Psychoactive plant derivatives (ayahuasca, ibogaine, kratom) and their application in opioid withdrawal and use disorder – a narrative review

References

• Keyes KM, Rutherford C, Hamilton A, Barocas JA, Gelberg KH, Mueller PP, Feaster DJ, El-Bassel N, Cerda M. What is the prevalence of and trend in opioid use disorder in the United States from 2010 to 2019? Using multiplier approaches to estimate prevalence for an unknown population size. Drug Alcohol Depend Rep. 2022;3:100052. doi:10.1016/j.dadr.2022.100052.
   PubMedGoogle Scholar
• CareSource. Hedis measure: initiation and engagement of alcohol and other drug abuse or dependence treatment (IET); 2021. [Last accessed 2022 Oct 30]. Available from: https://www.caresource.com/documents/ga-mcd-iet-hedis-measure/.
   Google Scholar
• Jones CM, McCance-Katz EF. Co-occurring substance use and mental disorders among adults with opioid use disorder. Drug Alcohol Depend. 2019;197:78–82. doi:10.1016/j.drugalcdep.2018.12.030.
   PubMed Web of Science ®Google Scholar
• Mancher CM, Leshner AI, National Academies of Sciences Engineering and Medicine, Health and Medicine Division, Board on Health Sciences Policy, Committee on Medication-Assisted Treatment for Opioid Use Disorder. Barriers to broader use of medications to treat opioid use disorder. In: Mancher, M., Leshner AI, eds. Medications for opioid use disorder save lives. Washington (DC): National Academy of Sciences; 2019:109–136.
   Google Scholar
• Smith KE, Lawson T. Prevalence and motivations for kratom use in a sample of substance users enrolled in a residential treatment program. Drug Alcohol Depend. 2017;180:340–8. doi:10.1016/j.drugalcdep.2017.08.034.
   PubMed Web of Science ®Google Scholar
• Swogger MT, Walsh Z. Kratom use and mental health: a systematic review. Drug Alcohol Depend. 2018;183:134–40. doi:10.1016/j.drugalcdep.2017.10.012.
   PubMed Web of Science ®Google Scholar
• Tupper KW, Wood E, Yensen R, Johnson MW. Psychedelic medicine: a re-emerging therapeutic paradigm. CMAJ. 2015;187(14):1054–9. doi:10.1503/cmaj.141124.
   PubMed Web of Science ®Google Scholar
• Veltri C, Grundmann O. Current perspectives on the impact of Kratom use. Subst Abuse Rehabil. 2019;10:23–31. doi:10.2147/SAR.S164261.
   PubMed Web of Science ®Google Scholar
• Winkelman M. Psychedelics as medicines for substance abuse rehabilitation: evaluating treatments with LSD, Peyote, Ibogaine and Ayahuasca. Curr Drug Abuse Rev. 2014;7(2):101–16. doi:10.2174/1874473708666150107120011.
   PubMedGoogle Scholar
• Bogenschutz MP, Johnson MW. Classic hallucinogens in the treatment of addictions. Prog Neuropsychopharmacol Biol Psychiatry. 2016;64:250–8. doi:10.1016/j.pnpbp.2015.03.002.
   PubMed Web of Science ®Google Scholar
• Bogenschutz MP, Ross S, Bhatt S, Baron T, Forcehimes AA, Laska E, Mennenga SE, O'Donnell K, Owens LT, Podrebarac S, et al. Percentage of heavy drinking days following psilocybin-assisted psychotherapy vs placebo in the treatment of adult patients with alcohol use disorder: a randomized clinical trial. JAMA Psychiatry. 2022;79(10):953–962. doi:10.1001/jamapsychiatry.2022.2096.
   PubMed Web of Science ®Google Scholar
• Konrath EL, Arbo MD, Arbo BD, Hort MA, Elisabetsky E, Leal MB. Plants with anti-addictive potential. In: Barreto GE, Sahebkar A, eds. Pharmacological properties of plant-derived natural products and implications for human health. Vol. 1308. Switzerland AG; Springer, Cham, 2021. p. 185–215.
