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These multiple aspects of structural information enrich our knowledge related to a structure in terms of size, density, and topography and give us more confidence of the veracity and accuracy of the MRI techniques used and the derived anatomical results. This study demonstrates that different aspects of brain morphology may be affected by cannabis.

In this study, shape- and voxel-based morphometry measures of subcortical regions were consistently affected in an exposure-dependent manner by cannabis, whereas volume was less affected. Since their initial application in addiction and psychiatric research e. For example, subcortical structural alterations have been reported in thalami of patients with schizophrenia Harms et al. Subcortical surface alterations may be more sensitive to the effects of cannabis than total volumes.

Volume alterations may also be more pronounced with greater duration of use.

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In our study, the nucleus accumbens and amygdala showed altered surface topology compared with controls, which could potentially lead to volume alterations with continued use. Both gray matter density and average volume were increased in marijuana participants in the left nucleus accumbens. The density increase was localized to a large area, which clearly represents the extended amygdala as defined by Heimer and Alheid , a neuroanatomical entity implicated in addiction Koob, The structures comprising the extended amygdala may be key substrates for the reinforcing actions of drugs and in the negative reinforcing aspect of dependence Koob, Increased gray matter density in this region is consistent with findings in animal studies of drug use.

Researchers have reported a 6. These results have been replicated using nicotine Gonzalez et al. In a study in which rats were given doses of THC that were within the range that might be experienced by human marijuana users, prior exposure to THC increased the length of the dendrites and the number of dendritic branches in the shell of the nucleus accumbens in contrast to an absence of effects in the hippocampus, striatum, orbital frontal cortex, parietal cortex, or occipital cortex; Kolb et al.

Dendritic arborization changes may relate to an increase in dopamine, because acute administration of drugs of abuse e. Interestingly, the left nucleus accumbens was consistently affected by cannabis use across all three modalities.

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This structure also showed differences between marijuana and control participants in the multimodal relationship between gray matter density and both shape and volume. Few other associations of measures across modalities differed between marijuana and control participants. It will be important for follow-up work to assess the emergence of further abnormalities with prolonged marijuana use. The present study did not find any differences in amygdala volumes between marijuana users and control participants, but did find that surfaces of the right amygdala were deformed inwards and this diminishment was highly correlated with drug use behavior.

Such an observation is also consistent with data showing a negative correlation between level of cannabis dependence and amygdala gray matter density Cousijn et al. Our observations indicate that such changes may occur before dependence, which is intriguing in the context that the amygdala appears to play an important role in drug craving Breiter et al. Countless studies have shown that prefrontal cortex dysfunction is involved with decision-making abnormalities in addiction e.

Furthermore, diffusion tensor imaging studies have shown that cannabis use may affect the integrity of white matter fiber tracts in prefrontal regions Gruber and Yurgelun-Todd, A study examining the structural effects of cannabis on the prefrontal cortex reported greater gray matter density in the precentral gyrus of marijuana users Matochik et al.


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More studies are needed with larger cohorts to fully examine the effect of cannabis use on prefrontal structures. This preliminary study has several caveats.


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First, the sample size does not provide power to examine complex interactions such as sex differences. Because this is a cross-sectional study, causation cannot be determined, although marijuana exposure parametrically correlated with structural differences, which suggests the possibility of causation.

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Longitudinal studies are needed to determine whether marijuana exposure explicitly leads to the differences observed in this study. Furthermore, this study did not include quantifiable marijuana metabolite levels, which would have provided further information about the amount of marijuana exposure.


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This measure could be incorporated into future studies as a complementary measure to detailed timeline follow-back measures of drug use. Finally, age of onset was collected for marijuana use only. Early exposure to alcohol may have also affected brain structure although no participant met criteria for past alcohol abuse or dependence. The results of this study indicate that in young, recreational marijuana users, structural abnormalities in gray matter density, volume, and shape of the nucleus accumbens and amygdala can be observed.

Pending confirmation in other cohorts of marijuana users, the present findings suggest that further study of marijuana effects are needed to help inform discussion about the legalization of marijuana. These results extend prior studies showing that drugs of abuse that are known to elevate DA release are associated with structural abnormalities in the brain and related disruptions in behavior Makris et al. The multimodal convergence of these findings also points to the salience of structural differences in the brain related to drug exposure and strongly argues that human addiction research, if not all psychiatric study, must move past a predominant focus on neurotransmission.

