Journal of Medical Toxicology

, Volume 12, Issue 1, pp 71–75 | Cite as

Naltrexone: Not Just for Opioids Anymore



Naltrexone is a semi-synthetic opioid with competitive antagonist activity at mu opioid receptors. Its efficacy has been demonstrated in the treatment of alcohol and opioid dependence, but adherence to daily dosing has been recognized as a factor limiting long-term effectiveness. Recently, a long-acting injectable formulation of naltrexone has received FDA-approval for treating alcohol and opioid dependence. This article reviews the pharmacology of naltrexone, the current evidence supporting the use of extended-release naltrexone, and the clinical challenges in the induction of patients to this medication.


Naltrexone Addiction Toxicology Alcohol dependence Opioid dependence 


  1. 1.
    Substance Abuse and Mental Health Services Administration. Results from the 2013 National Survey on Drug Use and Health: Summary of National Findings. Rockville, MD 2014.Google Scholar
  2. 2.
    Roerecke M, Rehm J. Alcohol use disorders and mortality: a systematic review and meta-analysis. Addiction. 2013;108(9):1562–78.CrossRefPubMedGoogle Scholar
  3. 3.
    Knudsen HK, Abraham AJ, Roman PM. Adoption and implementation of medications in addiction treatment programs. J Addiction Med. 2011;5(1):21–7.CrossRefGoogle Scholar
  4. 4.
    Wentland MP, Lou R, Lu Q, Bu Y, Denhardt C, Jin J, et al. Syntheses of novel high affinity ligands for opioid receptors. Bioorg Med Chem Lett. 2009;19(8):2289–94.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Weerts EM, Kim YK, Wand GS, Dannals RF, Lee JS, Frost JJ, et al. Differences in delta- and mu-opioid receptor blockade measured by positron emission tomography in naltrexone-treated recently abstinent alcohol-dependent subjects. Neuropsychopharmacol Off Pub Am College of Neuropsychopharmacol. 2008;33(3):653–65.CrossRefGoogle Scholar
  6. 6.
    Wall ME, Brine DR, Perez-Reyes M. The metabolism of naltrexone in man. NIDA Res Monogr. 1981;28:105–31.PubMedGoogle Scholar
  7. 7.
    Altshuler HL, Phillips PE, Feinhandler DA. Alteration of ethanol self-administration by naltrexone. Life Sci. 1980;26(9):679–88.CrossRefPubMedGoogle Scholar
  8. 8.
    Samson HH, Doyle TF. Oral ethanol self-administration in the rat: effect of naloxone. Pharmacol Biochem Behav. 1985;22(1):91–9.CrossRefPubMedGoogle Scholar
  9. 9.
    Volpicelli JR, Alterman AI, Hayashida M, O’Brien CP. Naltrexone in the treatment of alcohol dependence. Arch Gen Psychiatry. 1992;49(11):876–80.CrossRefPubMedGoogle Scholar
  10. 10.
    O’Malley SS, Jaffe AJ, Chang G, Schottenfeld RS, Meyer RE, Rounsaville B. Naltrexone and coping skills therapy for alcohol dependence. A controlled study. Arch Gen Psychiatry. 1992;49(11):881–7.CrossRefPubMedGoogle Scholar
  11. 11.
    Unterwald EM. Naltrexone in the treatment of alcohol dependence. J Addiction Med. 2008;2(3):121–7.CrossRefGoogle Scholar
  12. 12.
    Ray LA, Bujarski S, Chin PF, Miotto K. Pharmacogenetics of naltrexone in asian americans: a randomized placebo-controlled laboratory study. Neuropsychopharmacol Off Pub Am College of Neuropsychopharmacol. 2012;37(2):445–55.CrossRefGoogle Scholar
  13. 13.
    Oslin DW, Leong SH, Lynch KG, Berrettini W, O’Brien CP, Gordon AJ, et al. Naltrexone vs placebo for the treatment of alcohol dependence: a randomized clinical trial. JAMA Psychiat. 2015. doi:10.1001/jamapsychiatry.2014.3053.Google Scholar
