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Self-treatment of opioid withdrawal using kratom(
Mitragynia speciosa korth
)
Edward W. Boyer
1
, Kavita M. Babu
1
, Jessica E. Adkins
2
, Christopher R. McCurdy
2,3
& John H. Halpern
4
Division of MedicalToxicology,Department of Emergency Medicine,University of Massachusetts Medical School,Worcester,MA,USA,
1
Departments of MedicinalChemistry
2
and Pharmacology,
3
School of Pharmacy, University of Mississippi, Oxford, MS, USA and Biological Psychiatry Laboratory, Alcohol and Drug AbuseResearch Center, McLean Hospital, Harvard Medical School, Belmont, MA, USA
4
ABSTRACT
Background
Kratom (
Mitragynia speciosa korth
) is recognized increasingly as a remedy for opioid withdrawal byindividuals who self-treat chronic pain.
Case description
A patient who had abruptly ceased injection hydromor-phone abuse self-managed opioid withdrawal and chronic pain using kratom. After co-administering the herb withmodafinil he experienced a tonic-clonic seizure, but he reported only modest abstinence once kratom administrationstopped. We confirmed the identity of the plant matter he ingested as kratom and identified no contaminants oradulterants. We also conducted high-throughput molecular screening and the binding affinity at mu, delta and kappareceptors of mitragynine.
Conclusion
We report the self-treatment of chronic pain and opioid withdrawal withkratom.The predominant alkaloid of kratom, mitragynine, binds mu- and kappa-opioid receptors, but has additionalreceptor affinities that might augment its effectiveness at mitigating opioid withdrawal.The natural history of kratomuse, including its clinical pharmacology and toxicology, are poorly understood.
Keywords
Dependence, kratom, molecular screening, opioid, opioid replacement, withdrawal.
Correspondence to:
EdwardW.Boyer,Departmentof EmergencyMedicine,Universityof MassachusettsMedicalSchool,55LakeAvenueNorth,Worcester,MA 01655, USA. E-mail: edward.boyer@childrens.harvard.eduSubmitted 23 November 2007; initial review completed 17 January 2008; final version accepted 8 February 2008
INTRODUCTION
Kratom (
Mitragynia speciosa korth
) is a medicinal herbindigenous to Southeast Asia whose componentsmitragynine and 7-hydroxymitragynine agonize themu-opioid receptor with high affinity [1–3]. Recent find-ings suggest that kratom is purchased from internetsources by some of the 40 million Americans withchronicpaintoself-manageopioidwithdrawal[1].Unfor-tunately, the reasons underlying this practice, its efficacyor adverse effects are poorly understood. We present acase of kratom used to self-manage chronic pain andopioid withdrawal complicated by a potential interactionwith modafinil.
CASE PRESENTATION
A43-year-oldmalewasadmittedforevaluationof agen-eralizedtonic-clonicseizure.Hismedicalhistoryincludedchronic pain from thoracic outlet syndrome treated withhydromorphone. As his tolerance escalated, he beganinjectingsubcutaneously10 mghydromorphoneperdayfrom crushed pills. During periods when hydromorphonewas unavailable, he managed opioid withdrawal withkratom purchased from internet vendors.Approximately 3.5 years before presentation, socialstressorscompelledhimtoquithydromorphoneabruptly.He again averted opioid withdrawal by ingesting a teamadefromkratomfourtimesaday.Thepatientattributedsubstantial pain relief to kratom as well as improvedalertness.Hedidnot,however,experiencethedrowsinessthatoftenaccompaniedopioiduse.Hespent$15 000peryear on kratom, a sum confirmed by his wife.Inanattempttoimprovealertnessfurther,thepatientexperimented with the co-administration of 100 mgmodafinil with kratom. Twenty minutes following inges-tion, he experienced a generalized tonic-clonic seizurelasting 5 minutes. He had the following vital signs on
CASE REPORT
doi:10.1111/j.1360-0443.2008.02209.x© 2008 The Authors. Journal compilation © 2008 Society for the Study of Addiction
Addiction
,
103
, 1048–1050
presentation: pulse 123 beats per minute, blood pressure130/74 mm/Hg, respiratory rate 16; he was afebrile.After a brief post-ictal period, his physical examinationwas normal except for meiosis. He had no previoushistoryof seizuresorheadtrauma,andhedeniedalcoholorrecentillicitdrugabuse.Laboratorystudieswereunre-markable; qualitative urine drugs of abuse and compre-hensive toxicology screening identified only modafinil.Computerized tomography and magnetic resonanceimaging of the brain were normal. We identified no adul-terants or contaminants. Upon discharge, the patientabruptly ceased use of kratom and sought the care of anaddiction specialist.He described a period of withdrawal considerably lessintense but more protracted than that from prescriptionopioids. Physician-observed features of kratom includedrhinorrhea, insomnia, poor concentration, constrictedaffect and myalgias persisting for 10 days from his lastdoseof kratom.Topreventrelapse,anaddictionspecialistprescribed buprenorphine/naloxone, reaching a mainte-nance dose of 16 mg per day. Rhinorrhea ceased on thefirst day of suboxone therapy. The patient currentlyreports adequate pain control, and follow-up urinescreens for drugs of abuse have remained negative. Weconfirmedtheidentityof theplantmatteringestedbythepatient as kratom by comparison against a known stan-dard(PureLandEthnobotanicals,Madison,WI,USA)uti-lizing existing extraction and high-performance liquidchromatography protocols.
