CNS Drugs

, Volume 25, Issue 12, pp 999–1007 | Cite as

Herbal Medicines for the Management of Opioid Addiction

Safe and Effective Alternatives to Conventional Pharmacotherapy?
  • Jeanine Ward
  • Christopher Rosenbaum
  • Christina Hernon
  • Christopher R. McCurdy
  • Edward W. Boyer
Leading Article

Abstract

Striking increases in the abuse of opioids have expanded the need for pharmacotherapeutic interventions. The obstacles that confront effective treatment of opioid addiction — shortage of treatment professionals, stigma associated with treatment and the ability to maintain abstinence — have led to increased interest in alternative treatment strategies among both treatment providers and patients alike. Herbal products for opioid addiction and withdrawal, such as kratom and specific Chinese herbal medications such as WeiniCom, can complement existing treatments. Unfortunately, herbal treatments, while offering some advantages over existing evidence-based pharmacotherapies, have poorly described pharmacokinetics, a lack of supportive data derived from well controlled clinical trials, and severe toxicity, the cause for which remains poorly defined. Herbal products, therefore, require greater additional testing in rigorous clinical trials before they can expect widespread acceptance in the management of opioid addiction.

References

  1. 1.
    Okie S. A flood of opioids, a rising tide of deaths. N Engl J Med 2010; 363: 1981–5PubMedCrossRefGoogle Scholar
  2. 2.
    Mokri A. Brief overview of the status of drug abuse in Iran. Arch Iran Med 2002; 5: 184–90Google Scholar
  3. 3.
    Liu L, Fang Y, Wang X. Drug abuse in China: past, present and future. Cell Mol Neurobiol 2008; 28: 479–90CrossRefGoogle Scholar
  4. 4.
    Rawson R. Drug abuse problems in the Middle East: 2005 [online]. Available from URL: http://www.uclaisap.org/slides/rawson/Drug%20Abuse%20Problems%20in%20the%20Middle%20East.ppt [Accessed 2011 Apr 1]
  5. 5.
    Boyer E, Wines J. Impact of Internet pharmacy regulation on opioid analgesic availability. J Stud Alcohol Drugs 2008; 69: 703–8PubMedGoogle Scholar
  6. 6.
    Boyer EW, Babu KM, Adkins JE, et al. Self-treatment of opioid withdrawal using kratom (Mitragynia speciosa korth). Addiction 2008 Jun; 103(6): 1048–50PubMedCrossRefGoogle Scholar
  7. 7.
    Babu KM, McCurdy CR, Boyer EW. Opioid receptors and legal highs: Salvia divinorum and kratom. Clin Toxicol (Phila) 2008 Feb; 46(2): 146–52CrossRefGoogle Scholar
  8. 8.
    Adkins JE, Boyer EW, McCurdy CR. Mitragyna speciosa, a psychoactive tree from southeast Asia with opioid activity. Curr Topics Medicinal Chem 2011; 11: 1–11CrossRefGoogle Scholar
  9. 9.
    Sunwalert S. A study of kratom eaters in Thailand. Bull Narc 1975; 27: 21–7Google Scholar
  10. 10.
    Grewal KS. Observations on the pharmacology of mitragynine. J Pharmacol Exp Ther 1932 Nov; 46: 251–71Google Scholar
  11. 11.
    Takayama H. Chemistry and pharmacology of analgesic indole alkaloids from the rubiaceous plant, Mitragyna speciosa. Chem Pharm Bull 2004; 52(8): 916–28PubMedCrossRefGoogle Scholar
  12. 12.
    Matsumoto K, Mizowaki M, Suchitra T, et al. Antinociceptive action of mitragynine in mice: evidence for the involvement of supraspinal opioid receptors. Life Sci 1996; 59(14): 1149–55PubMedCrossRefGoogle Scholar
  13. 13.
    Matsumoto K, Horie S, Takayama H, et al. Antinociception, tolerance and withdrawal symptoms induced by 7-hydroxymitragynine, an alkaloid from the Thai medicinal herb Mitragyna speciosa. Life Sci 2005 Nov 19; 78(1): 2–7PubMedCrossRefGoogle Scholar
  14. 14.
    Takayama H, Ishikawa H, Kurihara M, et al. Studies on the synthesis and opioid agonistic activities of mitragynine-related indole alkaloids: discovery of opioid agonists structurally different from other opioid ligands. J Med Chem 2002 Apr 25; 45(9): 1949–56PubMedCrossRefGoogle Scholar
  15. 15.
