Research library

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1. Case reports · 2026

   7-Hydroxymitragynine Withdrawal Treated With Buprenorphine-Naloxone (opens in a new tab)

   Held JT, Varicat FP · Prim Care Companion CNS Disord

   Abstract not available in PubMed; see link.

2. Case reports · 2026

   7-Hydroxymitragynine: Not Your Garden Variety Kratom (opens in a new tab)

   Papsun DM, Schroeder W, Brower J, Krotulski A, Ellefsen K · Am J Forensic Med Pathol

   Abstract not available in PubMed; see link.

3. Reviews · 2026 · Open access

   7-OH and kratom vaping products: an emerging public health threat (opens in a new tab)

   Schichlein KD, Kim HH, Porter NA, Jaspers I · Toxicol Sci

   Abstract not available in PubMed; see link.

4. Case reports · 2026

   7-OH-Mitragynine-Induced Psychosis and Delirium (opens in a new tab)

   Elrokhsi NS, Lam CK, Balasanova AA · Prim Care Companion CNS Disord

   Abstract not available in PubMed; see link.

5. Reviews · 2026 · Open access

   A Call to Colleagues on Concentrated Synthetic 7-OH (opens in a new tab)

   Gold MS, Avena NM, Badgaiyan RD, Thanos PK, Blum K · Subst Abuse Rehabil

   Abstract not available in PubMed; see link.

6. Case reports · 2026

   A Case of 7-Hydroxymitragynine Use Disorder Treated With Buprenorphine (opens in a new tab)

   Hendler R, Karavolis Z, Kim J, Gonzalez G · J Addict Med

   7-HMG is a widely available, largely unregulated, underrecognized substance with potency at the µ-opioid receptor that may increasingly concern clinicians and policymakers.

7. Case reports · 2026

   A Case of 7-Hydroxymitragynine Use Requiring Inpatient Medically Managed Withdrawal (opens in a new tab)

   Wightman RS, Hu D · J Addict Med

   Given the widespread availability of kratom and kratom-related products it is important for health care providers to screen for use and development of use disorder and be prepared to provide counseling, support, and treatment for patients.

8. Human studies · 2026

   A Case of Precipitated Withdrawal From Naltrexone Treated With Buprenorphine in a Patient With Kratom Use Disorder (opens in a new tab)

   Williams JB, Erskine NA, Holt AG, Stepanek KD, Saha S · J Clin Psychopharmacol

   No abstract on PubMed; cited for its title and case details.

9. Human studies · 2026

   A Pilot, Dose-Finding, Pharmacodynamic and Pharmacokinetic Study of Orally Administered Botanical Kratom (opens in a new tab)

   Reissig CJ, Chen L, Nallani SC, Hawkins EG, Galati S, Bonson K et al. · J Clin Psychopharmacol

   This study investigated the safety of single-sourced botanical kratom; the results may not be representative of other kratom-containing products.

10. Reviews · 2026

    A Review of Kratom Product Evolution and Its Associated Health Outcomes (opens in a new tab)

    Aly S, Grundmann O · Subst Abuse Rehabil

    Purified compounds, predominantly mitragynine and semi-synthetic 7-hydroxymitragynine, are likely to be associated with a higher risk for dependence and overdose potential.

11. Reviews · 2026 · Open access

    ACMT 2026 Position Statement Public Health Concerns 7-OH and Other Kratom Compounds (opens in a new tab)

    ACMT · Agency / organization document

    Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

12. Reviews · 2026 · Open access

    ACMT Position Statement: Public Health Risks of 7-Hydroxymitragynine and Other Kratom-Associated Compounds (opens in a new tab)

    Moss MJ, Altholz J, Babu K, Perrone J, Stolbach A · J Med Toxicol

    Abstract not available in PubMed; see link.

13. Surveillance · 2026 · Open access

    Americas Poison Centers 2026 7-OH Exposure Advisory (opens in a new tab)

    Americas · Agency / organization document

    Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

14. Human studies · 2026

    Associations between kratom (Mitragyna speciosa) use and real-time anxiety and sadness: a 15-day ecological momentary assessment study (opens in a new tab)

    Timmons P, Daniulaityte R, Panlilio LV, Smith KE, Epstein DH, Mun CJ · Drug Alcohol Depend

    Over 15 days, 357 adults who use kratom reported slightly lower anxiety, and to a lesser degree sadness, in the hours after use. The authors say this is self-reported, short-term data and call for controlled and long-term studies before drawing conclusions about mental health.

15. Product testing · 2026 · Open access

    Avoiding False Identification of 7-Hydroxymitragynine in Kratom Products Using a Multicriteria LC-MS Confirmation (opens in a new tab)

    Sheehan D, Li Y, Meckler E, Upton R, Zhang M · J Am Soc Mass Spectrom

    These results highlight the importance of integrating chromatographic resolution with orthogonal MS/MS criteria for reliable identification of kratom alkaloids and provide an analytical framework for the characterization of complex botanical products.

16. Animal · 2026 · Open access

    Bayesian inference for integrated pharmacokinetic modelling of mitragynine and 7-hydroxymitragynine (opens in a new tab)

    Notario D, Gunawan U, Kambira PFA, Wulandari E, Prasetyanto EA · ADMET DMPK

    The pharmacokinetics of mitragynine and 7-hydroxymitragynine were successfully modelled simultaneously with two compartments and proportional residuals using Bayesian inference with high accuracy.

17. Other · 2026

    Beyond kratom: Concentrated 7-hydroxymitragynine and mitragynine pseudoindoxyl products, an MME potency assessment (opens in a new tab)

    Heywood J, Farnham H, Jackson E, Steimel K, Brown S, Riordan A · Regul Toxicol Pharmacol

    Drug Enforcement Administration's July 2026 notice of scheduling intent, while traditional preparations retain non-negligible, mitragynine-ceiling-limited opioid activity.

18. Case reports · 2026 · Open access

    Brugada Syndrome Unmasked by Kratom Use in a Young Man (opens in a new tab)

    Matthews JG, Perkins DR, Adrejiya P, Donkor DKA · JACC Case Rep

    Increased awareness of its cardiovascular risks is important for both clinicians and public health.

19. Case reports · 2026

    Buprenorphine for the Management of 7-Hydroxymitragynine (7-OH) Use: A Retrospective Case Series (opens in a new tab)

    Fenske E, Williams B, Hallock-Koppelman L, Buchheit BM · J Addict Med

    Buprenorphine initiation for problematic 7-OH use was feasible, well tolerated, and associated with symptom improvement, supporting development of pragmatic clinical approaches for this emerging substance use disorder.

20. Case reports · 2026 · Open access

    Cardio-pulmonary arrest in a patient revived with naloxone following reported use of 7-hydroxymitragynine (opens in a new tab)

    Pullman MK, Kanumuri SRR, Leon JF, Cutler SJ, McCurdy CR, Sharma A · Clin Toxicol (Phila)

    Abstract not available in PubMed; see link.

21. Reviews · 2026

    Cardiovascular Effects of Kratom (Mitragyna speciosa) (opens in a new tab)

    Wu C, Gastelum S, Al-Fakhoury J, Bowes N, Khamashta K, Crupi J et al. · Cardiol Rev

    Greater clinical awareness and prospective research using standardized kratom preparations are needed to clarify its cardiovascular risks, potential benefits, and clinically relevant drug interactions.

22. Surveillance · 2026 · Open access

    CDC MMWR 2026 Increases in Kratom-Related Reports to Poison Centers (opens in a new tab)

    CDC · Agency / organization document

    Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

23. Surveillance · 2026 · Open access

    CFSRE 2026 Monograph Dihydro-7-Hydroxy Mitragynine (opens in a new tab)

    CFSRE · Agency / organization document

    Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

24. Surveillance · 2026 · Open access

    CFSRE 2026 NPS Discovery Trend Reports Q1 (opens in a new tab)

    CFSRE · Agency / organization document

    Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

25. Product testing · 2026 · Open access

    CFSRE NPS Discovery: no-cost testing of drug materials and specimens (sample submission) (opens in a new tab)

    Center for Forensic Science Research and Education · Agency / organization document

    Grant-funded no-cost forensic testing of emerging drugs in products and body samples; submission forms for chemistry and toxicology.

26. Surveillance · 2026

    Characterizing Clinical Effects of 7-Hydroxymitragynine at a US Poison Control Center (opens in a new tab)

    Wahrenbrock TN, Bompard M, Downs JW · Am J Ther

    Abstract not available in PubMed; see link.

27. Agency documents · 2026 · Open access

    CRS 2026 Legal Sidebar LSB11457 Temporary Control of 7-OH (opens in a new tab)

    CRS · Agency / organization document

    Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

28. Agency documents · 2026 · Open access

    DEA 2026 Notice of Intent Temporary Placement of 7-OH Above a Threshold FR 2026-13580 (opens in a new tab)

    DEA · Agency / organization document

    DEA notice of intent to temporarily place 7-OH above a threshold in Schedule I (docket DEA-1570).

29. Agency documents · 2026 · Open access

    DEA 2026 Notice of Intent Temporary Placement of 7-OH and MGPI Above a Threshold FR 2026-20943 (opens in a new tab)

    DEA · Agency / organization document

    DEA notice of intent: temporary Schedule I placement of 7-OH and MGPI above a specified threshold.

30. Agency documents · 2026 · Open access

    DEA 2026 Press Release Temporarily Schedule 7-OH and Related Substances (opens in a new tab)

    DEA · Agency / organization document

    Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

31. Agency documents · 2026 · Open access

    DEA 2026 Temporary Placement of MGPI MGM-15 and MGM-16 in Schedule I FR 2026-17429 (opens in a new tab)

    DEA · Agency / organization document

    DEA temporary Schedule I placement of MGPI, MGM-15 and MGM-16.

32. Product testing · 2026 · Open access

    Dihydro-7-Hydroxy Mitragynine (MGM-15) - May 2026 (NPS Discovery product testing report) (opens in a new tab)

    Krotulski AJ, Denn MT, Walton SW, Logan BK · Agency / organization document

    MGM-15 first detected Sept 2025; found in products labeled MGM-15, "proprietary blend (DHM)" and "nano tech mitragynine"; early data suggest ~30x mitragynine potency.

33. In vitro · 2026

    Effects of 7-hydroxymitragynine on serotonin, amino acid profiles, and ion homeostasis in SH-SY5Y cells (opens in a new tab)

    Chujan S, Vajeethaveesin N, Rittapai N, Pholphana N, Nookabkaew S, Satayavivad J · Mol Biol Rep

    Together, these findings show that 7-HMG induced significant metabolic and ionic disturbances in neuronal cells, providing new mechanistic insight into its neurobiological activity and potential neurotoxicity.

34. Product testing · 2026 · Open access

    Effects of Botanical Variation, Plant Part, and Extraction Technique on Mitragynine and 7-Hydroxymitragynine in Kratom (Mitragyna speciosa) Extracts Quantified by a Validated HPLC-DAD Method (opens in a new tab)

    Krongrawa W, Ponphaiboon J, Koedruen J, Samran C, Limmatvapirat S, Limmatvapirat C · Molecules

    These findings highlight substantial phytochemical variability relevant to quality standardization of kratom-derived products.

