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Functional MRI Offers Clues to Schizophrenia and Comorbid Cannabis Disorder

Functional MRI (fMRI) may offer clues why some people with schizophrenia have a high rate of cannabis use disorder, according to findings presented in April at the AAN Annual meeting.

More than 40 percent of people with schizophrenia are heavy consumers of marijuana, the researchers noted, and the evidence suggests abnormalities in their brain's reward pathways may drive the drug behavior.

“People with schizophrenia who are heavy users of cannabis actually have poorer functional outcomes, yet they may be self-medicating to correct an imbalance in their brain's ability to anticipate a reward," said Mary Brunette, MD, professor in the department of psychiatry at the Geisel School of Medicine at Dartmouth.

She and her colleagues recruited 126 people for the study: 33 patients with schizophrenia and cannabis use disorder who abstained for two weeks before they underwent an fMRI scan, 48 people who do not have schizophrenia who were heavy cannabis users, 18 people with schizophrenia who do not use cannabis, and 27 healthy controls.

In the test, the Monetary Incentive Delay task, study participants were shown a picture of a possible dollar award and asked to press fast enough to get a reward, waiting until the reward either came or didn't come. They found the brain activity on fMRI measures during that anticipation period were different between those with schizophrenia and comorbid cannabis use disorder and the other three groups.

In adjusted statistical models, the schizophrenia/cannabis use group showed abnormal reward task-related activity compared with healthy controls; the primary hyperactivity was in the right caudate, a central part of the brain's reward circuit and the posterior cingulate gyrus, a component of the default mode network.

The patients with schizophrenia and cannabis disorder also showed increased activity in the precuneus, left inferior frontal gyrus and left superior temporal gyrus compared with the people with schizophrenia who did not use cannabis products.

The brain's default network involves some of these same regions activated during the reward task and are abnormal in people with schizophrenia who abuse cannabis, the researchers said. They speculated that these individuals have a harder time turning off the default network, regions that are active when the brain is allegedly doing nothing, a resting state.

While the finding that areas of the brain are abnormal in the schizophrenia/cannabis use disorder patients may be part of their disease, it is also possible that heavy cannabis use over time damaged these reward anticipation pathways, they said.

“We hope the finding will help to figure out what is driving this heavy use of cannabis," they said. “This is just the first step."
Christopher Hammond, MD, PhD, assistant professor of psychiatry and pediatrics at Johns Hopkins School of Medicine and director of the co-occurring disorders in adolescents/young adults clinical and research programs, works with young people with schizophrenia who abuse cannabis and agrees that the symptoms are more severe. “One of the questions has been: Could there be a reason why they abuse cannabis? And this group has set out to answer that."

“The “study findings support the idea that there is a complex relationship between schizophrenia and cannabis use. But it does not support a self-medication model for cannabis use. This is a cross-sectional study comparing these groups and we can't make any interpretations about what is causing the differences in the groups."

To test a self-medication hypothesis, the authors would have needed to conduct a longitudinal study and do repeat MRI scans in the same individuals with schizophrenia at different times when they are using cannabis and when they are not using cannabis and compare their brain activity on and off cannabis to individuals with schizophrenia who do not use cannabis and to healthy controls.

What's more, he added, “cannabis is not just a single product, it is a plant which contains multiple different cannabinoid compounds including delta-9-tetrahydrocannabinol (THC), cannabidiol (CBD), and other phytocannabinoids."

“When administered, these cannabinoids can produce different and sometimes opposite physiological effects and changes in brain activity, he said. (“Depending upon the source and chemotype, the amounts of THC, CBD, and other phytocannabinoids will vary. Given this, scientists who do cannabis research need to collect biospecimens and measure the levels of THC and CBD in study participants at the time of the scans and should conduct analyses to examine the influence of THC and CBD levels on brain activity among the individuals with schizophrenia who use cannabis regularly."

Dr. Brunette's institution has received funding from the National Institute on Drug Abuse.​

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