From the Journals

Cannabidiol linked to reduction in psychotic symptoms in schizophrenia



Patients with schizophrenia showed signs of improvement in positive psychotic symptoms and clinician-rated improvement after treatment with cannabidiol, a component of cannabis thought to counteract the effects of tetrahydrocannabinol (THC), an industry-funded phase 2 study reported.
According to the authors, the study is only the second to examine the use of cannabidiol in schizophrenia. “Because cannabidiol acts in a way different from conventional antipsychotic medication, it may represent a new class of treatment for schizophrenia,” wrote the study authors, including several employees of the drugmaker that helped to fund the research.
The study, led by Philip McGuire, FMedSci., of King’s College London, was published online Dec. 15 in the American Journal of Psychiatry.
Researchers have long been interested in the relationship between aspects of schizophrenia – especially psychosis – and cannabis. There’s been less focus on the effects of individual cannabinoids – components of cannabis such as THC (which is psychoactive), cannabinol (which is linked to sleep), and cannabidiol.

Researchers have linked cannabidiol to anxiety relief, and it’s been used to treat a wide variety of conditions, particularly epilepsy.
For the current study, a randomized, double-blind parallel-group trial, researchers assigned patients with schizophrenia or related psychotic disorders to receive 1,000 mg/day of cannabidiol (n = 43) or placebo (n = 45) for 6 weeks. The patients took the drug (10 mL of a 100-mg/mL oral solution) or a matching placebo twice a day in divided doses. They continued to take their existing antipsychotic medication; the study did not accept anyone taking more than one medication for that purpose.
The patients, aged 18-65, were at 15 hospitals in the United Kingdom, Romania, and Poland; 93% of the subjects were white, and 58% were male. The subjects were allowed to continue the use of alcohol or cannabis.
Eighty-three patients finished the trial after two withdrew because of adverse events and three withdrew consent. The intention-to-treat analysis involved 86 patients: 42 who took cannabidiol (including 3 who took it for 21 or fewer days) and 44 who took the placebo. At the end of treatment, the researchers found that the positive score on the Positive and Negative Syndrome Scale (PANSS) fell from baseline by a mean –1.7 points in the placebo group and –3.2 points in the cannabidiol group, a difference of –1.4 points (P = .019). PANSS total and general scores also fell in both groups, as did the Scale for the Assessment of Negative Symptoms score, but the differences between the groups were not statistically significant. PANSS negative scores fell by about the same level in both groups.

At the end of treatment, clinicians were more likely to rate subjects in the cannabidiol group as improved on the Clinical Global Impressions (CGI) Scale (P = 0.018), compared with those in the placebo group.
About 35% of patients in both groups reported adverse events, including gastrointestinal problems (21% of those in the cannabidiol group and 6.7% of those in the placebo group). Researchers determined that just 10 patients in each group had treatment-related adverse events.
The mechanism of action of cannabidiol is unclear. Its effects “do not appear to depend on dopamine D2 receptor antagonism,” the investigators said. Theories about its mechanism of action include inhibition of the fatty acid amide hydrolase, inhibition of adenosine reuptake, TRPV1 and 5-hydroxytryptamine 1A receptor agonism, and D2High partial agonism. “Because [cannabidiol] acts in a way different from conventional antipsychotic medication, it may represent a new class of treatment for schizophrenia,” the authors wrote.
The investigators acknowledged that the study has limitations. For example, nearly all the participants were white. And although research suggests that cannabis use is very common in patients with schizophrenia, the study authors reported that only three patients tested positive for THC at baseline. “Because so few patients tested positive for THC, it was not possible to assess whether the effects of cannabidiol were influenced by cannabis use,” the authors wrote.

GW Research funded the trial and supplied the investigational medicinal product. Other study funders included the National Institute for Health Research Biomedical Research Center at South London, Maudsley NHS Foundation Trust, and King’s College London. Four of the authors are employees of GW Pharmaceuticals and hold shares in the company; one of the four is a cosignatory on a patent for the use of cannabinoids in combination with aripiprazole. Two of the other authors reported various disclosures, including funding from GW Pharmaceuticals. Another two study authors reported no relevant disclosures.

SOURCE: McGuire P et al. Am J Psychiatry. 2017 Dec 15. doi: 10.1176/appi.ajp.2017.17030325

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