Marijuana Use Linked to Schizophrenia-like Brain Changes

Megan Brooks

December 19, 2013

Long-term marijuana use has been linked to structural brain changes similar to those observed in schizophrenia patients, and these changes correlate with poorer working memory, new research shows.

A study conducted by investigators at Northwestern University Feinberg School of Medicine in Chicago, Illinois, showed that teens who smoked marijuana daily for about 3 years performed poorly on tests of working memory and had abnormal changes in brain structures akin to those seen in patients with schizophrenia.

This study links the long-term use of marijuana to "concerning brain abnormalities that appear to last for at least a few years after people stop using it," lead investigator Matthew Smith, PhD, assistant research professor in psychiatry and behavioral sciences, said in a statement.

"With the movement to decriminalize marijuana, we need more research to understand its effect on the brain," he added.

In addition, memory problems and brain changes were observed 2 years after the teens stopped smoking marijuana, suggesting long-term use has long-term, negative effects.

The study was published online December 15 in Schizophrenia Bulletin.

Structural Changes

A total of 97 young people participated, including 44 healthy individuals who had no history of substance use disorder, 10 healthy individuals with cannabis-use disorder (CUD), 28 individuals with schizophrenia with no history of substance use disorder, and 15 individuals with schizophrenia and a CUD history.

Marijuana users started smoking daily between the ages of 16 and 17 years and continued for about 3 years. At the time of the study, they had been marijuana-free for approximately 2 years. The marijuana users did not abuse any other drugs.

Structural magnetic resonance imaging (MRI) studies revealed "shape differences" in the striatum, globus pallidus, and thalamus in the healthy and schizophrenic participants with CUD. These memory-related brain structures appeared to shrink or collapse inward in the CUD groups, possibly suggesting a decline in neurons, the researchers note.

Marijuana-related striatal and thalamic shape differences correlated with poorer working memory on standard tests and younger age at onset of CUD in both healthy participants and schizophrenic marijuana users.

The researchers point out that most of the schizophrenic users met diagnostic criteria for CUD prior to the onset of schizophrenia, suggesting that long-term marijuana use might contribute to the underlying disease process.

"If someone has a family history of schizophrenia, they are increasing their risk of developing schizophrenia if they abuse marijuana," said Dr. Smith.

Heavy marijuana use "may have dangerous implications for young people who are developing or have developed mental disorders," added co–senior author John Csernansky, MD, chair of psychiatry and behavioral sciences at Northwestern University Feinberg School of Medicine and Northwestern Memorial Hospital.

"This paper is among the first to reveal that the use of marijuana may contribute to the changes in brain structure that have been associated with having schizophrenia," he said.

The investigators note that their data are cross-sectional and therefore cannot indicate causality.

Still, they point out that, given the potential impact of cannabis on working memory and the underlying structures that support it, more careful consideration should be given to efforts to legalize recreational and medicinal cannabis.

"Of special concern is that cannabis use could begin long before an adolescent or young adult would know if they were in one of these vulnerable groups," they conclude.

Memory Findings Key

This is a "very good study," Matthijs Bossong, PhD, of the Institute of Psychiatry, Department of Psychosis Studies, King's College London, in the United Kingdom, who was not involved in the study, told Medscape Medical News.

He said the "particular strengths" are the inclusion of healthy control individuals with and without CUD and schizophrenia patients with and without CUD and the correlation between working memory function and anatomic changes.

"Most structural MRI studies just report anatomical abnormalities between groups without mentioning the functional impact," Dr. Bossong explained. "In my opinion, that structural abnormalities are related to working memory function is the news in this paper."

"It's still unclear whether cannabis has a bigger impact on schizophrenia patients than on healthy controls. They describe it qualitatively, but it has not been tested statistically," he noted.

Regarding the debate around the legalization of recreational and medicinal cannabis use, Dr. Bossong said it is important to note that the authors have shown structural and functional abnormalities in groups with a CUD, "which is in line with other papers that have demonstrated that particularly heavy cannabis use may have negative effects on the brain."

"The beneficial effects of cannabis prescribed for medicinal purposes (eg, chronic pain) may significantly outweigh the more subtle negative effects," Dr. Bossong said.

The research was supported by grants from the National Institute of Mental Health and the National Institute on Drug Abuse. The authors and Dr. Bossong report no relevant financial relationships.

Schizophr Bull. Published online December 15, 2013. Abstract

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