Cannabis cue-induced brain activation correlates with drug craving in limbic and visual salience regions: preliminary results

Abstract

Craving is a major motivator underlying drug use and relapse but the neural correlates of cannabis craving are not well understood. This study sought to determine whether visual cannabis cues increase cannabis craving and whether cue-induced craving is associated with regional brain activation in cannabis-dependent individuals. Cannabis craving was assessed in 16 cannabis-dependent adult volunteers while they viewed cannabis cues during a functional MRI (fMRI) scan. The Marijuana Craving Questionnaire was administered immediately before and after each of three cannabis cue-exposure fMRI runs. FMRI blood-oxygenation-level-dependent (BOLD) signal intensity was determined in regions activated by cannabis cues to examine the relationship of regional brain activation to cannabis craving. Craving scores increased significantly following exposure to visual cannabis cues. Visual cues activated multiple brain regions, including inferior orbital frontal cortex, posterior cingulate gyrus, parahippocampal gyrus, hippocampus, amygdala, superior temporal pole, and occipital cortex. Craving scores at baseline and at the end of all three runs were significantly correlated with brain activation during the first fMRI run only, in the limbic system (including amygdala and hippocampus) and paralimbic system (superior temporal pole), and visual regions (occipital cortex). Cannabis cues increased craving in cannabis-dependent individuals and this increase was associated with activation in the limbic, paralimbic, and visual systems during the first fMRI run, but not subsequent fMRI runs. These results suggest that these regions may mediate visually cued aspects of drug craving. This study provides preliminary evidence for the neural basis of cue-induced cannabis craving and suggests possible neural targets for interventions targeted at treating cannabis dependence.

Trial registration: ClinicalTrials.gov NCT00838448.

Keywords: Addiction; Drug abuse; Functional MRI.

© 2013 Elsevier Ireland Ltd. All rights reserved.

Figures

Figure 1. Craving score at baseline and after each cue exposure run

Data are plotted as mean ± standard error of the mean for MCQ=Marijuana Craving Questionnaire at baseline (MCQ-baseline) and after each cue-exposure run (MCQ-post run 1, MCQ-post run 2, MCQ-post run 3).

Figure 2. Brain activation during comparison of visual cannabis cues > Gaussian baseline

Both rows depict activation in response to visual cannabis cues versus baseline (activation is overlaid on sagittal, coronal, and horizontal sections of MNI single subject template). There were four clusters bilaterally in the occipital cortex including portions of calcarine, lingual, cuneus, fusiform and middle occipital gyri (Table 2). Four clusters were activated in bilateral temporal lobe, including parahippocampal gyrus, hippocampus, and amygdala. An additional confluent cluster included regions in both the occipital cortex and parahippocampal gyrus. Further clusters were present in the temporal gyrus including the superior temporal pole (left) and middle temporal gyrus (bilaterally), and in the posterior cingulate (bilaterally). In frontal cortex, activated clusters included the inferior orbitofrontal cortex (left), superior frontal gyrus (bilaterally), and medial frontal gyrus (left). Voxel threshold p=0.001, extent threshold k=30; for display, gray matter mask removed to show regional continuity. t-score color bar corresponding to activated regions is shown in figure 2. L=left side of brain for each figure.

Figure 3. Correlation of MCQ craving score with BOLD signal intensity (cannabis>Gaussian baseline) during Run 1

Scatterplots of craving score correlation with activation (BOLD signal intensity from the contrast of cannabis cues>Gaussian images) from Run 1. Rows correspond to the 5 clusters (highlighted in bold font in Table 2) that showed at least one significant correlation of marijuana craving questionnaire (MCQ) total score and BOLD signal intensity-run 1. X-axes indicate rank MCQ score from left to right as MCQ-baseline, MCQ-post run 1, MCQ-post run 2, MCQ-post run 3. Y-axes indicate rank BOLD signal intensity-run 1 extracted from each cluster. Correlations coefficients for the depicted data are shown in Table 2.

Figure 4. Brain regions activated during comparison of visual cannabis cues > nature cues

Statistical Parametric Analysis (SPM) was performed using a 1-sample t-test for all subjects across all runs with the contrast of activation during cannabis cues versus natures cues (n=16). This contrast revealed 5 clusters as shown in Table 3. Voxel threshold p=0.001, extent threshold k=30; for display, gray matter mask removed to show regional continuity. Montreal Neurological Institute (MNI) coordinates used for labeling. Color bar represents t-scores.

Figure 5. Brain regions activated during comparison of visual cannabis cues > food cues

Statistical Parametric Analysis (SPM) was performed using a 1-sample t-test for all subjects across all runs with the contrast of activation during cannabis cues versus food cues (n=16). This contrast revealed 5 clusters as shown in Table 4. Voxel threshold p=0.001, extent threshold k=30; for display, gray matter mask removed to show regional continuity. Montreal Neurological Institute (MNI) coordinates used for labeling. Color bar represents t-scores.