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Randomized Controlled Trial
. 2012 Jul;26(7):958-72.
doi: 10.1177/0269881111430746. Epub 2012 Jan 9.

Guanfacine effects on stress, drug craving and prefrontal activation in cocaine dependent individuals: preliminary findings

Helen C Fox  1 , Dongju Seo, Keri Tuit, Julie Hansen, Anne Kimmerling, Peter T Morgan, Rajita Sinha
Affiliations
Randomized Controlled Trial

Guanfacine effects on stress, drug craving and prefrontal activation in cocaine dependent individuals: preliminary findings

Helen C Fox et al. J Psychopharmacol. 2012 Jul.

Abstract

Cocaine dependence is associated with increased stress and drug cue-induced craving and physiological arousal but decreased prefrontal activity to emotional and cognitive challenge. As these changes are associated with relapse risk, we investigated the effects of α2 receptor agonist guanfacine on these processes. Twenty-nine early abstinent treatment-seeking cocaine dependent individuals were randomly assigned to either daily placebo or guanfacine (up to 3 mg) for four weeks. In a laboratory experiment, all patients were exposed to three 10-min guided imagery conditions (stress/stress, drug cue/drug cue, stress/drug cue), one per day, consecutively in a random, counterbalanced order. Subjective craving, anxiety and arousal as well as cardiovascular output were assessed repeatedly. Brain response to stress, drug cue and relaxing imagery was also assessed during a functional magnetic resonance (fMRI) imaging session. In the current study, guanfacine was found to be safe and well-tolerated. Lower basal heart rate and blood pressure was observed in the guanfacine versus placebo group. Guanfacine lowered stress and cue-induced nicotine craving and cue-induced cocaine craving, anxiety and arousal. The guanfacine group also showed increased medial and lateral prefrontal activity following stress and drug cue exposure compared with placebo. Data suggest further exploration of guanfacine is warranted in terms of its potential for reducing stress-induced and cue-induced drug craving and arousal.

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Conflict of interest statement

Conflict of interest

The authors declare that they have no competing financial interests pertaining to the aims and results of this study.

Figures

Figure 1
Figure 1
(a) Time-line of study procedures. Lab testing days (1 to 3): one imagery condition (stress, cue, combined stress/cue) presented per day in a randomized and counterbalanced order across participants. (b) fMRI imagery presentation: comprising six five-minute trials. Six imagery trials per condition (stress – two, cue – two, neutral – two) presented across one testing session in a quasi-randomized order.
Figure 2
Figure 2
Mean and standard error (SE) for basal heart rate and systolic and diastolic blood pressure across the three laboratory testing days in placebo versus guanfacine treated cocaine dependent individuals.
Figure 3
Figure 3
Change from baseline for subjective measures in response to imagery in placebo versus guanfacine treated cocaine dependent individuals. (As no significant time-point interactions were observed, bars show data averaged across time-points; means and standard errors shown). (a) Cocaine craving; (b) nicotine craving; (c) anxiety; (d) arousal. SS: stress/stress condition, SD: stress/drug cue condition, DD: drug cue/drug cue condition. Group differences: *p ≤ 0.05, **p < 0.01
Figure 4
Figure 4
Whole brain voxel-based fMRI images showing differential activations between guanfacine versus placebo groups during drug cue and stress exposure (p < 0.05 [two-tailed], whole-brain FWE corrected). (A) Drug cue: during exposure to drug cue, the guanfacine group displayed greater activity in the left dorsolateral PFC, ventromedial PFC, lateral PFC, premotor cortex, temporal lobe, inferior occipital lobe and cerebellum compared with the placebo group. The bar graph highlights the significant group difference in brain activation in the left dorsolateral PFC, a region typically associated with working memory (means and standard error shown). (B) Stress: during exposure to stress, the guanfacine group showed increased activity in the ventrolateral PFC, dorsomedial PFC, anterior/middle cingulate gyrus, insula, putamen, superior temporal lobe and premotor cortex compared with the placebo group. The bar graph highlights the significant group difference in brain activation in the ventrolateral PFC, also associated with working memory (means and standard error shown). For the neutral condition, no differences between the two groups were found with corrections for multiple comparisons at p < 0.05. Coordinates are given in MNI space.
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