Laboratory-induced stress and craving predict opioid use during follow-up among individuals with prescription opioid use disorder

Abstract

Background: Opioid use disorder (OUD) remains a public health crisis in the USA. Although stress and craving are common precipitants of substance use, no research to date has investigated the impact of laboratory-induced stress and craving on subsequent opioid use.

Method: Participants (N = 31) were individuals with prescription OUD who completed a human laboratory study followed by a one-month follow-up visit. Participants were randomly assigned to either a stress task (i.e., Trier Social Tress Task; TSST) or a no-stress condition, and then all participants completed an opioid cue paradigm. Measures of subjective (e.g., stress, craving), and neuroendocrine (e.g., cortisol, dehydroepiandrosterone) reactivity were assessed before and after each task. Survival and regression models tested the association between reactivity to the laboratory tasks and a) time to first opioid use and b) amount of opioid use during follow-up.

Results: On average, participants first used opioids 3.65 (SD = 2.08) days following the study. Craving after the opioid cue paradigm (B = 0.44, Exp(B) = 1.55, 95 % CI [1.06, 2.28], p = .02) and after the TSST/no-stress condition plus opioid cue paradigm (B = 1.06, Exp(B) = 2.88, 95 % CI [1.70, 4.85], p < .001) predicted time to first use. Additionally, there was a significant interaction between randomization to the TSST, stress reactivity, and amount of opioids used.

Conclusions: Findings demonstrate that elevated cue-induced craving, either in the context of a stressor or not, is associated with shortened time to opioid use, whereas stress reactivity impacts the amount of opioids consumed. Preliminary findings add to the literature on stress, craving and opioid use and implicate treatment.

Keywords: Cues; Opiates; Prescription opioids; Stress; Trier.

Figure 1. Laboratory Study Design

Note: Participants in this study were randomized to the Trier Social Stress Task (TSST) or a No-Stress condition followed by all participants completing an opioid cue paradigm. Stress, craving, cortisol, heart rate, and dehydroepiandrosterone (DHEA) reactivity were measured at baseline, immediately following each task, and 15-, 30-, and 60- minutes after the opioid cue paradigm. Participants were also asked to come back into the laboratory to complete 1-week and 1-month follow-up visits. For analyses, three change scores in reactivity were calculated: (a) reactivity to the stress condition was calculated by subtracting pre-stress scores from immediate post-stress scores after the TSST/No-Stress condition (i.e., post-stress—pre-stress); (b) reactivity to the TSST/No-Stress condition and the opioid cue paradigm was calculated by subtracting pre-stress scores from peak post-test scores following the opioid cue paradigm (i.e., peak post-test—pre-stress); (c) reactivity to the opioid cue paradigm was calculated by subtracting post-stress scores from peak post-test scores following the opioid cue paradigm (i.e., peak post-test—post-stress).

Figure 2. Predicted Values from the Interaction between Stress Reactivity to the Trier Social Stress Task (TSST) or No-Stress Task and Average Amount of Prescription Opioids Used during Follow-Up

Note: This figure demonstrates the predicted values from the multiple regression model for the interaction between stress reactivity and randomization to the Trier Social Stress Task (TSST) or to the No-Stress condition with follow-up opioid use. The model outcomes show that individuals randomized to the TSST showed variation in the number of opioid pills they used at 1-month follow-up depending on their changes in stress reactivity. Following the TSST, those with a greater change in stress reactivity (+1 SD Stress Reactivity; yellow line) consumed fewer opioid pills at one month follow up whereas those with less change in stress reactivity (−1 SD Stress Reactivity, green line) used more pills at 1-month follow-up.