DISCUSSION
We report the protracted use of kratom for chronic paintreatment and opioid replacement therapy. Opioid anal-gesicsremainhighlyeffectivemodalitiesforthetreatmentof chronic pain, but their long-term administration isassociated with the development of opioid misuse, abuse,dependence and addiction, the incidence of which isincreasing[4].Amongindividualswithchronicpainwhoare maintained on opioid analgesic agents, kratom isgainingawarenessasa‘natural’alternativetophysician-supervised opioid replacement therapy [1].One striking finding of this report is the extent towhich kratom attenuates potentially severe opioid with-drawal, yet cessation of kratom administration itself appears to be associated with modest abstinence symp-toms. The pharmacological bases underlying this effectare uncertain. For example, mitragynine is theorized tostimulate contributions from adrenergic and serotoner-gicpathwaysthataugmentanalgesia,butformalbindingdata have been obtained only for mu-, delta- and kappa-opioid receptors [5,6]. To delineate more clearly the
in vitro
pharmacology of kratom, we conducted high-throughput molecular screening of mitragynine activityat central nervous system receptors (Novascreen Bio-sciences Corp., Hanover, MD, USA); these studies identi-fied that mitragynine extensively inhibits radioligandbinding at several central nervous system receptorsystems(Table 1).Theclinicalimplicationof theseresultsis that mu-opioid agonism may avert withdrawal symp-toms,whilekappaagonismattenuatesreinforcementandproduces aversion [7]. In addition, mitragynine, throughits putative alpha-2 adrenergic agonist activity, maymimic adjunctive therapies for opioid withdrawal such asclonidine. Mitragynine, therefore, may exert several con-vergent pharmacological effects that could attenuateopioid withdrawal symptoms and blunt cravings.Adverse effects from kratom are poorly described.Althoughmitragyninesagonizemu-opioidreceptors,res-piratory depression, coma, pulmonary edema and deathhave not, to our knowledge, been associated with humankratom ingestion. Furthermore, the protracted use of kratom as a single therapy did not appear to produceany significant adverse effects in this patient; not untilco-administration with modafinil was a potential adverseeffect of kratom identified. The exact mechanisms thatcontribute to seizure are undefined. The mitragynines,their metabolites or other components of kratom couldpotentially exhibit proconvulsant properties similar toatypical opioids such as tramadol, the meperidinemetabolite normeperidine and propoxyphene [8]. Syner-gism between kratom and modafinil might also produceseizure, but considering that modafinil is not likely topossess proconvulsant properties, this latter mechanismappears speculative.The risk correlates of kratom use as well as outcomesfrom its long-term administration are unknown. Initia-tionof kratomusemayreflectincreasinginterestinalter-native therapies for chronic medical problems [9,10].Alternatively, some patients with chronic pain may per-
Table 1
Central nervous system receptor binding data formitragynine.Percentage inhibition of radioligand binding by mitragynine atselected receptor systemsAdenosine A2A: 65.66Adrenergic (Alpha 2): 61.92Dopamine D2s 54.22Opioid, mu 89.52Opioid, kappa 90.21Opioid, delta 7.00Serotonin, 5HT2C 58.77Serotonin, 5HT7 64.41Dissociation constants for opioid receptor bindingMu receptor: 204
26 nMDelta receptor: 2250
120 nMKappa receptor: 455
47 nM
CNS binding, kratom and opioid withdrawal
1049
© 2008 The Authors. Journal compilation © 2008 Society for the Study of Addiction
Addiction
,
103
, 1048–1050
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