Canadian Journal of Anaesthesia

, Volume 50, Issue 7, pp 663–671

Ultrarapid opiate detoxification: a review

  • Alan D. Kaye
  • Clifford Gevirtz
  • Hemmo A. Bosscher
  • Joe B. Duke
  • Elizabeth A. M. Frost
  • Todd A. Richards
  • Aaron M. Fields
General Anesthesia



This review on ultrarapid detoxification examines the pharmacology, techniques, and efficacy of this potentially promising technique and contrasts it with conventional treatment modalities.


The information found here is derived from experiences at the Texas Tech University, government reports, and peer reviewed journals.

Principal findings

Incidence and prevalence of heroin use is on the rise. Social and treatment costs suggest that this problem is staggering. Approximately 400,000 patients are enrolled in or are actively seeking methadone therapy. While many of these individuals want to undergo detoxification, traditional techniques, including methadone tapering are usually unsuccessful. The withdrawal syndrome is extremely unpleasant, may be fatal, and deters patients from completing the detoxification process. Ultrarapid detoxification entails general anesthesia in conjunction with large boluses of narcotic antagonists. This combination allows the individual to completely withdraw from the opiate without suffering the discomfort of the withdrawal syndrome. Unless performed properly, this procedure can be dangerous due to the sympathetic outflow. However, with proper support, this danger can be mitigated.


Ultrarapid opiate detoxification, performed under the proper circumstances, is associated with few adverse events and is relatively comfortable for patients who seek treatment for their addition.

Désintoxication opiacée ultrarapide: une revue



La présente étude portant sur la désintoxication ultrarapide revoit la pharmacologie, les techniques et l’efficacité de cette technique potentiellement prometteuse et la compare avec les modalités thérapeutiques traditionnelles.


Nos informations sont tirées des expériences à la Texas Tech University, des rapports officiels et des journaux scientifiques. Constatations principales : L’incidence et la prévalence de l’usage d’héroïne sont en hausse. Les coûts sociaux et thérapeutiques de ce problème sont renversants. Environ 400 000 patients suivent, ou cherchent activement, un traitement à la méthadone. Beaucoup acceptent une désintoxication, mais les techniques traditionnelles, incluant l’approche dégressive avec la méthadone, sont habituellement infructueuses. Le syndrome de sevrage est très désagréable, peut être fatal et décourage les patients d’aller jusqu’au bout. La désintoxication ultrarapide nécessite une anesthésie générale conjointement avec d’importants bolus d’antagonistes narcotiques. Cette combinaison permet la suppression complète des opiacés sans subir l’inconfort du syndrome de sevrage. Si elle n’est pas réalisée correctement, cette intervention comporte un danger, lié à l’influx sympathique, danger réduit par une assistance appropriée.


La désintoxication ultrarapide aux opiacés, réalisée dans des conditions appropriées, est associée à peu d’événements indésirables et est relativement confortable pour les patients qui cherchent un traitement à leur dépendance.


