Abstract
Kratom (Mitragyna speciosa), a naturally existing plant found in South-East Asia, is traditionally used as a herb to help elevate a person’s energy and also to treat numerous medical ailments. Other than the analgesic property, kratom has been used as an agent to overcome opioid withdrawal as it contains natural alkaloids, i.e. mitragynine, 7-hydroxymitragynine, and MGM-9, which has agonist affinity on the opioid receptors, including mu (µ) and kappa (κ). The role of neural reward pathways linked to µ-opioid receptors and both dopaminergic and gamma-Aminobutyric acid (GABA)-ergic interneurons that express µ-opioid receptors were deliberated. However, kratom has been reported to be abused together with other illicit substances with high risk of potential addiction. There are also anecdotes of adverse effects and toxicity of kratom, i.e. tremor, fatigue, seizure, and death. Different countries have distinctive regulation and policy on the plantation and use of this plant when most of the countries banned the use of it because of its addiction problems and side effects. The aim of this review is to highlight on the potential use of kratom, unique ‘herbs” as a substitution therapy for chronic pain and opioid addiction, based on the neurobiological perspective of pain and the underlying mechanism of actions of drug addiction.
Keywords: Ketum, kratom, mitragyna speciose, mitragynine, 7-hydroxymitragynine, opioid receptors.
Graphical Abstract
[1]
Singh D, Müller CP, Vicknasingam BK, Mansor SM. Social functioning of kratom (Mitragynaspeciosa) users in malaysia. J Psychoactive Drugs 2015; 47: 125-31.
[2]
Aris M, Moklas M, Suliman NA, et al. Sedative, cognitive impairment and anxiolytic effects of acute. J US-China Med Sci 2013; 10: 37-44.
[3]
Griffin OH 3rd, Daniels JA, Gardner EA. Do you get what you paid for? An examination of products advertised as kratom. J Psychoactive Drugs 2016; 1072: 1-6.
[4]
Lu S, Tran BN, Nelsen JL, Aldous KM. Quantitative analysis of mitragynine in human urine by high performance liquid chromatography-tandem mass spectrometry. J Chromatogr B Analyt Technol Biomed Life Sci 2009; 877: 2499-505.
[5]
Cinosi E, Martinotti G, Simonato P, et al.
Following “the roots” of
kratom (Mitragynaspeciosa): The evolution of an enhancer from a
traditional use to increase work and productivity in southeast asia
to a recreational psychoactive drug in western countries.
Biomed
Res Int 2015 2015.
[6]
Singh D, Müller CP, Vicknasingam BK. Kratom (Mitragynaspeciosa) dependence, withdrawal symptoms and craving in regular users. Drug Alcohol Depend 2014; 139: 132-7.
[8]
Jansen KLR, Prast CJ. Ethnopharmacology of kratom and the Mitragyna Alkaloids. J Ethnopharmacol 1988; 23: 115-9.
[9]
Watanabe K, Yano S, Horie S, Yamamoto LT. Inhibitory effect of mitragynine, an alkaloid with analgesic effect from Thai medicinal plant Mitragynaspeciosa, on electrically stimulated contraction of isolated guinea-pig ileum through the opioid receptor. Life Sci 1997; 60: 933-42.
[10]
Siebert D. The kratom user’s guide [Internet]. Sagewisdom.org.
2016 Oct 12 [cited 2017 Feb 24]. Available from http:// www.sagewisdom.org/kratomguide.html
[11]
Bernama Ketum snacks new trend go ketum abuse.
malaysiandigest.com. 2016 Jul 13 [cited 2017 Feb 20]. Available
from http://malaysiandigest.com/news/621212-ketum-snacks-new-trend-of-ketum-abuse.html
[12]
Prozialeck WC. Update on the pharmacology and legal status of Kratom. J Am Osteopath Assoc 2016; 116: 802-9.
[13]
Hassan Z, Muzaimi M, Navaratnam V, et al. From Kratom to mitragynine and its derivatives: Physiological and behavioural effects related to use, abuse, and addiction. Neurosci Biobehav Rev 2013; 37: 138-51.
[14]
Dumas EO, Pollack GM. Opioid tolerance development: A pharmacokinetic/pharmacodynamic perspective. AAPS J 2008; 10(4): 537-51.
[16]
Kruegel AC, Gassaway MM, Kapoor A, et al. 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: 6754-64.
[17]
Yamamoto LT, Horie S, Takayama H, et al. Opioid receptor agonistic characteristics of mitragyninepseudoindoxyl in comparison with mitragynine derived from Thai medicinal plant Mitragynaspeciosa. Gen Pharmacol 1999; 33: 73-81.
[18]
Idid SZ, Saad LB, Yaacob H, Shahimi MM. Evaluation of analgesia induced by mitragynine, morphine and paracetamol on mice. ASEAN Rev Biodivers Environ Conserv 1998; pp. pp. 1-7.
[19]
Matsumoto K, Horie S, Ishikawa H, et al. Antinociceptive effect of 7-hydroxymitragynine in mice: Discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragynaspeciosa. Life Sci 2004; 74: 2143-55.
