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

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.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.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.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).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.