Research

Kratom (Mitragyna speciosa)

41 peer-reviewed studies curated from PubMed and Semantic Scholar.

1
Meta-analyses
13
Systematic reviews
3
RCTs
24
Other studies
Meta-analyses (2%)
Systematic reviews (32%)
RCTs (7%)
Observational (15%)

Studies

Sorted by quality and recency

2025·Journal of psychoactive drugs·N. Govarthnapany, R. Gabrhelík, Darshan Singh

Kratom (Mitragyna speciosa Korth.) Use Among Poly-Drug Users in Southeast Asia: A Systematic Review.

Systematic review

Systematic review of nine cross-sectional studies on kratom use among poly-drug users in Southeast Asia. Kratom is used as an affordable substitute for opiates and amphetamines, to self-manage substance use disorder, decrease drug intake, alleviate withdrawal, and for rejuvenating effects. No significant health issues were associated with co-consumption.

Semantic ScholarRead on Semantic Scholar
2024·European addiction research·Yuting Yang, Christian P Müller, Darshan Singh

Kratom (Mitragyna speciosa) Use and Mental Health: A Systematic Review and Multilevel Meta-Analysis.

Meta-analysisMental Clarity Mood

This systematic review and multilevel meta-analysis examined the association between kratom use and mental health indicators. The study found a very small positive association between kratom use and negative mental health indicators, and no significant association with positive mental health indicators. Kratom use showed a small positive correlation with externalizing disorders, but no significant association with quality of life or internalizing disorders.

PubMedRead on PubMed
2022·The International journal on drug policy·Julia Tobacyk, Brian J Parks, Nakita Lovelady, et al

Qualitative content analysis of public responses to an FDA inquiry on the impact of scheduling changes to kratom.

Systematic reviewn = 6,353

The study conducted a qualitative content analysis of public responses to an FDA inquiry on kratom, analyzing 6,353 comments. Respondents reported using kratom for mental health, pain management, substance use disorder, focus, insomnia, and fatigue, with few reports of recreational use or adverse effects. The study highlights public perceptions of kratom's therapeutic uses and potential regulatory implications.

PubMedRead on PubMed
2022·The American journal of drug and alcohol abuse·Cornel Stanciu, Saeed Ahmed, Samantha Gnanasegaram, et al

Kratom as an opioid alternative: harm, or harm reduction? A systematic review of literature.

Systematic review

Systematic review of literature on kratom and its alkaloids as opioid substitutes. The review includes 16 preclinical studies, 25 case reports, and 10 observational studies. Findings suggest kratom alkaloids act on opioid receptors and may mitigate opioid withdrawal, but concerns about addiction and toxicity remain. No controlled human clinical trials reported, and evidence is insufficient to draw conclusions on safety and efficacy.

PubMedRead on PubMed
2021·Human psychopharmacology·Elisabeth Prevete, Kim Paula Colette Kuypers, Eef Lien Theunissen, et al

A systematic review of (pre)clinical studies on the therapeutic potential and safety profile of kratom in humans.

Systematic reviewn = 57

Systematic review of preclinical and clinical studies on kratom's therapeutic potential and safety profile. Preclinical studies suggest therapeutic value for pain and withdrawal, while clinical studies report reduced pain sensitivity and safety issues with chronic use. Further validation in large, controlled trials is needed.

PubMedRead on PubMed
2021·WMJ : official publication of the State Medical Society of Wisconsin·Cornel Stanciu, Saeed Ahmed, Bryan Hybki, et al

Pharmacotherapy for Management of 'Kratom Use Disorder': A Systematic Literature Review With Survey of Experts.

Systematic review

Systematic literature review and expert survey on the management of kratom use disorder (KUD). The review compiles 14 reports on long-term management of KUD, highlighting the use of buprenorphine, naltrexone, and methadone with favorable outcomes. The expert survey supports the use of these pharmacological modalities for KUD management.

