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A case report of inpatient detoxification after kratom (Mitragyna speciosa) dependence

McWhirter L, Morris S

Eur Addict Res, 2010;16(4):229-31.
PMID: 20798544 DOI: 10.1159/000320288

Kratom (Mitragyna speciosa) has been used for medicinal and recreational purposes. It has reported analgesic, euphoric and antitussive effects via its action as an agonist at opioid receptors. It is illegal in many countries including Thailand, Malaysia, Myanmar, South Korea and Australia; however, it remains legal or uncontrolled in the UK and USA, where it is easily available over the Internet. We describe a case of kratom dependence in a 44-year-old man with a history of alcohol dependence and anxiety disorder. He demonstrated dependence on kratom with withdrawal symptoms consisting of anxiety, restlessness, tremor, sweating and cravings for the substance. A reducing regime of dihydrocodeine and lofexidine proved effective in treating subjective and objective measures of opioid-like withdrawal phenomena, and withdrawal was relatively short and benign. There are only few reports in the literature of supervised detoxification and drug treatment for kratom dependence. Our observations support the idea that kratom dependence syndrome is due to short-acting opioid receptor agonist activity, and suggest that dihydrocodeine and lofexidine are effective in supporting detoxification.

Matched MeSH terms: Mitragyna/adverse effects*
The prevalence of psychotic symptoms in kratom (Mitragyna speciosa Korth.) Users in Malaysia

Leong Bin Abdullah MFI, Singh D, Swogger MT, Rahim AA, Vicknasingam B

Asian J Psychiatr, 2019 Jun;43:197-201.
PMID: 31302592 DOI: 10.1016/j.ajp.2019.07.008

BACKGROUND: Kratom is a traditional medicinal herb widely used in Malaysia and Thailand. Despite its widespread use and statements by regulatory agencies on the potential for kratom-associated psychosis, there is little data regarding the prevalence of psychotic symptoms among kratom users. This study investigated the prevalence of psychosis among kratom users, described psychotic symptomatology and severity, while examining associations between kratom use characteristics and the occurrence of psychotic symptoms.
METHODS: This cross-sectional clinical survey recruited 150 regular kratom users. The Mini International Neuropsychiatric Interview (MINI) and Diagnostic and Statistical Manual of Mental Disorders 5th Edition (DSM-V) diagnostic criteria were used to evaluate psychotic symptomatology among kratom users, and the Brief Psychiatric Rating Scale (BPRS) was used to assess the severity of psychiatric symptoms. Chi-square tests with Yate's correction were performed to determine the association between kratom use characteristics and the occurrence of psychotic symptoms among kratom users in this study.
RESULTS: Six out of 150 kratom users (4%) presented with any psychotic symptoms. The psychotic symptoms reported were positive symptoms and thought alienation, with a mean BPRS score of 33 (i.e., mild severity). Variables related to kratom use (such as intake of kratom with diphenhydramine, duration of kratom use, and quantity and frequency of daily kratom use) were not associated with the occurrence of psychotic symptoms among kratom users.
CONCLUSION: Although psychotic symptoms could occur among regular kratom users, they were rare and not significantly associated with kratom use characteristics. We found no evidence of elevated psychosis among regular users.

Matched MeSH terms: Mitragyna/adverse effects*
Fulltext The informal use of ketum (Mitragyna speciosa) for opioid withdrawal in the northern states of peninsular Malaysia and implications for drug substitution therapy

Vicknasingam B, Narayanan S, Beng GT, Mansor SM

Int J Drug Policy, 2010 Jul;21(4):283-8.
PMID: 20092998 DOI: 10.1016/j.drugpo.2009.12.003

