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Updated: Jul 18, 2026

A Procedure to Study Stress-Induced Relapse of Heroin Seeking after Punishment-Imposed Abstinence
Published on: March 23, 2022
Effects of lofexidine on stress-induced and cue-induced opioid craving and opioid abstinence rates: preliminary
Rajita Sinha1, Anne Kimmerling, Cheryl Doebrick
1Department of Psychiatry, Yale University School of Medicine, 34 Park Street, Room S110, New Haven, CT 06519, USA. Rajita.sinha@yale.edu
Objective:
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.
Results:
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.
Conclusions:
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.
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