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Cannabis Dependence Is Associated With Changes in Neural Circuitry That May Contribute to Psychopathology

May 21, 2019

People with cannabis dependence have changes in neural circuitry in brain regions related to reward processing, habit formation, and psychopathology. These changes in neural circuitry may provide a useful marker for tracking psychopathology associated with cannabis misuse.

Source:
Manza, P., Tomasi, D., and Volkow, N.D. Subcortical local functional hyperconnectivity in cannabis dependence. Biological Psychiatry 3(3):285-293, 2018.

Slideshow Transcript

Slide 1:

Caption:

A study found:

  • People with cannabis dependence have changes in neural circuitry in brain regions related to reward processing, habit formation, and psychopathology.
  • These changes in neural circuitry may provide a useful marker for tracking psychopathology associated with cannabis misuse.

Alt text:

The illustration shows magnetic resonance images of brain cross-sections with some areas deep within the brain highlighted in red, orange, yellow, and green. The two images at the top are lengthwise cross-sections, the two images at the bottom are vertical cross-sections.

Slide 2:

Caption:

People with cannabis use often show psychiatric symptoms, such as:

  • Lack of motivation
  • Negative thoughts or feelings
  • Increased risk of psychosis
    (e.g., schizophrenia)

Alt text:

The illustration shows a black and white image of a pensive-looking young woman.

Slide 3:

Caption:

Dr. Peter Manza of the National Institute on Alcohol Abuse and Alcoholism (NIAAA) and colleagues from NIDA suspected that cannabis exposure gives rise to psychological problems by disrupting normal functioning in brain regions that use the neurotransmitter dopamine.

The researchers hypothesized that the drug alters local functional connectivity (LFC) in dopamine-using brain regions.

LFC quantifies the extent to which neurons in a region activate in concert.

Alt text:

The illustration shows a magnetic resonance image of a lengthwise brain cross-section with some areas deep within the brain highlighted in red, orange, yellow, and green.

Slide 4:

Caption:

The researchers used fMRI to compare LFC in the subcortex of 30 cannabis-dependent and 30 nondependent people.

The image shows LFC as revealed in (from top) horizontal, sagittal, and coronal cross-sections of the brain.

Hot colors (red, yellow) indicate regions with high LFC.

Alt text:

The illustration shows magnetic resonance images of various brain cross-sections, with some areas deep within the brain highlighted in red, orange, yellow, and green. The images at the top show horizontal cross-sections, the images in the middle are lengthwise (sagittal) cross-sections, and the images at the bottom are vertical (coronal) cross sections. The areas highlighted in red and yellow indicate regions with high LFC.

Slide 5:

Caption:

Dr. Manza and colleagues found:

  • Study participants with a history of cannabis dependence had higher LFC in several brain regions.
  • Affected regions included the midbrain (including the ventral tegmental area and substantia nigra), ventral striatum, thalamus, and brainstem.
  • The ventral tegmental area and substantia nigra contain dopamine-producing neurons, and the ventral striatum contains abundant receptors for dopamine.

Alt text:

The illustration shows four magnetic resonance images of brain cross-sections. Some areas are highlighted in red and yellow, indicating that functional connectivity in these areas is greater in study participants with a history of cannabis dependence than in nondependent study participants. A colored bar in the top right of the image with a color gradient from dark red via red, orange, and yellow to white indicates a t-score from 3 (dark red) to 6 (white). The image on the left is a horizontal cross-section of the brain, with the front of the brain at the top. Red areas representing increased functional connectivity are located in the center of the image. The second image from the left is a different horizontal cross-section of the brain, also with the front of the brain at the top. In this image, a small red section indicating increased functional connectivity is located in the middle of the brain, a little bit to the right of the center. The third image from the left is a lengthwise cross-section, with the front of the brain on the right and the back of the brain on the left. In this image, red and yellow areas are located in the brain stem, at the base of the brain. The image on the right is a vertical cross-section of the brain, with a red area indicating increased functional connectivity deep in the left half of the brain, towards the midline.

Slide 6:

Caption:

The dopamine-using regions in the midbrain and ventral striatum where cannabis use was associated with increased LFC participate in networks that have been implicated in drug use (e.g., reward learning and habit formation) and/or psychiatric problems (e.g., schizophrenia).

Alt text:

The illustration shows a drawing of a lengthwise cross-section of the brain, with the front of the brain on the left and the back of the brain on the right. A large blue dot in the center of the brain indicates the location of the ventral striatum and a green dot to the right of it indicates the location of the thalamus. A smaller blue dot more towards the base of the brain indicates the location of the ventral tegmental area, and a dark brown dot next to it indicates the location of the substantia nigra. An orange oval at the base of the brain indicates the location of the brainstem.

Slide 7:

Caption:

The study also found:

  • People who began using cannabis at a younger age had higher LFC throughout the subcortex, compared with those who started later.
  • People with higher subcortical LFC showed a greater sense of alienation—an indicator of negative emotions.

Alt text:

The two graphs illustrate the association between local functional connectivity and age at first cannabis use and negative emotions. The bar chart on the left shows that earlier onset of cannabis use is associated with higher subcortical local functional connectivity (LFC). The horizontal x-axis shows five categories for age at first cannabis use; the vertical y-axis shows the subcortical LFC on a scale from 0 to 25. Study participants who began cannabis use at age 14 or younger (first bar on the left) had a LFC score of about 17; those who began cannabis use at age 15 to 17 (second bar) had a subcortical LFC score of about 14; those who initiated cannabis use at age 18 to 20 (third bar) had a subcortical LFC score of about 13; those who began cannabis use at age 21 or later (fourth bar) had a subcortical LFC score of about 10, as had those who never used cannabis (right bar). The difference between the groups was statistically significant as indicated by the horizontal line with two asterisks above the bar.

The graph on the right illustrates that greater subcortical LFC was associated with higher scores for negative emotions. The horizontal x-axis shows the alienation score (z-score) on a scale from -2 to +4 as an indicator of negative emotions. The vertical y-axis shows the subcortical LFC score on a scale from 0 to 30. Red dots indicate the results from individual cannabis-dependent study participants, and black dots indicate the results from individual nondependent participants. A red line indicates the slope representing the association between LFC and alienation score for cannabis-dependent participants, and a black line indicates the slope for the same association for nondependent participants. For cannabis-dependent participants, the alienation score of -2 was associated with an LFC score of about 10 and an alienation score of +2 was associated with an LFC score of about 20. For the nondependent participants, an alienation score of -2 was associated with an LFC score of about 10 and a score of +2 was associated with an LFC score of about 9.

Slide 8:

Caption:

The researchers concluded that:

  • Cannabis dependence is associated with altered local functional connectivity in key signaling pathways.
  • Earlier onset of cannabis use is associated with greater changes in connectivity.
  • Altered functional connectivity in these regions may provide a useful marker for tracking psychopathology associated with cannabis dependence.

Dr. Manza cautions that the data cannot determine if these brain changes preceded cannabis use, possibly increasing the risk for cannabis dependence, or if they resulted from cannabis dependence. Longitudinal studies such as the Adolescent Brain and Cognitive Development (ABCD) Study have potential to shed more light on these relationships.

Alt text:

The top illustration shows an image of a physician in a white lab coat sitting at a desk in an office and looking at a computer screen with three rows of brain scans.

The bottom illustration shows a tired- or sad-looking young man in a white shirt sitting on the steps in a stairwell with his arms folded on his knees and his head resting on his arms.

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This page was last updated May 2019

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