Cannabidiol as a new type of an antipsychotic: results from a placebo-controlled clinical trial

Background: There is urgent need for the identification of new pharmacological targets for the treatment of schizophrenia. We recently discovered that increase of anandamide levels by blocking its degradation by administration of cannabidiol, a purified phytocannabinoid, is accompanied by significant improvement of symptoms in acute schizophrenic patients. Methods: We performed a randomized, double-blind, placebocontrolled, cross-over clinical trial in acute, antipsychotic-naive, first-break paranoid schizophrenia patients, fulfilling diagnostic criteria of DSM-IV. 29 patients were treated after written informed consent with either cannabidiol (600 mg per day) or placebo for 14 days and than switched to the corresponding cross-over condition. Additional patients to gain a total of 18 patients treated per protocol replaced dropouts. Results: Cannabidiol significantly improved psychotic symptoms in the cannabidiol-placebo condition during the first 14 days of treatment when compared to baseline. A MMRM analysis of all randomized patients (n=29) yielded an mean improvement of 2.4 points (standard error 3.0) on PANSS total in favor of cannabidiol (vs. placebo), albeit not statistically significant. Only one patient on sequence cannabidiolplacebo terminated treatment early (last seen at visit 3) whereas 10 patients terminated early on sequence placebo-cannabidiol. The most frequent reason given was worsening of symptoms (5/11 patients). Discussion: Although limited by design issues (cross-over), duration of treatment (14 days), and relevant placebo-response rates, this is the second study to provide evidence for antipsychotic properties of cannabidiol accompanied by a superior side-effect profile. Future placebo-controlled parallel-group trials studying the antipsychotic properties of cannabidiol in acute schizophrenia are necessary to provide further evidence for its efficacy in the treatment of this devastating disease.