Skip to main content

Advertisement

Log in

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

  • Original Investigation
  • Published:
Psychopharmacology Aims and scope Submit manuscript

Abstract

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.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  • Aghajanian GK (1982) Central noradrenergic neurons: A locus for the functional interplay between alpha-2 adrenoceptors and opiate receptors. J Clin Psychiatry 43:20–24

    PubMed  CAS  Google Scholar 

  • Carroll KM, Ball SA, Nich C, O’Connor PG, Eagan DA, Frankforter TL et al (2001) Targeting behavioral therapies to enhance naltrexone treatment of opioid dependence. AMA Arch Gen Psychiatry 58:755–761

    Article  CAS  Google Scholar 

  • Charney DS, Sternberg DE, Kleber HD, Heninger GR, Redmond D (1981) The clinical use of clonidine in abrupt withdrawal from methadone: effects on blood pressure and specific signs and symptoms. AMA Arch Gen Psychiatry 38:1273–1277

    CAS  Google Scholar 

  • Fiellin DA, O’Connor PG (2002) Office-based treatment of opioid dependent patients. N Engl J Med 347(11):817–823

    Article  PubMed  Google Scholar 

  • Herman B, O’Brien C (1997) Clinical medications development for opiate addiction: focus on nonopioids and opioid antagonists for the amelioration of opiate withdrawal symptoms and relapse prevention. Semin Neurosci 9:158–172

    Article  CAS  Google Scholar 

  • Highfield D, Yap J, Grimm JW, Shalev U, Shaham Y (2001) Repeated lofexidine treatment attenuates stress-induced but not drug cues-induced reinstatement of a heroin-cocaine mixture (speedball) seeking in rats. Neuropsychopharmacology 25:320–331

    Article  PubMed  CAS  Google Scholar 

  • Izard C (1972) Patterns of emotions: a new analysis of anxiety and depression. Academic, New York

    Google Scholar 

  • Kleber HD (1999) Opiods: detoxification. In: Galanter M, Kleber H (eds) Textbook of substance abuse treatment, 2nd edn. American Psychiatric Press, Washington, DC, pp 251–270

    Google Scholar 

  • Krantz MJ, Mehler PS (2004) Treating opioid dependence: growing implications for primary care. Arch Intern Med 164:277–288

    Article  PubMed  CAS  Google Scholar 

  • Littell R, Milliken G, Strout W, Wolfinger R (1996) SAS system for mixed models. SAS Institute, Cary, NC

    Google Scholar 

  • National Center on Addiction and Substance (2005) Under the counter: the diversion and abuse of controlled prescription drugs in the U.S. The National Center on Addiction and Substance Abuse at Columbia University, July 2005

  • O’Brien CP, Childress AR, Ehrman RN, Robbins SJ (1998) Conditioning factors in drug abuse: can they explain compulsion? J Psychopharmacol 12:15–22

    PubMed  CAS  Google Scholar 

  • Rounsaville B (1995) Can psychotherapy rescue naltrexone treatment of opioid addiction? In Onken L, Blaine J (eds) Potentiating the efficacy of medications: integrating psychosocial therapies with pharmacotherapies in the treatment of drug dependence. NIDA research monograph series number 105, NIH Publication No. 95-3899, National Institute on Drug Abuse, Rockville, MD, pp 37–52

  • SAMHSA (2004) National household survey on drug abuse. Office of Applied Studies

  • Shaham Y, Stewart J (1995) Stress reinstates heroin-seeking in drug-free animals: an effect mimicking heroin, not withdrawal. Psychopharmacology (Berl) 119:334–341

    Article  CAS  Google Scholar 

  • Shaham Y, Stewart J (1996) Effects of opioid and dopamine receptor antagonists on relapse induced by stress and re-exposure to heroin in rats. Psychopharmacology (Berl) 125:385–391

    Article  CAS  Google Scholar 

  • Shaham Y, Highfield D, Delfs J, Leung S, Stewart J (2000) Clonidine blocks stress-induced reinstatement of heroin seeking in rats: An effect independent of locus coeruleus noradrenergic neurons. Eur J Neurosci 12:292–302

    Article  PubMed  CAS  Google Scholar 

  • Shaham Y, Shalev U, Lu L, de Wit H, Stewart J (2003) The reinstatement model of drug relapse: history, methodology and major findings. Psychopharmacology (Berl) 168:3–20

    Article  CAS  Google Scholar 

  • Shearman GT, Lal H, Ursillo RC (1980) Effectiveness of lofexidine in blocking morphine-withdrawal signs in the rat. Pharmacol Biochem Behav 12:573–575

    Article  PubMed  CAS  Google Scholar 

  • Shiekhattar R, Aston-Jones G (1993) Modulation of opiate responses in brain noradrenergic neurons by the cyclic AMP cascade: changes with chronic morphine. Neuroscience 57:879–885

    Article  PubMed  CAS  Google Scholar 

  • Sinha R (2001) How does stress increase risk of drug abuse and relapse? Psychopharmacology (Berl) 158:343–359

    Article  CAS  Google Scholar 

  • Sinha R, Fuse T, Aubin LR, O’Malley SS (2000) Psychological stress, drug-related cues and cocaine craving. Psychopharmacology (Berl) 152:140–148

    Article  CAS  Google Scholar 

  • Sinha R, Garcia M, Paliwal P, Kreek MJ, Rounsaville BJ (2006) Stress-induced cocaine craving and hypothalamic–pituitary–adrenal responses are predictive of cocaine relapse outcomes. AMA Arch Gen Psychiatry 63:324–331

    Article  Google Scholar 

  • Sinha R, Talih M, Malison R, Anderson GA, Cooney N, Kreek M (2003) Hypothalamic–pituitary–adrenal axis and sympatho-adreno-medullary responses during stress-induced and drug cue-induced cocaine craving states. Psychopharmacology (Berl) 170:62–72

    Article  CAS  Google Scholar 

  • Washton AM, Resnick RB, Geyer G (1983) Opiate withdrawal using lofexidine, a clonidine analogue with fewer side effects. J Clin Psychiatry 44:335–337

    PubMed  CAS  Google Scholar 

  • Weiss F (2005) Neurobiology of craving, conditioned reward and relapse. Curr Opin Pharmacol 5:9–19

    Article  PubMed  CAS  Google Scholar 

  • Zacny J, Bigelow G, Compton P, Foley K, Iguch M, Sannerud C (2003) College on problems of drug dependence taskforce on prescription opioid non-medical use and abuse: position statement. Drug Alcohol Depend 69:215–232

    Article  PubMed  Google Scholar 

Download references

Acknowledgements

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.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rajita Sinha.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sinha, R., Kimmerling, A., Doebrick, C. et al. Effects of lofexidine on stress-induced and cue-induced opioid craving and opioid abstinence rates: preliminary findings. Psychopharmacology 190, 569–574 (2007). https://doi.org/10.1007/s00213-006-0640-8

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00213-006-0640-8

Keywords

Navigation