A recent study found that people with cannabis dependence have changes in neural circuitry in brain regions related to habit formation, reward, and psychopathology. For more information, please visit the NIDA Notes website: https://www.drugabuse.gov/news-events/nida-notes You can view NIDA's Comment Policy here: https://www.drugabuse.gov/comment-policy

1. DRUGABUSE.GOV
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.
Cannabis Dependence Is Associated With Changes in
Neural Circuitry That May Contribute to Psychopathology

2. DRUGABUSE.GOV
People with cannabis use often
show psychiatric symptoms, such as:
• Lack of motivation
• Negative thoughts or feelings
• Increased risk of psychosis
(e.g., schizophrenia)
Cannabis Use Can Lead to Psychiatric Symptoms

3. DRUGABUSE.GOV
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.
Functional Connectivity Maps Coordination Among Neurons
Adapted from Manza et al. 2018. Permission
for use of data provided by Dr. P. Manza.

4. DRUGABUSE.GOV
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.
LFC Is Assessed With Functional Magnetic Resonance Imaging (fMRI)
Adapted from Manza et al. 2018. Permission for use of data provided by Dr. P. Manza.

5. DRUGABUSE.GOV
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.
Cannabis Dependence Was Associated With Increased LFC
in Dopamine-Using Brain Regions
Adapted from Manza et al. 2018. Permission for use of data provided by Dr. P. Manza.

6. DRUGABUSE.GOV
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).
Roles of Brain Regions With Increased LFC
Ventral striatum
Thalamus
Substantia
nigra
Ventral
tegmental
area
Brainstem

7. DRUGABUSE.GOV
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.
Adapted from Manza et al. 2018. Permission for use of data provided by Dr. P. Manza.
Earlier Age of Onset of Cannabis Use Was Associated With Greater LFC and
Negative Emotions

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