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Zinberg Fellowship in Addiction Psychiatry Research. NOTE: We request your email address only to inform the recipient that it was you who recommended this article, and that it is not junk mail. We do not retain these email addresses. I read with great interest the report by Gilman et al. The authors concluded that brain regions implicated in reward and drug addiction behavior, i. While this is an intriguing interpretation, I feel at least two points deserve further discussion. First, there were no measures of cognitive performance or any other behaviors in the current report.

This makes it nearly impossible to interpret the meaning of any brain measure differences. As Di Domenico and Eaton pointed out in their classic paper, "Without a quantifiable concept of behavior we run the risk of performing neurophysiological experiments that have no behavioral correlates but which entice us to make unwarranted speculations without the neural basis of behavior.

Second, the marijuana group reported use of multiple other substances, making it impossible to disentangle the effects of marijuana from those of other drugs.

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Without inclusion of a marijuana-only group or a group that reported use of multiple other drugs except marijuana, it seems premature to conclude that " Given the above concerns, measuring regional brain differences offers no basis for speculation about arbitrary drug addiction behavior between cannabis users and controls. Structural brain differences between men and women exist, however this does not prove that they differ in ability based on gender. Without overt quantifiable behavioral measures and controlling for poly-drug use, these anatomical differences should not be attributed to marijuana use primarily.

Brain, Behavior and Evolution The Journal of Neuroscience 34 16 I read with great interest this article correlating neuroanatomical changes in casual cannabis users versus non-users. However, the authors repeatedly and explicitly state a causative relationship between the cannabis use and the anatomic changes throughout the article, only to state in the second-to-last paragraph that no causative relationship can be concluded due to the cross-sectional design of this study.

Even mor Even more, the press release from the Society for Neuroscience [1] and the narrative in news stories resulting from this manuscript [2,3] do not explicitly state this very obvious caveat. While the correlative relationship reported here is statistically strong, a longitudinal study design is necessary to make the causative claims throughout the first 29 paragraphs and abstract of this manuscript. Again, this very critical distinction in study design is not noted until the end of the manuscript.

A plausible alternative interpretation of this data is that the neuroanatomical abnormalities predate the drug use and make the individuals more likely to use cannabis. By reversing the causative relationship here, we would suppose that greater anatomical changes would cause increased consumption. With that said, there is abundant evidence showing an empirical link between tetrahydrocannabinol administration and neuroanatomical changes in rodents. However, the repeated claims of a causative relationship in this manuscript and related press articles are not warranted based solely on the results reported here.

Society for Neuroscience Press Release. Ritter, M. Associated Press. Dobuzinskis, A. Skip to main content. Previous Next. Articles, Neurobiology of Disease. Jodi M. Gilman , John K. Blood and Hans C. Introduction Marijuana cannabis is the most commonly used illicit drug in the United States Materials and Methods Participants. Acquisition and processing of neuroimaging data.

Voxel-based morphometry analysis.

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Volume analysis. Multimodal data integration. Behavioral measures. View this table: View inline View popup. Table 1.

Participant demographics. Gray matter density measures The whole-brain gray matter density analysis revealed greater density values in marijuana users than in control participants in the left nucleus accumbens, extending to subcallosal cortex, hypothalamus, sublenticular extended amygdala, and left amygdala Fig.

Figure 1. Table 2. Table 3. Table 4. Linear regression between smoking behavior and structural measures. Volumes Of the four a priori volumes, the left nucleus accumbens volume was larger in marijuana users Figure 1 C , Table 2 , mirroring the increase in gray matter density, although this increase did not meet significance after controlling for multiple comparisons. Table 5. Figure 2. Multimodal relationships across structural measures When we investigated the relationship among gray matter density, volume, and vertices, we found that multimodal relationships in control participants were altered in marijuana users, particularly in the left nucleus accumbens.

Table 6. Table 7. Discussion The present study demonstrates that, even in young, nondependent marijuana users, morphometric abnormalities relative to nonusers are observable, many of which are exposure dependent. The authors declare no competing financial interests.

Lake Shore Dr. Neuroimage 11 : — , doi: J Neurosci 24 : — , doi: Bechara A Neurobiology of decision-making: risk and reward. Semin Clin Neuropsychiatry 6 : — , doi: Blood AJ , Zatorre RJ Intensely pleasurable responses to music correlate with activity in brain regions implicated in reward and emotion.