   Google Scholar
• Perkins D, Sarris J, Rossell S, Bonomo Y, Forbes D, Davey C, Hoyer D, Loo C, Murray G, Hood S, et al. Medicinal psychedelics for mental health and addiction: advancing research of an emerging paradigm. Aust N Z J Psychiatry. 2021;55(12):1127–33. doi:10.1177/0004867421998785.
   PubMed Web of Science ®Google Scholar
• Sessa B, Johnson MW. Can psychedelic compounds play a part in drug dependence therapy? Br J Psychiatry. 2015;206(1):1–3. doi:10.1192/bjp.bp.114.148031.
   PubMed Web of Science ®Google Scholar
• Srivastava AB, Mariani JJ, Levin FR. New directions in the treatment of opioid withdrawal. Lancet. 2020;395(10241):1938–48. doi:10.1016/s0140-6736(20)30852-7.
   PubMed Web of Science ®Google Scholar
• Baethge C, Goldbeck-Wood S, Mertens S. SANRA-a scale for the quality assessment of narrative review articles. Res Integr Peer Rev. 2019;4:5. doi:10.1186/s41073-019-0064-8.
   PubMedGoogle Scholar
• Liester MB, Prickett JI. Hypotheses regarding the mechanisms of ayahuasca in the treatment of addictions. J Psychoact Drugs. 2012;44(3):200–8. doi:10.1080/02791072.2012.704590.
   PubMed Web of Science ®Google Scholar
• Daldegan-Bueno D, Simionato NM, Favaro VM, Maia LO. The current state of ayahuasca research in animal models: a systematic review [Internet]. PsyArXiv; 2022. [last accessed 2022 Sept 1]. Available from: psyarxiv.com/7s3b8.
   Google Scholar
• Thelwell E. Why do people take ayahuasca? BBC News; 2014. [accessed 2022 Aug 22]. Available from: https://www.bbc.com/news/magazine-27203322. Last
   Google Scholar
• Jaffe A. Ayahuasca for addiction? That’s a trip. Psychology Today; 2018 Dec 10. [last accessed 2022 Aug 22]. Available from: https://www.psychologytoday.com/us/blog/all-about-addiction/201812/ayahuasca-addiction-thats-trip
   Google Scholar
• Thomas G, Lucas P, Capler NR, Tupper KW, Martin G. Ayahuasca-assisted therapy for addiction: results from a preliminary observational study in Canada. Curr Drug Abuse Rev. 2013;6(1):30–42. doi:10.2174/15733998113099990003.
   PubMedGoogle Scholar
• Graziano S, Orsolini L, Rotolo MC, Tittarelli R, Schifano F, Pichini S. Herbal highs: review on psychoactive effects and neuropharmacology. Curr Neuropharmacol. 2017;15(5):750–61. doi:10.2174/1570159X14666161031144427.
   PubMed Web of Science ®Google Scholar
• Hamill J, Hallak J, Dursun SM, Baker G. Ayahuasca: psychological and physiologic effects, pharmacology and potential uses in addiction and mental illness. Curr Neuropharmacol. 2019;17(2):108–28. doi:10.2174/1570159X16666180125095902.
   PubMed Web of Science ®Google Scholar
• Ruffell SGD, Netzband N, Tsang W, Davies M, Butler M, Rucker JJH, Tofoli LF, Dempster EL, Young AH, Morgan CJA. Ceremonial ayahuasca in Amazonian retreats-mental health and epigenetic outcomes from a six-month naturalistic study. Front Psychiatry. 2021;12:687615. doi:10.3389/fpsyt.2021.687615.
   PubMed Web of Science ®Google Scholar
• Talin P, Sanabria E. Ayahuasca’s entwined efficacy: an ethnographic study of ritual healing from ‘addiction’. Int J Drug Policy. 2017;44:23–30. doi:10.1016/j.drugpo.2017.02.017.
   PubMed Web of Science ®Google Scholar
• dos Santos RG. Safety and side effects of ayahuasca in humans–an overview focusing on developmental toxicology. J Psychoact Drugs. 2013;45(1):68–78. doi:10.1080/02791072.2013.763564.
