Adjunctive Cannabidiol Therapy in Schizophrenia

• There is some evidence that treatment with CBD may reduce psychosis in both Parkinson disease and schizophrenia [1,2]

• The mechanism of action of CBD is unclear, but, in contrast to all FDA-approved antipsychotics for schizophrenia, is not thought to involve antagonism of dopamine D2 receptors

• McGuire and colleagues[3] performed a 6-week trial of adjunctive CBD or placebo in patients who had been partially responsive to antipsychotic medication

• The study examined the effects of CBD on positive and negative psychotic symptoms, cognitive performance, level of functioning, and the treating psychiatrist’s overall clinical impression

• This randomized, double-blind, placebo-controlled trial was conducted at 15 sites in the United Kingdom, Poland, and Romania

• Inclusion criteria were age 18–65; DSM-IV diagnosis of schizophrenia or a related psychotic disorder; history of at least a partial response to antipsychotic medication; and receiving a stable dosage of antipsychotic medication for at least 4 weeks

• Exclusion criteria were a Positive and Negative Syndrome Scale (PANSS) score <60 at screening; taking multiple antipsychotic medications; presence of delirium or dementia; substance-induced psychosis; pregnancy or lactation

• Comorbid use of alcohol, cannabis, or other substances was not exclusionary

• Assessments of symptoms, general functioning, cognitive performance, substance use, extrapyramidal signs, weight, BMI, waist circumference, and routine laboratory tests were assessed at baseline and trial day 8, 22, and 43

• Subjects were randomly assigned in a 1:1 ratio to receive 1,000mg/day of CBD or placebo in two divided doses

• Key outcome measures included scores on the PANSS; Scale for the Assessment of Negative Symptoms (SANS); Clinical Global Impressions Scale improvement (CGI-I); Global Assessment of Functioning (GAF) scale; and the Brief Assessment of Cognition in Schizophrenia (BACS)

• The authors performed an intention-to-treat analysis

• The change in PANSS total score from baseline to end of treatment (using the last observation carried forward) was analyzed using analysis of covariance

• The number of responders (defined as patients who had an improvement >20% in PANSS total score) per treatment group was analyzed using logistic regression

• 89 patients were screened, 88 underwent randomization, and 83 patients completed the trial

• 83 subjects had a diagnosis of schizophrenia

• The most common medications were aripiprazole, olanzapine, and risperidone

• Mean subject age was 41, 58% were male, 93% were Caucasian, and mean subject BMI was 28.4

• There was a trend for improvement in GAF scores between the CBD and placebo groups (3.0 points)

• There was a trend for greater improvement in the BACS composite score in the CBD group (treatment difference=1.31 points)

• Gastrointestinal adverse events were the most common and were reported by 9 patients in the CBD group

• They found that 6 weeks of treatment with CBD in adjunct to antipsychotics was associated with significant effects both on positive psychotic symptoms and on the treating clinicians’ impressions of improvement and illness severity, although effects were modest.

• There was also a trend for improvements in cognitive performance and in the level of overall functioning with CBD

REFERENCES:

1. Zuardi AW, Crippa JA, Hallak JE, et al. Cannabidiol for the treatment of psychosis in Parkinson’s disease. J Psychopharmacol. 2009;23:979–983.

2. Leweke FM, Piomelli D, Pahlisch F, et al. Cannabidiol enhances anandamide signaling and alleviates psychotic symptoms of schizophrenia. Transl Psychiatry. 2012; 2:e94

3.  McGuire P, Robson P, Cubala WJ, et al. Cannabidiol (CBD) as an Adjunctive Therapy in Schizophrenia: A Multicenter Randomized Controlled Trial. Am J Psychiatry. 2018. doi: 10.1176/appi.ajp.2017.17030325)