35. Product testing · 2026 · Open access

    Elevated 7-Hydroxymitragynine Levels Found in Products Misbranded as Kratom (opens in a new tab)

    Brown PN, Chan M, Zhang X, Brendler T · J AOAC Int

    The products were verified to contain very high levels of 7-hydroxymitragynine, achievable only by synthetic means.

36. Agency documents · 2026 · Open access

    FDA 2026 Hiding in Plain Sight 7-OH Products (opens in a new tab)

    FDA · Agency / organization document

    Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

37. Agency documents · 2026 · Open access

    FDA 2026 Import Alert 54-15 Kratom (opens in a new tab)

    FDA · Agency / organization document

    Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

38. In vitro · 2026 · Open access

    Genotoxicity risk assessment of a 7-hydroxymitragynine-enriched Kratom preparation: An integrated in silico and in vitro approach (opens in a new tab)

    Harnkit N, Sahad T, Noonate I, Primpai P, Radapong S, Pipatrattanaseree W et al. · Toxicol Rep

    This study underscores the value of a combined computational and experimental workflow for the robust genotoxicity assessment of complex natural products.

39. Agency documents · 2026 · Open access

    HHS 2026 Extension of Comment Period 7-OH Threshold FR 2026-17409 (opens in a new tab)

    HHS · Agency / organization document

    Federal Register notice extending the comment period on the 7-OH threshold proposal.

40. Agency documents · 2026 · Open access

    HHS 2026 Press Release HHS and FDA Support DEA 7-OH Scheduling (opens in a new tab)

    HHS · Agency / organization document

    Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

41. Agency documents · 2026 · Open access

    HHS 2026 Press Release HHS Recommends Thresholds for Enhanced Kratom Products (opens in a new tab)

    HHS · Agency / organization document

    Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

42. Agency documents · 2026 · Open access

    House Bill 328, Regulate Hemp-Derived Consumables: Conference Report (PCCS30639-CE-1) (opens in a new tab)

    North Carolina General Assembly · NC General Assembly

    Senate adopted 37-6 on July 2, 2026; House has not voted (in House Rules since July 30). New G.S. 14-401.28 would ban selling or possessing synthetic kratom products (names synthetic 7-OH), ban kratom products for under-21s, covers products for ingestion or inhalation; no mg threshold.

43. Product testing · 2026

    Identification and Characterization of Mitragynine or 7-Hydroxymitraynine Oral Dosage Form Products That Appeal to Children (opens in a new tab)

    White CM, Atallah M, Khoury DE · J Pediatr Pharmacol Ther

    Mitragynine and 7-hydroxymitragynine are present in many products that could cause small children and teens to be exposed.

44. Surveillance · 2026 · Open access

    Increase in Poison Center Reports Linked to Kratom-Containing Kava Products - National Poison Data System, United States, 2000-2025 (opens in a new tab)

    Towers EB, Williams IL, Holstege CP, Farah R · MMWR Morb Mortal Wkly Rep

    The findings in this report suggest the need for enhanced surveillance for, clinical awareness of, and public education regarding commercial products containing kava.

45. Surveillance · 2026 · Open access

    Increases in Kratom-Related Reports to Poison Centers - National Poison Data System, United States, 2015-2025 (opens in a new tab)

    Towers EB, Thomas YT, Holstege CP, Farah R · MMWR Morb Mortal Wkly Rep

    NPDS data indicate that kratom-related reports to poison centers are increasing and expanding among demographic groups, underscoring the value of ongoing surveillance to identify high-risk patterns of kratom use and guide strategies to reduce risks from multiple-substance expo...

46. Case reports · 2026 · Open access

    Increasing Awareness of 7-Hydroxymitragynine and the Threat of Emerging Opioids (opens in a new tab)

    Engle K, Downey AE, Vais S, Raymond-Flesch M · J Adolesc Health

    Abstract not available in PubMed; see link.

47. Product testing · 2026

    Kratom Brands in Vape Shops Across the US (opens in a new tab)

    LoParco CR, Tillett KK, Berg CJ, Rossheim ME · Health Behav Res

    Interstate brand presence indicates likely violations of federal laws and the need to strengthen regulation and enforcement.

48. Surveillance · 2026

    Kratom exposure cases reported to United States Poison Centers: 2016-July 2025 (opens in a new tab)

    Leonard JB, Brown K, Colvin JM · Am J Emerg Med

    There has been a significant increase in kratom exposures reported to US Poison Centers, but the overall outcomes have remained similar.

49. Reviews · 2026

    Kratom Is an Opioid (opens in a new tab)

    Kolodny A, Holstege CP · J Clin Psychopharmacol

    Commentary (online ahead of print Oct 15, 2026) by an opioid policy researcher (Brandeis) and a medical toxicologist (UVA, Blue Ridge Poison Center) arguing kratom should be treated as an opioid. No abstract on PubMed.

50. Reviews · 2026

    Kratom use in adolescents and college students: a systematic review of prevalence, patterns, and risk factors across community and rehabilitation settings (opens in a new tab)

    Govarthnapany N, Dékány L, Gabrhelík R, Singh D · Am J Drug Alcohol Abuse

    This review points the need for targeted interventions, education, and regulatory frameworks.

51. Human studies · 2026 · Open access

    Kratom-Associated Pulmonary Toxicity: A Systematic Review of Case Reports and Forensic Series with a Proposed Clinical Phenotype Classification (opens in a new tab)

    Kanchustambham V, Saladi S · J Med Toxicol

    Reported kratom-associated pulmonary presentations cluster into five provisional, hypothesis-generating categories spanning primary lung injury and secondary systemic effects.

52. Product testing · 2026

    Kratom-labeled Products in the US Compared With Traditionally Consumed Natural Kratom in Southeast Asia (opens in a new tab)

    Karunakaran T, Vicknasingam K, Chawarski MC · J Addict Med

    Consumers of these products and health care practitioners in the United States may not be aware that the natural kratom products traditionally consumed in SEA (ie, freshly harvested unprocessed whole leaves and a water-based decoction prepared from such leaves) have different chemistry and are consumed differently t…

53. Reviews · 2026 · Open access

    Labcorp 2026 Kratom and 7-OH Common Provider Questions (opens in a new tab)

    Labcorp · Agency / organization document

    Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

54. Human studies · 2026

    Liver Injury Associated With Kratom ( Mitragyna speciosa ): A Systematic Review (opens in a new tab)

    Calicdan XA, Kopczynski A, Medina E, Singh S, Sotelo D, Wu AC et al. · J Addict Med

    Further research is needed to better characterize kratom's mechanisms of liver injury and to inform clinical decision-making and public health policy.

55. Case reports · 2026 · Open access

    Management of acute withdrawal from 7-hydroxymitragynine after high-dose chronic use: A case report (opens in a new tab)

    Lybik N, Cone B, Skelton S, Elfessi Z · J Am Pharm Assoc (2003)

    Concentrated 7-OH products differ from kratom leaf and can produce dependence and withdrawal; pharmacists should screen for these products, time buprenorphine initiation to moderate withdrawal, provide harm-reduction counseling, and incorporate evolving state regulations into ...

56. Case reports · 2026 · Open access

    Managing 7-Hydroxymitragynine Use Disorder with Buprenorphine-Naloxone (opens in a new tab)

    Kiyokawa M, Chun A, Hsia C · Hawaii J Health Soc Welf

    Therefore, clinicians are recommended to routinely inquire about patients' use of botanical supplements in addition to illicit substances.

57. Other · 2026 · Open access

    Mills v Savla 2026 Complaint Exhibit A in Kinsale v Hydroxie Allegations (opens in a new tab)

    Mills · Agency / organization document

    Public court filing (legal allegations, not scientific evidence); included only as a record of a reported fatality involving 7-OH products.

58. Product testing · 2026

    Mislabeling and Status of Semisynthetic Kratom-Derived Products in the US Market (opens in a new tab)

    Gour A, Kanumuri SRR, Mukhopadhyay S, Pullman MK, León F, Cutler SJ et al. · Drug Test Anal

    Collectively, this highlights the need for improved regulatory oversight and strengthened post-marketing surveillance, including real-time poison control center data, to ensure consumer safety.

59. Product testing · 2026 · Open access

    Mitragynine & 7-Hydroxy Mitragynine - May 2026 (NPS Discovery product testing report) (opens in a new tab)

    Krotulski AJ, Denn MT, Eccarius LK, Logan BK · Agency / organization document

    Forensic lab bought and tested shop products: 7-OH tablets near or below label with unlisted MGPI; one liquid labeled 25 mg mitragynine had >150 mg mitragynine and 36.7 mg MGPI.

60. Product testing · 2026

    Nonswallowed Kratom-Derived Products: Unlawful Dietary Supplements That Endanger Public Health (opens in a new tab)

    White CM, Sedensky A, Belcourt J, Kulkarni P · Public Health Rep

    With no clinical, safety, or pharmacokinetic data for kratom-derived products that bypass first-pass metabolism (ie, where a chemical absorbed through the stomach or intestines is metabolized in the liver before reaching the general bloodstream), people should be advised to avoid these products, and regulatory actio…

61. Animal · 2026 · Open access

    Physiologically Based Pharmacokinetic Model for Clinical Translation and Prediction of Drug Interaction of the Major Kratom Alkaloid, Mitragynine (opens in a new tab)

    Chiang YH, Kanumuri SRR, Berthold EC, Kamble SH, Gour A, Kuntz MA et al. · ACS Pharmacol Transl Sci

    This comprehensive model supports the therapeutic development of MTG.

62. Human studies · 2026

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

    Grundmann O, Green M, Berthold E, Yoon SL, Ray D · J Psychoactive Drugs

    The lack of standardization and consistency in kratom products results in unpredictable effects, emphasizing the need for increased research to establish reliable safety guidelines for dosage recommendations.

63. In vitro · 2026 · Open access

    Quantitative analysis of 7-hydroxymitragynine in commercial kratom products and its stability under chemical and physiological conditions (opens in a new tab)

    Avula B, Ali SK, Tatapudi KK, Pandey P, Cheepilla L, Husain I et al. · Phytochemistry

    These findings underscore significant safety concerns over oral 7-OH products and necessitate validated analytical monitoring to guide regulatory oversight and consumer protection.

64. Case reports · 2026

    Rhabdomyolysis, renal failure and chronic neurologic deficits after prolonged immobilization from use of a 7-hydroxymitragynine product (opens in a new tab)

    Dorey A, Gerona R, Bell J, Ellison R, Moss M · Clin Toxicol (Phila)

    Abstract not available in PubMed; see link.

65. Human studies · 2026

    Risk of respiratory and neurologic effects in children ingesting kratom and related alkaloids (opens in a new tab)

    Hoffmann NA, Lee SC, Oakland CL, Cole JB, Olives TD, Fuchs RT et al. · Am J Emerg Med

    High potency kratom alkaloids may pose significant respiratory and neurologic risks to pediatric patients when unintentionally exposed.

66. Agency documents · 2026 · Open access

    Schedules of Controlled Substances: Temporary Placement of 7-Hydroxymitragynine and Mitragynine Pseudoindoxyl Above a Specified Threshold in Schedule I (Notice of Intent, Docket DEA-1570) (opens in a new tab)

    Drug Enforcement Administration · Federal Register (public inspection, publishes Oct 14, 2026)

    New 30-day notice: 7-OH and MGPI (alone or combined) become temporary Schedule I above 1 mg/g (solids) or 1 mg/mL (liquids), or when mitragynine is less than 100 times their amount; order not before 30 days after publication; DEA says notice-and-comment rules do not apply; lists vapes among product forms.