   PubMed Web of Science ®Google Scholar
• Loizaga-Velder A, Verres R. Therapeutic effects of ritual ayahuasca use in the treatment of substance dependence–qualitative results. J Psychoact Drugs. 2014;46(1):63–72. doi:10.1080/02791072.2013.873157.
   PubMed Web of Science ®Google Scholar
• Argento E, Socias ME, Hayashi K, Choi J, Mackay L, Christie D, Milloy MJ, DeBeck K. Psychedelic use is associated with reduced daily opioid use among people who use illicit drugs in a Canadian setting. Int J Drug Policy. 2022;100:103518. doi:10.1016/j.drugpo.2021.103518.
   PubMed Web of Science ®Google Scholar
• Pisano VD, Putnam NP, Kramer HM, Franciotti KJ, Halpern JH, Holden SC. The association of psychedelic use and opioid use disorders among illicit users in the United States. J Psychopharmacol. 2017;31(5):606–13. doi:10.1177/0269881117691453.
   PubMed Web of Science ®Google Scholar
• Berlowitz I, Walt H, Ghasarian C, Mendive F, Martin-Soelch C. Short-term treatment effects of a substance use disorder therapy involving traditional Amazonian medicine. J Psychoact Drugs. 2019;51(4):323–34. doi:10.1080/02791072.2019.1607956.
   PubMed Web of Science ®Google Scholar
• Nunes AA, Dos Santos RG, Osorio FL, Sanches RF, Crippa JA, Hallak JE. Effects of ayahuasca and its alkaloids on drug dependence: a systematic literature review of quantitative studies in animals and humans. J Psychoact Drugs. 2016;48(3):195–205. doi:10.1080/02791072.2016.1188225.
   PubMed Web of Science ®Google Scholar
• O'Shaughnessy DM, Berlowitz I, Rodd R, Sarnyai Z, Quirk F. Within-treatment changes in a novel addiction treatment program using traditional Amazonian medicine. Ther Adv Psychopharmacol. 2021;11:2045125320986634. doi:10.1177/2045125320986634.
   Web of Science ®Google Scholar
• Rush B, Marcus O, Garcia S, Loizaga-Velder A, Loewinger G, Spitalier A, Mendive F. Protocol for outcome evaluation of ayahuasca-assisted addiction treatment: the case of Takiwasi Center. Front Pharmacol. 2021;12:659644. doi:10.3389/fphar.2021.659644.
   PubMed Web of Science ®Google Scholar
• Brown TK. Ibogaine in the treatment of substance dependence. Curr Drug Abuse Rev. 2013;6(1):3–16. doi:10.2174/15672050113109990001.
   PubMedGoogle Scholar
• Koenig X, Hilber K. The anti-addiction drug ibogaine and the heart: a delicate relation. Molecules. 2015;20(2):2208–28. doi:10.3390/molecules20022208.
   PubMed Web of Science ®Google Scholar
• Schenberg EE, de Castro Comis MA, Alexandre JFM, Chaves BDR, Tófoli LF, da Silveira DX. Treating drug dependence with the aid of ibogaine: a qualitative study. J Psychedelic Stud. 2017;1(1):10–9. doi:10.1556/2054.01.2016.002.
   Google Scholar
• Oaklander M. Inside ibogaine, one of the most promising and perilous psychedelics for addiction. Time. 2021. [last accessed 2022 Oct 15]. Available from: https://time.com/5951772/ibogaine-drug-treatment-addiction/
   Google Scholar
• Glue P, Lockhart M, Lam F, Hung N, Hung CT, Friedhoff L. Ascending-dose study of noribogaine in healthy volunteers: pharmacokinetics, pharmacodynamics, safety, and tolerability. J Clin Pharmacol. 2015;55(2):189–94. doi:10.1002/jcph.404.
   PubMed Web of Science ®Google Scholar
• Malcolm BJ, Polanco M, Barsuglia JP. Changes in withdrawal and craving scores in participants undergoing opioid detoxification utilizing ibogaine. J Psychoact Drugs. 2018;50(3):256–65. doi:10.1080/02791072.2018.1447175.
   PubMed Web of Science ®Google Scholar
• Köck P, Froelich K, Walter M, Lang U, Dursteler KM. A systematic literature review of clinical trials and therapeutic applications of ibogaine. J Subst Abuse Treat. 2022;138:108717. doi:10.1016/j.jsat.2021.108717.
