It has been discovered that the acute effects of cannabis can be modified by the subject's level of vulnerability to psychosis. This review is limited by the small number of controlled studies available on the subject, but the review of studies on CBD and THC, together with a careful review of the methodology and findings of the study, provide an important current evaluation of the evidence on the effect of cannabis on schizophrenia. For instance, some second-generation antipsychotics, such as ziprasidone and aripiprazole, also activate 5-HT1A receptors, which could explain, at least in part (in addition to the absence of dopamine antagonism), the absence of extrapyramidal AEs in CBD. In a 6-week augmentation trial, McGuire and colleagues conducted a double-blind, parallel-group RCT with a higher dose of CBD (500 mg twice daily) compared to the effects of cannabidiol (CBD) on cognition and symptoms in outpatients with chronic schizophrenia.
The effects of CBD on the regulation of anandamide in different brain regions associated with the physiopathology of schizophrenia could explain its antipsychotic action. In a 4-week trial in hospitalized patients with acute psychotic disorder without ECU (average age of 30 years), 800 mg of CBD was found to be similar to that of amisupride in improving psychosis and cognition. This study was limited by a very small size and it is possible that the tests were performed before the full absorption of CBD. The initial observation that CBD reduced psychotic symptoms induced by THC led researchers to carry out a pioneering study to test the effects of CBD in a model commonly used to identify drugs with an antipsychotic profile in laboratory animals.
The researchers interpreted their findings to indicate that changes in these regions underlie the antipsychotic effects of CBD. In addition, serum anandamide levels increased more among people treated with CBD than with amisulpride, and the degree of increase was associated with an improvement in the total PANSS score in the CBD group, but not in the amisulpride group. Taken together, these findings suggest that the effects of CBD on brain functioning in schizophrenia cannot be easily explained by disease-related factors, such as medication history and chronicity. The evidence suggests that CBD may be beneficial for treating psychosis. However, more research is needed to understand how it works and how it can be used safely and effectively for this purpose.
It is also important to note that CBD should not be used as a substitute for traditional antipsychotic medications.