    Beckett AH, Casy A. Synthetic analgesics: stereochemical considerations. J Pharm Pharmacol 1954; 6: 986–1001PubMedCrossRefGoogle Scholar
  16. 16.
    McCurdy CR, Prisinzano T. Narcotic analgesics. In: Abraham D, editor. Burger’s medicinal chemistry, drug discovery and development. Vol. 7. 6th ed. Hoboken (NJ): John Wiley & Sons, 2010: 569–73Google Scholar
  17. 17.
    Jansen K, Prast C. Ethnopharmacology of kratom and the Mitragyna alkaloids. J Ethnopharmacol 1988; 23: 115–9PubMedCrossRefGoogle Scholar
  18. 18.
    Jansen K, Prast C. Psychoactive properties of mitragynine (kratom). J Psychoactive Drugs 1988; 20: 455–7PubMedCrossRefGoogle Scholar
  19. 19.
    Boyer E, Babu K, McCurdy S, et al. Self-treatment of opioid withdrawal with kratom. Addiction 2008; 103: 1048–50PubMedCrossRefGoogle Scholar
  20. 20.
    Macko E, Weisbach J, Douglas B. Some observations on the pharmacology of mitragynine. Arch Int Pharmcodynamics 1972; 198: 145–61Google Scholar
  21. 21.
    Nelson J, Lapoint J, Hodgman M, et al. Seizure and coma following kratom (Mitragynina speciosa Korth) exposure. J Med Toxicol 2010; 6: 424–6CrossRefGoogle Scholar
  22. 22.
    Boyer E, Babu K, Macalino G. Self-treatment of opioid withdrawal with a dietary supplement, Kratom. Am J Addictions 2007; 16: 352–6CrossRefGoogle Scholar
  23. 23.
    Osterhaus H. Natural herb flavors student’s day: the University Daily Kansan 2008 Jan 23 [online]. Available from URL: http://www.kansan.com/news/2008/jan/23/osterhaus_natural_herb_flavors_students_day/ [Accessed 2011 Oct 16]
  24. 24.
    Krauth D. Substance called ‘kratom’ becoming a growing problem. Palm Beach Post 2011 Jul 1 [online]. Available from URL: http://www.palmbeachpost.com/health/substance-called-kratom-becoming-a-growing-problem-1575630.html [Accessed 2011 Oct 16]
  25. 25.
    Mash D. Ibogaine therapy for substance abuse disorders: clinical addiction psychiatry. Cambridge: Cambridge University Press, 2010: 50–60Google Scholar
  26. 26.
    Lotsof H. Ibogaine in the treatment of chemical dependence disorders: clinical perspectives. Newsletter of the Multidisciplinary Association for Psychedelic Studies 1995; 5: 16–27Google Scholar
  27. 27.
    A chronology of selected abstracts for ibogaine: rapid method for the interruption of the narcotic addiction syndrome, presented as a courtesy to the American Association for the Treatment of Opioid Dependence. Bear (DE): Addiction Research Institute, 2004Google Scholar
  28. 28.
    Vastag B. Addiction treatment strives for legitimacy. JAMA 2002; 288: 3096–101PubMedCrossRefGoogle Scholar
  29. 29.
    Controlled substance schedules [online]. Available from URL: http://www.justice.gov/dea/pubs/scheduling.html [Accessed 2011 Oct 16]
  30. 30.
    Kontrimaviciute V, Olivier M, Mathieu-Daude J. Distribution of ibogaine and noribogaine in a man following poisoning involving root bark of the Tabernanthe iboga shrub. J Analyt Toxicol 2006; 30: 434–40Google Scholar
  31. 31.
    Hough L, Bagal A, Glick S. Pharmacokinetic characterization of the indole alkaloid ibogaine in rats. Methods Findings Exp Clin Pharmacol 2000; 22: 77–81CrossRefGoogle Scholar
  32. 32.
    Helsley S, Rabin R, Winter J. Further investigations of the serotonergic properties of the ibogaine-induced discriminative stimulus. Prog Neuropsychophamacol Biol Psychiatry 1999; 23: 317–26CrossRefGoogle Scholar
  33. 33.
    Deecher D, Teitler M, Soderland D, et al. Mechanisms of action of ibogaine and harmaline congeners based on radioligand binding studies. Brain Res 1992; 571: 242–7PubMedCrossRefGoogle Scholar
  34. 34.
    Sweetnam P, Lancaster J, Snowman A, et al. Receptor binding profile suggests multiple mechanisms of action are responsible for ibogaine’s putative anti-addictive activity. Psychopharmacology 1995; 118: 369–76PubMedCrossRefGoogle Scholar
  35. 35.
