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
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
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