The antipsychotic effects of cannabidiol, a cannabis extract, are a little less mysterious now that functional magnetic resonance imaging (fMRI) has been used to reveal exactly where cannabidiol exerts its effects in the brain. Cannabidiol, scientists based at King’s College London report, modulates activation in the striatum, the medial cortex, and the midbrain—three regions known to be involved in psychosis.
The findings reinforce what scientists already suspected: cannabidiol seems to act via mechanisms distinct from those associated with conventional antipsychotic drugs. Because cannabidiol works differently, and because it appears to be safe and well tolerated, the King’s College London scientists are optimistic that cannabidiol may progress to the clinic, where it could bring relief to patients at high risk of developing psychosis.
“The mainstay of current treatment for people with psychosis are drugs that were first discovered in the 1950s and unfortunately do not work for everyone,” says Sagnik Bhattacharyya, M.D., Ph.D., a researcher at the Institute of Psychiatry, Psychology, and Neuroscience (IoPPN), Kings College London. “Our results have started unravelling the brain mechanisms of a new drug that works in a completely different way to traditional anti-psychotics.”
Details of the study appeared in JAMA Psychiatry, in an article titled, “Effect of Cannabidiol on Medial Temporal, Midbrain, and Striatal Dysfunction in People at Clinical High Risk of Psychosis: A Randomized Clinical Trial.” The article describes how the researchers studied a group of 33 young people who had not yet been diagnosed with psychosis but who were experiencing distressing psychotic symptoms, along with 19 healthy controls. A single dose of cannabidiol was given to 16 participants while the other 17 received a placebo.
All participants were studied in an MRI scanner while performing a memory task which engages three regions of the brain known to be involved in psychosis.
As expected, the brain activity in the participants at risk of psychosis was abnormal compared to the healthy participants. However, among those who had cannabidiol, the abnormal brain activity was less severe than for those who received a placebo, suggesting cannabidiol can help re-adjust brain activity to normal levels.
“Cannabidiol may partially normalize alterations in parahippocampal, striatal, and midbrain function associated with the clinical high-risk state,” the article’s authors wrote. “As these regions are critical to the pathophysiology of psychosis, the influence of cannabidiol at these sites could underlie its therapeutic effects on psychotic symptoms.”
Intriguingly, previous research from King's College London shows cannabidiol appears to work in opposition to tetrahydrocannabinol (THC), the ingredient in cannabis responsible for getting users high, and which has been strongly linked to the development of psychosis. THC can be thought of as mimicking some of the effects of psychosis, while cannabidiol has broadly opposite neurological and behavioral effects.
“There is an urgent need for a safe treatment for young people at risk of psychosis,” emphasizes Dr. Bhattacharyya. “One of the main advantages of cannabidiol is that it is safe and seems to be very well tolerated, making it in some ways an ideal treatment.
“The mainstay of current treatment for people with psychosis are drugs that were first discovered in the 1950s and unfortunately do not work for everyone. Our results have started unraveling the brain mechanisms of a new drug that works in a completely different way to traditional antipsychotics.”
Dr. Bhattacharyya and colleagues at IoPPN are now launching the first large-scale, multicenter trial to investigate whether cannabidiol can be used to treat young people at high risk of developing psychosis. “If successful,” Dr. Bhattacharyya notes, “this trial will provide definitive proof of cannabidiol's role as an antipsychotic treatment and pave the way for use in the clinic.”
