Medial temporal structures and memory functions in adolescents with heavy cannabis use

Abstract

Converging lines of evidence suggest an adverse effect of heavy cannabis use on adolescent brain development, particularly on the hippocampus. In this preliminary study, we compared hippocampal morphology in 14 "treatment-seeking" adolescents (aged 18-20) with a history of prior heavy cannabis use (5.8 joints/day) after an average of 6.7 months of drug abstinence, and 14 demographically matched normal controls. Participants underwent a high-resolution 3D MRI as well as cognitive testing including the California Verbal Learning Test (CVLT). Heavy-cannabis users showed significantly smaller volumes of the right (p < 0.04) and left (p < 0.02) hippocampus, but no significant differences in the amygdala region compared to controls. In controls, larger hippocampus volumes were observed to be significantly correlated with higher CVLT verbal learning and memory scores, but these relationships were not observed in cannabis users. In cannabis users, a smaller right hippocampus volume was correlated with a higher amount of cannabis use (r = -0.57, p < 0.03). These data support a hypothesis that heavy cannabis use may have an adverse effect on hippocampus development. These findings, after an average 6.7 month of supervised abstinence, lend support to a theory that cannabis use may impart long-term structural and functional damage. Alternatively, the observed hippocampal volumetric abnormalities may represent a risk factor for cannabis dependence. These data have potential significance for understanding the observed relationship between early cannabis exposure during adolescence and subsequent development of adult psychopathology reported in the literature for schizophrenia and related psychotic disorders.

Figure 1

An example of the automated extraction of the left (green) and right (red) hippocampi and left (blue) and right (yellow) amygdalae superimposed onto the brain template constructed from all 28 study participants.

Figure 2

Results for hippocampus and amygdala volumes in heavy cannabis users and controls. Significant differences were observed for hippocampus volume bilaterally, after controlling for WRAT-III and TBV separately. However, when both variables were controlled for at the same time, only the left hippocampus volume was significant (F = 4.51, p = .04) and the right hippocampus volume was significant at a trend level (F = 3.45, p = .07). No significant volumetric differences for the amygdala were found between cannabis users and controls.

Figure 3

Correlation between scaled scores of WRAT-III and total brain volume. There was a significant correlation among the normal control group but no correlations for the heavy cannabis users.

Figure 4

Correlation between the right hippocampal volume (mm³) and total number of joints smoked.

Figure 5

Correlations between the left and right hippocampus volumes and the CVLT subtests for normal controls. Note the more robust and significant correlations of the CVLT tests (verbal test) with left as opposed to the right hippocampus volume.

Figure 6

Results for the left and right hippocampus volumes and the CVLT subtests for heavy cannabis users. Note the lack of significant correlations for either the left or right hippocampus volumes with the CVLT measures among the cannabis users.