67. Agency documents · 2026 · Open access

    Schedules of Controlled Substances: Temporary Placement of MGM-15 and MGM-16 in Schedule I (Notice of Intent, Docket DEA-1644) (opens in a new tab)

    Drug Enforcement Administration · Federal Register (public inspection, publishes Oct 14, 2026)

    Separates MGM-15 and MGM-16 from MGPI so they stay in Schedule I with no threshold; the Aug 26, 2026 order stays in effect until replaced.

68. Product testing · 2026

    Semi-synthetic kratom derivatives in the Czech online market prior to regulatory reform: a baseline surveillance study (opens in a new tab)

    Govarthnapany N, Lisak V, Dékány L, Vacek J, Mravčík V, Singh D, Hill K, Gabrhelík R · Am J Drug Alcohol Abuse

    8 of 147 Czech sites sold 22 distinct semi-synthetic 7-OH/MGPI products; most 15-25 mg per unit but some up to 970 mg; 71% sold as 'collector's items' not for consumption.

69. Case reports · 2026 · Open access

    Severe Early-Onset Withdrawal Following Intentional Use of Mitragynine Pseudoindoxyl: A Case Report and Emerging Clinical Considerations (opens in a new tab)

    Stanciu CN · Cureus

    Clinicians should recognize its severe withdrawal profile, the limitations of standard toxicology, and the potential role of naltrexone in relapse prevention once an opioid-free interval is established.

70. Human studies · 2026

    The assessment and treatment of kratom dependence: findings from a physician survey in Malaysia (opens in a new tab)

    Singh D, Yee LC, Narayanan S · Am J Drug Alcohol Abuse

    Nearly 68% percent of those treating kratom dependence believed kratom to have similar effects as opioids and therefore prescribed treatments for kratom withdrawal that were designed for opioid withdrawal.Conclusions: Our findings suggest that opioid agonists are commonly used for the treatment of kratom withdrawal.

71. Case reports · 2026

    The Bitter Aftertaste of Kratom: A Toxicologic and Neurologic Challenge (opens in a new tab)

    Lal Vallath A, Pippari R, Yadav R, Bass M, Deyulis M · Cureus

    This case highlights the potential for severe and prolonged neurocardiac and neuropsychiatric toxicity following 7-OH ingestion and underscores the importance of clinical awareness of kratom-related complications, particularly in patients with polysubstance use and psychiatric comorbidities.

72. Reviews · 2026

    Tianeptine misuse and addiction: A systematic review of withdrawal, toxicity, and clinical management (opens in a new tab)

    Anand A, Alessi MR, Toussi RA, Tian J, Raffoul JJ, Pratt N et al. · Drug Alcohol Depend

    Continued clinical and epidemiological observation is warranted.

73. Reviews · 2026

    Toxicity, chemistry, and public health relevance of emerging nicotine analog vapes, pods, and pouches (opens in a new tab)

    (review) · Chem Res Toxicol

    Reviews 6-MN products: Spree Bar, SBX (Metatine), Kumi Six (SFN/NoNic6), Katchmi/Nixodine.

74. Case reports · 2026

    Treatment of Kratom Use Disorder With Methadone in an Opioid Treatment Program (opens in a new tab)

    Sherrick RC · J Addict Med

    Methadone was well tolerated and effective in stabilizing patients with KUD, supporting its use as a viable alternative when buprenorphine is not suitable.

75. Surveillance · 2026

    UNC Street Drug Analysis Lab: substances detected in North Carolina (live) (opens in a new tab)

    UNC Opioid Data Lab · Agency / organization document

    Free drug checking for NC samples (mail-in GC-MS); live list of all substances found in NC samples since 2022; 7-OH reported in NC samples (Oct 2024 newsletter).

76. Product testing · 2026 · Open access

    Unlabeled kratom alkaloids detected in products marketed as kava (opens in a new tab)

    Marshall S, Leisch L, Scott KS, Rivera J, Whiddon J, Bradford D et al. · Clin Toxicol (Phila)

    Unrecognized exposure to opioid-active kratom compounds may occur through products marketed as kava, highlighting the need for improved surveillance and increased awareness.

77. Reviews · 2026 · Open access

    UW ADAI 2026 7-OH Explainer (opens in a new tab)

    UW · Agency / organization document

    Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

78. Case reports · 2026 · Open access

    Ventricular Tachycardia Following Kratom Ingestion Requiring Extracorporeal Membrane Oxygenation in a Young Woman: Case Report (opens in a new tab)

    McLin-Evans M, Tiscareno J, Beneke LL · Clin Pract Cases Emerg Med

    Concentrated kratom extracts can precipitate life-threatening ventricular arrhythmias in previously healthy individuals.

79. Human studies · 2026

    When "Kava" Isn't Kava: Opioid-like Withdrawal Responsive to Buprenorphine: A Case Study (opens in a new tab)

    Malhotra A, McPherson GE, Scott KS, Li L · J Addict Med

    Review of product labeling indicated the presence of akuamma (Picralima nitida), a botanical containing μ-opioid receptor-active alkaloids; secondary qualitative testing of independently purchased samples of the same product by the UAB toxicology lab confirmed the presence of kratom (Mitragyna speciosa) derivatives…

80. In vitro · 2025

    6-methyl nicotine in electronic cigarettes: chemical analysis and toxicological properties (opens in a new tab)

    Duke (ATS 2025 abstract) · Am J Respir Crit Care Med (abstract)

    New 6-MN trademarks (Imotine, Nixotine, NoNic, SFN); labels diverged from measured amounts; 6-MN more toxic than nicotine in airway cells.

81. Case reports · 2025 · Open access

    7-Hydroxymitragynine and Nicotine Pouch Withdrawal Syndrome: A Case Report (opens in a new tab)

    Sharma A, Nair BS, Pemminati S · Cureus

    This case report highlights the diagnostic and therapeutic complexities of managing withdrawal from novel psychoactive substances, the need for multidisciplinary and flexible approaches, and the importance of systematic assessment and harm reduction as these products become in...

82. Surveillance · 2025

    A Descriptive Assessment of Products Containing the Opioid Receptor Stimulator Mitragynine Pseudoindoxyl (opens in a new tab)

    White CM, Belcourt J, Sedensky A · Subst Use Misuse

    Conclusions: There are many products that contain mitragynine pseudoindoxyl sold as dietary supplements and many have features that would appeal to children.

83. Case reports · 2025 · Open access

    A Kratomic Bomb: Cardiotoxicities From Mitragyna speciosa Extract (opens in a new tab)

    Jain V, Lloyd MS · JACC Case Rep

    Abstract not available in PubMed; see link.

84. Surveillance · 2025 · Open access

    Americas Poison Centers 2025 Kratom and 7-OH Alert (opens in a new tab)

    Americas · Agency / organization document

    Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

85. Surveillance · 2025

    An Outbreak of Synthetic Cannabinoid-Adulterated Tianeptine Products in New Jersey - Case Series (opens in a new tab)

    Counts CJ, Spadaro AV, Cerbini TA, Krotulski AJ, Walton SE, Greller HA et al. · J Med Toxicol

    Clinicians should be aware that tianeptine containing products are widely available, unregulated, and can be adulterated.

86. Case reports · 2025

    Bilateral hippocampal toxicity in a patient using kratom (opens in a new tab)

    Rao AK, Lee TJ, Bodle J · BMJ Case Rep

    This case highlights the importance of considering kratom as a potential cause of neurological symptoms in patients presenting with an altered mental status due to toxic ingestion.

87. Case reports · 2025 · Open access

    Case Report: Cannabis and kratom-induced self-amputation of ears and penis (opens in a new tab)

    Broul M, Rudenko X, Bajus A, Král J, Kyenge DM, Staňková Z et al. · Front Psychiatry

    This case underscores the importance of using a multidisciplinary approach to manage severe self-harm behaviors, and highlights the critical role of patient motivation in achieving positive outcomes.

88. Surveillance · 2025 · Open access

    CFSRE 2025 Monograph Mitragynine Pseudoindoxyl (opens in a new tab)

    CFSRE · Agency / organization document

    Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

89. Surveillance · 2025 · Open access

    CFSRE 2025 NPS Discovery Public Alert 7-Hydroxy Mitragynine (opens in a new tab)

    CFSRE · Agency / organization document

    Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

90. Human studies · 2025 · Open access

    Chemical Analysis and Alkaloid Intake for Kratom Products Available in the United States (opens in a new tab)

    Sharma A, Smith KE, Kuntz MA, Berthold EC, Elashkar OI, Guadagnoli N et al. · Drug Test Anal

    These findings on kratom products' chemical composition and daily kratom alkaloid consumption can also inform clinicians, policymakers, and consumers, particularly for whole-leaf material.

91. Case reports · 2025 · Open access

    Chronic kratom use as a precipitant for acquired Brugada syndrome (opens in a new tab)

    Abubaker M, Adrejiya P, Berhe L, Chennareddy S, Kanugula A · HeartRhythm Case Rep

    Abstract not available in PubMed; see link.

92. Case reports · 2025

    Complicating Factors Surrounding Concurrent Use of Kratom and a Novel 7-hydroxymitragynine Product Among a Participant Enrolled in a Kratom Clinical Trial (opens in a new tab)

    Smith KE, Rama Raju Kanumuri S, Sharma A, Rattenni R, LeComte R, McCurdy CR et al. · J Addict Med

    As 7-OH products are misleadingly marketed as kratom, and as both long-time kratom consumers and kratom-naive individuals may experiment with these novel products, improved assessment methods are urgently needed in the absence of real-time confirmatory testing.

93. Surveillance · 2025 · Open access

    De facto opioids: Characterization of novel 7-hydroxymitragynine and mitragynine pseudoindoxyl product marketing (opens in a new tab)

    Hill K, Boyer EW, Grundmann O, Smith KE · Drug Alcohol Depend

    Several products had names alluding to prescription opioids.

94. Product testing · 2025

    Detection and quantification of synthetic cannabinoids in seven illicitly sourced disposable vapes submitted by an individual presenting to a UK drug and alcohol service (opens in a new tab)

    Craft S, Sunderland P, Millea MF, Pudney CR, Sutcliffe OB, Freeman TP · Addiction

    The SC 5F-MDMB-PICA was detected at a median concentration of 0.85 mg/ml in seven disposable vapes which were illegally sourced in the United Kingdom, were mis-sold as cannabis products and closely resembled legal, regulated products.

95. In vitro · 2025 · Open access

    Discovery of rhynchophylline and mitraphylline in two Thai Mitragyna species and the investigation of their biological activity via opioid gene expression analysis (opens in a new tab)

    Sudmoon R, Tanee T, Wonok W, Ameamsri U, Liehr T, Daduang S et al. · Sci Rep

    These Mitragyna species and the combination (formula details are patent registered), substances and their biological activities can be used for the innovative production of new medicines and further clinical investigation.

