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  • Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia.

Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia.

Translational psychiatry (2012-07-27)
F M Leweke, D Piomelli, F Pahlisch, D Muhl, C W Gerth, C Hoyer, J Klosterkötter, M Hellmich, D Koethe
ABSTRACT

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.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Palmitoylethanolamide
Sigma-Aldrich
N-(4-Hydroxyphenyl)-arachidonylamide, ≥98%, ethanol solution
Supelco
Cannabidiol solution, 1.0 mg/mL in methanol, analytical standard, for drug analysis
Sigma-Aldrich
Cannabidiol
Supelco
Cannabidiol solution, 1.0 mg/mL in methanol, ampule of 1 mL, certified reference material, Cerilliant®