Review of: McGuire P et al, Am J Psychiatry 2017;175(315). doi:10.1176/appi.ajp.2017.17030325

Type of study: Double-blind, randomized controlled trial

Traditional antipsychotic medications leave much to be desired. Their therapeutic response rate for schizophrenia is low, and their side effects are troubling and lead to high rates of noncompliance. Clearly, there is an urgent need for alternative agents. Although patients—including those diagnosed with schizophrenia—have long attested to the benefits of marijuana, only recently have researchers begun taking it seriously as a therapeutic option. In this pilot study, investigators evaluated the benefits of cannabidiol (CBD), which is one of the two main active components of marijuana (the other being THC), for the treatment of ­schizophrenia.

In this 6-week, double-blind, randomized controlled trial, adult patients diagnosed with schizophrenia or a related psychotic disorder were recruited from multiple sites across Europe. All patients were actively psychotic, though they could not be entirely ­treatment-resistant (ie, patients had to have displayed at least a partial response to antipsychotic medications). Patients entered the study only after they had been on a stable dosage of antipsychotic medication for at least 4 weeks, and this medication was continued throughout the course of the study. CBD was dosed at 1,000 mg/day in the form of an oral solution. Active substance use was not grounds for exclusion. The primary efficacy measure used was the Positive and Negative Syndrome Scale (PANSS), while cognition was measured using the Brief Assessment of Cognition in Schizophrenia (BACS) scale.

43 patients were randomized to CBD and 45 to placebo. Positive symptoms (eg, delusions or hallucinations) were significantly reduced at endpoint for patients receiving CBD compared to placebo. Improvement in negative symptoms (eg, flat affect) favored CBD, but this difference did not reach statistical significance. Patients receiving CBD also fared better on global assessment of functioning, clinicians’ global assessment of improvement, and cognitive measures, though this latter difference fell just short of statistical significance (p = 0.07). No major adverse events occurred that were attributed to CBD, and the participants were not able to tell if they were taking CBD or placebo.

TCPR’s Take
CBD’s therapeutic potential has received a lot of attention lately and is covered elsewhere in this issue. This is the most rigorous study of CBD in schizophrenia to date, and its intriguing findings warrant replication with a larger sample and longer duration. Given the many limitations and pitfalls associated with traditional antipsychotic medications, a novel compound that might be devoid of those pitfalls is a most welcome ­development.