BACKGROUND: Ketum (krathom) has been mentioned in the literature as a traditional alternative to manage drug withdrawal symptoms though there are no studies indicating its widespread use for this purpose. This study examines the reasons for ketum consumption in the northern areas of peninsular Malaysia where it is widely used.
METHODS: A cross-sectional survey of 136 active users was conducted in the northern states of Kedah and Penang in Malaysia. On-site urine screening was done for other substance use.
FINDINGS: Ketum users were relatively older (mean 38.7 years) than the larger substance using group. Nearly 77% (104 subjects) had previous drug use history, whilst urine screening confirmed 62 subjects were also using other substances. Longer-term users (use >2 years) had higher odds of being married, of consuming more than the average three glasses of ketum a day and reporting better appetite. Short-term users had higher odds of having ever used heroin, testing positive for heroin and of using ketum to reduce addiction to other drugs. Both groups used ketum to reduce their intake of more expensive opiates, to manage withdrawal symptoms and because it was cheaper than heroin. These findings differ from those in neighbouring Thailand where ketum was used primarily to increase physical endurance.
CONCLUSIONS: No previous study has shown the use of ketum to manage opioid withdrawal symptoms except for a single case reported in the US. Ketum was described as affordable, easily available and having no serious side effects despite prolonged use. It also permitted self-treatment that avoids stigmatisation as a drug dependent. The claims of so many subjects on the benefits of ketum merits serious scientific investigation. If prolonged use is safe, the potential for widening the scope and reach of substitution therapy and lowering its cost are tremendous, particularly in developing countries.

Matched MeSH terms: Mitragyna/adverse effects
Long-Term Cognitive Effects of Kratom (Mitragyna speciosa Korth.) Use

Singh D, Narayanan S, Müller CP, Vicknasingam B, Yücel M, Ho ETW, et al.

J Psychoactive Drugs, 2018 12 15;51(1):19-27.
PMID: 30556488 DOI: 10.1080/02791072.2018.1555345

Kratom or Mitragyna speciosa (Korth.) is a medicinal plant of Southeast Asia. As a result of its opioid-like effects, it remains unknown whether consumption of kratom tea is associated with impaired cognitive function. We assessed the cognitive function of 70 regular kratom users and 25 control participants using the Cambridge Neuropsychological Test Automated Battery. Participants performed six neuropsychological tasks that assessed motor, learning and memory, attention and executive function. Relative to control participants, higher consumption (>3 glasses daily or mitragynine doses between 72.5 mg and 74.9 mg) of kratom tea was selectively associated with impaired performance on the Paired Associates Learning task, reflecting deficits in visual episodic memory and new learning. Overall, the performance of kratom users compared to control participants, and the performance of high (>3 glasses per day) as well as low (≤3 glasses per day) kratom using groups, were comparable on all neuropsychological domains. Higher intake of kratom juice (>3 glasses daily) did not appear to impair motor, memory, attention or executive function of regular kratom users.

Matched MeSH terms: Mitragyna/adverse effects*
Fulltext Kratom policy: The challenge of balancing therapeutic potential with public safety

Prozialeck WC, Avery BA, Boyer EW, Grundmann O, Henningfield JE, Kruegel AC, et al.

Int J Drug Policy, 2019 08;70:70-77.
PMID: 31103778 DOI: 10.1016/j.drugpo.2019.05.003

Kratom (Mitragyna speciosa) is a tree-like plant indigenous to Southeast Asia. Its leaves, and the teas brewed from them have long been used by people in that region to stave off fatigue and to manage pain and opioid withdrawal. Evidence suggests kratom is being increasingly used by people in the United States and Europe for the self-management of opioid withdrawal and treatment of pain. Recent studies have confirmed that kratom and its chemical constituents have potentially useful pharmacological actions. However, there have also been increasing numbers of reports of adverse effects resulting from use of kratom products. In August 2016, the US Drug Enforcement Administration announced plans to classify kratom and its mitragynine constituents as Schedule I Controlled Substances, a move that triggered a massive response from pro-kratom advocates. The debate regarding the risks, and benefits and safety of kratom continues to intensify. Kratom proponents tout kratom as a safer and less addictive alternative to opioids for the management of pain and opioid addiction. The anti-kratom faction argues that kratom, itself, is a dangerous and addictive drug that ought to be banned. Given the widespread use of kratom and the extensive media attention it is receiving, it is important for physicians, scientists and policy makers to be knowledgeable about the subject. The purpose of this commentary is to update readers about recent developments and controversies in this rapidly evolving area. All of the authors are engaged in various aspects of kratom research and it is our intention to provide a fair and balanced overview that can form the basis for informed decisions on kratom policy. Our conclusions from these analyses are: (a) User reports and results of preclinical studies in animals strongly suggest that kratom and its main constituent alkaloid, mitragynine may have useful activity in alleviating pain and managing symptoms of opioid withdrawal, even though well-controlled clinical trials have yet to be done. (b) Even though kratom lacks many of the toxicities of classic opioids, there are legitimate concerns about the safety and lack of quality control of purported "kratom" products that are being sold in the US. (c) The issues regarding the safety and efficacy of kratom and its mitragynine constituent can only be resolved by additional research. Classification of the Mitragyna alkaloids as Schedule I controlled substances would substantially impede this important research on kratom.