PubMedRead on PubMed
2021·Journal of perinatology : official journal of the California Perinatal Association·Mary Ellen Wright, Claire Ginsberg, Abigail M Parkison, et al

Outcomes of mothers and newborns to prenatal exposure to kratom: a systematic review.

Systematic review

Systematic review analyzing six case reports of prenatal kratom exposure. Maternal and infant withdrawal from kratom exposure was described in each case, resulting in pharmacologic treatment for both mothers and infants.

PubMedRead on PubMed
2025·Journal of psychoactive drugs·O. Grundmann, MeShell Green, Erin Berthold, et al

Prevalence and Use Patterns of Kratom (Mitragyna speciosa Korth.) in a US Nationally Representative Sample.

Cross-sectionaln = 11,545Stress Energy Sleep

Cross-sectional survey of 11,545 respondents found a 9.1% prevalence of kratom use, with pills, gummies, and powder being the most common forms. Kratom was primarily used for pain relief, relaxation/stress relief, and energy boost. Benefits included increased energy and improved sleep, but adverse effects increased with higher doses.

Semantic ScholarRead on Semantic Scholar
2025·Frontiers in pharmacology·Toby Turla, Grayson Abele, My Hua, et al

Reported associations between kratom and seizures: a systematic review.

Systematic reviewn = 20

Systematic review examining the association between kratom use and seizures. The review included 11 studies, primarily case reports and case series, documenting self-reported kratom use with minimal quantitative toxicological data. The review concludes there is insufficient evidence to suggest kratom causes seizures due to lack of quantitative dose-response data and incomplete medical records.

PubMedRead on PubMed
2024·Molecules (Basel, Switzerland)·Marilyn A Huestis, Martin A Brett, John Bothmer, et al

Human Mitragynine and 7-Hydroxymitragynine Pharmacokinetics after Single and Multiple Daily Doses of Oral Encapsulated Dried Kratom Leaf Powder.

RCT

This study investigated the pharmacokinetics of mitragynine and 7-hydroxymitragynine in humans after single and multiple daily doses of oral encapsulated dried kratom leaf powder. Plasma concentrations of these alkaloids were measured, showing dose-proportional increases and providing guidance for future clinical kratom dosing studies.

PubMedRead on PubMed
2023·Toxicology letters·Bin Yang, Ruiling Zhang, Mohammad Farris Iman Leong Bin Abdullah

The association between neuropsychiatric effects of substance use and occurrence of endoplasmic reticulum and unfolded protein response: A systematic review.

Systematic review

Systematic review assessing the association between neuropsychiatric effects of substance use and occurrence of ER stress and unfolded protein response. The review included 21 studies, revealing that substances like alcohol, methamphetamine, cocaine, opioid, and kratom contribute to neuropsychiatric effects and are associated with ER stress and UPR activation.

PubMedRead on PubMed
2021·Journal of addiction medicine·Stephanie T Weiss, Heather E Douglas

Treatment of Kratom Withdrawal and Dependence With Buprenorphine/Naloxone: A Case Series and Systematic Literature Review.

Systematic reviewn = 8

The study includes a systematic review and case series assessing the treatment of kratom-dependent patients with buprenorphine-naloxone. It found a strong correlation between kratom dose and the buprenorphine-naloxone dose required for treating kratom-associated opioid use disorder.

PubMedRead on PubMed
2019·Journal of psychoactive drugs·Cornel N Stanciu, Samantha A Gnanasegaram, Saeed Ahmed, et al

Kratom Withdrawal: A Systematic Review with Case Series.

Systematic review

Systematic review and case series examining kratom withdrawal, highlighting dependence, tolerance, and withdrawal symptoms. The paper discusses kratom's use for opioid withdrawal and the need for clinicians to manage kratom withdrawal similarly to opioid withdrawal.

PubMedRead on PubMed
2019·Asian journal of psychiatry·Kimheang Ya, Wimonchat Tangamornsuksan, C Norman Scholfield, et al

Pharmacokinetics of mitragynine, a major analgesic alkaloid in kratom (Mitragyna speciosa): A systematic review.

