Modeling stress and drug craving in the laboratory: implications for addiction treatment development

Abstract

Addition is a chronic relapsing illness affected by multiple social, individual and biological factors that significantly impact course and recovery of the illness. Stress interacts with these factors and increases addiction vulnerability and relapse risk, thereby playing a significant role in the course of the illness. This paper reviews our efforts in developing and validating laboratory models of stress and drug cue-related provocation to assess stress responses and stress-related adaptation in addicted individuals compared with healthy controls. Empirical findings from human laboratory and brain imaging studies are presented to show the specific stress-related dysregulation that accompanies the drug-craving state in addicted individuals. In order to adequately validate our laboratory model, we have also carefully examined relapse susceptibility in the addicted individuals and these data are reviewed. The overarching goal of these efforts is to develop a valid laboratory model to identify the stress-related pathophysiology in addiction with specific regard to persistent craving and compulsive seeking. Finally, the significant implications of these findings for the development of novel treatment interventions that target stress processes and drug craving to improve addiction relapse outcomes are discussed.

Figures

Figure 1

Mean and standard errors for peak drug craving and anxiety ratings during exposure to stress, drug cues and neutral imagery conditions in separate groups of alcoholic, cocaine- and opioid-dependent individuals and healthy social drinkers combined across three studies (Hyman et al. 2007; Fox et al. 2008; Sinha et al. 2008). (a) Peak craving during stress and drug-cue conditions is significantly higher in abstinent alcoholics, cocaine- and naltrexone-treated opioid patients compared with social drinkers (P < 0.0001 for both conditions). (b) Peak anxiety ratings are significantly higher in abstinent alcoholics, cocaine- and naltrexone-treated opioid patients compared with social drinkers in both stress and drug-cue conditions (stress: P < 0.005; drug cue: P < 0.0001)

Figure 2

Mean and standard errors for (a) basal heart rate measured at baseline prior to imagery exposure over several timepoints across three separate days of experimental testing in alcoholic (AD) and cocaine (COC) patients compared with social drinkers (SD) (AD > COC > SD, P < 0.01); and (b) basal salivary cortisol averaged for two baseline assessments across three separate testing days (AD > SD, P < 0.01; COC > SD, P < 0.11); (c) peak heart rate responses in the stress (S), drug cue (D) and neutral (N) conditions: SD group shows S > N, P < 0.0001; D > N, P < 0.02; S > D, P < 0.04), whereas AD group only shows increases response in D > N, P < 0.01; and no differences between conditions in the COC group; (d): average salivary cortisol responses to stress (S), drug cue (D) and neutral (N) conditions: SD group shows S > N, P < 0.05,AD group shows D > N, P < 0.05, and COC group shows no differences between groups in responses (combined data averaged from Fox et al. 2008; Sinha et al. 2008)