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Articles, Neurobiology of Disease

Cannabis Use Is Quantitatively Associated with Nucleus Accumbens and Amygdala Abnormalities in Young Adult Recreational Users

Jodi M. Gilman, John K. Kuster, Sang Lee, Myung Joo Lee, Byoung Woo Kim, Nikos Makris, Andre van der Kouwe, Anne J. Blood and Hans C. Breiter
Journal of Neuroscience 16 April 2014, 34 (16) 5529-5538; DOI: https://doi.org/10.1523/JNEUROSCI.4745-13.2014
Jodi M. Gilman
1Laboratory of Neuroimaging and Genetics, Department of Psychiatry,
4Athinoula A. Martinos Center in Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts 02129,
5Harvard Medical School, Boston, Massachusetts 02115, and
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John K. Kuster
1Laboratory of Neuroimaging and Genetics, Department of Psychiatry,
2Mood and Motor Control Laboratory,
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Sang Lee
1Laboratory of Neuroimaging and Genetics, Department of Psychiatry,
6Warren Wright Adolescent Center, Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois 06011
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Myung Joo Lee
1Laboratory of Neuroimaging and Genetics, Department of Psychiatry,
6Warren Wright Adolescent Center, Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois 06011
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Byoung Woo Kim
1Laboratory of Neuroimaging and Genetics, Department of Psychiatry,
6Warren Wright Adolescent Center, Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois 06011
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Nikos Makris
3Center for Morphometric Analysis, Department of Psychiatry, and
5Harvard Medical School, Boston, Massachusetts 02115, and
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Andre van der Kouwe
4Athinoula A. Martinos Center in Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts 02129,
5Harvard Medical School, Boston, Massachusetts 02115, and
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Anne J. Blood
1Laboratory of Neuroimaging and Genetics, Department of Psychiatry,
2Mood and Motor Control Laboratory,
4Athinoula A. Martinos Center in Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts 02129,
5Harvard Medical School, Boston, Massachusetts 02115, and
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Hans C. Breiter
1Laboratory of Neuroimaging and Genetics, Department of Psychiatry,
2Mood and Motor Control Laboratory,
4Athinoula A. Martinos Center in Biomedical Imaging, Department of Radiology, Massachusetts General Hospital, Charlestown, Massachusetts 02129,
6Warren Wright Adolescent Center, Department of Psychiatry and Behavioral Sciences, Northwestern University Feinberg School of Medicine, Chicago, Illinois 06011
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Abstract

Marijuana is the most commonly used illicit drug in the United States, but little is known about its effects on the human brain, particularly on reward/aversion regions implicated in addiction, such as the nucleus accumbens and amygdala. Animal studies show structural changes in brain regions such as the nucleus accumbens after exposure to Δ9-tetrahydrocannabinol, but less is known about cannabis use and brain morphometry in these regions in humans. We collected high-resolution MRI scans on young adult recreational marijuana users and nonusing controls and conducted three independent analyses of morphometry in these structures: (1) gray matter density using voxel-based morphometry, (2) volume (total brain and regional volumes), and (3) shape (surface morphometry). Gray matter density analyses revealed greater gray matter density in marijuana users than in control participants in the left nucleus accumbens extending to subcallosal cortex, hypothalamus, sublenticular extended amygdala, and left amygdala, even after controlling for age, sex, alcohol use, and cigarette smoking. Trend-level effects were observed for a volume increase in the left nucleus accumbens only. Significant shape differences were detected in the left nucleus accumbens and right amygdala. The left nucleus accumbens showed salient exposure-dependent alterations across all three measures and an altered multimodal relationship across measures in the marijuana group. These data suggest that marijuana exposure, even in young recreational users, is associated with exposure-dependent alterations of the neural matrix of core reward structures and is consistent with animal studies of changes in dendritic arborization.