  14. 14.
    Swift R, Oslin DW, Alexander M, Forman R. Adherence monitoring in naltrexone pharmacotherapy trials: a systematic review. J Stud Alcohol Drugs. 2011;72(6):1012–8.CrossRefPubMedGoogle Scholar
  15. 15.
    Gastfriend DR. Intramuscular extended-release naltrexone: current evidence. Ann N Y Acad Sci. 2011;1216:144–66.CrossRefPubMedGoogle Scholar
  16. 16.
    Dunbar JL, Turncliff RZ, Dong Q, Silverman BL, Ehrich EW, Lasseter KC. Single- and multiple-dose pharmacokinetics of long-acting injectable naltrexone. Alcohol Clin Exp Res. 2006;30(3):480–90.CrossRefPubMedGoogle Scholar
  17. 17.
    Garbutt JC. Efficacy and tolerability of long-acting injectable naltrexone for alcohol dependence. JAMA J Am Med Assoc. 2005;293(13):1617–28.CrossRefGoogle Scholar
  18. 18.
    Pettinati HM, Gastfriend DR, Dong Q, Kranzler HR, O’Malley SS. Effect of extended-release naltrexone (XR-NTX) on quality of life in alcohol-dependent patients. Alcohol Clin Exp Res. 2009;33(2):350–6.CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Lukas SE, Lowen SB, Lindsey KP, Conn N, Tartarini W, Rodolico J, et al. Extended-release naltrexone (XR-NTX) attenuates brain responses to alcohol cues in alcohol-dependent volunteers: a bold FMRI study. Neuroimage. 2013;78:176–85.CrossRefPubMedGoogle Scholar
  20. 20.
    Krupitsky E, Nunes EV, Ling W, Illeperuma A, Gastfriend DR, Silverman BL. Injectable extended-release naltrexone for opioid dependence: a double-blind, placebo-controlled, multicentre randomised trial. Lancet. 2011;377(9776):1506–13. doi:10.1016/s0140-6736(11)60358-9.CrossRefPubMedGoogle Scholar
  21. 21.
    Krupitsky E, Nunes EV, Ling W, Gastfriend DR, Memisoglu A, Silverman BL. Injectable extended-release naltrexone (XR-NTX) for opioid dependence: long-term safety and effectiveness. Addiction. 2013;108(9):1628–37.CrossRefPubMedGoogle Scholar
  22. 22.
    Langleben DD, Ruparel K, Elman I, Loughead JW, Busch EL, Cornish J, et al. Extended-release naltrexone modulates brain response to drug cues in abstinent heroin-dependent patients. Addict Biol. 2014;19(2):262–71.CrossRefPubMedGoogle Scholar
  23. 23.
    Mitchell MC, Memisoglu A, Silverman BL. Hepatic safety of injectable extended-release naltrexone in patients with chronic hepatitis C and HIV infection. J Stud Alcohol Drugs. 2012;73(6):991–7.CrossRefPubMedGoogle Scholar
  24. 24.
    Sigmon SC, Bisaga A, Nunes EV, O’Connor PG, Kosten T, Woody G. Opioid detoxification and naltrexone induction strategies: recommendations for clinical practice. Am J Drug Alcohol Abuse. 2012;38(3):187–99.CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Resnick RB, Washton AM, Thomas MA, Kestenbaum RS. Naltrexone in the treatment of opiate dependence. NIDA Res Monogr. 1978;19:321–32.PubMedGoogle Scholar
  26. 26.
    Hartung DM, McCarty D, Fu R, Wiest K, Chalk M, Gastfriend DR. Extended-release naltrexone for alcohol and opioid dependence: a meta-analysis of healthcare utilization studies. J Subst Abuse Treat. 2014.Google Scholar
  27. 27.
    Curatolo C, Trinh M. Challenges in the perioperative management of the patient receiving extended-release naltrexone. A & A Ccase Rrep. 2014;3(11):142–4.Google Scholar

Copyright information

© American College of Medical Toxicology 2015

Authors and Affiliations

  1. 1.Oregon Health and Science UniversityPhilomathUSA

Personalised recommendations