Would You Use Marijuana if You Knew This?

Summary and Comment |
November 24, 2014

Would You Use Marijuana if You Knew This?

  1. Jonathan Silver, MD

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

  1. Jonathan Silver, MD

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.


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.

Editor Disclosures at Time of Publication

  • Disclosures for Jonathan Silver, MD at time of publication Editorial boards Journal of Neurology, Neurosurgery and Psychiatry; Journal of Neuropsychiatry and Clinical Neuroscience; UpToDate Leadership positions in professional societies North American Brain Injury Association (Board Member)


Reader Comments (3)

Kent Hill MD PhD Physician, Psychiatry, Child and family Behavioral Health Service, Madigan Army Medical Center

Yes, the well known fact that statiistcal correlation does not equal causation. I would observe that the tobacco industry made the same statement as the evidence accumulated about the risks of tobacco smoke.

It does add and extend the accumulating evidence that cannabis is not good for developing brains, ie lowered IQ and school performance, increase mood and anxiety disorders and increased risk of schizophrenia. It would be naive to assume that just because some on turns 21 that there is no effect on the brain with use of cannabis which appear to be associated with neurotoxic effects on a developing brain. Research is clear that the brain remains more neuroplastic that was previously assumed.


This is a cross-sectional study, and can therefore only show an association between the exposure of cannabis use and the outcome of observed cortical changes on MRI. Therefore, to imply that "Chronic heavy marijuana use has structural and functional consequences in the orbitofrontal cortex" is incorrect, as only an association is proven, not an actual "consequence" (i.e. a causal inference).

You say that "Chronic use has long-term adverse effects on brain structure and function", but again, a cross-sectional study is not able to prove a direct cause-effect relationship. Is it not possible that changes in the OFC may in fact precede addictive behaviors by somehow biologically predisposing a person to increased cannabis use? How can we be sure it is the cannabis that is leading to the cortical changes, and not the cortical changes themselves that are leading to increased cannabis use? To claim that this study proves that cannabis is the cause of changes in the OFC is disingenuous given the inherent limitation of the study design.

Michael Lapidus MD Physician, Psychiatry, Private Practice

How does functional connectivity work? SSRI use seems to decrease connectivity in whole brain except thalamus and cerebellum within 3 hours of first dose.

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