   PubMed Web of Science ®Google Scholar
• Davis AK, Barsuglia JP, Windham-Herman AM, Lynch M, Polanco M. Subjective effectiveness of ibogaine treatment for problematic opioid consumption: short- and long-term outcomes and current psychological functioning. J Psychedelic Stud. 2017;1(2):65–73. doi:10.1556/2054.01.2017.009.
   PubMedGoogle Scholar
• Mazoyer C, Carlier J, Boucher A, Peoc’h M, Lemeur C, Gaillard Y. Fatal case of a 27-year-old male after taking iboga in withdrawal treatment: GC-MS/MS determination of ibogaine and ibogamine in iboga roots and postmortem biological material. J Forensic Sci. 2013;58(6):1666–72. doi:10.1111/1556-4029.12250.
   PubMed Web of Science ®Google Scholar
• Asua I. Growing menace of ibogaine toxicity. Br J Anaesth. 2013;111(6):1029–30. doi:10.1093/bja/aet396.
   PubMed Web of Science ®Google Scholar
• Marta CJ, Ryan WC, Kopelowicz A, Koek RJ. Mania following use of ibogaine: a case series. Am J Addict. 2015;24(3):203–5. doi:10.1111/ajad.12209.
   PubMed Web of Science ®Google Scholar
• Brown TK, Alper K. Treatment of opioid use disorder with ibogaine: detoxification and drug use outcomes. Am J Drug Alcohol Abuse. 2018;44(1):24–36. doi:10.1080/00952990.2017.1320802.
   PubMed Web of Science ®Google Scholar
• Noller GE, Frampton CM, Yazar-Klosinski B. Ibogaine treatment outcomes for opioid dependence from a twelve-month follow-up observational study. Am J Drug Alcohol Abuse. 2018;44(1):37–46. doi:10.1080/00952990.2017.1310218.
   PubMed Web of Science ®Google Scholar
• Dickinson J, McAlpin J, Wilkins C, Fitzsimmons C, Guion P, Paterson T, Greene D, Chabes BR. Clinical guidelines for ibogaine-assisted detoxification. The Global Ibogaine Therapy Alliance; 2015. [accessed 2022 Sept 2]. Available from: https://s3.ca-central-1.amazonaws.com/ibosafe-pdf-resources/Ibogaine/Clinical+guidelines+for+ibogaine-assisted+detoxification.pdf
   Google Scholar
• Erowid. The vaults of Erowid: psychoactive plants and drugs. 1995. [accessed 2022 Sept 2]. Available from: https://erowid.org/psychoactives/
   Google Scholar
• Obembe SB. Common psychoactive drugs. In: Obembe SB, Ed. Practical skills and clinical management of alcoholism & drug addiction. Waltham, MA: Elsevier, Inc.; 2012. p. 11–32. https://www.sciencedirect.com/science/article/pii/B978012398518700002X.
   Google Scholar
• Belgers M, Leenaars M, Homberg JR, Ritskes-Hoitinga M, Schellekens AF, Hooijmans CR. Ibogaine and addiction in the animal model, a systematic review and meta-analysis. Transl Psychiatry. 2016;6(5):e826. doi:10.1038/tp.2016.71.
   PubMedGoogle Scholar
• Mash DC, Ameer B, Prou D, Howes JF, Maillet EL. Oral noribogaine shows high brain uptake and anti-withdrawal effects not associated with place preference in rodents. J Psychopharmacol. 2016;30(7):688–97. doi:10.1177/0269881116641331.
   PubMed Web of Science ®Google Scholar
• Ahmad I, Prabowo WC, Arifuddin M, Fadraersada J, Indriyanti N, Herman H, Purwoko RY, Nainu F, Rahmadi A, Paramita S, et al. Mitragyna species as pharmacological agents: from abuse to promising pharmaceutical products. Life (Basel). 2022;12(2):193. doi:10.3390/life12020193.
   PubMed Web of Science ®Google Scholar
• Anwar M, Law R, Schier J. Notes from the field: kratom (Mitragyna speciosa) exposures reported to poison centers - United States, 2010-2015. MMWR Morb Mortal Wkly Rep. 2016;65(29):748–9. doi:10.15585/mmwr.mm6529a4.
