Structural Brain Differences Seen in Casual Marijuana Users

Megan Brooks

April 16, 2014

Even occasional marijuana smoking appears to be associated with significant structural differences in key brain regions involved in motivation, emotion, and reward compared with nonsmoking controls, a new study indicates.

The researchers found dose-dependent differences in gray matter density, volume, and shape of the nucleus accumbens and amygdala in young healthy recreational marijuana smokers vs never-users of marijuana.

"Most studies have looked at long-term heavy marijuana users and show brain changes," Jodi Gilman, PhD, from the Department of Psychiatry, Massachusetts General Hospital, Boston, told Medscape Medical News.

"Our study is different in that it looks at young adult recreational users who are not addicted based on a psychological interview and we found observable brain changes in this group. This is concerning, given that there are roughly 18.5 million recreational users," she said.

Dr. Gilman and colleagues report their findings April 16 in the Journal of Neuroscience.

Altered Brain Organization

The researchers assessed brain morphology using high-resolution MRI in 40 young adults aged 18 to 25 years recruited from Boston-area colleges; 20 used marijuana recreationally (mean, 11.2 joints per week) and 20 did not use the drug at all.

Comparing the scans, the researchers found abnormalities in all 3 structural measures assessed (gray matter density, volume, and shape) in casual marijuana users relative to nonusers.

Gray matter density analyses revealed greater gray matter density in marijuana users than nonusers in the left nucleus accumbens extending to subcallosal cortex, hypothalamus, sublenticular extended amygdala, and left amygdala, even after adjustment for age, sex, alcohol use, and cigarette smoking, the researchers report.

They also observed "trend-level effects" for a volume increase in the left nucleus accumbens and significant shape differences in the left nucleus accumbens and right amygdala in marijuana users.

"The left nucleus accumbens showed salient exposure-dependent alterations across all 3 measures and an altered multimodal relationship across measures in the marijuana group," they report.

"The findings were a little bit unexpected because these were young adults who hadn't been using for that long and some were only using once or twice a week," Dr. Gilman told Medscape Medical News.

"These abnormal structural changes in the amygdala and nucleus accumbens could indicate that the experience with marijuana alters brain organization and may produce changes in function and behavior," study investigator Anne Blood, PhD, from the Department of Psychiatry, Massachusetts General Hospital, added in a statement. "It also is possible that the brain is adapting to marijuana exposure and that these new connections may encourage further marijuana use."

"Our findings, which need to be followed up with longer-term studies, raise serious concerns about efforts to legalize recreational marijuana use, particularly for young adults," said study investigator Hans C. Breiter, MD, professor of psychiatry and behavioral science at Northwestern University Feinberg School of Medicine, Chicago, Illinois.

"This is just a structural study. The next logical step is to figure out how these structural changes relate to behavior and functional outcomes such a memory or reward or motivation," Dr. Gilman said.

Clinical Implications

The study is "quite elegant and appears to be the first study to associate recreational cannabis use with brain abnormalities," Matthew Smith, PhD, assistant research professor in psychiatry and behavioral sciences, Northwestern University Feinberg School of Medicine, told Medscape Medical News. Dr. Smith wasn't involved in the study but has also found brain changes with marijuana use in his own studies.

This new study, Dr. Smith said, "appears to demonstrate that increasing amounts of cannabis used recreationally are associated with increasing severity in brain abnormalities. Their findings are also consistent with my recent work in young adults who were daily cannabis users as teens, as both studies observed abnormalities in the nucleus accumbens," Dr. Smith said.

"This area of the brain is responsible for experiencing reward and is largely considered the pleasure center of the brain. It is interesting that these abnormalities exist given the low levels of cannabis consumed. These findings will be quite concerning if they are present after an extended period of abstinence," Dr. Smith said.

The study was supported by grants from the National Institute on Drug Abuse, the Office of National Drug Control Policy, and the National Institute of Neurological Disorders and Stroke. The authors and Dr. Smith have disclosed no relevant financial relationships.

J Neurosci. 2014;34:5529-5538. Abstract

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