REVIEW OF: Leweke FM et al, Transl Psychiatry 2012;2:e94

Research has shown that heavy cannabis use is associated with new-onset psychosis, so a study exploring the drug’s use as a treatment for schizophrenia is surprising, to say the least. Recall that cannabis is composed of more than 100 compounds, and that delta-9-tetrahydrocannabinol (THC) is the most psychoactive one.

Cannabidiol, on the other hand, does not have the same psychoactive properties as THC or its potential to induce psychosis. However, cannabidiol does inhibit the breakdown of anandamide, an endogenous cannabinoid. In studies, the prevention of anandamide breakdown has improved psychotic symptoms. So it is thought, by inhibiting anandamide degradation, cannabidiol might act as an antipsychotic in patients with schizophrenia.

Leweke et al’s study, which took place in Germany, sought to test this claim by looking at 42 men and women ages 18–50, all hospitalized and suffering from acute exacerbations of schizophrenia. In a double-blinded fashion, subjects were randomly assigned to receive either cannabidiol (n = 21) or the second-generation antipsychotic amisulpride (n = 21), at doses up to 800 mg/day each, for 4 weeks. (Amisulpride is an atypical antipsychotic, not marketed in Canada or the US, that is associated with moderate amounts of extrapyramidal symptoms and prolactin elevation.) The main outcome measures were obtained at baseline, day 14, and day 28, and included serum anandamide and prolactin levels, a Positive and Negative Symptoms of Schizophrenia (PANSS) score, weight gain, and extrapyramidal movements.

Overall, patients treated with either agent showed significant clinical improvement and reduction in schizophrenia symptoms. Patients assigned to cannabidiol showed a total PANSS reduction of 30.5, and those on amisulpride showed a reduction of 30.1. There was no significant difference between the two treatments. Still, compared with amisulpride, there were significantly fewer extrapyramidal symptoms with cannabidiol, less weight gain, and lower prolactin increase. Serum anandamide levels were higher in patients who received cannabidiol, and were associated with reduced psychotic symptoms.

CATR’s Take
The results of this small, single-site study suggest cannabidiol may be as effective in treating psychosis as standard antipsychotics and may have a superior side effect profile. If larger studies can reproduce these findings, cannabinoid may represent a breakthrough in schizophrenia treatment.