Authors:
Leweke FM1, Piomelli D, Pahlisch F, Muhl D, Gerth CW, Hoyer C, Klosterkötter J, Hellmich M, Koethe D.
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.