History of Kratom: From Traditional Use to Modern Research

This article traces that development using primary literature, peer-reviewed studies and official sources. Reports of traditional practice are not presented as clinical evidence of efficacy. The text is provided for information only and does not recommend any use.

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Traditional use in Thailand and Malaysia

Fresh leaves were documented as being chewed in Thailand, while decoctions were also consumed in the northern Malay Peninsula. In a 1975 Thai study, market gardeners, farmers and other labourers reported using kratom in connection with physically demanding work. The same source recorded traditional use for diarrhoea and as a substitute associated with opium use1.

In 1930, Burkill and Haniff recorded information collected from Malay healers and botanically identified specimens, including the use of pounded leaves as a wound poultice and a decoction in connection with opium craving2. A later cross-sectional survey of 136 active users in northern Malaysia documented self-reported ketum use to relieve opioid-withdrawal symptoms3. These ethnographic findings describe contexts of use; they do not establish efficacy or safety.

No sufficiently reliable primary sources could be assigned to the prehistoric, archaeological, spiritual and proverbial claims previously included in this article. Those claims have therefore been removed.

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Early written and botanical documentation (1836–1897)

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Early chemical and pharmacological research (1921–1967)

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Thailand: From prohibition to a regulated legal framework

WHO review: Surveillance rather than international scheduling

The 8th Working Group of the WHO Expert Committee on Drug Dependence recommended in April 2020 that kratom, mitragynine and 7-hydroxymitragynine be placed under WHO surveillance21. A pre-review followed at the 44th ECDD meeting in October 2021. The Committee found insufficient evidence to recommend a critical review of kratom and recommended continued surveillance22. This was neither a marketing authorisation nor a general finding that kratom is safe.

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Modern scientific research (2000–2025)

Alkaloid research and metabolism

A 2019 preclinical study showed that mitragynine is converted to 7-hydroxymitragynine (7-OH) by CYP3A isoforms in mouse and human liver preparations in vitro. In the mouse model used, 7-OH contributed substantially to the opioid-receptor-mediated analgesic effect. These findings do not establish clinical efficacy or the same contribution to effects in humans23.

A 2020 in-vitro study also showed that 7-OH can be converted to mitragynine pseudoindoxyl in human plasma. In the opioid-receptor assays used, this compound was more potent than mitragynine and 7-OH; its actual contribution to effects in the human body has not been established clinically24.

Pharmacokinetics in humans

The first published human pharmacokinetic study appeared in 2015. It enrolled ten male regular kratom users, with the principal parameters evaluated for nine participants, which limits generalisability25. A 2019 systematic review evaluated 17 animal and human studies and identified substantial remaining gaps in the evidence26.

A randomised, double-blind, placebo-controlled dose-escalation study published in 2024 investigated mitragynine and 7-hydroxymitragynine after a single dose and after 15 daily doses of analytically characterised dried kratom leaf powder27.

Drug–drug interactions

Laboratory studies show that kratom alkaloids can affect cytochrome P450 enzymes28. In a controlled clinical interaction study, twelve healthy adults received a single tea preparation made from 2 g of kratom leaf powder. Exposure to dextromethorphan, a CYP2D6 probe, was not materially altered. For midazolam, a CYP3A probe, AUC increased by 39% and maximum plasma concentration by 50%. At this low single dose, the findings primarily indicate inhibition of intestinal CYP3A and cannot automatically be generalised to higher or repeated doses or to other products29.

Completed clinical and observational studies

Two studies previously described as ongoing have now been completed. The NIDA-led observational study NCT05457803 ended on 15 December 2022; the registry reports 396 participants30. The Phase 1 dose-escalation study NCT06072170 enrolled 40 participants and ended on 23 January 2024; results were posted to the registry on 29 September 202531.

A 2025 publication analysed 15-day ecological momentary assessment data from 357 regular kratom users in the United States. Bedtime kratom use occurred on 23.4% of observed days and was associated with an average of 13 additional minutes of self-reported sleep and a 5.93-point higher sleep-quality rating on a 0–100 scale. Because of the observational design, the findings do not establish causation or demonstrate that kratom is an effective sleep aid32.

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Conclusion: Historical continuity, but limited evidence

Kratom has a documented traditional history in parts of Thailand and Malaysia, a repeatedly revised botanical naming history and a growing research base since the twentieth century. At the same time, many findings from preclinical models, small human studies or observational data cannot be directly generalised to clinical effects and risks. The WHO decision in 2021 was also a recommendation for continued surveillance, not a safety judgement22.

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