  • cannabis
  • gray matter density
  • marijuana
  • multimodal imaging
  • reward
  • topology/shape
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The Journal of Neuroscience: 34 (16)
Journal of Neuroscience
Vol. 34, Issue 16
16 Apr 2014
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Cannabis Use Is Quantitatively Associated with Nucleus Accumbens and Amygdala Abnormalities in Young Adult Recreational Users
Jodi M. Gilman, John K. Kuster, Sang Lee, Myung Joo Lee, Byoung Woo Kim, Nikos Makris, Andre van der Kouwe, Anne J. Blood, Hans C. Breiter
Journal of Neuroscience 16 April 2014, 34 (16) 5529-5538; DOI: 10.1523/JNEUROSCI.4745-13.2014

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Cannabis Use Is Quantitatively Associated with Nucleus Accumbens and Amygdala Abnormalities in Young Adult Recreational Users
Jodi M. Gilman, John K. Kuster, Sang Lee, Myung Joo Lee, Byoung Woo Kim, Nikos Makris, Andre van der Kouwe, Anne J. Blood, Hans C. Breiter
Journal of Neuroscience 16 April 2014, 34 (16) 5529-5538; DOI: 10.1523/JNEUROSCI.4745-13.2014
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Keywords

  • cannabis
  • gray matter density
  • marijuana
  • multimodal imaging
  • reward
  • topology/shape

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  • Regional Brain Differences in Recreational Marijuana Smokers and Controls
    Nidia J. Melendez
    Published on: 12 May 2014
  • Correlative Measures of Cannabis Use
    Ryan M. Smith
    Published on: 17 April 2014
  • Published on: (12 May 2014)
    Page navigation anchor for Regional Brain Differences in Recreational Marijuana Smokers and Controls
    Regional Brain Differences in Recreational Marijuana Smokers and Controls
    • Nidia J. Melendez, Research Assistant

    I read with great interest the report by Gilman et al. (2014) examining the effects of recreational marijuana use by young adults. The authors concluded that brain regions implicated in reward and drug addiction behavior, i.e., the nucleus accumbens and amygdala "...revealed greater density values in marijuana users than in control participants." After comparing MRI brain scans of casual users to those of controls, rese...

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    I read with great interest the report by Gilman et al. (2014) examining the effects of recreational marijuana use by young adults. The authors concluded that brain regions implicated in reward and drug addiction behavior, i.e., the nucleus accumbens and amygdala "...revealed greater density values in marijuana users than in control participants." After comparing MRI brain scans of casual users to those of controls, researchers speculated that regional differences were abnormalities caused by cannabis use that attribute to drug addiction. 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 (1988) 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." As a result, causal explanations regarding drug addiction cannot be determined by these differences in complex anatomical brain structures.

    Second, the marijuana group reported use of multiple other substances, making it impossible to disentangle the effects of marijuana from those of other drugs. 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 "...marijuana exposure, even in young recreational users, is associated with exposure-dependent alterations of the neural matrix of core reward structures..." Moreover, it is unclear whether these regional differences predate cannabis use or are a result of poly-drug use.

    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.

    References: DiDomenico R, Eaton RC (1988) Seven principles for command and the neural causation of behavior. Brain, Behavior and Evolution 31:125-140

    Gilman GM, Kuster JK, Lee S, Lee MF, Kim BW, Makris N,Van der Kouwe A, Blood AJ, Breiter HC (2004) Cannabis Use Is Quantitatively Associated with Nucleus Accumbens and Amygdala Abnormalities in Young Adult Recreational Users. The Journal of Neuroscience 34(16):5529-5538

    Conflict of Interest:

    None declared

    Show Less
    Competing Interests: None declared.
  • Published on: (17 April 2014)
    Page navigation anchor for Correlative Measures of Cannabis Use
    Correlative Measures of Cannabis Use
    • Ryan M. Smith, Research Assistant Professor

    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...

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    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 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.

    References

    [1]. Society for Neuroscience Press Release. "BRAIN CHANGES ARE ASSOCIATED WITH CASUAL MARIJUANA USE IN YOUNG ADULTS". Accessed April 16th, 2014 at http://www.sfn.org/Press-Room/News-Release- Archives/2014/Brain-Changes-Are-Associated-with-Casual-Marijuana-Use-in- Young-Adults

    [2]. Ritter, M. "Study finds signs of brain changes in pot smokers". Associated Press. Access April 16th, 2014 at http://hosted.ap.org/dynamic/stories/U/US_MED_MARIJUANA_BRAIN?SITE=AP&SECTION=HOME&TEMPLATE=DEFAULT&CTIME=2014 -04-15-18-07-53

    [3]. Dobuzinskis, A. "Casual pot use causes brain abnormalities in the young: study". Reuters. Accessed April 16th, 2014 at http://www.reuters.com/article/2014/04/16/us-usa-marijuana-study- idUSBREA3F04F20140416"

    Conflict of Interest:

    None declared

    Show Less
    Competing Interests: None declared.

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