   PubMed Web of Science ®Google Scholar
• Eastlack SC, Cornett EM, Kaye AD. Kratom-pharmacology, clinical implications, and outlook: a comprehensive review. Pain Ther. 2020;9(1):55–69. doi:10.1007/s40122-020-00151-x.
   PubMed Web of Science ®Google Scholar
• Head shop. Merriam-Webster.com Dictionary, Merriam-Webster. [accessed 2022 Sept 8]. Available from: https://www.merriam-webster.com/dictionary/head%20shop
   Google Scholar
• Garcia-Romeu A, Cox DJ, Smith KE, Dunn KE, Griffiths RR. Kratom (Mitragyna speciosa): user demographics, use patterns, and implications for the opioid epidemic. Drug Alcohol Depend. 2020;208:107849. doi:10.1016/j.drugalcdep.2020.107849.
   PubMed Web of Science ®Google Scholar
• Oppel RA.Jr. Opioid users call kratom a godsend. The F.D.A. Says it’s a menace. The New York Times. 2019 Apr 17. [accessed 2022 Sept 8]. Available from: https://www.nytimes.com/2019/04/17/us/kratom-overdose-deaths.html.
   Google Scholar
• Sharma A, McCurdy CR. Assessing the therapeutic potential and toxicity of Mitragyna speciosa in opioid use disorder. Expert Opin Drug Metab Toxicol. 2021;17(3):255–7. doi:10.1080/17425255.2021.1853706.
   PubMed Web of Science ®Google Scholar
• Thomson J. Kratom vs. CBD: key differences between the herbal drugs taking over U.S. Newsweek. 2022 Aug 31. [accessed 2022 Sept 10]. Available from: https://www.newsweek.com/kratom-cbd-herbal-drugs-increased-usage-americans-1738625.
   Google Scholar
• United States Drug Enforcement Administration (DEA). Kratom. 2022. [Last accessed 2022 Sept 10]. Available from: https://www.dea.gov/factsheets/kratom
   Google Scholar
• Gianutsos G. The DEA changes its mind on kratom. U.S. Pharmacist. 2017;41 (3):7–9. [Last accessed 2022 Sept 10]. Available from: https://www.uspharmacist.com/article/the-dea-changes-its-mind-on-kratom.
   Google Scholar
• Bestha D. Kratom and the opioid crisis. Innov Clin Neurosci. 2018;15(5-6):11.
   PubMedGoogle Scholar
• Hiranita T, Obeng S, Sharma A, Wilkerson JL, McCurdy CR, McMahon LR. In vitro and in vivo pharmacology of kratom. Adv Pharmacol. 2022;93:35–76. doi:10.1016/bs.apha.2021.10.001.
   PubMedGoogle Scholar
• Kruegel AC, Gassaway MM, Kapoor A, Varadi A, Majumdar S, Filizola M, Javitch JA, Sames D. Synthetic and receptor signaling explorations of the mitragyna alkaloids: mitragynine as an atypical molecular framework for opioid receptor modulators. J Am Chem Soc. 2016;138(21):6754–64. doi:10.1021/jacs.6b00360.
   PubMed Web of Science ®Google Scholar
• Kruegel AC, Grundmann O. The medicinal chemistry and neuropharmacology of kratom: a preliminary discussion of a promising medicinal plant and analysis of its potential for abuse. Neuropharmacology. 2018;134(Pt A):108–20. doi:10.1016/j.neuropharm.2017.08.026.
   PubMed Web of Science ®Google Scholar
• Todd DA, Kellogg JJ, Wallace ED, Khin M, Flores-Bocanegra L, Tanna RS, McIntosh S, Raja HA, Graf TN, Hemby SE, et al. Chemical composition and biological effects of kratom (Mitragyna speciosa): in vitro studies with implications for efficacy and drug interactions. Sci Rep. 2020;10(1):19158. doi:10.1038/s41598-020-76119-w.
   PubMed Web of Science ®Google Scholar
• Weiss ST, Douglas HE. Treatment of kratom withdrawal and dependence with buprenorphine/naloxone: a case series and systematic literature review. J Addict Med. 2021;15(2):167–72. doi:10.1097/ADM.0000000000000721.