Systematic review

This systematic review summarizes available pharmacokinetic information about mitragynine, the major indole alkaloid in kratom. It describes mitragynine's absorption, metabolism, and excretion, noting its rapid absorption and extensive metabolism. The review highlights the need for more detailed studies on metabolism and tissue redistribution.

PubMedRead on PubMed
2017·Drug and alcohol dependence·Marc T Swogger, Zach Walsh

Kratom use and mental health: A systematic review.

Systematic reviewMood Mental Clarity

Systematic review of studies on kratom use and mental health from 1960 to 2017. Kratom shows potential as a harm reduction tool, particularly as an opioid substitute, and may enhance mood and relieve anxiety. However, withdrawal symptoms can be mild to severe, affecting abstinence maintenance.

PubMedRead on PubMed
2013·Journal of dietary supplements·Catherine Ulbricht, Dawn Costa, Julie Dao, et al

An evidence-based systematic review of kratom (Mitragyna speciosa) by the Natural Standard Research Collaboration.

Systematic review

Systematic review of kratom (Mitragyna speciosa) consolidating safety and efficacy data from scientific literature. Includes analysis of clinical trials, expert opinion, history, pharmacology, interactions, adverse effects, and dosing.

PubMedRead on PubMed
2025·Drug testing and analysis·Abhisheak Sharma, Kirsten E. Smith, Michelle A Kuntz, et al

Chemical Analysis and Alkaloid Intake for Kratom Products Available in the United States.

Observationaln = 357

The study presents content analyses of kratom products used by US adult consumers, quantifying 10 kratom alkaloids. It found no evidence of adulteration and calculated mitragynine intake per use and per day based on self-reported data. This analysis is foundational for designing controlled clinical trials of kratom.

Semantic ScholarRead on Semantic Scholar
2024·Drug and alcohol dependence·Jeffrey M. Rogers, S. Weiss, David H. Epstein, et al

Kratom addiction per DSM-5 SUD criteria, and kratom physical dependence: Insights from dosing amount versus frequency.

Observationaln = 395

Observational study of 395 US adult kratom consumers examining the relationship between dosing amounts/frequencies and outcomes such as acute effects, withdrawal symptoms, and kratom-use disorder (KUD) symptoms. Findings suggest that dose frequency is more closely associated with withdrawal and KUD symptoms than dose amount, with men reporting more acute effects and symptoms than women.

Semantic ScholarRead on Semantic Scholar
2024·JAMA Network Open·Kirsten E. Smith, Leigh V. Panlilio, J. Feldman, et al

Ecological Momentary Assessment of Self-Reported Kratom Use, Effects, and Motivations Among US Adults

Cross-sectionaln = 357Mood

Cross-sectional study using ecological momentary assessment of 357 kratom consumers in the US. Most reported using kratom daily to relieve pain, improve mood, or increase productivity, with some using it as an opioid substitute. Frequent use was associated with tolerance, withdrawal, and craving, but not with social or functional impairment.

Semantic ScholarRead on Semantic Scholar
2024·Psychopharmacology·Elisabeth Prevete, Eef L Theunissen, Kim P C Kuypers, et al

An exploratory study of the safety profile and neurocognitive function after single doses of mitragynine in humans.

RCTn = 15Mental Clarity Focus

Phase 1 study evaluating the safety profile and acute effects of mitragynine in humans. Low doses (5-10 mg) increased subjective feelings of stimulation and enhanced attention, while the highest dose (40 mg) caused feelings of amnesia and mild psychopathological symptoms. Mitragynine was well tolerated up to 40 mg.

PubMedRead on PubMed
2020·The Yale journal of biology and medicine·Balasingam Vicknasingam, Weng Tink Chooi, Azlan Abdul Rahim, et al

Kratom and Pain Tolerance: A Randomized, Placebo-Controlled, Double-Blind Study.

RCTn = 26

A randomized, placebo-controlled, double-blind study assessed kratom's effects on pain tolerance in 26 males with a history of daily kratom use. Pain tolerance increased significantly 1 hour after kratom ingestion compared to placebo, with no withdrawal symptoms reported during discontinuation.

