Chronic marijuana use linked to structural differences in the brain

1. Researchers used fMRI and diffusion tensor imaging to identify differences in brain structure and function associated with chronic marijuana (CM) use.

2. When compared with non-users, CM users had less gray matter volume in the orbitofrontal cortex, a region associated with decision making and long-term planning, and different levels of structural and functional connectivity.

Evidence Rating Level: 3 (Average)

Study Rundown: While previous studies have investigated whether CM use causes structural changes in the brain, these studies generated conflicting findings resulting from methodological differences. To address these discrepancies, this current study used three complementary imaging techniques to characterize the structural and functional features of the human brain in CM users and nonusers. The authors evaluated the orbitofrontal cortex, a brain region previously implicated in marijuana-related structural changes. This region expresses high levels of cannabinoid 1 (CB1) receptors that bind tetrahydrocannabinol (THC), the primary psychoactive ingredient in marijuana.

Consistent with previous studies, researchers found lower gray matter volume bilaterally in the orbitofrontal cortices of CM users. Given that CM use is often co-morbid with other substance abuse, the authors compared the subset of subjects who solely use marijuana (no other drugs or alcohol) with the control non-user group. The findings of a reduction in orbitofrontal gray matter volume held in this subset study. In addition to lower OFC gray matter volume, researches also found CM users displayed higher measures of structural and functional connectivity in the brain. These differences appeared to depend on age of onset and duration of marijuana use.

This retrospective study collected no information on brain structure or function pre- or at multiple timepoints during marijuana use; hence only correlational conclusions can be drawn. That said, the significant structural differences in the brains of CM users when compared to non-users, suggest such drug use may lead to changes in brain function.

Click to read the study in PNAS

Relevant Reading: Brain Neuroimaging in Cannabis Use: A Review

In-Depth [retrospective cohort]: In this study, researchers used several distinct scanning methods to examine association of CM use with structural and functional differences in the brain. Sixty-two non-using control subjects were compared with 48 CM users. Chronic users were defined as > 6 months of marijuana use at a minimum of 4 times per week. To remove potential contaminating effects of other substance use, a subset study compared 26 solely-marijuana users to the control group. A variety of MRI brain scans were collected to evaluate gray matter volume, functional connectivity, and structural connectivity.

High-resolution T1 images showed a lower gray matter volume in marijuana users in the regions of the orbitofrontal area. Scoring of functional connectivity maps revealed higher connectivity in all four nodes of the orbitofrontal area in CM users when compared to non-users (p < 0.05). To evaluate structural connectivity, diffusion tensor imaging was used to examine the forceps minor, which connect the right and left orbitofrontal cortices. CM users exhibited a greater structural connectivity between the two cortices, as evaluated by fractional anisotropy (FA). To examine if CM use impacted changes in the forceps minor, the authors examined the structural connectivity of the forceps minor as a function of the full duration of CM use at the time of study. Interestingly, they found a quadratic relationship between FA and length of use, with a peak in FA at approximately 4 years of use. Analysis did not reveal CM use was significantly correlated with OFC gray matter volume, functional or structural connectivity, and any outcome, such as different IQs or behavior.

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