96. Product testing · 2025

    Elevated toxic element emissions from popular disposable e-cigarettes (opens in a new tab)

    Salazar M, Poulin BA et al. · ACS Cent Sci

    Esco Bar, Flum Pebble, ELF Bar: lead (Esco Bar, leaded bronze), nickel from coils, antimony; several exceeded cancer/non-cancer risk thresholds.

97. Agency documents · 2025

    Emergence of potent kratom-related products containing 7-OH and/or mitragynine pseudoindoxyl (opens in a new tab)

    UNODC Early Warning Advisory · Agency / organization document

    Semi-synthetic kratom products come as tablets, strips, gummies, shots, syrups, vape pens and more; sold in vape shops; all six tested 7-OH products also had MGPI.

98. Agency documents · 2025 · Open access

    FDA 2025 7-Hydroxymitragynine Assessment of the Scientific Data and Toxicological Concerns (opens in a new tab)

    FDA · Agency / organization document

    FDA 2025 scientific assessment: 7-OH is a potent mu-opioid agonist with abuse and toxicity concerns; supports recommending scheduling.

99. Agency documents · 2025 · Open access

    FDA 2025 Consumer Update Products Containing 7-OH Can Cause Serious Harm (opens in a new tab)

    FDA · Agency / organization document

    Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

100. Agency documents · 2025 · Open access

     FDA 2025 Press Release FDA Seizes 7-OH Opioids (opens in a new tab)

     FDA · Agency / organization document

     Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

101. Agency documents · 2025 · Open access

     FDA 2025 Press Release Steps to Restrict 7-OH Opioid Products (opens in a new tab)

     FDA · Agency / organization document

     Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

102. Agency documents · 2025 · Open access

     FDA 2025 Press Release Warning Letters to Firms Marketing 7-OH (opens in a new tab)

     FDA · Agency / organization document

     Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

103. Agency documents · 2025

     FDA and CBP seize nearly $34 million worth of illegal e-cigarettes (opens in a new tab)

     FDA · Agency / organization document

     Feb 2025 Chicago seizure of ~2 million unauthorized vapes incl. Raz and Snoopy Smoke.

104. Reviews · 2025 · Open access

     From kratom to 7-hydroxymitragynine: evolution of a natural remedy into a public-health threat (opens in a new tab)

     Alsbrook S, Pro G, Koturbash I · Pharm Biol

     Collectively, the evidence demonstrates that concentrated 7-OH products are pharmacologically and toxicologically distinct from kratom leaf and pose significant risks of morbidity and mortality under typical conditions of use.

105. Reviews · 2025

     From Kratom to Semi-Synthetic Opioids: The Rise and Risks of MGM-15 (opens in a new tab)

     Gour A, Mukhopadhyay S, Henderson A, Awad A, Seabra MA, Pullman M et al. · Drug Test Anal

     MGM-15 shows greater hMOR and hDOR binding affinities than 7-HMG, indicating the potential for higher opioid effects and risks, emphasizing the urgent need for more research to advise regulation and hopefully prevent misuse and harm.

106. Reviews · 2025

     Gas station heroin- tianeptine and its impact: a systematic review and exploratory analysis (opens in a new tab)

     Parnia S, Jain L, Ali M, Sarfraz Z, Nasir MJ, Shah D et al. · BMC Public Health

     Targeted prevention, regulation, and treatment interventions are urgently needed to address these challenges.

107. In vitro · 2025

     In Vitro and In Vivo Pharmacokinetic Characterization of 7-Hydroxymitragynine, an Active Metabolite of Mitragynine, in Sprague-Dawley Rats (opens in a new tab)

     Chiang YH, Kanumuri SRR, Kuntz MA, Senetra AS, Berthold EC, Kamble SH et al. · Eur J Drug Metab Pharmacokinet

     This study reports the pharmacokinetic parameters of 7-HMG to help with the development of mitragynine, as a therapeutic.

108. In vitro · 2025 · Open access

     In Vitro Pharmacology of Mitragynine at α-Adrenoceptors (opens in a new tab)

     Chen Y, Seto J, Obeng S, Mottinelli M, Mukhopadhyay S, Tyagi R et al. · ACS Chem Neurosci

     Mitragynine's dual α2AR antagonist/α1R partial agonist pharmacology might contribute to mitragynine's psychostimulant-like properties.

109. In vitro · 2025 · Open access

     Inhibitory effects of Kratom constituents, mitragynine and 7-hydroxymitragynine, on 4-methylumbelliferone glucuronidation by human UDP-glucuronosyltransferases (opens in a new tab)

     Uchaipichat V · Toxicol Rep

     The experimental Ki values found here are relatively high compared to the maximum plasma concentrations of mitragynine and 7-hydroxymitragynine reported in humans, suggesting an unlikely potential for herb-drug interactions via UGT inhibition.

110. Case reports · 2025 · Open access

     Kratom Cardiotoxicity: Reversible Brugada Pattern and QTc Prolongation (opens in a new tab)

     Miller AHF, Krotulski AJ, Walton SE, Dulaney AR, Frolichstein AP, Dusek HL et al. · JACC Case Rep

     We present a patient who developed a reversible Brugada pattern and QT prolongation after self-treating his attention-deficit/hyperactivity disorder with kratom.

111. Human studies · 2025

     Kratom's Use and Impact on Pediatric Populations (opens in a new tab)

     White CM · J Pediatr Pharmacol Ther

     No abstract on PubMed; cited for its title and case details.

112. Reviews · 2025 · Open access

     LA County DPH 2025 Health Alert 7-OH (opens in a new tab)

     LA · Agency / organization document

     Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

113. Agency documents · 2025 · Open access

     LAPPA 2025 Kratom Summary of State Laws (opens in a new tab)

     LAPPA · Agency / organization document

     Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

114. Animal · 2025 · Open access

     Mitragynine and 7-hydroxymitragynine: Bidirectional effects on breathing in rats (opens in a new tab)

     Zuarth Gonzalez JD, Ragsdale AK, Mukhopadhyay S, McCurdy CR, McMahon LR, Obeng S et al. · J Pharmacol Exp Ther

     These findings highlight critical pharmacological differences between kratom-related alkaloids, emphasizing potential risks associated with products containing high concentrations of 7-HMG.

115. Agency documents · 2025

     More than two million illicit vaping products seized in nationwide sweep (opens in a new tab)

     DOJ / FDA · Agency / organization document

     2.1M+ unauthorized nicotine vapes seized from 5 distributors and 6 retailers in 7 states; includes Dream Distro LLC (Garner, NC). Allegations only.

116. Reviews · 2025 · Open access

     NC STAR 2025 Clinical Tip Sheet Kratom and 7-OH (opens in a new tab)

     NC · Agency / organization document

     Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

117. Agency documents · 2025

     North Carolina Vapor Products and Consumable Products Directory (S.L. 2024-31) (opens in a new tab)

     NC Department of Revenue · Agency / organization document

     Only directory-listed vapes may be sold at retail in NC since 2025; warnings, fines, seizure for repeat violations; public can report.

118. Agency documents · 2025

     Operation Vape Trail cracks down on illegal substances in vape shops (opens in a new tab)

     DEA · Agency / organization document

     Sept 15-19, 2025: 2,357,755 vape pens/cartridges seized, 106 arrests; DEA names 7-OH, synthetic cannabinoids and cathinones as sold in vape shops. Does not publish product-level lab results.

119. Reviews · 2025 · Open access

     Pennsylvania DOH 2025 Health Advisory Kratom and 7-OH (opens in a new tab)

     Pennsylvania · Agency / organization document

     Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

120. Product testing · 2025 · Open access

     Phytochemical analysis of water and ethanol liquid extracts prepared using freshly harvested leaves of Mitragyna speciosa (Korth.) (opens in a new tab)

     Karunakaran T, Vicknasingam B, Chawarski MC · Nat Prod Res

     Further rigorous and comprehensive evaluations of the phytochemical composition of freshly harvested kratom leaves utilising advanced spectrometric methods are needed to establish the full spectrum of phytochemicals within the plant.

121. Case reports · 2025

     Postmortem distribution of mitragynine and 7-hydroxymitragynine in 51 cases (opens in a new tab)

     Osawa KA, Johnson RD · J Anal Toxicol

     Methanolic preparations of mitragynine and 7-hydroxymitragynine were stable following 3 months of storage at -20°C.

122. Human studies · 2025 · Open access

     Reported associations between kratom and seizures: a systematic review (opens in a new tab)

     Turla T, Abele G, Hua M, Paustenbach D · Front Pharmacol

     OR SIGNIFICANCE: Currently, the available literature primarily consists of a limited number of studies, including case reports and case series, which document self-reported kratom use and provide minimal quantitative toxicological data on mitragynine.

123. Case reports · 2025

     Substance Use Disorder Following Consumption of a Novel Synthetic 7-Hydroxymitragynine Product (opens in a new tab)

     Reif B, Adkins A, Boyer EW, Kanumuri SRR, Sharma A, Smith KE · J Addict Med

     The potency of 7-OH places unwitting consumers who may believe they are using kratom, not a partial MOR agonist, at risk.

124. Reviews · 2025 · Open access

     Texas DSHS 2025 Serious Illnesses Associated with 7-OH Use (opens in a new tab)

     Texas · Agency / organization document

     Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

125. Reviews · 2025

     The acute adverse health effects of kratom: an evaluation of case reports (opens in a new tab)

     Smallets S, Litvin S, Abele G, Kirsh S, Paustenbach D · Front Pharmacol

     More research is necessary to isolate the effects of kratom from those of polypharmacy.

126. Reviews · 2025

     The Impact of Diverse Kratom Products on Use Patterns, Dependence, and Toxicity (opens in a new tab)

     Vadiei N, Evoy KE, Grundmann O · Curr Psychiatry Rep

     And based on misleading advertising, consumers may be unaware of the differences and increased risks associated with these products compared with traditional whole leaf kratom.

127. Reviews · 2025 · Open access

     The rise of novel, semi-synthetic 7-hydroxymitragnine products (opens in a new tab)

     Smith KE, Boyer EW, Grundmann O, McCurdy CR, Sharma A · Addiction

     Abstract not available in PubMed; see link.

128. Human studies · 2025

     The successful use of buprenorphine to manage kratom withdrawal secondary to self-treatment of opioid withdrawal (opens in a new tab)

     Sivakumar D, Pascual J, Kennedy M, Clark KT, Mason JM, Walfield AL et al. · Clin Toxicol (Phila)

     No abstract on PubMed; cited for its title and case details.

129. Surveillance · 2025

     Tianeptine Exposures Reported to United States Poison Centers, 2015-2023 (opens in a new tab)

     Quadir M, Rine NI, Badeti J, Hays HL, Michaels NL, Yang J et al. · J Med Toxicol

     Uniform regulation of tianeptine across all states may offer an important strategy to help mitigate this public health problem.

130. Reviews · 2025

     What to Know About 7-OH, the New Vape Shop Hazard (opens in a new tab)

     Anderer S · JAMA

     Abstract not available in PubMed; see link.

131. Reviews · 2024

     A Systematic Review of Phenibut Withdrawals (opens in a new tab)

     Stewart C, Simonsen H, Satyasi SK, Ashraf N, Sukpraprut-Braaten S · Cureus

     This review highlights the importance of collecting a thorough patient history, including supplements, to help prevent phenibut misuse and subsequent withdrawals.

