“CBD did not improve psychotic symptoms in the subjects in our study. These results are in contrast to the published case reports (Zuardi et al. 2006; Zuardi et al. 1995), and the two published clinical trials in schizophrenia (Leweke et al. 2012)(McGuire et al. 2017). Leweke et al. found CBD (800 mg) to be as efficacious as amisulpride in reducing positive psychotic symptoms in 42 acutely decompensated patients with schizophrenia (Leweke et al. 2012). More recently, in a larger study in antipsychotic-treated outpatients with schizophrenia (n = 86), McGuire et al. found that CBD augmentation resulted in a small although statistically significant improvement in PANSS positive scores (1.5 points) with CBD compared to placebo (McGuire et al. 2017). However, our results are similar to a separate study also by Leweke et al. who tested the effects of the same dose (600 mg) of CBD in schizophrenia. At this dose, CBD only produced very small improvements in PANSS total scores (~ 2.4) that were not statistically significant (Leweke et al. 2014). Although, this dose (600 mg/day) has been shown to attenuate psychosis-like effects in acute laboratory studies (Bhattacharyya et al. 2010), it appears that a higher dose may be needed to produce beneficial effects on psychotic symptoms in schizophrenia.

“A second consideration worth discussing is the stage of illness being tested. Our study included patients with chronic schizophrenia unlike those studied in Leweke et al. who have also demonstrated that patients demonstrate alterations in endocannabinoid levels during early psychosis (Koethe et al. 2009; Leweke et al. 2012). Thus, it is possible that CBD may be even more effective during this critical period rather than in chronic schizophrenia and more studies are needed on the benefits of CBD earlier in the course of psychosis, perhaps even during the prodromal stage. This may be particularly relevant to CIAS. In our study, the mean age of participants was in their mid-to late-40s and mean illness duration was greater than 25 years similar to McGuire et al. 2017 (mean age 41 years) who also failed to demonstrate any benefits on CIAS in their study (McGuire et al. 2017). Interestingly, given the data that cannabis use during adolescence may be associated with a less cognitively severe form of schizophrenia (Yucel et al. 2012), more studies are needed to fully examine the endocannabinoid system as a potential target for the cognitive deficits of schizophrenia.

“Overall, subjects in our study tolerated CBD treatment well with no worsening of psychosis, mood, or suicidality.