Is Gray Matter Volume Indicative Of Alterations In The Brains Of Drug Users?

Today, there is a drastically wide spectrum of views on drugs and drug use. While many scientists and researchers emphasize the vast negative effects that coincide with using illegal substances, there are some who push back and argue that drug use may not be as bad as we generally perceive it to be. For instance, Dr. Carl Hart, a neuroscientist and professor, has openly discussed his own use of drugs and desire to decriminalize recreational drugs in order to facilitate our primary goal of chasing happiness. 

In Hart’s book “Drug Use For Grown-Ups”, he pushes back on many misconceptions related to drug use and counters several scientific studies which he believes have more of an intent on vilifying drug use than presenting the actual results (Hart, 2021). In one study conducted by researchers at Massachusetts General Hospital and Northwestern University, the group wanted to examine whether marijuana users differed from non-marijuana users in terms of brain structures (Gilman et al., 2014). In order to conduct this study, the researchers gathered 40 participants: 20 to be placed in the marijuana condition and 20 to be placed in the control group. Marijuana participants reported using the drug at least once a week, but were not dependent. Additionally, marijuana participants were not excluded if they had used other illegal substances in the past. The control group reported having not used marijuana in the last year and throughout their lifetime having used the drug less than five times. 

After conducting brain scans, the researchers saw greater gray matter density in marijuana users than in control participants in the left nucleus accumbens extending to the subcallosal cortex, hypothalamus, sublenticular extended amygdala, and left amygdala. The researchers also identified significant shape differences in the left nucleus accumbens and right amygdala. These findings led the researchers to conclude that marijuana exposure is associated with alterations of reward structures in the brain.

While this finding suggests that there are some differences in the brain structures between marijuana users and non-marijuana users, it fails to address the significance of greater gray matter density in the brains of the marijuana users. Increased gray matter volume is typically associated with higher-level brain processing and mental development (Mercadante et al., 2022). Shouldn’t this mean more gray matter is a good thing?

Several other studies have examined differences in brain structures when comparing users of a particular drug to non-drug users, particularly by looking at gray matter density and other reward regions of the brain. For instance, one study examined the density of gray matter in 30 lifetime heroin-dependent individuals and 34 healthy participants (Yuan et al., 2009). The researchers in this study found that the heroin users, compared with the healthy subjects, showed significantly decreased gray matter density in the prefrontal, anterior cingulate, and temporal regions of the brain, contrasting the study conducted with marijuana users. 

Another study conducted on gray matter density between drug users and non-drug users, this time focusing on methamphetamine, found a similar finding to the heroin study. In this experiment, gray matter was measured in three groups: 18 Control Nonsmokers, 25 Control Smokers (cigarette smoking), and 39 Methamphetamine-dependent Smokers (Morales et al., 2012). The researchers found that, compared with control nonsmokers, control smokers and methamphetamine-dependent smokers had smaller gray-matter volume in the orbitofrontal cortex and caudate nucleus. 

The differences in findings among various studies suggest that more intricate experiments may need to be conducted in order to determine what the causal mechanism is behind higher or lower levels of gray matter density in the brain. A potential future avenue that researchers could take to more accurately identify the cause of alterations in gray matter volume is to conduct a longitudinal study, examining brain images over a larger period of time. Of the three studies I mentioned above, only the methamphetamine study examined brain images on more than one occasion. Additionally, future studies should include extra groups in order to account for factors contributing to brain alterations. For example, when comparing marijuana and non-marijuana users, a third group could be added consisting of tobacco and / or alcohol use, but not marijuana. By taking this extra step, brain alterations can more specifically be attributed to one (or several) drug(s). 


Gilman JM, Kuster JK, Lee S, Lee MJ, Kim BW, Makris N, van der Kouwe A, Blood AJ, Breiter HC (2014), “Cannabis Use Is Quantitatively Associated with Nucleus Accumbens and Amygdala Abnormalities in Young Adult Recreational Users,” Journal of Neuroscience 34: 5529-38.

Hart, C. L. (2022). Drug use for grown-ups: Chasing liberty in the land of fear. Penguin Books, imprint of Penguin Random House LLC.

Mercadante AA, Tadi P. Neuroanatomy, Gray Matter. [Updated 2022 Jul 25]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-. Available from:

Morales AM, Lee B, Hellemann G, O’Neill J, London ED (2012), “Gray-Matter Volume In Methamphetamine Dependence: Cigarette Smoking and Changes With Abstinence from Methamphetamine,” Drug and Alcohol Dependence, 230-238.

Yuan Y, Zhu Z, Shi J, Zou Z, Yuan F, Liu Y, Lee T, Weng X (2009), “Gray Matter Density Negatively Correlates With Duration Of Heroin Use In Young Lifetime Heroin-Dependent Individuals,” Brain and Cognition, 223-228.

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