  1. 1. Scholar
  2. 2.
    Zwillich T. Prescription drug abuse said to be on the rise. Reuters 2001; April 10.Google Scholar
  3. 3. ry_1171.html.Google Scholar
  4. 4. in2.html#scopeGoogle Scholar
  5. 5.
    Stafford K, Gomes AB, Shen J, Yoburn BC. mu-opioid receptor downregulation contributes to opioid tolerance in vivo. Pharmacol Biochem Behav 2001; 69: 233–7.PubMedCrossRefGoogle Scholar
  6. 6.
    Gold MS. Opiate addiction and locus coeruleus. The clinical utility of clonidine, naltrexone, methadone, and buprenorphine. Psychiatr Clin North Am 1993; 16: 61–73.PubMedGoogle Scholar
  7. 7. Scholar
  8. 8.
    Koob GF. Neurobiology of addiction. Toward the development of new therapies. Ann N Y Acad Sci 2000; 909: 170–85.PubMedGoogle Scholar
  9. 9.
    Spanagel R. Is there a pharmacological basis for therapy with rapid opioid detoxification? Lancet 1999; 354: 2017–8.PubMedCrossRefGoogle Scholar
  10. 10.
    Roizen MF. How does μ-opioid receptor blockade work in addicted patients? Anesthesiology 1998; 88: 1142–3.PubMedCrossRefGoogle Scholar
  11. 11.
    Bovill JG. Opioid detoxification under anaesthesia. Eur J Anaesthesiol 2000; 17: 657–61.PubMedCrossRefGoogle Scholar
  12. 12.
    Nestler EJ. Under siege: the brain on opiates. Neuron 1996; 16: 897–900.PubMedCrossRefGoogle Scholar
  13. 13.
    Blendy JA, Maldonado R. Genetic analysis of drug addiction: the role of cAMP response element binding protein. J Mol Med 1998; 76: 104–10.PubMedCrossRefGoogle Scholar
  14. 14.
    Maldonado R, Blendy JA, Tzavara E, et al. Reduction of morphine abstinence in mice with a mutation in the gene encoding CREB. Science 1996; 273: 657–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Maldonado R, Stinus L, Koob GF, et al. Neurobiological Mechanisms of Opiate Withdrawal. New York: USA Springer; 1996.Google Scholar
  16. 16.
    Mattick RP, Hall W. Are detoxification programmes effective? Lancet 1996; 347: 97–100.PubMedCrossRefGoogle Scholar
  17. 17.
    Jasinski DR. Tolerance and dependence to opiates. Acta Anaesthesiol Scand 1997; 41: 184–6.PubMedCrossRefGoogle Scholar
  18. 18.
    Kleber HD, Topazian M, Gaspari J, Riordan CE, Kosten T. Clonidine and naltrexone in the outpatient treatment of heroin withdrawal. Am J Drug Alcohol Abuse 1987; 13: 4–17.CrossRefGoogle Scholar
  19. 19.
    O’Brien CP, McLellan AT. Myths about the treatment of addiction. Lancet 1996; 347: 237–40.PubMedCrossRefGoogle Scholar
  20. 20.
    Broers B, Giner F, Dumont P, Mino A. Inpatient opiate detoxification in Geneva: follow-up at 1 and 6 months. Drug Alcohol Depend 2000; 58: 85–92.PubMedCrossRefGoogle Scholar
  21. 21.
    Fudula PJ, Jaffe JH, Dax EM, Johnson RE. Use of buprenorphine in the treatment of opiate addiction. II. Physiologic and behavioral effects of daily and alternate-day administration and abrupt withdrawal. Clin Pharmacol Ther 1990; 47: 525–34.Google Scholar
  22. 22.
    Alling FA, Johnson BD, Elmoghazy E. Cranial electrostimulation (CES) use in the detoxification of opiatedependent patients. J Subst Abuse Treat 1990; 7: 173–80.PubMedCrossRefGoogle Scholar
  23. 23.
    Poshychinda V. Thailand: treatment at the Tam Kraborg Temple.In: Edwards G, Arif A (Eds.). Drug Problems in the Sociocultural Context: a Basis for Policies and Program Planning. Geneva: World Health Organization; 1980: 121–5.Google Scholar
  24. 24.
    Kienbaum P, Scherbaum N, Thurauf N, Michel MC, Gastpar M, Peters J. Acute detoxification of opioidaddicted patients with naloxone during propofol or methohexital anesthesia: a comparison of withdrawal symptoms, neuroendocrine, metabolic, and cardiovascular patterns. Crit Care Med 2000; 28: 969–76.PubMedCrossRefGoogle Scholar
  25. 25.
    Christie MJ, Williams JT, Osborne PB, Bellchambers CE. Where is the locus in opioid withdrawal? Trends Pharmacol Sci 1997; 18: 134–40.PubMedCrossRefGoogle Scholar
  26. 26.
    Keinbaum P, Thurauf N, Michel MC, Scherbaum N, Gastpar M, Peters J. Profound increase in epinephrine concentration in plasma and cardiovascular stimulation after μ-opioid receptor blockade in opioid addicted patients during barbiturate-induced anesthesia for acute detoxification. Anesthesiology 1998; 88: 1154–61.CrossRefGoogle Scholar
