RESUMO
Cannabidiol is a component of marijuana that does not activate cannabinoid receptors, but moderately inhibits the degradation of the endocannabinoid anandamide. We previously reported that an elevation of anandamide levels in cerebrospinal fluid inversely correlated to psychotic symptoms. Furthermore, enhanced anandamide signaling let to a lower transition rate from initial prodromal states into frank psychosis as well as postponed transition. In our translational approach, we performed a double-blind, randomized clinical trial of cannabidiol vs amisulpride, a potent antipsychotic, in acute schizophrenia to evaluate the clinical relevance of our initial findings. Either treatment was safe and led to significant clinical improvement, but cannabidiol displayed a markedly superior side-effect profile. Moreover, cannabidiol treatment was accompanied by a significant increase in serum anandamide levels, which was significantly associated with clinical improvement. The results suggest that inhibition of anandamide deactivation may contribute to the antipsychotic effects of cannabidiol potentially representing a completely new mechanism in the treatment of schizophrenia.
Assuntos
Antipsicóticos/uso terapêutico , Ácidos Araquidônicos/fisiologia , Canabidiol/uso terapêutico , Endocanabinoides/fisiologia , Esquizofrenia/tratamento farmacológico , Psicologia do Esquizofrênico , Transdução de Sinais/efeitos dos fármacos , Sulpirida/análogos & derivados , Doença Aguda , Adulto , Amidas , Amissulprida , Ácidos Araquidônicos/sangue , Método Duplo-Cego , Quimioterapia Combinada , Endocanabinoides/sangue , Etanolaminas/sangue , Feminino , Humanos , Masculino , Ácidos Oleicos/sangue , Ácidos Palmíticos/sangue , Alcamidas Poli-Insaturadas/sangue , Escalas de Graduação Psiquiátrica , Esquizofrenia/fisiopatologia , Transdução de Sinais/fisiologia , Sulpirida/uso terapêutico , Adulto JovemRESUMO
The efficacy of an adjuvant application of carbamazepine in cannabis-related schizophrenia-like psychosis not responsive to neuroleptic treatment is reported for the first time. In two patients, psychotic states occurred after continuous cannabis consumption over a period of 8 and 18 months, respectively, which were mainly characterized by severe thought disorders, disturbances of perception, delusions and weak affect. Both patients were admitted to hospital with no previous clinical history of psychotic episodes. After nonresponsive treatment with neuroleptics over several weeks, they both rapidly responded to additional medication with carbamazepine within a week after onset with a marked reduction in clinical signs and symptoms.