binding is related to negative symptoms in schizophrenia and is modulated by antipsychotic drug therapy. Neuroimage (2013) 79:304-312.

C. J. A. Morgan, E. Page, C. Schaefer, K. Chatten, A. Manocha, S. Gulati, B. Brandner, V. Curran, F. M. Leweke: Cerebrospinal fluid anandamide levels differ with cannabis use and relate to psychotic-like symptoms. Br J Psychiatr (2013) 202: 381-382.

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E. Schwarz, P. Whitfield, S. Nahnsen, L. Wang, H. Major, F. M. Leweke, D. Koethe, P. Lio, S. Bahn: Alterations of primary fatty acid amides in serum of patients with severe mental illness. Front Biosci (Elite Ed) (2011) 3: 308-314.

D. Koethe, A. Giuffrida, D. Schreiber, M. Hellmich, F. Schultze-Lutter, S. Ruhrmann, J. Klosterkötter, D. Piomelli, F. M. Leweke: Anandamide elevation in CSF of prodromal states of schizophrenia. Brit J Psychiat, (2009) 194:371-372.

D. Koethe, D. Schreiber, A. Giuffrida*, C. Mauss, B. Heydenreich, R. Graf, J. Klosterkötter, D. Piomelli, F. M. Leweke: Sleep deprivation increases cerebrospinal levels of oleoylethanolamide, an endogenous PPAR-a agonist. J Neural Transm (2009) 116:301-305.

D. Schreiber, S. Harlfinger, B. M. Nolden, C. W. Gerth, U. Jaehde, E. Schömig, J. Klosterkötter, A. Giuffrida, G. Astarita, D. Piomelli, F. M. Leweke: Determination of anandamide and other fatty acylethanolamides in human serum by electrospray tandem mass spectrometry. Anal Biochem (2007) 361:162–168.

A. Giuffrida, F. M. Leweke, C. W. Gerth, D. Schreiber, D. Koethe, J. Faulhaber, J. Klosterkötter, D. Piomelli: Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptoms. Neuropsychopharmacology (2004) 29: 2108-2114.

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