PubMedRead on PubMed
2025·Drug and Alcohol Dependence Reports·Cianna J. Piercey, Joseph Bunch, Joseph Cameron, et al

Kratom use among ethnobotanical tea bar patrons in Colorado: Subjective drug effects, adverse reactions, and perceived benefits of use

Observationaln = 102Mental Clarity Physical Performance Mood

Observational study using surveys of 102 ethnobotanical tea bar patrons in Colorado to assess kratom use patterns, perceived benefits, and adverse reactions. Participants reported mental and physical health benefits, social enhancement, and substance use harm reduction, but also experienced gastrointestinal issues, anxiety, and withdrawal symptoms.

Semantic ScholarRead on Semantic Scholar
2025·Journal of Substance Use·Teresa Perry, Sayorn Chin

Kratom drinks and consumption trends: insights from Reddit

Observational

Retrospective observational study using content analysis of Reddit posts to analyze trends in kratom drink consumption. The study found an increase in interest in kratom drinks starting in mid-2022, highlighting the need for public awareness of potential risks and further research.

Semantic ScholarRead on Semantic Scholar
2025·Horticulturae·Nisa Leksungnoen, Tushar Andriyas, Yongkriat Ku-Or, et al

The Effect of Light Intensity and Polyethylene-Glycol-Induced Water Stress on the Growth, Mitragynine Accumulation, and Total Alkaloid Content of Kratom (Mitragyna speciosa)

Study

The study investigates the effects of light intensity and water stress on the growth and alkaloid content of Mitragyna speciosa (kratom) using hydroponic techniques. Water potential was found to be the dominant factor affecting plant growth and alkaloid accumulation, with moderate water potential leading to the highest mitragynine accumulation. Leaf age and thickness were also associated with alkaloid levels.

Semantic ScholarRead on Semantic Scholar
2025·Nature Chemical Biology·Allwin McDonald, Yoko Nakamura, Carsten Schotte, et al

Enzymatic epimerization of monoterpene indole alkaloids in kratom

Study

The paper reports on the enzymatic epimerization of monoterpene indole alkaloids in Mitragyna speciosa (kratom), focusing on the biosynthesis of 3R-MIAs. It identifies the iminium species (20S)-3-dehydrocorynantheidine and the oxidase/reductase pair responsible for the isomerization of 3S to 3R, suggesting a pathway for the formation of pharmacologically active spirooxindole alkaloids.

Semantic ScholarRead on Semantic Scholar
2025·PLOS One·Nisa Leksungnoen, Tushar Andriyas, Rossarin Tansawat, et al

Higher accumulation of mitragynine in Mitragyna speciosa (kratom) leaves affected by insect attack

Study

The study investigated the effect of insect herbivory on the secondary metabolites of kratom leaves, focusing on the accumulation of mitragynine. It found that insect attacks led to higher mitragynine levels as a defense mechanism, with a correlation between increased mitragynine and elevated leaf acidity. The study suggests managing insect herbivory to modulate alkaloid accumulation in kratom.

Semantic ScholarRead on Semantic Scholar
2025·The American Journal of Drug and Alcohol Abuse·Katherine Hill, Jeffrey M. Rogers, Oliver Grundmann, et al

At least four groups of kratom consumers in the United States: latent-class analysis of motivations for kratom use

Reviewn = 395

The study used latent-class analysis to identify subgroups of kratom consumers based on their motivations for use. Four classes were identified: self-treatment for chronic pain, long-term replacement for other substances, management of anxiety and depressive symptoms, and recreational use. The study highlights the diverse motivations for kratom use among consumers.

