Impact of acute guanfacine administration on stress and cue reactivity in cocaine-dependent individuals

Abstract

Background: Stress and drug-paired cues increase drug craving and noradrenergic activity in cocaine-dependent individuals. Thus, medications that attenuate noradrenergic activity may be effective therapeutic treatment options for cocaine-dependent individuals. Objectives: To examine the impact of acute administration of the α2 adrenergic receptor agonist guanfacine on responses to multiple risk factors for relapse in cocaine-dependent individuals. Methods: In a double-blind, placebo-controlled study, cocaine-dependent individuals (n = 84), were randomized to receive either 2 mg guanfacine (n = 50) or placebo (n = 34). Within each treatment arm, subjects were randomized to either a stress (guanfacine n = 26; placebo n = 15) or a no-stress (guanfacine n = 24; placebo n = 19) group. Participants in the stress group performed the Trier Social Stress Test. Subjects in each group were exposed to a neutral cue and then to cocaine-related cues. Plasma cortisol and subjective responses were compared between the four groups. Results: The no-stress guanfacine group reported greater craving in response to cocaine cues as compared to the neutral cue (p < 0.001). The guanfacine stress group reported greater subjective stress at the neutral cue than at baseline (p = 0.032). The cocaine cue increased subjective stress in the guanfacine (p < 0.001) no-stress group. There were no effects of guanfacine on cortisol levels in either the stress or no stress groups (all p > 0.70). Conclusion: This study found no effects of a single 2 mg dose of guanfacine on reactivity to stress and cues alone or on the interaction of stress and drug cues. In cocaine-dependent individuals an acute 2 mg dose of guanfacine may not be an effective therapeutic treatment strategy.

• Cocaine
• cocaine cues
• guanfacine
• stress

Acknowledgements

This work was supported by National Institutes of Health; National Institute on Drug Abuse (R01DA021690), National Institute of Child Health and Human Development K12HD055885, National Center for Advancing Translational Sciences (UL1TR000062).

Declaration of interest

Authors Moran-Santa Maria, Baker and Ramakrishnan declare no conflicts of interest. Kathleen Brady lists: Consultant AstraZeneca Pharmaceuticals Aimee McRae lists: Forest Pharmaceuticals medication provided for separate NIH grant. The authors alone are responsible for the content and writing of this paper.