[20]
Matsumoto K, Horie S, Takayama H, et al. Antinociception, tolerance and withdrawal symptoms induced by 7-hydroxymitragynine, an alkaloid from the Thai medicinal herb Mitragynaspeciosa. Life Sci 2005; 78: 2-7.
[21]
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; 45: 1949-56.
[22]
Dhawan BN, Cesselin F, Raghubir R, et al. International Union of Pharmacology. XII. Classification of opioid receptors. Pharmacol Rev 1996; 48: 567-92.
[23]
Matsumoto K, Takayama H, Narita M, et al. MGM-9 [(E)-methyl 2-(3-ethyl-7a, 12a-(epoxyethanoxy)-9-fluoro-1, 2, 3, 4, 6, 7, 12, 12b-octahydro-8-methoxyindolo [2, 3-a] quinolizin-2-yl)-3-methoxyacrylate], a derivative of the indole alkaloid mitragynine: A novel dual-acting μ-and κ-opioid agonist with potent antinociceptive and weak rewarding effects in mice. Neuropharmacology 2008; 55: 154-65.
[24]
Prozialeck WC, Jivan JK, Andurkar SV. Pharmacology of kratom: an emerging botanical agent with stimulant, analgesic and opioid-like effects. J Am Osteopath Assoc 2012; 112: 792-9.
[25]
Guo Y, Wang HL, Xiang XH, Zhao Y. The role of glutamate and its receptors in mesocorticolimbic dopaminergic regions in opioid addiction. Neurosci Biobehav Rev 2009; 33: 864-73.
[26]
Lingford-Hughes A, Watson B, Kalk N, Reid A. Neuropharmacology of addiction and how it informs treatment. Br Med Bull 2010; 96: 93-110.
[27]
Hyman SE, Malenka RC, Nestler EJ. Neural mechanisms of addiction: The Role of Reward-Related Learning and Memory. Annu Rev Neurosci 2006; 29(1): 565-98.
[28]
Vicknasingam B, Narayanan S, Beng GT, Mansor SM. The informal use of ketum (Mitragynaspeciosa) for opioid withdrawal in the northern states of peninsular Malaysia and implications for drug substitution therapy. Int J Drug Policy 2010; 21: 283-8.
[29]
Swogger MT, Hart E, Erowid F, et al. Experiences of kratom users: A qualitative analysis. J Psychoactive Drugs 2015; 47(5): 360-7.
[30]
Singh D, Müller CP, Vicknasingam BK, Mansor SM. Social functioning of kratom (Mitragynaspeciosa) users in malaysia. J Psychoactive Drugs 2015; 47: 125-31.
[31]
Boyer EW, Babu KM, Adkins JE, McCurdy CR, Halpern JH. Self-treatment of opioid withdrawal using kratom (Mitragyniaspeciosakorth). Addiction 2008; 103: 1048-50.
[32]
Reanmongkol W, Keawpradub N, Sawangjaroen K. Effects of the extracts from MitragynaspeciosaKorth. leaves on analgesic and behavioral activities in experimental animals. Songklanakarin J Sci Technol 2007; 29: 39-48.
[33]
Nelsen JL, Lapoint J, Hodgman MJ, Aldous KM. Seizure and coma following kratom (MitragyninaspeciosaKorth) exposure. J Med Toxicol 2010; 6: 424-6.
[34]
Neerman MF, Frost RE, Deking J. A drug fatality involving kratom.
J Forensic Sci 2013; 58(SUPPL. 1).
[35]
McWhirter L, Morris S. A case report of inpatient detoxification after kratom (Mitragynaspeciosa) dependence. Eur Addict Res 2010; 16: 229-31.
[37]
Farah Idayu N, Taufik Hidayat M, Moklas MAM, et al. Antidepressant-like effect of mitragynine isolated from MitragynaspeciosaKorth in mice model of depression. Phytomedicine 2011; 18: 402-7.
[38]
Land BB, Bruchas MR, Lemos JC, et al. The dysphoric component of stress is encoded by activation of the dynorphin κ-opioid system. J Neurosci 2008; 28: 407-14.
[40]
Leonhart MM. “Drugs of Abuse: A Dea Resource Guide” edited by Department of Justice, 84. Washington, DC: Drug Enforcement Administration-US DOJ 2011.
[41]
Yusoff NHM, Suhaimi FW, Vadivelu RK, et al. Abuse potential and adverse cognitive effects of mitragynine (kratom). Addict Biol 2016; 21: 98-110.
[42]
Fishbain D, Rosomoff H. Drug abuse, dependence, and addiction in chronic pain patients. Clin J Pain 1992; 8: 77-85.
[43]
Boyer E, Babu K, Macalino G, Compton W. Self-treatment of opioid withdrawal with a dietary supplement, Kratom. Am J Addict 2007; 16: 352-6.
[44]
Takayama H, Ishikawa H, Kurihara M, Kitajima M, Aimi N, Ponglux D. 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; 45: 1949-56.
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