Semantic ScholarRead on Semantic Scholar
2025·BMC Complementary Medicine and Therapies·Dwi Wahyu Indriani, S. I. Rahmawati, A. Bayu, et al

Serotonin release mediates analgesia via opioidergic system and withdrawal symptoms in chronic kratom extract-treated mice

Animal study

The study investigates the role of serotonin in kratom-induced analgesia and withdrawal symptoms in mice. Kratom alkaloid extract produced analgesic effects comparable to morphine, mediated by MOR activation and increased serotonin transmission. Kratom extracts also resulted in less severe withdrawal symptoms compared to morphine, with increased serotonin and dopamine levels contributing to these effects.

Semantic ScholarRead on Semantic Scholar
2025·Scientific Reports·Nantiya Nawaka, M. Lertcanawanichakul, S. Porntadavity, et al

Kratom leaf extracts exert hypolipidaemic effects via the modulation of PCSK9 and LDLR pathways in HepG2 cells

In vitro

The study investigated the hypolipidaemic effects of kratom leaf extracts on HepG2 cells, focusing on LDLR and PCSK9 expression. Kratom extracts increased LDLR protein expression and decreased PCSK9 expression, suggesting potential for ameliorating hypercholesterolemia.

Semantic ScholarRead on Semantic Scholar
2025·JURNAL FARMASI DAN ILMU KEFARMASIAN INDONESIA·Iqmal Zulhakim, Kathina Deswiaqsa, Jane Arantika

Formulation and Physical Evaluation of Kratom (Mitragyna speciosa Korth.) Leaf Extract Emulgel as Analgesic in Mice (Mus musculus)

Animal study

The study evaluated the analgesic effectiveness of kratom leaf extract emulgel applied topically in mice. Emulgels with 11.6% and 17.6% extract concentrations showed optimal analgesic effects, reducing pain responses significantly.

Semantic ScholarRead on Semantic Scholar
2025·International Journal of Applied Pharmaceutics·Puja Adi Priatna, S. Rahmah, R. Widyowati, et al

IDENTIFICATION OF LC-MS/MS AND DOCKING ANALYSIS OF TOPOISOMERASE IIΑ INHIBITION FROM KRATOM LEAVES (MITRAGYNA SPECIOSA) AS POTENTIAL ANTICANCER AGENTS

In vitro

The study used LC-MS/MS to identify metabolites in kratom leaves and predicted their activity to inhibit topoisomerase IIα using molecular docking. Rutin, 5(S)-5-carboxystrictosidine, and procyanidin showed the highest affinity for inhibition, suggesting potential anticancer activity.

Semantic ScholarRead on Semantic Scholar
2024·Scientific Reports·S. I. Rahmawati, Dwi Wahyu Indriani, Febby Nurdiya Ningsih, et al

Dual anti-inflammatory activities of COX-2/5-LOX driven by kratom alkaloid extracts in lipopolysaccharide-induced RAW 264.7 cells

In vitroInflammation

The study investigates the anti-inflammatory effects of kratom alkaloid extracts, particularly mitragynine, on COX-2/5-LOX enzymes in LPS-induced RAW 264.7 macrophage cells. The alkaloid extract showed dual inhibition activity towards these enzymes and reduced several inflammation parameters, suggesting potential as a safer NSAID.

Semantic ScholarRead on Semantic Scholar
2021·Journal of medicinal chemistry·S. Chakraborty, J. Diberto, Abdelfattah Faouzi, et al

A Novel Mitragynine Analog with Low-Efficacy Mu Opioid Receptor Agonism Displays Antinociception with Attenuated Adverse Effects.

Animal study

The study investigates the structure-activity relationships of mitragynine and 7-hydroxymitragynine analogs, focusing on their mu opioid receptor agonism. A novel analog, 6 (SC13), demonstrated MOR-dependent analgesia in mice with reduced adverse effects compared to traditional opioids.

Semantic ScholarRead on Semantic Scholar
2025·Cureus·Bryan Tassavor, Chae Young Eun, Olga Nikolskaia, et al

Hyperpigmentation From Chronic Kratom Use: A Case Report and Review of the Literature

Case reportSkin Hair Health

Case report of a patient with over a decade of kratom use experiencing diffuse, photodistributed hyperpigmentation. The report includes clinical presentation, histopathological findings, and potential mechanism, along with a literature review on kratom's adverse effects.