    Codd E. High affinity ibogaine binding to a mu opioid agonist site. Addiction Biol 1995; 57: 315–20Google Scholar
  36. 36.
    Itzak Y, Ali S. Effects of ibogaine on the various sites of the NMDA receptor comles and sigma binding sites in the brain. Ann NY Acad Sci 1998; 844: 245–51CrossRefGoogle Scholar
  37. 37.
    Leal M, Michelin K, Sousa D, et al. Ibogaine attenuation of morphine withdrawal in mice: role of glutamate N-methy-D-aspartate receptors. Prog Neuropsychophamacol Biol Psychiatry 2003; 27: 781–5CrossRefGoogle Scholar
  38. 38.
    Arias H, Rosenberg A, Targowska-Duda K, et al. Interaction of ibogaine with human a3b4-nicotinic acetylcholine receptors in different conformational states. Int J Biochem Cell Biol 2010; 42: 1525–35PubMedCrossRefGoogle Scholar
  39. 39.
    Glick S, Maisonneuve I, Kitchen B, et al. Antagonism of a3b4 nicotinic receptors as a strategy to reduce opioid and stimulant self-administration. Eur J Pharmacol 2002; 438: 99–105PubMedCrossRefGoogle Scholar
  40. 40.
    Onaivi E, Ali S, Chirwa S, et al. Ibogaine signals addiction genes and methamphetamine alteration of long-term potentiation. Ann NY Acad Sci 2002; 965: 28–46PubMedCrossRefGoogle Scholar
  41. 41.
    He D, Ron D. Autoregulation of glial cell line-derived neurotrophic factor expression: implications for the long-lasting actions for the anti-addiction drug ibogaine. FASEB J 2002; 20: E1820–7Google Scholar
  42. 42.
    Sheppard S. A preliminary investigation of ibogaine: case reports and recommendations for further study. J Subst Abuse Treat 1994; 11: 379–85PubMedCrossRefGoogle Scholar
  43. 43.
    Alper K, Lotsof H, Frenken G, et al. Treatment of acute opioid withdrawal with ibogaine. Am J Addictions 1999; 8: 234–42CrossRefGoogle Scholar
  44. 44.
    Alper K, Lotsof H, Kaplan C. The ibogaine medical subculture. J Ethnopharmacol 2008; 115: 9–24PubMedCrossRefGoogle Scholar
  45. 45.
    Mash D, Kovera C, Pablo J, et al. Ibogaine: complex pharmacokinetics, concerns for safety, and preliminary efficacy measures. Ann NY Acad Sci 2000; 914: 394–401PubMedCrossRefGoogle Scholar
  46. 46.
    Witter S. Ibogaine. The Times (London) magazine. London: TIME, 1998 JunGoogle Scholar
  47. 47.
    Alper K, Glick S. Ibogaine: proceedings of the First International Conference. San Diego (CA): Academic Press, 2001Google Scholar
  48. 48.
    Shulgin A, Shulgin A. Tihkal: the continuation. Berkeley (CA): Transform PR, 1997 [online]. Available from URL: http://www.erowid.org/library/books_online/tihkal/tihkal.shtml [Accessed 2011 Oct 16]
  49. 49.
    Luciano D. Observations on treatment with ibogaine. Am J Addictions 1998; 7: 89–90CrossRefGoogle Scholar
  50. 50.
    Hoelen D, Spiering W, Valk G. Long-QT syndrome induced by the antiaddiction drug ibogaine. N Engl J Med 2009; 360: 308–9PubMedCrossRefGoogle Scholar
  51. 51.
    Lotsof H, Wachtel E. Manual for ibogaine therapy: screening, safety, monitoring, and aftercare. The ibogaine dossier 2003 [online]. Available from URL: http://www.ibogaine.org/manual.html [Accessed 2011 Apr 4]
  52. 52.
    Maas U, Strubelt S. Fatalities after taking ibogaine in addiction treatment could be related to sudden cardiac death caused by autonomic dysfunction. Medical Hypoth 2006; 67: 960–4CrossRefGoogle Scholar
  53. 53.
    Miller L. Herbal medicinals. Arch Intern Med 1998; 158: 2200–11PubMedCrossRefGoogle Scholar
  54. 54.
    Espinoza EO, Mann M-J, Bleasdell B. Arsenic and mercury in traditional Chinese herbal balls. N Engl J Med 1995; 333: 803–4PubMedCrossRefGoogle Scholar
  55. 55.
    Chen M, Jin G. Role of d-tetrahydropamatine in the inhibition of dopamine and serotonin or synaptosomes in the rat brain. Chin J Physiol Sci 1996; 12: 25–30Google Scholar
  56. 56.
    Liu Y, Liang J, Yan L, et al. Effects of l-tetrahydropalmatine on locomotor sensitization to oxycodone in mice. Acta Pharmacol Sinica 2005; 26: 533–8CrossRefGoogle Scholar