   PubMed Web of Science ®Google Scholar
• Kapp FG, Maurer HH, Auwarter V, Winkelmann M, Hermanns-Clausen M. Intrahepatic cholestasis following abuse of powdered kratom (Mitragyna speciosa). J Med Toxicol. 2011;7(3):227–31. doi:10.1007/s13181-011-0155-5.
   PubMedGoogle Scholar
• Prozialeck WC, Edwards JR, Lamar PC, Plotkin BJ, Sigar IM, Grundmann O, Veltri CA. Evaluation of the mitragynine content, levels of toxic metals and the presence of microbes in kratom products purchased in the western suburbs of Chicago. Int J Environ Res Public Health. 2020;17(15):5512. doi:10.3390/ijerph17155512.
   PubMed Web of Science ®Google Scholar
• Tobarran N, Wolf C, Cumpston KL, Wills BK. Pressure necrosis requiring fasciotomy after kratom overdose. J Addict Med. 2022;16(2):252–3. doi:10.1097/ADM.0000000000000873.
   PubMed Web of Science ®Google Scholar
• Umbehr G, Lukaszewicz M. Acute liver injury following short-term use of the herbal supplement kratom. JAAPA. 2022;35(2):39–41. doi:10.1097/01.JAA.0000805820.94245.3d.
   PubMedGoogle Scholar
• Singh D, Muller CP, Vicknasingam BK. Kratom (Mitragyna speciosa) dependence, withdrawal symptoms and craving in regular users. Drug Alcohol Depend. 2014;139(2):132–7. doi:10.1016/j.drugalcdep.2014.03.017.
   PubMedGoogle Scholar
• United States Drug Enforcement Administration (DEA). DEA announces intent to schedule kratom. 2016. [Last accessed 2022 Sept 12]. Available from: https://www.dea.gov/es/node/5295.
   Google Scholar
• Trakulsrichai S, Sathirakul K, Auparakkitanon S, Krongvorakul J, Sueajai J, Noumjad N, Sukasem C, Wananukul W. Pharmacokinetics of mitragynine in man. Drug Des Devel Ther. 2015;9:2421–9. doi:10.2147/DDDT.S79658.
   PubMed Web of Science ®Google Scholar
• Bowe A, Kerr PL. A complex case of kratom dependence, depression, and chronic pain in opioid use disorder: effects of buprenorphine in clinical management. J Psychoact Drugs. 2020;52(5):447–52. doi:10.1080/02791072.2020.1773586.
   PubMed Web of Science ®Google Scholar
• Gittins R, Cole S. Buprenorphine for the management of kratom dependency during covid-19: a case report. Drug Science, Policy and Law; 2021, p. 7. doi:10.1177/20503245211021193.
   Google Scholar
• Rogers JM, Smith KE, Strickland JC, Epstein DH. Kratom use in the US: both a regional phenomenon and a white middle-class phenomenon? Evidence from NSDUH 2019 and an online convenience sample. Front Pharmacol. 2021;12:789075. doi:10.3389/fphar.2021.789075.
   PubMed Web of Science ®Google Scholar
• Grundmann O. Patterns of kratom use and health impact in the US-results from an online survey. Drug Alcohol Depend. 2017;176:63–70. doi:10.1016/j.drugalcdep.2017.03.007.
   PubMed Web of Science ®Google Scholar
• Schimmel J, Amioka E, Rockhill K, Haynes CM, Black JC, Dart RC, Iwanicki JL. Prevalence and description of kratom (Mitragyna speciosa) use in the United States: a cross-sectional study. Addiction. 2021;116(1):176–81. doi:10.1111/add.15082.
   PubMed Web of Science ®Google Scholar
• Singh D, Yeou Chear NJ, Narayanan S, Leon F, Sharma A, McCurdy CR, Avery BA, Balasingam V. Patterns and reasons for kratom (Mitragyna speciosa) use among current and former opioid poly-drug users. J Ethnopharmacol. 2020;249:112462. doi:10.1016/j.jep.2019.112462.