132. Case reports · 2024 · Open access

     Acquired Type 1 Brugada Syndrome Induced by Chronic High-Dose Kratom Use (opens in a new tab)

     Holton K, Sanchez Corredera C, Haidar J, Valentin RG, Perez D, Boccio E · Cureus

     While the clinical management of kratom toxicity is mostly supportive, physicians should consider potentially fatal cardiac dysrhythmias including Brugada syndrome.

133. Reviews · 2024 · Open access

     An update on the clinical pharmacology of kratom: uses, abuse potential, and future considerations (opens in a new tab)

     McCurdy CR, Sharma A, Smith KE, Veltri CA, Weiss ST, White CM et al. · Expert Rev Clin Pharmacol

     While many patients may benefit from kratom use with few or no reported adverse effects, escalating dose and increased use frequency raise the risk for toxic events in the setting of polysubstance use or development of a use disorder.

134. Product testing · 2024

     Characteristics and ingredients of disposable Elfbar e-cigarettes sold in the US and UK (opens in a new tab)

     Leigh NJ et al. · Addiction

     US Elfbar BC5000: ~41.8 mg/mL nicotine in ~6.5 mL (about 8 UK devices worth); WS-23 ~17.8 mg/mL.

135. Reviews · 2024

     Controversies in Assessment, Diagnosis, and Treatment of Kratom Use Disorder (opens in a new tab)

     Smith KE, Epstein DH, Weiss ST · Curr Psychiatry Rep

     We propose an algorithm that takes into consideration whether KUD occurs with comorbid opioid use disorder.

136. Surveillance · 2024

     E-cigarette and nicotine pouch use among middle and high school students, 2024 (opens in a new tab)

     CDC / FDA · MMWR Morb Mortal Wkly Rep

     Students who vape: Elf Bar 36.1%, Breeze 19.9%, Mr. Fog 15.8%, Vuse 13.7%, JUUL 12.6%, Esco Bars 10.2%, Geek Bar 5.8%.

137. Human studies · 2024 · Open access

     Effects of Itraconazole on Pharmacokinetics of Mitragynine and 7-Hydroxymitragynine in Healthy Volunteers (opens in a new tab)

     Mongar P, Jaisi A, Inkviya T, Wungsintaweekul J, Wiwattanawongsa K · ACS Pharmacol Transl Sci

     This study provides the first evidence of metabolic conversion of mitragynine to 7OH in humans.

138. Product testing · 2024

     Elemental impurities (heavy metals) in kratom products: an assessment of published individual product analyses (opens in a new tab)

     Snow Caroti K, Joseph A, Sapowadia A, Michael White C · Clin Toxicol (Phila)

     Daily use of these products can result in exposures exceeding regulatory thresholds and adverse health effects.

139. Product testing · 2024 · Open access

     High variability in nicotine analog contents, misleading labeling, and artificial sweetener in FDA-exempt e-cigarettes (opens in a new tab)

     (see paper) · PMC (peer-reviewed)

     Spree Bar labeled 5% 6-MN measured 0.61-0.64%; Nixotine had unlisted 6-MN; neotame and WS-23 in Spree Bar.

140. Human studies · 2024 · Open access

     Human Mitragynine and 7-Hydroxymitragynine Pharmacokinetics after Single and Multiple Daily Doses of Oral Encapsulated Dried Kratom Leaf Powder (opens in a new tab)

     Huestis MA, Brett MA, Bothmer J, Atallah R · Molecules

     These mitragynine and 7-hydroxymitragynine data provide guidance for future clinical kratom dosing studies and an interpretation of clinical and forensic mitragynine and 7-hydroxymitragynine concentrations.

141. Case reports · 2024

     Isolated Kratom Use Disorder Treated With Extended-Release Buprenorphine Taper (opens in a new tab)

     Swart BB, Reznikoff C, Steen K · J Addict Med

     His case underscores some of the current uncertainties around kratom use disorder diagnosis and treatment.

142. Human studies · 2024 · Open access

     Kratom addiction per DSM-5 SUD criteria, and kratom physical dependence: Insights from dosing amount versus frequency (opens in a new tab)

     Rogers JM, Weiss ST, Epstein DH, Grundmann O, Hill K, Smith KE · Drug Alcohol Depend

     Greater dose amount and frequency were systematically related to the number of withdrawal symptoms upon cessation and to KUD symptoms; the relationship was stronger for dose frequency than amount.

143. Human studies · 2024

     Kratom Neurotoxicity: T1 Hyperintensity in the Basal Ganglia (opens in a new tab)

     Hoshina Y, Liang JZ · Neurohospitalist

     No abstract on PubMed; cited for its title and case details.

144. Reviews · 2024

     Not all kratom is equal: The important distinction between native leaf and extract products (opens in a new tab)

     Grundmann O, Garcia-Romeu A, McCurdy CR, Sharma A, Smith KE, Swogger MT et al. · Addiction

     Abstract not available in PubMed; see link.

145. Product testing · 2024

     Purchasing "Nootropics" Online: Identification and Quantification of Ingredients in Phenibut-Containing Products (opens in a new tab)

     Upmanis T, Sevostjanovs E, Zvejniece L, Kazoka H, Kisis V, Pugovics O et al. · Medicina (Kaunas)

     The combinations of these additional ingredients with phenibut have not been tested for activity or safety and their use warrants further attention to avoid potential health problems.

146. Human studies · 2024

     Survey of U.S. Residents and Their Usage of Electronic Cigarettes with Drugs Other Than Nicotine (opens in a new tab)

     Holt AK, Rudy AK, Sawyer AN, Poklis JL, Breland AB, Peace MR · J Psychoactive Drugs

     Results from this study are useful for developing future national surveys to consider a comprehensive substance use-focused strategy that includes vaping, building awareness of DOTN e-cig use, and highlighting public safety issues in driving impairment, crime scene investigations, and death investigations.

147. In vitro · 2024 · Open access

     The Mitragyna speciosa (kratom) alkaloid mitragynine: Analysis of adrenergic α2 receptor activity in vitro and in vivo (opens in a new tab)

     Obeng S, Crowley ML, Mottinelli M, León F, Zuarth Gonzalez JD, Chen Y et al. · Eur J Pharmacol

     Together, these data demonstrate that mitragynine acts in vivo like an Aα2R agonist, although its failure to induce hypothermia or stimulate [35S]GTPγS binding in vitro, suggests that mitragynine maybe a low efficacy Aα2R agonist.

148. Case reports · 2024

     Tianeptine's Obscured Withdrawal, Presentation, and Treatment (opens in a new tab)

     Farsani A, Reyes C · Cureus

     The discussion emphasizes the importance of prompt identification and management of tianeptine-related complications and calls for heightened awareness among healthcare providers.

149. Human studies · 2024 · Open access

     Time course of kratom effects via ecological momentary assessment, by product type, dose amount, and assayed alkaloid content (opens in a new tab)

     Smith KE, Panlilio LV, Sharma A, McCurdy CR, Feldman JD, Mukhopadhyay S et al. · Drug Alcohol Depend

     Alkaloid content was surprisingly consistent across kratom products, and participants were consistent in the amount they used across events.

150. Case reports · 2024 · Open access

     Ventricular fibrillation during football training as a consequence of kratom and caffeine use in an adolescent: case report (opens in a new tab)

     Dodulík J, Plášek J, Handlos P, Gřegořová A, Václavík J · Eur Heart J Case Rep

     We would like to stress the importance of reporting further case series for more scientific evidence and thus increasing the pressure for stricter availability and regulation of kratom in some countries, especially where it is over-the-counter.

151. Reviews · 2023 · Open access

     A Critical Review of the Neuropharmacological Effects of Kratom: An Insight from the Functional Array of Identified Natural Compounds (opens in a new tab)

     Hossain R, Sultana A, Nuinoon M, Noonong K, Tangpong J, Hossain KH et al. · Molecules

     In this context, this review focuses on the research gap to resolve ambiguities about the neuronal effects of kratom and demonstrate its prospects as a therapeutic target for neurological disorders associated with other pharmacological effects.

152. Product testing · 2023

     A synthetic coolant (WS-23) in disposable e-cigarettes impairs cytoskeletal function in EpiAirway microtissues (opens in a new tab)

     (see paper) · Sci Rep

     WS-23 in all 22 disposables tested (Flum Float, ELFBAR, Puff XL/Plus/Bar Plus); mean 21.4 mg/mL; airway tissue effects.

153. Reviews · 2023

     A systematic review of phenibut withdrawal focusing on complications, therapeutic approaches, and single substance versus polysubstance withdrawal (opens in a new tab)

     Feldman R, Autry B, Dukes J, Lofy T, Marchetti G, Patt A et al. · Clin Toxicol (Phila)

     Significant study is warranted to develop methods of triaging phenibut withdrawal (e.g., severity scoring, inpatient versus outpatient management) and creating optimal treatment regimens.

154. Product testing · 2023 · Open access

     An e-cigarette pod system delivering 6-methyl nicotine marketed in the US as PMTA exempt (opens in a new tab)

     (see paper) · PMC (peer-reviewed)

     Spree Bar (Metatine) confirmed to contain 6-methyl nicotine by LC-MS.

155. Surveillance · 2023

     An evaluation of adverse drug reactions and outcomes attributed to kratom in the US Food and Drug Administration Adverse Event Reporting System from January 2004 through September 2021 (opens in a new tab)

     Li X, Ndungu P, Taneja SB, Chapin MR, Egbert SB, Akenapalli K et al. · Clin Transl Sci

     Although further research is needed to assess the safety of kratom, clinicians and consumers should be aware that real-world evidence points to potential safety threats.

156. Product testing · 2023

     Analysis of vape products from high schools (opens in a new tab)

     CFSRE with DEA Pittsburgh · Agency / organization document

     Forensic testing of vapes recovered from high schools to tell nicotine from cannabis and spot adulteration (full report PDF on the page).

157. Animal · 2023 · Open access

     Assessment of the potential of novel and classical opioids to induce respiratory depression in mice (opens in a new tab)

     Hill R, Sanchez J, Lemel L, Antonijevic M, Hosking Y, Mistry SN et al. · Br J Pharmacol

     In addition to providing effective anti-nociception, the novel opioids, oliceridine, tianeptine and SR-17018 depress respiration in male mice.

158. Case reports · 2023

     Case Report: Possible Serotonin Syndrome in a Patient Taking Kratom and Multiple Serotonergic Agents (opens in a new tab)

     Eudaley ST, Brooks SP, Hamilton LA · J Pharm Pract

     Because substances contained in kratom can inhibit metabolism of prescription serotonergic medications, clinicians must be aware of potential development of serotonin syndrome.

159. Human studies · 2023 · Open access

     Clinical Assessment of the Drug Interaction Potential of the Psychotropic Natural Product Kratom (opens in a new tab)

     Tanna RS, Nguyen JT, Hadi DL, Layton ME, White JR, Cech NB et al. · Clin Pharmacol Ther

     These data fill critical knowledge gaps about the safe use of this increasingly popular natural product, thereby addressing ongoing public health concerns.