  57. 57.
    Ge X, Zhang H, Xu Z, et al. Experimental study of tetrahydroprotoberberines inhibiting morphine withdrawal syndromes. Chin J Drug Depend 1999; 8: 178–84Google Scholar
  58. 58.
    Yang Z, Shao Y, Li S, et al. Medication of l-tetrahydropalmatine significantly ameliorates opiate craving and increases the abstinence rate in heroin users: a pilot study. Acta Pharmacol Sinica 2008; 29: 781–8CrossRefGoogle Scholar
  59. 59.
    Gillis C. Panax ginseng pharmacology: a nitric oxide link. Biochem Pharmcol 1997; 54: 1–8CrossRefGoogle Scholar
  60. 60.
    Attele A, Wu J, Yuan C. Ginseng pharmacology: multiple constituents and multiple actions. Biochem Pharmcol 1999; 58: 1685–93CrossRefGoogle Scholar
  61. 61.
    Takahashi M, Tokuyama S. Pharmacological and physiological effects of ginseng on actions induced by opioids and psychostimulants. Methods Find Exp Clin Pharmacol 1998; 20: 77–84PubMedCrossRefGoogle Scholar
  62. 62.
    Shi J, Xu G, Liu T, et al. A comparative clinical study of the effects of the traditional Chinese medicine Jinnui capsules and lofexidine on acute heroin withdrawal symptoms. Am J Drug Alcohol Abuse 2008; 34: 792–800PubMedCrossRefGoogle Scholar
  63. 63.
    Harris I. Regulatory and ethical issues with dietary supplements. Pharmacotherapy 2000; 20(11): 1295–302PubMedCrossRefGoogle Scholar
  64. 64.
    Li Z, Wu C, Pei G, et al. Antagonistic effect of psuedoginsenoside-F11 on the behavioral actions of morphine in mice. Pharmacol Biochem Behav 2000; 66: 595–601PubMedCrossRefGoogle Scholar
  65. 65.
    Li Z, Xu N, Wu C, et al. Pseudoginsenoside-F11 attenuates morphine-induced signalling in Chinese hamster ovary-mu cells. Neuroreport 2001; 12: 1453–6PubMedCrossRefGoogle Scholar
  66. 66.
    Seo J, Lee J, Lee W, et al. Inhibitory effects of ginseng total saponin on up-regulation of cAMP pathway induced by repeated administration of morphine. Arch Pharm Res 2008; 31: 167–70PubMedCrossRefGoogle Scholar
  67. 67.
    KTBotanicals.com [online]. Available from URL: http://www.ktbotanicals.com/xuan-xia-qudu-jiaonang-100-capsules-p-7994.html [Accessed 2009 Apr]
  68. 68.
    Hao W, Zhao M. A comparative clinical study of the effect of WeiniCom, a Chinese herbal compound, on alleviation of withdrawal symptoms and craving for heroin in detoxification treatment. J Psychoactive Drugs 2000; 32: 277–84PubMedCrossRefGoogle Scholar
  69. 69.
    Kang L, Li B, Gao L, et al. Tai-Kang-Ning, a Chinese herbal medicine formula, alleviates acute heroin withdrawal. Am J Drug Alcohol Abuse 2009; 34: 269–76CrossRefGoogle Scholar
  70. 70.
    Wang X, Li J, Huang M, et al. A study of Fu-Yuan Pellet, a traditional Chinese medicine formula for detoxification of heroin addicts. Am J Drug Alcohol Abuse 2009; 35: 408–11PubMedCrossRefGoogle Scholar
  71. 71.
    Aldhous P. Drug rehabilitation: cold turkey, Vietnamese style. Nature 2005; 433: 568–9PubMedCrossRefGoogle Scholar
  72. 72.
    Cohen H, Law-Yone B, Lu S. Poppy to fugu: a historical perspective of the treatment of opiate addiction in China. J Chinese Med 2002; 68: 15–20Google Scholar
  73. 73.
    Boggan S. Heroin cure may have killed six. The Independent 1998 Feb 25 [online]. Available from URL: http://www.independent.co.uk/news/heroin-cure-may-have-killed-six-1146810.html [Accessed 2011 Oct 16]

Copyright information

© Adis Data Information BV 2011

Authors and Affiliations

  • Jeanine Ward
    • 1
  • Christopher Rosenbaum
    • 1
  • Christina Hernon
    • 1
  • Christopher R. McCurdy
    • 2
  • Edward W. Boyer
    • 1
  1. 1.Division of Medical Toxicology, Department of Emergency MedicineUniversity of Massachusetts Medical SchoolWorcesterUSA
  2. 2.Department of Medicinal Chemistry, Laboratory for Applied Drug Design and Synthesis, School of PharmacyUniversity of MississippiUniversityUSA

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