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Clonidine blocks stress-induced craving in cocaine users.

ABSTRACT: RATIONALE:Reactivity to stressors and environmental cues, a putative cause of relapse in addiction, may be a useful target for relapse-prevention medication. In rodents, alpha-2 adrenergic agonists such as clonidine block stress-induced reinstatement of drug seeking, but not drug cue-induced reinstatement. OBJECTIVE:The objective of this study is to test the effect of clonidine on stress- and cue-induced craving in human cocaine users. METHODS:Healthy, non-treatment-seeking cocaine users (n?=?59) were randomly assigned to three groups receiving clonidine 0, 0.1, or 0.2 mg orally under double-blind conditions. In a single test session, each participant received clonidine or placebo followed 3 h later by exposure to two pairs of standardized auditory-imagery scripts (neutral/stress and neutral/drug). Subjective measures of craving were collected. RESULTS:Subjective responsivity ("crave cocaine" Visual Analog Scale) to stress scripts was significantly attenuated in the 0.1- and 0.2-mg clonidine groups; for drug-cue scripts, this attenuation occurred only in the 0.2-mg group. Other subjective measures of craving showed similar patterns of effects but Dose × Script interactions were not significant. CONCLUSIONS:Clonidine was effective in reducing stress-induced (and, at a higher dose, cue-induced) craving in a pattern consistent with preclinical findings, although this was significant on only one of several measures. Our results, though modest and preliminary, converge with other evidence to suggest that alpha-2 adrenergic agonists may help prevent relapse in drug abusers experiencing stress or situations that remind them of drug use.

SUBMITTER: Jobes ML

PROVIDER: S-EPMC3401928 | biostudies-literature | 2011 Nov

REPOSITORIES: biostudies-literature

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Clonidine blocks stress-induced craving in cocaine users.

Jobes Michelle L ML Ghitza Udi E UE Epstein David H DH Phillips Karran A KA Heishman Stephen J SJ Preston Kenzie L KL

Psychopharmacology 20110312 1

<h4>Rationale</h4>Reactivity to stressors and environmental cues, a putative cause of relapse in addiction, may be a useful target for relapse-prevention medication. In rodents, alpha-2 adrenergic agonists such as clonidine block stress-induced reinstatement of drug seeking, but not drug cue-induced reinstatement.<h4>Objective</h4>The objective of this study is to test the effect of clonidine on stress- and cue-induced craving in human cocaine users.<h4>Methods</h4>Healthy, non-treatment-seeking ...[more]

PMID: 21399902

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Project description:BackgroundPrenatal cocaine exposure (PCE) is associated with increased rates of illicit-substance use during adolescence. In addition, both PCE and illicit-substance use are associated with alterations in cortico-striato-limbic neurocircuitry, development of which is ongoing throughout adolescence. However, the relationship between illicit-substance use, PCE and functional neural responses has not previously been assessed concurrently.MethodsSixty-eight adolescents were recruited from an ongoing longitudinal study of childhood and adolescent development. All participants had been followed since birth. Functional magnetic resonance imaging (fMRI) data were acquired during presentation of personalized stressful, favorite-food and neutral/relaxing imagery scripts and compared between 46 PCE and 22 non-prenatally-drug-exposed (NDE) adolescents with and without lifetime illicit-substance use initiation. Data were analyzed using multi-level ANOVAs (pFWE<.05).ResultsThere was a significant three-way interaction between illicit-substance use, PCE status and cue condition on neural responses within primarily cortical brain regions, including regions of the left and right insula. Among PCE versus NDE adolescents, illicit-substance use was associated with decreased subcortical and increased cortical activity during the favorite-food condition, whereas the opposite pattern of activation was observed during the neutral/relaxing condition. Among PCE versus NDE adolescents, illicit-substance use during stress processing was associated with decreased activity in cortical and subcortical regions including amygdala, hippocampus and prefrontal cortex. Neural activity within cortico-striato-limbic regions was significantly negatively associated with subjective ratings of anxiety and craving among illicit-substance users, but not among non-users.ConclusionsThese findings suggest different neural substrates of experimentation with illicit drugs between adolescents with and without in utero cocaine exposure.

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Clonidine blocks stress-induced craving in cocaine users.

Publications

Clonidine blocks stress-induced craving in cocaine users.

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