Endocannabinoid Research
The physiological and pathophysiological significance of the body's endocannabinoid system (ECS) is not fully understood. Our experimental studies on healthy volunteers and psychiatric patients have enhanced our understanding of its role in disease processes related to mental health disorders.
In recent years, we have focused specifically on the role of endogenous cannabinoids (eCBs) in psychiatric conditions. Our results reveal that levels of eCBs, particularly anandamide, are significantly higher in the cerebrospinal fluid of patients with schizophrenic psychoses compared to healthy individuals. Anandamide acts as a natural counter-regulator against other neurotransmitter systems that are highly active in these disorders.
These findings provide valuable insights into the neurobiological mechanisms underlying endocannabinoid functions in psychiatric disorders. They also open up new avenues for developing therapeutic strategies that target the endocannabinoid system.
Funding:
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 a Start-up grant from the Deputy Vice-Chancellor Research of the University of Sydney.
Publications:
T. A. Couttas, C. Boost, F. Pahlisch, E. B. Sykorova, J. K. Mueller, B. Jieu, J. E. Leweke, I. Dammann, A. E. Hoffmann, M. Loeffler, O. Grimm, F. Enning, H. Flor, A. Meyer-Lindenberg, D. Koethe, C. Rohleder, F. M. Leweke (2024) Dose-dependent effects of oral cannabidiol and delta-9-tetrahydrocannabinol on serum anandamide and related N-acylethanolamides in healthy volunteers. BMJ Mental Health 27:e301027
B. Jieu, E. B. Sykorova, C. Rohleder, E. Marcolini, A. E. Hoffmann, D. Koethe, F. M. Leweke, T. A. Couttas (2024) Alterations to sphingolipid metabolism from antipsychotic administration in healthy volunteers are restored following the use of cannabidiol. Psychiatry Res 229:116005
T. A. Couttas, C. Boost, F. Pahlisch, E. B. Sykorova, D. Koethe, J. E. Leweke, H. Endepols, C. Rohleder, F. M. Leweke (2022) Simultaneous assessment of serum levels and pharmacologic effects of cannabinoids on endocannabinoids and N-acylethanolamines by liquid chromatography–tandem mass spectrometry. Cannabis Cannabinoid Res 8:657-669
D. Koethe, F. Pahlisch, M. Hellmich, C. Rohleder, C. Hoyer, A. Meyer-Lindenberg, E. F. Torrey, D. Piomelli, F. M. Leweke (2019) Familial abnormalities of endocannabinoid signalling in schizophrenia. World J Biol Psychiatry 20:117-125
A. R. Reuter, J. M. Bumb, J. K. Mueller, E. Arens, F. M. Leweke, D. Koethe, E. Schwarz (2017) Differential association of anandamide with binocular depth inversion in schizophrenia. World J Biol Psychiatry 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 (2017) Electroconvulsive therapy enhances endocannabinoids in the cerebrospinal fluid of patients with major depression: a preliminary prospective study. Eur Arch Psychiatry Clin Neurosci 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 (2014) Understanding the role of oleoylethanolamide in obesity: differential association with body mass index and food cue-induced brain activation. JAMA Psychiatry 71:1254-1261
D. Muhl, M. Kathmann, C. Hoyer, L. Kranaster, M. Hellmich, C. W. Gerth, J. Faulhaber, E. Schlicker, F. M. Leweke (2014) Increased CB2 mRNA and anandamide in human blood after cessa¬tion of cannabis abuse. Naunyn-Schmiedeberg’s Arch Pharmacol 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 (2013) Endogenous cannabinoids are altered in complex post traumatic stress and borderline personality disorders. Eur Arch Psychiatry Clin Neurosci 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 (2013) Increased ventral striatal CB1 receptor binding is related to negative symptoms in schizophrenia and is modulated by antipsychotic drug therapy. Neuroimage 79:304-312.
C. J. A. Morgan, E. Page, C. Schaefer, K. Chatten, A. Manocha, S. Gulati, B. Brandner, V. Curran, F. M. Leweke (2013) Cerebrospinal fluid anandamide levels differ with cannabis use and relate to psychotic-like symptoms. Br J Psychiatr 202:381-382.
F. M. Leweke (2012) Anandamide dysfunction in prodromal and established psychosis. Curr Pharm Design 18:5188-93.
E. Schwarz, P. Whitfield, S. Nahnsen, L. Wang, H. Major, F. M. Leweke, D. Koethe, P. Lio, S. Bahn (2011) Alterations of primary fatty acid amides in serum of patients with severe mental illness. Front Biosci (Elite Ed) 3:308-314.
D. Koethe, A. Giuffrida, D. Schreiber, M. Hellmich, F. Schultze-Lutter, S. Ruhrmann, J. Klosterkötter, D. Piomelli, F. M. Leweke (2009) Anandamide elevation in CSF of prodromal states of schizophrenia. Brit J Psychiat 194:371-372.
D. Koethe, D. Schreiber, A. Giuffrida*, C. Mauss, B. Heydenreich, R. Graf, J. Klosterkötter, D. Piomelli, F. M. Leweke (2009) Sleep deprivation increases cerebrospinal levels of oleoylethanolamide, an endogenous PPAR-a agonist. J Neural Transm 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 (2007) Determination of anandamide and other fatty acylethanolamides in human serum by electrospray tandem mass spectrometry. Anal Biochem 361:162–168.
A. Giuffrida, F. M. Leweke, C. W. Gerth, D. Schreiber, D. Koethe, J. Faulhaber, J. Klosterkötter, D. Piomelli (2004) Cerebrospinal anandamide levels are elevated in acute schizophrenia and are inversely correlated with psychotic symptoms. Neuropsychopharmacology 29:2108-2114.
F. M. Leweke, A. Giuffrida, U. Wurster, H. M. Emrich, D. Piomelli (1999) Elevated endogenous cannabinoids in schizophrenia. Neuroreport 10:1665-1669.