1. Cue-induced cocaine craving enhances psychosocial stress and vice versa in chronic cocaine users

Both stress and craving contribute to the development, maintenance, and relapse in cocaine use disorder. Previous research has shown altered physiological responses to psychosocial stress and increased vegetative responding to substance-related cues in chronic cocaine users. However, how psychosocial stress and cue-induced craving interact in relation to the physiological response of cocaine users is largely unknown.

We investigated the interaction between acute psychosocial stress and cocaine cue-related reactivity in 47 cocaine users and 38 substance-naïve controls. Participants were randomly exposed to both a video-based cocaine-cue paradigm and the Trier Social Stress Test (TSST) in a crossed and balanced order to investigate possible mutually augmenting effects of both stressors on the physiological stress response. Plasma cortisol, ACTH, noradrenaline, subjective stress and craving were assessed repeatedly over the course of the experimental procedure. Growth models and discontinuous growth models were used to estimate the responses during the stress challenges.

Overall, groups did not differ in their endocrinological responses to the TSST and the TSST did not elevate craving in cocaine users. However, if the cocaine-cue video was shown first, cocaine users displayed an enhanced cortisol response to the subsequent TSST. Cocaine-cues robustly evoked craving in cocaine users but no stress response, while cue-induced craving was intensified after the TSST.

Cocaine users did not show an altered acute stress response during the TSST per se but stress and craving together seem to have mutually augmenting effects on their stress response, which might contribute to continued relapse vulnerability. Their interactions should therefore be targeted in new treatment approaches.

Disclosure of interest statement: This research was funded by a grant from the Swiss National Science Foundation (grant number: 105319_162639) and by a grant from the Coordination for the Improvement of Higher Education Personnel, CAPES, Brazil (grant number: 99999.001968/2015-07). No pharmaceutical grants were received in the development of this study.