160. Surveillance · 2023

     Description of Kratom Exposure Events in Wisconsin as Reported to the Wisconsin Poison Center, January 1, 2010 to September 1, 2022 (opens in a new tab)

     DeJonge P, Gummin D, Titelbaum N, Meiman J · WMJ

     Wisconsinites who choose to use kratom might benefit from education regarding health risks and safe storage practices to avoid unintentional pediatric exposure.

161. Product testing · 2023

     Kratom availability in California vape shops (opens in a new tab)

     Bowdring MA, Leas EC, Vishwakarma M, Schleicher NC, Prochaska JJ, Henriksen L · Prev Med Rep

     Widespread availability in tobacco specialty shops suggests the need for research on dual use with tobacco, kratom advertising and cross-product promotion, and the potential of state and local tobacco retail licensing to prohibit sales.

162. Case reports · 2023

     Kratom use disorder: case reports on successful treatment with home induction of buprenorphine-naloxone (opens in a new tab)

     Kiyokawa M, Kwon AK, Cape MC, Streltzer JM · Fam Pract

     In addition to daily doses of kratom use, other factors, such as duration of kratom use and individual psychological factors may determine the most comfortable dose of buprenorphine-naloxone.

163. Animal · 2023 · Open access

     Pharmacokinetic and Pharmacodynamic Consequences of Cytochrome P450 3A Inhibition on Mitragynine Metabolism in Rats (opens in a new tab)

     Kamble SH, Obeng S, León F, Restrepo LF, King TI, Berthold EC et al. · J Pharmacol Exp Ther

     These data highlight potential interactions between kratom and CYP3A inhibitors, which include numerous medications and citrus juices.

164. Surveillance · 2023 · Open access

     SAMHSA 2023 NSDUH 2022 Detailed Tables 8-21 to 8-23 (opens in a new tab)

     SAMHSA · Agency / organization document

     Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

165. Product testing · 2023 · Open access

     Seasonal and Geographic Variation in Alkaloid Content of Kratom (Mitragyna speciosa (Korth.) Havil.) from Thailand (opens in a new tab)

     Sengnon N, Vonghirundecha P, Chaichan W, Juengwatanatrakul T, Onthong J, Kitprasong P et al. · Plants (Basel)

     In conclusion, the present study suggested that the alkaloid content in kratom diverges based on seasonal and geographical origin.

166. Human studies · 2023

     Seizure Occurring During Baclofen Monotherapy for Phenibut Withdrawal (opens in a new tab)

     Patt A, Fox H, Wells L, Theobald J, Feldman R · Clin Neuropharmacol

     Treatment done in consultation with providers experienced in managing withdrawal such as a toxicologist may help reduce this risk.

167. Human studies · 2023

     The Health Impact of Long-Term Kratom (Mitragyna Speciosa) Use in Southern Thailand (opens in a new tab)

     Saingam D, Singh D, Geater AF, Assanangkornchai S, Jitpiboon W, Latkin C · Subst Use Misuse

     Medical records revealed no death due to traditional kratom use, but the high prevalence of tobacco or/and hand rolled cigarette smoking among kratom users should be of concern.

168. In vitro · 2023 · Open access

     Total Synthesis and Structural Plasticity of Kratom Pseudoindoxyl Metabolites (opens in a new tab)

     Angyal P, Hegedüs K, Mészáros BB, Daru J, Dudás Á, Galambos AR et al. · Angew Chem Int Ed Engl

     Synthetic-chemistry paper (link only; omitted from summary).

169. Case reports · 2023

     Toxidrome of an Easily Obtainable Nootropic: A Case Report of Phenibut Intoxication and Withdrawal Delirium (opens in a new tab)

     Martin R, Buffenstein I, Cho D, Kiyokawa M · J Clin Psychopharmacol

     High-dose phenibut intoxication and withdrawal can appear as dramatic and dangerous as high-dose sedative withdrawal, however given its specified receptor affinity and binding profile we found that a pharmacotherapeutic approach targeting GABA-B, GABA-A, and gabapentenoid receptors were effective in stabilizing this…

170. Reviews · 2023 · Open access

     Understanding and countering opioid-induced respiratory depression (opens in a new tab)

     Bateman JT, Saunders SE, Levitt ES · Br J Pharmacol

     To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc.

171. Surveillance · 2023 · Open access

     Ventricular Arrhythmias Associated With Over-the-Counter and Recreational Opioids (opens in a new tab)

     Krantz MJ, Rudo TJ, Haigney MCP, Stockbridge N, Kleiman RB, Klein M et al. · J Am Coll Cardiol

     The nonprescription drugs loperamide and mitragynine are associated with disproportionate reports of life-threatening ventricular arrhythmia in North America.

172. Case reports · 2022

     Acute Renal Insufficiency Associated With Consumption of Hydrocodone- and Morphine-Adulterated Kratom (Mitragyna Speciosa) (opens in a new tab)

     LeSaint KT, Yin S, Sharma A, Avery BA, McCurdy CR, Waksman JC · J Emerg Med

     This case illustrates the vital importance of recognizing that adulteration of unregulated products is certainly a possibility and clinicians may continue to see a rise in adverse effects, given kratom's increasing popularity.

173. Human studies · 2022 · Open access

     Clinical Pharmacokinetic Assessment of Kratom (Mitragyna speciosa), a Botanical Product with Opioid-like Effects, in Healthy Adult Participants (opens in a new tab)

     Tanna RS, Nguyen JT, Hadi DL, Manwill PK, Flores-Bocanegra L, Layton ME et al. · Pharmaceutics

     This first comprehensive pharmacokinetic characterization of kratom alkaloids in humans provides the foundation for further research to establish safety and effectiveness of this emerging botanical product.

174. Animal · 2022 · Open access

     Interactive Effects of µ-Opioid and Adrenergic-α 2 Receptor Agonists in Rats: Pharmacological Investigation of the Primary Kratom Alkaloid Mitragynine and Its Metabolite 7-Hydroxymitragynine (opens in a new tab)

     Obeng S, Leon F, Patel A, Zuarth Gonzalez JD, Chaves Da Silva L, Restrepo LF et al. · J Pharmacol Exp Ther

     When combined with Aα2R agonists, mitragynine could also produce hypothermic synergism.

175. Case reports · 2022 · Open access

     Long-term buprenorphine treatment for kratom use disorder: A case series (opens in a new tab)

     Broyan VR, Brar JK, Allgaier Student T, Allgaier JT · Subst Abus

     Our findings suggest buprenorphine/naloxone can be used as an effective treatment option for KUD.

176. Reviews · 2022

     Mechanisms of opioid-induced respiratory depression (opens in a new tab)

     Baldo BA, Rose MA · Arch Toxicol

     Methadone, administered to alleviate symptoms of NAS in humans, desensitizes rats to RD.

177. In vitro · 2022 · Open access

     Metabolism of Speciociliatine, an Overlooked Kratom Alkaloid for its Potential Pharmacological Effects (opens in a new tab)

     Kamble SH, Berthold EC, Kanumuri SRR, King TI, Kuntz MA, León F et al. · AAPS J

     The metabolism of speciociliatine was predominantly mediated by CYP3A4 with minor contributions by CYP2D6.

178. Human studies · 2022 · Open access

     Searching for a Signal: Self-Reported Kratom Dose-Effect Relationships Among a Sample of US Adults With Regular Kratom Use Histories (opens in a new tab)

     Smith KE, Rogers JM, Dunn KE, Grundmann O, McCurdy CR, Schriefer D et al. · Front Pharmacol

     These can help inform the development of controlled observational and experimental studies needed to advance the public health understanding of kratom product use.

179. Human studies · 2022

     The association between E-cigarette use and Kratom use among US adults (opens in a new tab)

     Lee J, Terashima JP, Parker MA · Prev Med

     These findings might help inform the need for continuing education for physicians and healthcare providers related to practice in managing patients with kratom use, future studies for regulatory policies on e-cigarettes (e.g., e-liquids), or other FDA policies related to kratom.

180. Animal · 2022 · Open access

     The Lack of Contribution of 7-Hydroxymitragynine to the Antinociceptive Effects of Mitragynine in Mice: A Pharmacokinetic and Pharmacodynamic Study (opens in a new tab)

     Berthold EC, Kamble SH, Raju KS, Kuntz MA, Senetra AS, Mottinelli M et al. · Drug Metab Dispos

     The results of this study suggest a lack of involvement of 7HMG in the antinociceptive effects of MTG in mice.

181. Animal · 2022 · Open access

     The respiratory depressant effects of mitragynine are limited by its conversion to 7-OH mitragynine (opens in a new tab)

     Hill R, Kruegel AC, Javitch JA, Lane JR, Canals M · Br J Pharmacol

     Both the anti-nociceptive effects and the respiratory depressant effects of mitragynine are partly due to its metabolic conversion to 7-OH mitragynine.

182. In vitro · 2021 · Open access

     Activity of Mitragyna speciosa ("Kratom") Alkaloids at Serotonin Receptors (opens in a new tab)

     León F, Obeng S, Mottinelli M, Chen Y, King TI, Berthold EC et al. · J Med Chem

     The 5-HT1AR agonism by kratom alkaloids may contribute to the mood-enhancing effects associated with kratom use.

183. Case reports · 2021 · Open access

     Breakthrough Seizure Associated With Kratom Use in Patients With Epilepsy (opens in a new tab)

     Burke DJ, Mahonski SG, Van Cott AC · Neurol Clin Pract

     Neurologists need to be aware of its association with seizure and other neurologic side effects.

184. Surveillance · 2021

     Characteristics of tianeptine effects reported to a poison control center: a growing threat to public health (opens in a new tab)

     Rushton W, Whitworth B, Brown J, Kurz M, Rivera J · Clin Toxicol (Phila)

     Health care practitioners should be increasingly aware of this xenobiotic as usage may be on the rise.

185. In vitro · 2021 · Open access

     Exploring the Chemistry of Alkaloids from Malaysian Mitragyna speciosa (Kratom) and the Role of Oxindoles on Human Opioid Receptors (opens in a new tab)

     Chear NJ, León F, Sharma A, Kanumuri SRR, Zwolinski G, Abboud KA et al. · J Nat Prod

     These findings have important implications for evaluating the combined effects of the minor oxindole alkaloids in the overall therapeutic activity of M. speciosa.

186. Human studies · 2021

     Is kratom (Mitragyna speciosa Korth.) use associated with ECG abnormalities? Electrocardiogram comparisons between regular kratom users and controls (opens in a new tab)

     Leong Abdullah MFI, Tan KL, Narayanan S, Yuvashnee N, Chear NJY, Singh D et al. · Clin Toxicol (Phila)

     We found no link between regular kratom use and electrocardiographic abnormalities with an estimated average daily intake of 434.28 mg of mitragynine.

187. Reviews · 2021 · Open access

     Kratom Abuse Potential 2021: An Updated Eight Factor Analysis (opens in a new tab)

     Henningfield JE, Wang DW, Huestis MA · Front Pharmacol

     Regulation to minimize risks of contaminated, adulterated, and inappropriately marketed products is recommended.

188. Animal · 2021 · Open access

     Kratom Alkaloids, Natural and Semi-Synthetic, Show Less Physical Dependence and Ameliorate Opioid Withdrawal (opens in a new tab)

     Wilson LL, Chakraborty S, Eans SO, Cirino TJ, Stacy HM, Simons CA et al. · Cell Mol Neurobiol

     In conclusion, while retaining some liabilities, kratom, mitragynine, and mitragynine pseudoindoxyl produced significantly less physical dependence and ameliorated precipitated withdrawal in morphine-dependent animals, suggesting some clinical value.

