Compared with the placebo group, the CBD group showed greater improvement of positive psychotic symptoms over the course of the treatment. Mean improvement of PANSS positive score was 3.2 (SD 2.60) in the CBD group compared with 1.7 (SD 2.76) in the placebo group. Moreover, by the end of the treatment, more patients in the CBD group were rated as “improved” on the CGI-I scale compared with those in the placebo group (78.6% and 54.6%, respectively). Patients who received CBD also showed a trend-level improvement in their cognitive functioning, and a significant improvement of their motor speed compared with controls.
In a similar study, Boggs and colleagues13 investigated the therapeutic effects of adjunctive CBD 600 mg daily (in two divided doses) compared with placebo in a 6-week double blind placebo-controlled randomized clinical trial, in individuals with chronic schizophrenia (N = 36). However, their results showed no significant differences between CBD and placebo on psychotic symptoms or cognitive performances.
Mechanism of action
The exact mechanism of action is still unknown for CBD’s potential anti-psychotic properties. Unlike other antipsychotic medications, CBD does not greatly affect dopaminergic neurons, and unlike THC, it does not bind to cannabinoid receptors. However, CBD reportedly increases the CSF levels of anandamide, one of the main endocannabinoid ligands, by blocking its degrading enzyme, fatty acid amide hydrolase, or by competing with anandamide intracellular transporters. It is interesting to note that anandamide levels are negatively correlated with severity of psychotic symptoms, whereas increased anandamide levels in psychotic patients treated with CBD are correlated with clinical improvement. This may suggest that CBD contributes to amelioration of psychosis by increasing the endogenous levels of anandamide. However, further studies are needed to confirm this.
The current pharmacological treatment for schizophrenia is only partially effective and mainly for positive symptoms. This has led investigators to investigate new pharmacological targets and the endocannabinoid system has been one of the newest ones. Over the past few decades, increasing evidence has shown the presence of endocannabinoid system abnormalities in schizophrenia.14 However, the current studies on the potential therapeutic effects of CBD are not conclusive and the mechanism of action is poorly understood. The discrepancies in clinical results could be related to different doses of CBD, stages of psychosis, or possibly heterogeneity of schizophrenia itself.
In addition to the potential therapeutic effects of CBD for schizophrenia, CBD may also have a role in preventing or treating the psychosis related to recreational use of cannabis in vulnerable individuals. Cannabis continues to be the most commonly used illicit drug in the US, and with the spreading legalization for medical and recreational purposes, a lower proportion of people perceive the risk associated with regular cannabis use. At the same time, there is a decreasing ratio of CBD-to-THC in street cannabis from 1:14 in 1995 to 1:80 in 2014. Low CBD content may affect the overall impact of frequent cannabis use on mental health, which may become evident in the future. When discussing the medicinal use of cannabis, it is important to distinguish CBD, with its potential beneficial effects, from THC, with its controversial adverse effects, especially on individuals with psychotic disorders.
Dr Bassir Nia is Assistant Professor of Psychiatry, Yale University School of Medicine, New Haven, CT. Dr Bassir Nia reports that she has no conflicts of interest concerning the subject matter of this article.
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