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Cannabidiol may normalize dysfunction in brain regions implicated in psychosis
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Study findings showed that a single oral dose of cannabidiol modulated activation in parahippocampal, striatal and midbrain function, which are regions critical to the pathophysiology of psychosis.
“We know from a couple of small-sized studies in patients with psychosis that cannabidiol has antipsychotic effects. However, how cannabidiol might work to treat psychosis (ie, its mechanisms) have not been clear until now,” Sagnik Bhattacharyya, MD, PhD, from the department of psychosis studies at King’s College London, told Healio Psychiatry.
“Currently there are no safe, well-tolerated treatments that work for those who have a clinical high-risk state for psychosis,” he continued. “These are young people presenting with early symptoms of psychosis who have not yet developed a frank psychotic disorder but have a very high risk of doing so and are very distressed by their experiences. There is an urgent need for a treatment for these young people as currently available antipsychotics or psychological treatments either do not work or are not tolerated very well.”
The investigators conducted a parallel-group, double-blind, placebo-controlled randomized clinical trial in the U.K. to examine the neurocognitive mechanisms that underlie the therapeutic effects of cannabidiol in psychosis.
Using functional MRI data taken while participants performed a verbal learning task, researchers examined the differences between 16 antipsychotic medication-naive participants at clinical high risk of psychosis who received a single oral dose of cannabidiol (600 mg), 17 high-risk participants who received placebo and 19 control participants who received no drug. They measured participants’ brain activation during verbal encoding and recall, which was indexed using the median sum of squares ratio of the blood oxygen level–dependent hemodynamic response functional MRI signal.
Bhattacharyya and colleagues found that participants randomized to placebo had reduced brain activation in the right caudate during encoding compared with controls (P < .001) and in the parahippocampal gyrus and midbrain during recall (P < .001). According to the researchers, these three areas are believed to be important to the pathophysiology of the clinical high-risk state.
Brain activation in participants receiving cannabidiol was greater than in those receiving placebo within these three regions, but lower than in controls. This indicated that the level of activation in the cannabidiol group was intermediate to that in the other groups, according to the researchers. The results showed no significant differences in task performance between groups.
“The mainstay of current treatment for people with psychosis are drugs that target the dopamine chemical signaling system in the brain. These results have started unraveling the brain mechanisms of action of a drug that does not seem to have any direct effect on the dopamine signaling system,” Bhattacharyya said. “Although, further work is needed to understand the key molecular mechanisms underlying cannabidiol’s antipsychotic effect, these results are very likely to pave the way for developing a novel class of antipsychotic treatments.” – by Savannah Demko
Disclosures: Bhattacharyya reports no relevant financial disclosures. Please see the study for all other authors’ relevant financial disclosures.