  27. 27.
    Langer SZ. Presynaptic regulation of release of catecholamines. Pharmacol Rev 1981; 32: 337–62.Google Scholar
  28. 28.
    Gold MS, Redmond DE Jr, Kleber HD. Noradrenergic hyperactivity in opiate withdrawal supported clonidine reversal of opiate withdrawal. Am J Psychiatry 1979; 136: 100–2.PubMedGoogle Scholar
  29. 29.
    Diaz A, Pazos A, Florez J, Ayesta FJ, Santana V, Hurle MA. Regulation of mu-opioid receptors, G-proteincoupled receptor kinases and beta-arrestin 2 in the rat brain after chronic opioid receptor antagonism. Neuroscience 2002; 112: 345–53.PubMedCrossRefGoogle Scholar
  30. 30.
    Charney DS, Heninger GR, Kleber D. The combined use of clonidine and naltrexone as a rapid, safe, and effective treatment of abrupt withdrawal from methadone. Am J Psychiatry 1986; 143: 831–7.PubMedGoogle Scholar
  31. 31.
    Ward J, Hall W, Mattick RP. Role of maintenance treatment in opioid dependence. Lancet 1999; 353: 221–6.PubMedCrossRefGoogle Scholar
  32. 32.
    Farrel M. Opioid withdrawal. Addiction 1994; 89: 1471–7.CrossRefGoogle Scholar
  33. 33.
    Senft RA. Experience with clonidine-naltrexone for rapid opiate detoxification. J Subst Abuse Treat 1991; 8: 257–9.PubMedCrossRefGoogle Scholar
  34. 34.
    Resnick RB, Kestenbaum RS, Washton A. Poole D. Naloxone-precipitated withdrawal: a method for rapid induction onto naltrexone. Clin Pharmacol Ther 1977; 21: 409–13.PubMedGoogle Scholar
  35. 35.
    Loimer N, Schmid R, Lenz K, Presslich O, Grunberger J. Acute blocking of naloxone-precipitated opiate withdrawal symptoms by methohexitone. Br J Psychiatry 1990; 157: 748–52.PubMedCrossRefGoogle Scholar
  36. 36.
    Presslich O, Loimer N. Opiate detoxification under general anesthesia by large doses of naloxone. J Toxicol Clin Toxicol 1989; 27: 263–70.PubMedGoogle Scholar
  37. 37.
    Simon DL. Rapid opioid detoxification using opioid antagonists: history, theory and the state of the art. J Addict Dis 1997; 16: 103–22.PubMedCrossRefGoogle Scholar
  38. 38.
    Legarda JJ, Gossop M. A 24-h inpatient detoxification treatment for heroin addicts: a preliminary investigation. Drug Alcohol Depend 1994; 35: 91–3.PubMedCrossRefGoogle Scholar
  39. 39.
    Rasmussen K, Beitner-Johnson DB, Krystal JH, Aghajanian GK, Nestler EJ. Opiate withdrawal and the rat locus coeruleus: behavioral, electrophysiological, and biochemical correlates. J Neurosci 1990; 10: 2308–17.PubMedGoogle Scholar
  40. 40.
    Gold CG, Cullen DJ, Gonzales S, Houtmeyers D, Dwyer MJ. Rapid opioid detoxification during general anesthesia. Anesthesiology 1999; 91: 1639–47.PubMedCrossRefGoogle Scholar
  41. 41.
    Lorenzi P, Marsili M, Boncinelli S, et al. Searching for a general anaesthesia protocol for rapid detoxification from opioids. Eur J Anaesthesiol 1999; 16: 719–27.PubMedCrossRefGoogle Scholar
  42. 42.
    Cucchia AT, Monnat M, Spagnoli J, Ferrero F, Bertschy G. Ultra-rapid opiate detoxification using deep sedation with midazolam: short and long-term results. Drug Alcohol Depend 1998; 52: 243–50.PubMedCrossRefGoogle Scholar
  43. 43.
    Gevirtz C, Frost E. Ultra rapid opiate detoxification current concepts. Curr Opin Clin Exp Res 2000; 2: 151–68.Google Scholar
  44. 44.
    McDonald T, Berkowitz R, Hoffman WE. Plasma naltrexone during opioid detoxification. J Addict Dis 2000: 19: 59–64.PubMedCrossRefGoogle Scholar
  45. 45.
    Walters CL, Aston-Jones G, Druhan JP. Expression of fos-related antigens in the nucleus accumbens during opiate withdrawal and their attenuation by a D2 dopamine receptor agonist. Neuropsychopharmacology 2000; 23: 307–15.PubMedCrossRefGoogle Scholar
  46. 46.
    McDonald T, Berkowitz R, Hoffman WE. Median EEG frequency is more sensitive to increases in sympathetic activity than bispectral index. J Neurosurg Anesthesiol 1999; 11:255–9.PubMedCrossRefGoogle Scholar
  47. 47.
    Tweedle D, Nightingale P. Anesthesia and gastrointestinal surgery. Acta Chir Scand Suppl 1989; 550: 131–9.PubMedGoogle Scholar
  48. 48.
