Cannabis abstinence during treatment and one-year follow-up: relationship to neural activity in men

Abstract

Cannabis is among the most frequently abused substances in the United States. Cognitive control is a contributory factor in the maintenance of substance-use disorders and may relate to treatment response. Therefore, we assessed whether cognitive-control-related neural activity before treatment differs between treatment-seeking cannabis-dependent and healthy individuals and relates to cannabis-abstinence measures during treatment and 1-year follow-up. Cannabis-dependent males (N=20) completed a functional magnetic resonance imaging (fMRI) cognitive-control (Stroop) task before a 12-week randomized controlled trial of cognitive-behavioral therapy and/or contingency management. A healthy-comparison group (N=20) also completed the fMRI task. Cannabis use was assessed by urine toxicology and self-report during treatment, and by self-report across a 1-year follow-up period (N=18). The cannabis-dependent group displayed diminished Stroop-related neural activity relative to the healthy-comparison group in multiple regions, including those strongly implicated in cognitive-control and addiction-related processes (eg, dorsolateral prefrontal cortex and ventral striatum). The groups did not differ significantly in response times (cannabis-dependent, N=12; healthy-comparison, N=14). Within the cannabis-dependent group, greater Stroop-related activity in regions including the dorsal anterior cingulate cortex was associated with less cannabis use during treatment. Greater activity in regions including the ventral striatum was associated with less cannabis use during 1-year posttreatment follow-up. These data suggest that lower cognitive-control-related neural activity in classic 'control' regions (eg, dorsolateral prefrontal cortex and dorsal anterior cingulate) and classic 'salience/reward/learning' regions (eg, ventral striatum) differentiates cannabis-dependent individuals from healthy individuals and relates to less abstinence within-treatment and during long-term follow-up. Clinically, results suggest that treatment development efforts that focus on enhancing cognitive control in addition to abstinence may improve treatment outcomes in cannabis dependence.

Figure 1

Differences in Stroop-related neural activity between cannabis-dependent and healthy-comparison individuals. Between-group differences in Stroop-related neural activity were computed as: healthy comparison (incongruent > congruent)>cannabis dependent (incongruent>congruent). Bar graphs represent the extracted cluster-averaged percent signal change from incongruent and congruent trials (±SEM). Results are family-wise-error corrected (FWE) at p<0.05. Left side of the brain is displayed on the left; N=40. Comparison subjects exhibited greater Stroop-related neural activity than cannabis-dependent subjects in regions of right dorsolateral prefrontal cortex (dlPFC), including middle frontal gyrus (MFG) and precentral gyrus; right dorsal prefrontal cortex (dPFC)/superior frontal gyrus (SFG) and left dlPFC/MFG; ventral striatum (VS), dorsal striatum (DS), thalamus, and midbrain. HC, healthy comparison; CD, cannabis dependent.

Figure 2

Pretreatment Stroop-related neural activity correlated with three within-treatment abstinence measures in cannabis-dependent individuals. Robust correlations were computed between Stroop-related neural activity (incongruent > congruent) and three different measures of within-treatment abstinence within the cannabis-dependent group (N=20). Regions of overlap are shown at a conjunction threshold of p<0.000125, with a cluster threshold of 20 3 × 3 × 3 mm voxels. Scatter plots represent the extracted cluster-averaged percent signal change from Stroop-effect (incongruent > congruent) contrast in overlap region of dorsal anterior cingulate cortex (dACC) identified in the conjunction. Left side of the brain is displayed on the left. Three variables, including maximum consecutive days of self-reported cannabis abstinence during treatment (max days abstinent), percent of days of self-reported cannabis abstinence during treatment (% days abstinent), and percent of cannabis-negative urines during treatment (% negative urine) were all correlated with Stroop-related neural activity in the dorsal anterior cingulate (cluster average R²=0.37, 0.30 and 0.42, respectively).

Figure 3

Pretreatment Stroop-related neural activity correlates with abstinence during 1-year follow-up in cannabis-dependent individuals. Robust correlations were computed between Stroop-related neural activity (incongruent > congruent) and percent of days of self-reported abstinence during 1-year posttreatment follow-up period within cannabis-dependent individuals with available follow-up data (N=18). Results are family-wise-error corrected (FWE) at p<0.05. Scatter plots represent the extracted cluster-averaged percent signal change from Stroop-effect (incongruent > congruent) contrast. Left side of the brain is displayed on the left. Stroop-related neural activity in ventral striatum correlated positively with abstinence rates during 1-year follow-up (cluster average R²=0.39). A similar relationship was seen in superior temporal gyrus (STG)/inferior frontal/lateral orbitofrontal gyrus (cluster average R²=0.79). Conversely, Stroop-related neural activity in insula/putamen negatively correlated with abstinence during 1-year follow-up (cluster average R²=0.61).