title: Sex differences in guanfacine effects on drug craving and stress arousal in cocaine-dependent individuals.
abstract: Currently, no FDA-approved medication exists for the treatment of cocaine use disorder. Furthermore, as women become increasingly more at risk for the consequences of cocaine addiction, the need to establish better-tailored treatment medications is paramount. We examine the effects of the alpha2 adrenergic agonist, guanfacine HCl, on responses to stress and drug cue in a group of cocaine-dependent men and women who also abuse alcohol and nicotine. Forty early abstinent treatment-seeking cocaine-dependent males and females were randomly assigned to receive either daily placebo (12 M/7 F) or guanfacine (2 or 3 mg) (15 M/6 F) for 3 weeks. In week 4, they participated in a laboratory experiment and were exposed to three 10-min guided imagery conditions (stress/stress, cue/cue, and stress/cue), one per day, consecutively in a random, counterbalanced order. Craving, negative emotion, anxiety, and cardiovascular function were assessed at baseline, immediately following imagery exposure, and at various recovery time points. Guanfacine significantly attenuated cocaine craving, alcohol craving, anxiety, and negative emotion following exposure to all three imagery conditions in females, but not males. Guanfacine did, however, reduce sympathetic tone as well as stress and cue-induced nicotine craving and systolic blood pressure (SBP) in both males and females. These findings highlight sex-specific effects of guanfacine on drug craving, anxiety, and negative mood with significant effects in women and not men. The findings suggest further evaluation of guanfacine in the treatment of cocaine use disorder with a specific focus on sex differences in treatment response.
authors.affiliation: Department of Psychiatry, The Connecticut Mental Health Center, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Helen C
authors.initials: HC
authors.lastname: Fox
authors.affiliation: Department of Psychiatry, The Connecticut Mental Health Center, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Peter T
authors.initials: PT
authors.lastname: Morgan
authors.affiliation: Department of Psychiatry, The Yale Stress Center, Yale University School of Medicine, New Haven, CT, USA.
authors.forename: Rajita
authors.initials: R
authors.lastname: Sinha
mesh_terms: D058647:Adrenergic alpha-2 Receptor Agonists / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D000339:Affect / Q000187:drug effects / Q000502:physiology; D001007:Anxiety / Q000188:drug therapy / Q000503:physiopathology; D001143:Arousal / Q000187:drug effects / Q000502:physiology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D019970:Cocaine-Related Disorders / Q000188:drug therapy* / Q000503:physiopathology* / Q000523:psychology; D003463:Cues; D004305:Dose-Response Relationship, Drug; D004644:Emotions / Q000187:drug effects / Q000502:physiology; D005260:Female; D016316:Guanfacine / Q000009:adverse effects / Q000627:therapeutic use*; D006339:Heart Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D008297:Male; D012727:Sex Characteristics; D013315:Stress, Psychological / Q000188:drug therapy* / Q000503:physiopathology*; D016896:Treatment Outcome
chemical_list: D058647:Adrenergic alpha-2 Receptor Agonists; D016316:Guanfacine