Weihua Zhao, PhD*; Kaeli Zimmermann, PhD*; Xinqi Zhou, MS; Feng Zhou, MS; Meina Fu, BS; Christian Dernbach, PhD; Dirk Scheele, PhD; Bernd Weber, PhD; Monika Eckstein, PhD; René Hurlemann, PhD; Keith M. Kendrick, PhD; Benjamin Becker, PhD
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.
Submitted Feb. 21, 2019; Revised Apr. 15, 2019; Accepted Apr. 15, 2019; Published online Sept. 11, 2019
*These authors contributed equally to this work.
Affiliations: From the Clinical Hospital of Chengdu Brain Science Institute, MOE Key Laboratory for Neuroinformation, University of Electronic Science and Technology of China, Chengdu, China (Zhao, Zhou, Zhou, Fu, Kendrick, Becker); the Department of Psychiatry and Division of Medical Psychology, University of Bonn, Bonn, Germany (Zimmermann, Dernbach, Scheele, Hurlemann); the Center for Economics and Neuroscience, Department of Epileptology, University of Bonn, Bonn, Germany (Weber); the Department of NeuroCognition, Life and Brain Center, Bonn, Germany (Weber); and the Institute of Medical Psychology, Center for Psychosocial Medicine, University Hospital, Heidelberg University, Heidelberg, Germany (Eckstein).
Funding: This work was supported by the National Natural Science Foundation of China (NSFC, 91632117; 31530032), the Fundamental Research Funds for the Central Universities of China (ZYGX2015Z002), the Sichuan Science and Technology Department (2018JY0001) and the German Research Foundation (DFG, grant: BE5465/2-1, HU1302/4-1).
Competing interests: None declared.
Contributors: K. Zimmermann, D. Scheele, B.Weber, R. Hurlemann, K. Kendrick and B. Becker designed the study. K. Zimmermann, C. Dernbach and M. Eckstein acquired the data, which W. Zhao, X. Zhou, F. Zhou and M. Fu analyzed. W. Zhao, D. Scheele and B. Becker wrote the article, which all authors reviewed. All authors approved the final version to be published and can certify that no other individuals not listed as authors have made substantial contributions to the paper.
Correspondence to: B. Becker, Center for Information in Medicine, University of Electronic Science and Technology, Chengdu 611731, China; email@example.com