, Volume 190, Issue 4, pp 569–574 | Cite as

Effects of lofexidine on stress-induced and cue-induced opioid craving and opioid abstinence rates: preliminary findings

  • Rajita SinhaEmail author
  • Anne Kimmerling
  • Cheryl Doebrick
  • Thomas R. Kosten
Original Investigation



A preliminary study examined whether lofexidine decreases stress-induced and cue-induced opioid craving and improves opioid abstinence in naltrexone-treated opioid-dependent individuals.

Materials and methods

Eighteen opioid-dependent patients were stabilized for 4 weeks with naltrexone (50 mg daily) and lofexidine (2.4 mg bid) before entering a 4-week randomized, double-blind placebo-controlled discontinuation study where one group continued on lofexidine for an additional 4 weeks, while the second was tapered to placebo (Lofexidine–naltrexone vs Placebo–naltrexone). Ten patients also participated in guided imagery exposure to stress, drug cue, and neutral scenarios in a single laboratory session.


Lofexidine–naltrexone patients had higher opioid abstinence rates and improved relapse outcomes as compared to the Placebo–naltrexone group. Furthermore, Lofexidine–naltrexone patients had significantly lower heart rates and an attenuated stress and drug cue-induced opioid craving response in the laboratory as compared to the Placebo–naltrexone group.


Although preliminary, these findings are the first to document lofexidine’s potential in addressing stress-related opioid craving and relapse outcomes in humans. The results also suggest that combination therapies that target both drug-related reinforcement (naltrexone) and stress- and cue-related aspects of drug seeking could be beneficial in addiction relapse prevention. Further development of lofexidine to address stress-related opioid craving and relapse is warranted.


Opioid dependence Stress Drug cues Naltrexone Lofexidine Alpha-2 adrenergic agonists 



This research was supported by the National Institutes of Health grants R01-DA18219 (RS), P50-DA16556 (RS), K02-DA17232(RS), P50-DA12762 (TRK), and K05-DA0454 (TRK) to Yale University. Findings reported in this manuscript were presented at the Annual Meetings of the American College of Neuropsychopharmacology in San Juan, PR, December 15, 2005. We thank the staff of the Substance Abuse Treatment Unit of the Connecticut Mental Health Center for their support of this research. Britannia Pharmaceuticals, UK provided lofexidine and placebo tablets.


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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • Rajita Sinha
    • 1
    Email author
  • Anne Kimmerling
    • 1
  • Cheryl Doebrick
    • 1
  • Thomas R. Kosten
    • 1
  1. 1.Department of PsychiatryYale University School of MedicineNew HavenUSA

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