Regional brain abnormalities associated with long-term heavy cannabis use

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 associated with 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.