189. Human studies · 2021 · Open access

     Kratom Use in the US: Both a Regional Phenomenon and a White Middle-Class Phenomenon? Evidence From NSDUH 2019 and an Online Convenience Sample (opens in a new tab)

     Rogers JM, Smith KE, Strickland JC, Epstein DH · Front Pharmacol

     In the interim, focus should be on our finding that lifetime nonmedical opioid use was associated with an up to five times greater likelihood of past-year kratom use, suggesting that drug-use history may presently be the strongest predictor of kratom use.

190. Case reports · 2021 · Open access

     Liver injury associated with kratom, a popular opioid-like product: Experience from the U.S. drug induced liver injury network and a review of the literature (opens in a new tab)

     Ahmad J, Odin JA, Hayashi PH, Fontana RJ, Conjeevaram H, Avula B et al. · Drug Alcohol Depend

     Kratom can cause severe liver injury with jaundice.

191. Human studies · 2021

     Management of kratom dependence with buprenorphine/naloxone in a veteran population (opens in a new tab)

     Lei J, Butz A, Valentino N · Subst Abus

     Further research is needed on the impact and the treatment of kratom dependence.

192. Human studies · 2021

     Medication for Adolescents and Young Adults With Opioid Use Disorder (opens in a new tab)

     Society for Adolescent Health and Medicine · J Adolesc Health

     A broad research agenda is proposed with the goal of expanding the evidence base for the use and delivery of MOUD for AYAs.

193. Animal · 2021 · Open access

     Methadone, Buprenorphine, and Clonidine Attenuate Mitragynine Withdrawal in Rats (opens in a new tab)

     Hassan R, Sreenivasan S, Müller CP, Hassan Z · Front Pharmacol

     This may suggest them as treatment options also for problematic mitragynine/kratom use in humans.

194. Animal · 2021 · Open access

     Oral Pharmacokinetics in Beagle Dogs of the Mitragynine Metabolite, 7-Hydroxymitragynine (opens in a new tab)

     Maxwell EA, King TI, Kamble SH, Raju KSR, Berthold EC, León F et al. · Eur J Drug Metab Pharmacokinet

     These results provide the first pharmacokinetic and safety data for 7-HMG in the dog and therefore contribute to the understanding of the putative pharmacologic role of 7-HMG resulting from an oral delivery of mitragynine from kratom.

195. Human studies · 2021 · Open access

     Outcomes of mothers and newborns to prenatal exposure to kratom: a systematic review (opens in a new tab)

     Wright ME, Ginsberg C, Parkison AM, Dubose M, Sherbondy M, Shores E · J Perinatol

     Maternal and infant withdrawal from kratom exposure was described in each case, resulting in pharmacologic treatment for both mothers and infants.

196. In vitro · 2021 · Open access

     Oxidative Metabolism as a Modulator of Kratom's Biological Actions (opens in a new tab)

     Chakraborty S, Uprety R, Slocum ST, Irie T, Le Rouzic V, Li X et al. · J Med Chem

     Our results indicate that the oxidative metabolism of the mitragynine template beyond 7-hydroxymitragynine may have implications in its overall pharmacology in vivo.

197. Human studies · 2021 · Open access

     Past-Year Kratom Use in the U.S.: Estimates From a Nationally Representative Sample (opens in a new tab)

     Palamar JJ · Am J Prev Med

     Kratom use is particularly prevalent among those with prescription opioid use disorder, but it is also prevalent among people who use other drugs.

198. Animal · 2021 · Open access

     Pharmacokinetics of Eleven Kratom Alkaloids Following an Oral Dose of Either Traditional or Commercial Kratom Products in Rats (opens in a new tab)

     Kamble SH, Berthold EC, King TI, Raju Kanumuri SR, Popa R, Herting JR et al. · J Nat Prod

     This information will contribute to understanding the role of each alkaloid in the overall pharmacology of kratom and elucidating the pharmacokinetic differences between traditional and commercial kratom products.

199. In vitro · 2021 · Open access

     Pharmacological Comparison of Mitragynine and 7-Hydroxymitragynine: In Vitro Affinity and Efficacy for μ-Opioid Receptor and Opioid-Like Behavioral Effects in Rats (opens in a new tab)

     Obeng S, Wilkerson JL, León F, Reeves ME, Restrepo LF, Gamez-Jimenez LR et al. · J Pharmacol Exp Ther

     These results are consistent with 7-hydroxymitragynine being a highly selective MOR agonist and with mitragynine having a complex pharmacology that combines low efficacy MOR agonism with activity at nonopioid receptors.

200. Animal · 2021

     Preclinical pharmacokinetic study of speciociliatine, a kratom alkaloid, in rats using an UPLC-MS/MS method (opens in a new tab)

     Berthold EC, Kamble SH, Raju KS, King TI, Popa R, Sharma A et al. · J Pharm Biomed Anal

     The speciociliatine pharmacokinetic parameters described here will help to better understand the overall effects reported with kratom product use.

201. Reviews · 2021

     Prolactin levels as a criterion to differentiate between psychogenic non-epileptic seizures and epileptic seizures: A systematic review (opens in a new tab)

     Wang YQ, Wen Y, Wang MM, Zhang YW, Fang ZX · Epilepsy Res

     However, PRL levels are of limited use for differentiating FIAS or FAS from PNES, and a negative PRL measure is not predictive of PNES.

202. Case reports · 2021

     Seizures among young adults consuming kratom beverages in Malaysia: A case series (opens in a new tab)

     Halim SA, Low JH, Chee YC, Alias MR · Epilepsy Behav

     This study provided indirect evidence that chronic kratom use with or without concomitant drug abuse can cause recurrent seizures in susceptible individuals, which may progress to epilepsy or require antiepileptic medication.

203. Reviews · 2021 · Open access

     The Adverse Cardiovascular Effects and Cardiotoxicity of Kratom (Mitragyna speciosa Korth.): A Comprehensive Review (opens in a new tab)

     Leong Bin Abdullah MFI, Singh D · Front Pharmacol

     Conclusion: Although kratom use has been associated with death and cardiotoxicity, especially at higher doses and when associated with other psychoactive drugs, the dearth of data and methodological limitations reported in existing studies do not allow a definitive conclusion,...

204. Case reports · 2021

     Treatment of Kratom Withdrawal and Dependence With Buprenorphine/Naloxone: A Case Series and Systematic Literature Review (opens in a new tab)

     Weiss ST, Douglas HE · J Addict Med

     Based on our analysis, patients using <20 g of kratom/d could be initiated on opioid agonist therapy with 4/1 mg-8/2 mg buprenorphine-naloxone/d, while patients using kratom doses >40 g/d could be initiated with 12/3 mg-16/4 mg of buprenorphine-naloxone/day.

205. Case reports · 2020 · Open access

     A Case of Kratom-induced Seizures (opens in a new tab)

     Afzal H, Esang M, Rahman S · Cureus

     This case highlights the life-threatening complications of Kratom that is easily available online.

206. Reviews · 2020

     Adherence to and Retention in Medications for Opioid Use Disorder Among Adolescents and Young Adults (opens in a new tab)

     Viera A, Bromberg DJ, Whittaker S, Refsland BM, Stanojlović M, Nyhan K et al. · Epidemiol Rev

     Ways MOUD providers can tailor treatment to increase retention of adolescents and young adults are highlighted, as is the need for more research explaining MOUD adherence and retention disparities in this age group.

207. Surveillance · 2020

     Adverse experience reports of seizures in youth and young adult ENDS users (opens in a new tab)

     FDA CTP authors · PubMed 31866055

     FDA reviewed voluntary reports of seizures after e-cigarette use in youth and young adults; causality not established.

208. Animal · 2020 · Open access

     Bioanalytical method development and validation of corynantheidine, a kratom alkaloid, using UPLC-MS/MS, and its application to preclinical pharmacokinetic studies (opens in a new tab)

     King TI, Sharma A, Kamble SH, León F, Berthold EC, Popa R et al. · J Pharm Biomed Anal

     Corynantheidine was detected in the corpus callosum and some regions of the hippocampus.

209. In vitro · 2020 · Open access

     Chemical composition and biological effects of kratom (Mitragyna speciosa): In vitro studies with implications for efficacy and drug interactions (opens in a new tab)

     Todd DA, Kellogg JJ, Wallace ED, Khin M, Flores-Bocanegra L, Tanna RS et al. · Sci Rep

     All three kratom alkaloids tested inhibited select cytochrome P450 enzymes, suggesting a potential risk for adverse interactions when kratom is co-consumed with drugs metabolized by these enzymes.

210. Reviews · 2020 · Open access

     Combining opioids and benzodiazepines: effects on mortality and severe adverse respiratory events (opens in a new tab)

     Boon M, van Dorp E, Broens S, Overdyk F · Ann Palliat Med

     However, the risk for harm and benefit of the drug combination strongly correlates to its context and there are situations, such as in the hospice setting, where benefits may outweigh the risks.

211. Human studies · 2020

     Critical Illness Secondary to Synthetic Cannabinoid Ingestion (opens in a new tab)

     Kourouni I, Mourad B, Khouli H, Shapiro JM, Mathew JP · JAMA Netw Open

     Frontline clinicians must be aware of the presentation and be vigilant in suspecting SC intoxication.

212. In vitro · 2020 · Open access

     Evaluating kratom alkaloids using PHASE (opens in a new tab)

     Ellis CR, Racz R, Kruhlak NL, Kim MT, Zakharov AV, Southall N et al. · PLoS One

     The verified binding profiles demonstrate the ability of PHASE to identify potential safety signals and provide a tool for prioritizing experimental evaluation of high-risk compounds.

213. Product testing · 2020

     Evaluation of the Mitragynine Content, Levels of Toxic Metals and the Presence of Microbes in Kratom Products Purchased in the Western Suburbs of Chicago (opens in a new tab)

     Prozialeck WC, Edwards JR, Lamar PC, Plotkin BJ, Sigar IM, Grundmann O et al. · Int J Environ Res Public Health

     These findings highlight the need for more stringent standards for the production and sale of kratom products.

214. Animal · 2020 · Open access

     Evaluation of the rewarding effects of mitragynine and 7-hydroxymitragynine in an intracranial self-stimulation procedure in male and female rats (opens in a new tab)

     Behnood-Rod A, Chellian R, Wilson R, Hiranita T, Sharma A, Leon F et al. · Drug Alcohol Depend

     These initial findings indicate that mitragynine and 7-hydroxymitragynine are not rewarding in the ICSS procedure.

215. In vitro · 2020 · Open access

     Exploration of cytochrome P450 inhibition mediated drug-drug interaction potential of kratom alkaloids (opens in a new tab)

     Kamble SH, Sharma A, King TI, Berthold EC, León F, Meyer PKL et al. · Toxicol Lett

     In conclusion, MTG and COR may lead to clinically significant adverse drug interactions upon coadministration of drugs that are substantially metabolized by CYP2D6.

