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Clonidine blocks stress-induced craving in cocaine users

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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.

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Acknowledgements

This research was supported by the Intramural Research Program (IRP) of the National Institute on Drug Abuse (NIDA), National Institutes of Health.

Financial disclosures

None of the authors has any relevant financial interests to declare.

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Authors and Affiliations

  1. Clinical Pharmacology and Therapeutics Research Branch, Intramural Research Program, National Institute on Drug Abuse, 251 Bayview Blvd., Suite 200, Baltimore, MD, 21224, USA

    Michelle L. Jobes, David H. Epstein, Karran A. Phillips, Stephen J. Heishman & Kenzie L. Preston

  2. Center for the Clinical Trials Network, National Institute on Drug Abuse, 6001 Executive Blvd., Room 3151, MSC 9557, Bethesda, MD, 20892–9557, USA

    Udi E. Ghitza

Authors
  1. Michelle L. Jobes
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  2. Udi E. Ghitza
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  3. David H. Epstein
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  4. Karran A. Phillips
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  5. Stephen J. Heishman
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  6. Kenzie L. Preston
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Corresponding author

Correspondence to Michelle L. Jobes.

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Principal Editor: Harriet de Wit

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Jobes, M.L., Ghitza, U.E., Epstein, D.H. et al. Clonidine blocks stress-induced craving in cocaine users. Psychopharmacology 218, 83–88 (2011). https://doi.org/10.1007/s00213-011-2230-7

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  • DOI: https://doi.org/10.1007/s00213-011-2230-7

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