Abstract
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Context: Cannabis is the most widely used illicit drug
in the developed world. Despite this, there is a paucity
of research examining its long-term effect on the human
brain.
Objective: To determine whether long-term heavy cannabis
use is associated with gross anatomical abnormalities
in 2 cannabinoid receptor–rich regions of the brain,
the hippocampus and the amygdala.
Design: Cross-sectional design using high-resolution
(3-T) structural magnetic resonance imaging.
Setting: Participants were recruited from the general
community and underwent imaging at a hospital research
facility.
Participants: Fifteen carefully selected long-term (10
years) and heavy (5 joints daily) cannabis-using men
(mean age, 39.8 years; mean duration of regular use, 19.7
years) with no history of polydrug abuse or neurologic/
mental disorder and 16 matched nonusing control subjects
(mean age, 36.4 years).
Main Outcome Measures: Volumetric measures of
the hippocampus and the amygdala combined with measures
of cannabis use. Subthreshold psychotic symptoms
and verbal learning ability were also measured.
Results: Cannabis users had bilaterally reduced hippocampal
and amygdala volumes (P=.001), with a relatively
(and significantly [P=.02]) greater magnitude of
reduction in the former (12.0% vs 7.1%). Left hemisphere
hippocampal volume was inversely associated with
cumulative exposure to cannabis during the previous 10
years (P=.01) and subthreshold positive psychotic symptoms
(P.001). Positive symptom scores were also associatedwith
cumulative exposure to cannabis (P=.048).
Although cannabis users performed significantly worse
than controls on verbal learning (P.001), this did not
correlate with regional brain volumes in either group.
Conclusions: These results provide new evidence of exposure-
related structural abnormalities in the hippocampus
and amygdala in long-term heavy cannabis users and
corroborate similar findings in the animal literature. These
findings indicate that heavy daily cannabis use across protracted
periods exerts harmful effects on brain tissue and
mental health.