Matched MeSH terms: Mitragyna/adverse effects*
From Kratom to mitragynine and its derivatives: physiological and behavioural effects related to use, abuse, and addiction

Hassan Z, Muzaimi M, Navaratnam V, Yusoff NH, Suhaimi FW, Vadivelu R, et al.

Neurosci Biobehav Rev, 2013 Feb;37(2):138-51.
PMID: 23206666 DOI: 10.1016/j.neubiorev.2012.11.012

Kratom (or Ketum) is a psychoactive plant preparation used in Southeast Asia. It is derived from the plant Mitragyna speciosa Korth. Kratom as well as its main alkaloid, mitragynine, currently spreads around the world. Thus, addiction potential and adverse health consequences are becoming an important issue for health authorities. Here we reviewed the available evidence and identified future research needs. It was found that mitragynine and M. speciosa preparations are systematically consumed with rather well defined instrumentalization goals, e.g. to enhance tolerance for hard work or as a substitute in the self-treatment of opiate addiction. There is also evidence from experimental animal models supporting analgesic, muscle relaxant, anti-inflammatory as well as strong anorectic effects. In humans, regular consumption may escalate, lead to tolerance and may yield aversive withdrawal effects. Mitragynine and its derivatives actions in the central nervous system involve μ-opioid receptors, neuronal Ca²⁺ channels and descending monoaminergic projections. Altogether, available data currently suggest both, a therapeutic as well as an abuse potential.

Matched MeSH terms: Mitragyna/adverse effects*
Is kratom (Mitragyna speciosa Korth.) use associated with ECG abnormalities? Electrocardiogram comparisons between regular kratom users and controls

Leong Abdullah MFI, Tan KL, Narayanan S, Yuvashnee N, Chear NJY, Singh D, et al.

Clin Toxicol (Phila), 2021 May;59(5):400-408.
PMID: 32870119 DOI: 10.1080/15563650.2020.1812627

OBJECTIVES: Little is known about the cardiotoxic effects of kratom (Mitragyna speciosa Korth.), a medicinal plant. This analytical cross-sectional study investigated the prevalence of electrocardiogram (ECG) abnormalities and QTc intervals in regular kratom users compared with non-kratom-using control subjects.
METHODS: We enrolled regular kratom users and non-kratom-using control subjects from three communities. Demographic data, clinical data, kratom use characteristics, and ECG findings were recorded. The mitragynine content of kratom juice was quantified using a validated gas chromatography-mass spectrometry (GC-MS) method.
RESULTS: A total of 200 participants (100 kratom users and 100 control subjects) participated in this study. The prevalence of ECG abnormalities in kratom users (28%) did not differ from that of control subjects (32%). Kratom use was not associated with ECG abnormalities, except for significantly higher odds of sinus tachycardia (OR = 8.61, 95% CI = 1.06-70.17, p = 0.035) among kratom users compared with control subjects. The odds of observing borderline QTc intervals were significantly higher for kratom users compared with control subjects, regardless of the age of first use, the duration of use, the daily quantity consumed, and the length of time that had elapsed between last kratom use and ECG assessment. Nevertheless, there were no differences in the odds of having prolonged QTc intervals between kratom users and controls. The estimated average daily intake of mitragynine consumed by kratom users was 434.28 mg.
CONCLUSION: We found no link between regular kratom use and electrocardiographic abnormalities with an estimated average daily intake of 434.28 mg of mitragynine.

Matched MeSH terms: Mitragyna/adverse effects*