The human endocannabinoid system interacts with various neurotransmitter systems and the endocannabinoid anandamide was found significantly elevated in CSF and inversely correlated to psychopathology (Giuffrida et al. 2004) providing a link to the neurobiology of schizophrenia. While delta-9-tetrahydrocannabinol, the psychoactive compound of Cannabis sativa, shows psychedelic properties, the major herbal cannabinoid compound cannabidiol was suggested recently a re-uptake inhibitor of anandamide. In addition potential antipsychotic properties have been hypothezised.

We performed an explorative, 4-week, double-blind, controlled clinical trial on the effects of purified cannabidiol in acute schizophrenia compared to the antipsychotic amisulpride. The antipsychotic properties of both drugs were the primary target of the study. Furthermore, side-effects and anxiolytic capabilities of both treatments were investigated.

42 patients fulfilling DSM-IV criteria of acute paranoid schizophrenia or schizophreniform psychosis participated in the study. Both treatments were associated with a significant decrease of psychotic symptoms after 2 and 4 weeks as assessed by BPRS and PANSS. However, there was no statistical difference between both treatment groups. In contrast, cannabidiol induced significantly less side effects (EPS, increase in prolactin, weight gain) when compared to amisulpride.

Cannabidiol proved substantial antipsychotic properties in acute schizophrenia. This is in line with our suggestion of an adaptive role of the endocannabinoid system in paranoid schizophrenia, and raises further evidence that this adaptive mechanism may represent a valuable target for antipsychotic treatment strategies.

The Stanley Medical Research Institute (00-093 to FML) and the Koeln Fortune Program (107/2000 + 101/2001 to FML) funded this study.