    Brewer C. Ultra rapid, antagonist-precipitated opiate detoxification under general anaesthesia or sedation. Addiction Biol 1997; 2: 291–302.CrossRefGoogle Scholar
  49. 49.
    Wilde MI, Markham A. Ondansetron. A review of its pharmacology and preliminary clinical findings in novel applications. Drugs 1996; 52: 773–94.PubMedCrossRefGoogle Scholar
  50. 50.
    Madsen BW, Albuquerque EX. The narcotic antagonist naltrexone has a biphasic effect on the nicotinic acetylcholine receptor. FEBS Lett 1985; 182: 20–4.PubMedCrossRefGoogle Scholar
  51. 51.
    Kienbaum P, Thuauf N, Michel MC, Scherbaum N, Gastpar M, Peters J. Profound increase in epinephrine concentration in plasma and cardiovascular stimulation after mu-opioid receptor blockade in opioid-addicted patients during barbiturate-induced anesthesia for acute detoxification. Anesthesiology 1998; 1154–161.Google Scholar
  52. 52.
    Hoffman WE, Berkowitz R, McDonald T, Hass F. Ultra-rapid opioid detoxification increases spontaneous ventilation. J Clin Anesth 1998; 10: 372–6.PubMedCrossRefGoogle Scholar
  53. 53.
    McDonald T, Hoffman WE, Berkowitz R, Cunningham F, Cooke B. Heart rate variability and plasma catecholamines in patients during opioid detoxification. J Neurosurg Anesthesiol 1999; 11: 195–9.PubMedGoogle Scholar
  54. 54.
    Manilli P, De Risio S, Pozzi G, Janiri L, De Giacomo M. Serendipitous rapid detoxification from opiates: the importance of time-dependent processes. Addiction 1999; 94: 589–91.CrossRefGoogle Scholar
  55. 55.
    Ronnback L, Eriksson PS, Zeuchner J, Rosengren L, Wronski A. Aspects of abstinence after morphine ingestion. Pharmacol Biochem Behav 1987; 28: 87–93.PubMedCrossRefGoogle Scholar
  56. 56.
    Handelsman L, Cochrane KJ, Aronson MJ, Ness R, Rubinstein KJ, Kanof PD. Two new rating scales for opiate withdrawal. Am J Drug Alcohol Abuse 1987; 13: 293–308.PubMedCrossRefGoogle Scholar
  57. 57.
    Kosten TR, Kreek MJ, Ragunath J, Kleber HD. Cortisol levels during chronic naltrexone maintenance treatment in ex-opiate addicts. Biol Psychiatry 1986; 21: 217–20.PubMedCrossRefGoogle Scholar
  58. 58.
    Dunlap CE 3rd,Valego NK, Rose JC. Comparison of high-dose opioid antagonist effects on ovine fetal cardiovascular function Dev Pharmacol Ther 1989; 13: 28–37.PubMedGoogle Scholar
  59. 59.
    Jepsen PW. Naltrexone. An opioid antagonist to support the drug-free state in previous opioid addicts having stopped the habit (Danish). Ugeskr Laeger 1990; 152: 2546–9.PubMedGoogle Scholar
  60. 60.
    Chanmugam AS, Hengeller M, Ezenkwele U. Development of rhabdomyolysis after rapid opioid detoxification with subcutaneous naltrexone maintenance therapy. Acad Emerg Med 2000; 7: 303–5.PubMedCrossRefGoogle Scholar
  61. 61.
    Burleigh DE. Opioid and non-opioid actions of loperamide on cholinergic nerve function in human isolated colon. Eur J Pharmacol 1988; 152: 39–46.PubMedCrossRefGoogle Scholar
  62. 62.
    Staedt J, Wassmuth F, Stoppe G, et al. Effects of chronic treatment with methadone and naltrexone on sleep in addicts. Eur Arch Psychiatry Clin Neurosci 1996; 246: 305–9.PubMedCrossRefGoogle Scholar
  63. 63.
    Millman RP. Therapy of insomnia. Med Health RI 2002; 85: 99–100.Google Scholar
  64. 64.
    Shah AA, Thjodleifsson B, Murray FE, et al. Selective inhibition of COX-2 in humans is associated with less gastrointestinal injury: a comparison of nimesulide and naproxen. Gut 2001; 48: 339–46.PubMedCrossRefGoogle Scholar

Copyright information

© Canadian Anesthesiologists 2003

Authors and Affiliations

  • Alan D. Kaye
    • 1
  • Clifford Gevirtz
    • 3
  • Hemmo A. Bosscher
    • 1
    • 4
  • Joe B. Duke
    • 1
    • 4
  • Elizabeth A. M. Frost
    • 3
  • Todd A. Richards
    • 1
    • 4
  • Aaron M. Fields
    • 1
    • 4
  1. 1.Departments of AnesthesiologyTexas Tech University School of MedicineLubbock
  2. 2.Departments of PharmacologyTexas Tech University School of MedicineLubbock
  3. 3.Department of AnesthesiologyMount Sinai School of MedicineNew YorkUSA
  4. 4.Department of AnesthesiologyLubbockUSA

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