Would You Use Marijuana if You Knew This?

Chronic use has long-term adverse effects on brain structure and function.

The consequences of long-term marijuana use are increasingly in the spotlight because of marijuana's legalization in many states. Investigators used magnetic resonance imaging to examine brain structure and function (gray-matter volume, functional connectivity, and white-matter integrity) in 42 marijuana users (≥4 times weekly; mean years of use, 9) and 62 nonusing controls matched for age and sex.

Users had lower gray-matter volume in right middle and left superior orbitofrontal gyri, higher connectivity in all orbitofrontal networks (bilateral orbitofrontal cortex and temporal lobe), and greater fractional anisotropy (FA) and lower radial diffusivity (RD) of the forceps minor tract (which connects the orbitofrontal regions). These structural changes correlated with behavioral indicators of marijuana use. Earlier age at onset of use was associated with higher functional connectivity of the orbitofrontal cortex. Post hoc analysis suggested that FA and RD rose at initiation of heavy use and then fell with chronic use. Controlling for use of tobacco and alcohol did not change the results. Although mean IQ was higher in the control group (111 vs. 106 in users), the observed structural changes did not appear to mediate this effect.

Comment

Chronic heavy marijuana use has structural and functional consequences in the orbitofrontal cortex (central to the reward system), probably via cannabinoid CB-1 receptors. The observed increases in functional connectivity represent higher, and less efficient, energy use by the brain. The changes in RD and FA may indicate greater myelination, possibly arising from marijuana's anti-inflammatory and antioxidant properties; cannabinoids also might alter synaptic pruning. This study illustrates marijuana's neurotoxic effects. Whether abstinence reverses such effects remains unknown, but our patients (and the public) must be made aware of these findings to guide their decisions about using this substance.

Reviewing Author

Jonathan Silver, MD

Disclosures

RoyaltiesTextbook of Traumatic Brain Injury, 2nd and 3rd editions

Editorial BoardsUpToDate; Journal of Neuropsychiatry and Clinical Neuroscience

Leadership Positions in Professional SocietiesNorth American Brain Injury Association (Board Member); National Institute on Disability, Independent Living, and Rehabilitation Research (Chair of Data Monitoring Safety Board for study of donepezil on cognition after traumatic brain injury)