Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia

Transl Psychiatry. 2012 Mar 20;2(3):e94. doi: 10.1038/tp.2012.15.

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.

Publication types

  • Clinical Trial, Phase II
  • Comparative Study
  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Disease
  • Adult
  • Amisulpride
  • Antipsychotic Agents / therapeutic use*
  • Arachidonic Acids / blood
  • Arachidonic Acids / physiology*
  • Cannabidiol / therapeutic use*
  • Double-Blind Method
  • Drug Therapy, Combination
  • Endocannabinoids / blood
  • Endocannabinoids / physiology*
  • Ethanolamines / blood
  • Female
  • Humans
  • Male
  • Oleic Acids / blood
  • Palmitic Acids / blood
  • Polyunsaturated Alkamides / blood
  • Psychiatric Status Rating Scales
  • Schizophrenia / drug therapy*
  • Schizophrenia / physiopathology
  • Schizophrenic Psychology*
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology
  • Sulpiride / analogs & derivatives*
  • Sulpiride / therapeutic use
  • Young Adult

Substances

  • Antipsychotic Agents
  • Arachidonic Acids
  • Endocannabinoids
  • Ethanolamines
  • Oleic Acids
  • Palmitic Acids
  • Polyunsaturated Alkamides
  • Cannabidiol
  • oleoylethanolamide
  • palmidrol
  • Sulpiride
  • Amisulpride
  • anandamide