Die Bedeutung des endogenen Cannabinoidsystems bei verschiedenen neuro-psychiatrischen Erkrankungen

Zusammenfassung:

Das körpereigene Cannabinoidsystem wurde erstmals im Jahr 1988 beschrieben. Es gibt zwei spezifische Rezeptoren, den CB2-Rezeptor, der im lymphatischen Gewebe (Milz, Lymphknoten) exprimiert wird und den CB1-Rezeptor, der überwiegend im Zentralnervensystem vorkommt und ein distinktes Verteilungsmuster aufweist mit einer sehr hohen Dichte im Zerebellum, den Basalganglien und im Hippocampus. 1992 wurden erstmals körpereigene Liganden, Anandamid und 2-Arachidonylglykerol (Arachidonsäureabkömmlinge) entdeckt, deren physiologische Bedeutung noch unklar ist. Implikationen dieser neueren Erkenntnisse für das Gilles-de-la-Tourette-Syndrom, ischämische Hirnläsionen, schizophrene Psychosen und Opiatabhängigkeit werden beschrieben.

Eine Dysregulation im endogenen Cannabinoid-System spielt möglicherweise in der Ätiologie des Gilles-de-la-Tourette-Syndroms und bei schizophrenen Psychosen eine Rolle, wobei sich die Applikation von Cannabinoiden auf die Symptome des Gilles-de-la-Tourette-Syndroms offenbar positiv auswirkt, während bei der Schizophrenie Cannabinoide wahrscheinlich eher negative Folgen haben. Bei ischämischen Hirnläsionen sind Cannabinoide höchstwahrscheinlich neuroprotektiv, indem sie die Glutaminatfreisetzung reduzieren und dadurch das Ausmaß der Läsion minimieren. Außerdem wird eine mögliche Bedeutung des endogenen Cannabinoidsystems für die Entwicklung der Opiatabhängigkeit aufgrund von Interaktionen zwischen dem endogenen Opioidsystem und dem endogenen Cannabinoidsystem diskutiert, da tierexperimentell gezeigt werden konnte, dass das Fehlen von CB1-Rezeptoren die positiven Verstärkereigenschaften der Opiate verminderte.

The Importance of the Endogenous Cannabinoid System in Various Neuropsychiatric Disorders:

The endogenous cannabinoid system was first described in 1988. There are two specific receptors, the CB2-receptor, located in the lymphatic system (spleen, lymphocytes), and the CB1-receptor occurring predominantly in the central nervous system. The CB1-receptor shows a distinct distribution in the CNS with a very high density in the cerebellum, the basal ganglia and in the hippocampus. In 1992 endogenous ligands of the cannabinoid system were discovered for the first time (e.g. anandamide and 2-arachidonylglycerol). The physiological role of these arachidonic acid derivates is still unclear. Implications of these recent discoveries for the Gilles de la Tourette syndrome, ischaemic brain lesions, schizophrenic psychoses and opiate drug dependence are described. A dysregulation in the endogenous cannabinoid/anandamide system could possibly play an import role in the etiology of Gilles de la Tourette syndrome and schizophrenic psychoses; administration of cannabinoids affects the symptoms of the Gilles de la Tourette syndrome positively, whereas cannabinoids probably have rather negative effects in schizophrenic psychoses. In ischaemic brain lesions cannabinoids seem to have a neuroprotective effect; they appear to minimize the extent of a lesion by reduction of glutamate release. Additionally the meaning of the endogenous cannabinoid system for the development of opioid drug dependency is discussed and interactions between the endogenous opioid system and the endogenous cannabainoid system are pointed out. This is of interest since it could be shown in animal experiments that the absence of CB1 receptors reduces the positive reinforcement of opiate administration.

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