   PubMed Web of Science ®Google Scholar
• Harun N, Kamaruzaman NA, Mohamed Sofian Z, Hassan Z. Mini review: potential therapeutic values of mitragynine as an opioid substitution therapy. Neurosci Lett. 2022;773:136500. doi:10.1016/j.neulet.2022.136500.
   PubMed Web of Science ®Google Scholar
• Prevete E, Kuypers KPC, Theunissen EL, Corazza O, Bersani G, Ramaekers JG. A systematic review of (pre)clinical studies on the therapeutic potential and safety profile of kratom in humans. Hum Psychopharmacol. 2022;37(1):e2805. doi:10.1002/hup.2805.
   PubMed Web of Science ®Google Scholar
• Hassan R, Pike See C, Sreenivasan S, Mansor SM, Muller CP, Hassan Z. Mitragynine attenuates morphine withdrawal effects in Rats-A comparison with methadone and buprenorphine. Front Psychiatry. 2020;11:411. doi:10.3389/fpsyt.2020.00411.
   PubMed Web of Science ®Google Scholar
• Hemby SE, McIntosh S, Leon F, Cutler SJ, McCurdy CR. Abuse liability and therapeutic potential of the Mitragyna speciosa (kratom) alkaloids mitragynine and 7-hydroxymitragynine. Addict Biol. 2019;24(5):874–85. doi:10.1111/adb.12639.
   PubMed Web of Science ®Google Scholar
• Meepong R, Sooksawate T. Mitragynine reduced morphine-induced conditioned place preference and withdrawal in rodents. Thai J Pharm Sci. 2019;43 (1):21–29. [Last accessed 2022 Sept 12]. Available from: http://www.tjps.pharm.chula.ac.th/ojs/index.php/tjps/article/view/892.
   Google Scholar
• Yue K, Kopajtic TA, Katz JL. Abuse liability of mitragynine assessed with a self-administration procedure in rats. Psychopharmacology (Berl)). 2018;235(10):2823–9. doi:10.1007/s00213-018-4974-9.
   PubMed Web of Science ®Google Scholar
• Wilson LL, Harris HM, Eans SO, Brice-Tutt AC, Cirino TJ, Stacy HM, Simons CA, Leon F, Sharma A, Boyer EW, et al. Lyophilized kratom tea as a therapeutic option for opioid dependence. Drug Alcohol Depend. 2020;216:108310. doi:10.1016/j.drugalcdep.2020.108310.
   PubMed Web of Science ®Google Scholar
• Cheaha D, Reakkamnuan C, Nukitram J, Chittrakarn S, Phukpattaranont P, Keawpradub N, Kumarnsit E. Effects of alkaloid-rich extract from Mitragyna speciosa (Korth.) Havil. on naloxone-precipitated morphine withdrawal symptoms and local field potential in the nucleus accumbens of mice. J Ethnopharmacol. 2017;208:129–37. doi:10.1016/j.jep.2017.07.008.
   PubMed Web of Science ®Google Scholar
• Fakurazi S, Rahman SA, Hidayat MT, Ithnin H, Moklas MA, Arulselvan P. The combination of mitragynine and morphine prevents the development of morphine tolerance in mice. Molecules. 2013;18(1):666–81. doi:10.3390/molecules18010666.
   PubMed Web of Science ®Google Scholar
• Harun N, Johari IS, Mansor SM, Shoaib M. Assessing physiological dependence and withdrawal potential of mitragynine using schedule-controlled behaviour in rats. Psychopharmacology (Berl)). 2020;237(3):855–67. doi:10.1007/s00213-019-05418-6.
   PubMed Web of Science ®Google Scholar
• Kosten TR, Baxter LE. Review article: effective management of opioid withdrawal symptoms: a gateway to opioid dependence treatment. Am J Addict. 2019;28(2):55–62. doi:10.1111/ajad.12862.
   PubMed Web of Science ®Google Scholar
• Kampman K, Jarvis M, American Society of Addiction Medicine (ASAM). National practice guideline for the use of medications in the treatment of addiction involving opioid use. J Addict Med. 2015;9(5):358–67. doi:10.1097/ADM.0000000000000166.
   PubMed Web of Science ®Google Scholar