Evidence-Based Reviews

Cannabidiol for psychosis: A review of 4 studies

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There has been increasing interest in the medicinal use of cannabidiol (CBD) for a wide variety of health conditions. CBD is one of more than 80 chemicals identified in the Cannabis sativa plant, otherwise known as marijuana or hemp. Delta-9-tetrahydrocannabinol (THC) is the psychoactive ingredient found in marijuana that produces a “high.” CBD, which is one of the most abundant cannabinoids in Cannabis sativa, does not produce any psychotomimetic effects.

The strongest scientific evidence supporting CBD for medicinal purposes is for its effectiveness in treating certain childhood epilepsy syndromes that typically do not respond to antiseizure medications. Currently, the only FDA-approved CBD product is a prescription oil cannabidiol (brand name: Epidiolex) for treating 2 types of epilepsy. Aside from Epidiolex, state laws governing the use of CBD vary. CBD is being studied as a treatment for a wide range of psychiatric conditions, including bipolar disorder, schizophrenia, dystonia, insomnia, and anxiety. Research supporting CBD’s benefits is limited, and the US National Library of Medicine’s MedlinePlus indicates there is “insufficient evidence to rate effectiveness” for these indications.1

Despite having been legalized for medicinal use in many states, CBD is classified as a Schedule I controlled substance by the US Drug Enforcement Agency. Because of this classification, little has been done to regulate and oversee the sale of products containing CBD. In a 2017 study of 84 CBD products sold by 31 companies online, Bonn-Miller et al2 found that nearly 70% percent of products were inaccurately labeled. In this study, blind testing found that only approximately 31% of products contained within 10% of the amount of CBD that was listed on the label. These researchers also found that some products contained components not listed on the label, including THC.2

The relationship between cannabis and psychosis or psychotic symptoms has been investigated for decades. Some recent studies that examined the effects of CBD on psychosis found that individuals who use CBD may experience fewer positive psychotic symptoms compared with placebo. This raises the question of whether CBD may have a role in the treatment of schizophrenia and other psychotic disorders. One of the first studies on this issue was conducted by Leweke et al,3 who compared oral CBD, up to 800 mg/d, with the antipsychotic amisulpride, up to 800 mg/d, in 39 patients with an acute exacerbation of psychotic symptoms. Amisulpride is used outside the United States to treat psychosis, but is FDA-approved only as an antiemetic. Patients were treated for 4 weeks. By Day 28, there was a significant reduction in positive symptoms as measured using the Positive and Negative Syndrome Scale (PANSS), with no significant difference in efficacy between the treatments. Similar findings emerged for negative, total, and general symptoms, with significant reductions by Day 28 in both treatment arms, and no significant between-treatment differences.

These findings were the first robust indication that CBD may have antipsychotic efficacy. However, of greater interest may be CBD’s markedly superior adverse effect profile. Predictably, amisulpride significantly increased extrapyramidal symptoms (EPS), weight gain, and prolactin levels from baseline to Day 28. However, no significant change was found in any of these adverse effects in the CBD group, and the between-treatment difference was significant (all P < .01).

Here we review 4 recent studies that evaluated CBD as a treatment for schizophrenia. These studies are summarized in the Table.4-7

CBD for psychosis: 4 Studies

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