Impaired cognitive performance under psychosocial stress in cannabis-dependent men is associated with attenuated precuneus activity

Abstract

Background: Deficient regulation of stress plays an important role in the escalation of substance use, addiction and relapse. Accumulating evidence suggests dysregulations in cognitive and reward-related processes and the underlying neural circuitry in cannabis dependence. However, despite the important regulatory role of the endocannabinoid system in the stress response, associations between chronic cannabis use and altered stress processing at the neural level have not been systematically examined.

Methods: Against this background, the present functional MRI study examined psychosocial stress processing in cannabis-dependent men (n = 28) and matched controls (n = 23) using an established stress-induction paradigm (Montreal Imaging Stress Task) that combines computerized (adaptive) mental arithmetic challenges with social evaluative threat.

Results: During psychosocial stress exposure, but not the no-stress condition, cannabis users demonstrated impaired performance relative to controls. In contrast, levels of experienced stress and cardiovascular stress responsivity did not differ from controls. Functional MRI data revealed that stress-induced performance deteriorations in cannabis users was accompanied by decreased precuneus activity and increased connectivity of this region with the superior frontal gyrus.

Limitations: Only male cannabis-dependent users were examined; the generalizability in female users remains to be determined.

Conclusion: Together, the present findings provide first evidence for exaggerated stress-induced cognitive performance deteriorations in cannabis users. The neural data suggest that deficient stress-related recruitment of the precuneus may be associated with the deterioration of performance at the behavioural level.

Fig. 1

(A) Cannabis craving assessed before and after stress induction. (B) Performance accuracy during the no-stress and stress conditions. Error bars reflect the standard error of the mean. *p < 0.05.

Fig. 2

Stress-related network in (A) the entire sample and (B) differences between cannabis users and controls, showing that cannabis users exhibited decreased precuneus activity during psychosocial stress. Extracted parameter estimates from the precuneus for the contrasts (C) stress > no stress and (D) no stress v. baseline, stress v. baseline further revealed that the effect was driven by lower activity during the stress condition. Image (A) is thresholded at p_FWE < 0.05. Image (B) is thresholded at p_FWE,SVC < 0.05. Error bars reflect the standard error of the mean. *p < 0.05; **p < 0.01; #p = 0.09. FWE = family-wise error; L = left; R = right; SVC = small volume correction.

Fig. 3

Cannabis users exhibited increased functional connectivity between the precuneus (seed region) and the superior frontal gyrus during stress. (A) Location of the precuneus–superior frontal gyrus (SFG) pathway that exhibited group differences. (B) Extracted connectivity estimates from the pathway for the contrast (stress > no stress). Image is thresholded at p < 0.001, uncorrected. Error bars reflect the standard error of the mean. **p < 0.01. L = left; R = right.