Semantic ScholarRead on Semantic Scholar
2025·Lasers in Surgery and Medicine·Alanoud A Alhadyani, Christen Samaan, Girish Munavalli

The 730 nm Picosecond Titanium Sapphire Laser for Treatment of Kratom‐Induced Hyperpigmentation

Case reportSkin Hair Health

This case series reports on the use of the 730-nm picosecond titanium-sapphire laser for treating kratom-induced hyperpigmentation, a dermatological side effect associated with the use of Mitragyna speciosa.

Semantic ScholarRead on Semantic Scholar
2025·Pharmaceutical Biology·Scott Alsbrook, George Pro, Igor Koturbash

From kratom to 7-hydroxymitragynine: evolution of a natural remedy into a public-health threat

Review

The paper reviews the evolution of kratom into concentrated 7-hydroxymitragynine products, highlighting their pharmacological and toxicological differences. It discusses the increased potency and risks associated with these products, including severe intoxications, fatalities, and pediatric risks.

Semantic ScholarRead on Semantic Scholar
2025·Pharmaceuticals·A. S. Alford, H. Moreno, Menny M. Benjamin, et al

Exploring the Therapeutic Potential of Mitragynine and Corynoxeine: Kratom-Derived Indole and Oxindole Alkaloids for Pain Management

Review

This systematic review explores the pharmacological properties, mechanisms of action, dosing considerations, interactions, and long-term effects of mitragynine and corynoxeine, alkaloids from the Southeast Asian plant Mitragyna speciosa (kratom). These compounds demonstrate significant therapeutic potential for managing diverse pain types, including cancer pain, without the adverse effects associated with traditional opioids.

Semantic ScholarRead on Semantic Scholar
2024·Expert Review of Clinical Pharmacology·Christopher R McCurdy, Abhisheak Sharma, Kirsten E. Smith, et al

An update on the clinical pharmacology of kratom: uses, abuse potential, and future considerations

Review

This narrative review discusses the pharmacology, pharmacokinetics, and potential drug-drug interactions of kratom and its alkaloids. It covers the clinical pharmacology and toxicology of kratom, user surveys, and the concepts of tolerance, dependence, and withdrawal associated with kratom use disorder.

Semantic ScholarRead on Semantic Scholar
2024·Frontiers in Pharmacology·Jack E. Henningfield, Oliver Grundmann, M. Huestis, et al

Kratom safety and toxicology in the public health context: research needs to better inform regulation

Review

This narrative review synthesizes research on kratom's benefits, risks, pharmacology, and epidemiology to inform United States-based regulation. It highlights kratom's complex pharmacology and its characterization as an opioid with potential risks for addiction or overdose. The review provides a foundation for future studies and regulatory efforts.

Semantic ScholarRead on Semantic Scholar
2022·Disease-a-month : DM·O. Grundmann, R. Hendrickson, M. Greenberg

Kratom: History, pharmacology, current user trends, adverse health effects and potential benefits.

Review

Narrative review of kratom (Mitragyna speciosa), discussing its history, pharmacology, user trends, adverse health effects, and potential benefits. Highlights dose-dependent stimulant and opioid-like effects, use in mood and substance use disorders, and associated toxicities including hepatic, cardiac, and CNS effects. Discusses drug-drug interactions and variability in product composition.

Semantic ScholarRead on Semantic Scholar
2016·Brain research bulletin·Darshan Singh, Suresh Narayanan, Balasingam Vicknasingam

Traditional and non-traditional uses of Mitragynine (Kratom): A survey of the literature.

Review

The paper surveys literature on kratom use in South East Asia and the West, highlighting differences in traditional and non-traditional uses. It notes kratom's evolution to a recreational drug and reports of adverse effects in the West, contrasting with its longer history of use in South East Asia. The paper calls for more scientific studies to explore kratom's therapeutic potential.

PubMedRead on PubMed