216. In vitro · 2020 · Open access

     G protein-biased kratom-alkaloids and synthetic carfentanil-amide opioids as potential treatments for alcohol use disorder (opens in a new tab)

     Gutridge AM, Robins MT, Cassell RJ, Uprety R, Mores KL, Ko MJ et al. · Br J Pharmacol

     Our results suggest that kratom extracts can decrease alcohol intake but still carry significant risk upon prolonged use.

217. Case reports · 2020

     Home induction and outpatient treatment of kratom use disorder with buprenorphine-naloxone: A case report in a young adult (opens in a new tab)

     Schmuhl KK, Gardner SM, Cottrill CB, Bonny AE · Subst Abus

     Healthcare providers should be aware of the use of kratom and consider utilizing BUP/NAL to treat dependence to this botanical drug.

218. In vitro · 2020 · Open access

     Investigation of the Adrenergic and Opioid Binding Affinities, Metabolic Stability, Plasma Protein Binding Properties, and Functional Effects of Selected Indole-Based Kratom Alkaloids (opens in a new tab)

     Obeng S, Kamble SH, Reeves ME, Restrepo LF, Patel A, Behnke M et al. · J Med Chem

     The observed polypharmacology of kratom alkaloids may support its utilization to treat opioid use disorder and withdrawal.

219. Case reports · 2020

     Kratom (Mitragyna Speciosa) Liver Injury: A Comprehensive Review (opens in a new tab)

     Schimmel J, Dart RC · Drugs

     It remains unclear which subgroups of users are at heightened risk.

220. Human studies · 2020 · Open access

     Kratom (Mitragyna speciosa): User demographics, use patterns, and implications for the opioid epidemic (opens in a new tab)

     Garcia-Romeu A, Cox DJ, Smith KE, Dunn KE, Griffiths RR · Drug Alcohol Depend

     Kratom is used among White, middle-aged Americans for symptoms of pain, anxiety, depression, and opioid withdrawal.

221. Case reports · 2020

     Kratom Adulterated with Phenylethylamine and Associated Intracerebral Hemorrhage: Linking Toxicologists and Public Health Officials to Identify Dangerous Adulterants (opens in a new tab)

     Nacca N, Schult RF, Li L, Spink DC, Ginsberg G, Navarette K et al. · J Med Toxicol

     Medical toxicologists should form working relationships with laboratories and public health officials to aid in early identification of adulterated products that carry risk to the general population.

222. Reviews · 2020

     Kratom Dependence and Treatment Options: A Comprehensive Review of the Literature (opens in a new tab)

     Bin Abdullah MFIL · Curr Drug Targets

     We conclude by adding a note on the research gap concerning kratom dependence, which future studies should focus on.

223. Reviews · 2020 · Open access

     Kratom-Pharmacology, Clinical Implications, and Outlook: A Comprehensive Review (opens in a new tab)

     Eastlack SC, Cornett EM, Kaye AD · Pain Ther

     This manuscript will discuss the most current epidemiology, pharmacology, toxicity, and management related to kratom, while seeking to provide a contemporary perspective on the issue and its role in the greater context of the opioid epidemic.

224. In vitro · 2020 · Open access

     Metabolism of a Kratom Alkaloid Metabolite in Human Plasma Increases Its Opioid Potency and Efficacy (opens in a new tab)

     Kamble SH, León F, King TI, Berthold EC, Lopera-Londoño C, Siva Rama Raju K et al. · ACS Pharmacol Transl Sci

     This novel metabolite is formed in human plasma to a much greater extent than in the preclinical species tested (mouse, rat, dog, and cynomolgus monkey) and due to its μ-opioid potency may substantially contribute to the pharmacology of kratom in humans to a greater extent tha...

225. In vitro · 2020

     Temperature and pH-Dependent Stability of Mitragyna Alkaloids (opens in a new tab)

     Basiliere S, Kerrigan S · J Anal Toxicol

     These findings are discussed within the context of the identification of Mitragyna alkaloids in toxicological specimens.

226. Reviews · 2020

     The ASAM National Practice Guideline for the Treatment of Opioid Use Disorder: 2020 Focused Update (opens in a new tab)

     · J Addict Med

     Abstract not available in PubMed; see link.

227. In vitro · 2019 · Open access

     7-Hydroxymitragynine Is an Active Metabolite of Mitragynine and a Key Mediator of Its Analgesic Effects (opens in a new tab)

     Kruegel AC, Uprety R, Grinnell SG, Langreck C, Pekarskaya EA, Le Rouzic V et al. · ACS Cent Sci

     Further, they raise important questions about the interpretation of existing data on mitragynine and highlight critical areas for further research in animals and humans.

228. Animal · 2019

     Abuse liability and therapeutic potential of the Mitragyna speciosa (kratom) alkaloids mitragynine and 7-hydroxymitragynine (opens in a new tab)

     Hemby SE, McIntosh S, Leon F, Cutler SJ, McCurdy CR · Addict Biol

     The present findings indicate that MG does not have abuse potential and reduces morphine intake, desired characteristics of candidate pharmacotherapies for opiate addiction and withdrawal, whereas 7-HMG should be considered a kratom constituent with high abuse potential that m...

229. Surveillance · 2019

     Kratom exposures reported to United States poison control centers: 2011-2017 (opens in a new tab)

     Post S, Spiller HA, Chounthirath T, Smith GA · Clin Toxicol (Phila)

     Individuals who choose to use kratom should be educated about its potential risks, including the dangers of using it in combination with other substances.

230. Surveillance · 2019

     Kratom Use and Toxicities in the United States (opens in a new tab)

     Eggleston W, Stoppacher R, Suen K, Marraffa JM, Nelson LS · Pharmacotherapy

     Kratom use is increasing and is associated with significant toxicities.

231. Case reports · 2019

     Kratom Withdrawal: A Systematic Review with Case Series (opens in a new tab)

     Stanciu CN, Gnanasegaram SA, Ahmed S, Penders T · J Psychoactive Drugs

     Clinicians need to be aware of the withdrawal symptomatology and implement a similar approach as for opioid withdrawal with long-term maintenance to prevent relapse.

232. Human studies · 2019

     Metabolite profiling and identification of enzymes responsible for the metabolism of mitragynine, the major alkaloid of Mitragyna speciosa (kratom) (opens in a new tab)

     Kamble SH, Sharma A, King TI, León F, McCurdy CR, Avery BA · Xenobiotica

     The CYP3A4 enzyme plays a predominant role in the metabolic clearance of mitragynine and also in the formation of 7-hydroxymitragynine (Met2), a known active minor alkaloid identified in the leaf material.

233. In vitro · 2019 · Open access

     Mitragynine, an euphoric compound inhibits hERG1a/1b channel current and upregulates the complexation of hERG1a-Hsp90 in HEK293-hERG1a/1b cells (opens in a new tab)

     Tay YL, Amanah A, Adenan MI, Wahab HA, Tan ML · Sci Rep

     In conclusion, mitragynine inhibits hERG1a/1b current through direct channel blockade at lower concentration, but at higher concentration, it upregulates the complexation of hERG1a-Hsp90 which may be inhibitory towards channel trafficking.

234. Surveillance · 2019 · Open access

     Notes from the Field: Unintentional Drug Overdose Deaths with Kratom Detected - 27 States, July 2016-December 2017 (opens in a new tab)

     Olsen EO, O'Donnell J, Mattson CL, Schier JG, Wilson N · MMWR Morb Mortal Wkly Rep

     Abstract not available in PubMed; see link.

235. Animal · 2019 · Open access

     Rate and extent of mitragynine and 7-hydroxymitragynine blood-brain barrier transport and their intra-brain distribution: the missing link in pharmacodynamic studies (opens in a new tab)

     Yusof SR, Mohd Uzid M, Teh EH, Hanapi NA, Mohideen M, Mohamad Arshad AS et al. · Addict Biol

     The presented findings from this systematic investigation of brain pharmacokinetics of mitragynine and 7-hydroxymitragynine are essential for design and interpretation of in vivo experiments aiming to establish exposure-response relationship.

236. Reviews · 2019

     Risk of death associated with kratom use compared to opioids (opens in a new tab)

     Henningfield JE, Grundmann O, Babin JK, Fant RV, Wang DW, Cone EJ · Prev Med

     More research on kratom safety and risks is needed, as is regulation of commercial kratom products to ensure that consumers are informed by FDA labeling and that kratom products are not contaminated or adulterated with other substances.

237. Product testing · 2019 · Open access

     Simultaneous quantification of ten key Kratom alkaloids in Mitragyna speciosa leaf extracts and commercial products by ultra-performance liquid chromatography-tandem mass spectrometry (opens in a new tab)

     Sharma A, Kamble SH, León F, Chear NJ, King TI, Berthold EC et al. · Drug Test Anal

     Minor kratom alkaloids (corynantheidine, corynoxine, corynoxine B, 7-hydroxymitragynine, isocorynantheidine) were also quantified (0.01%-2.8% w/w) in the analyzed products; however mitraphylline was below the lower limit of quantification in all analyses.

238. Reviews · 2019

     Tramadol and the occurrence of seizures: a systematic review and meta-analysis (opens in a new tab)

     Nakhaee S, Amirabadizadeh A, Brent J, Miri-Moghaddam E, Foadoddini M, Farrokhfall K et al. · Crit Rev Toxicol

     Naloxone administration was not associated to the occurrence of seizures (pooled OR: 0.47, 95% CI: 0.15-1.49).Conclusions: Our results demonstrate that the occurrence of seizures in patients exposed to tramadol are dose-dependent and related to male gender, but not related to naloxone administration.

239. Product testing · 2018

     A Prospective Evaluation of Drug Discrimination in Pharmacology (opens in a new tab)

     Walker EA · Curr Top Behav Neurosci

     This final chapter represents one investigator's perspective on the utility and possibilities for a methodology that she fell in love with over 30 years ago.

240. Human studies · 2018

     Assessment of gonadotropins and testosterone hormone levels in regular Mitragyna speciosa (Korth.) users (opens in a new tab)

     Singh D, Murugaiyah V, Hamid SBS, Kasinather V, Chan MSA, Ho ETW et al. · J Ethnopharmacol

     Regular kratom tea/juice consumption over prolonged periods (>2 years) was not associated with testosterone impairing effects in humans.

241. Case reports · 2018 · Open access

     Kratom, an Emerging Drug of Abuse, Raises Prolactin and Causes Secondary Hypogonadism: Case Report (opens in a new tab)

     LaBryer L, Sharma R, Chaudhari KS, Talsania M, Scofield RH · J Investig Med High Impact Case Rep

     A number of adverse events or side effects have been reported, but this is the first report of hyperprolactinemia as the result of ingestion of kratom.

242. Case reports · 2018

     Neonatal Abstinence Syndrome Due to Maternal Kratom Use (opens in a new tab)

     Eldridge WB, Foster C, Wyble L · Pediatrics

     Pediatricians and parents should be aware of the risk of NAS due to Kratom use during pregnancy.

243. Case reports · 2018 · Open access

     Recurrent seizures from chronic kratom use, an atypical herbal opioid (opens in a new tab)

     Tatum WO, Hasan TF, Coonan EE, Smelick CP · Epilepsy Behav Case Rep

     Our case suggests Kratom abuse may be associated with structural brain lesions on MRI and symptomatic focal epilepsy.

244. Human studies · 2018

     Severity of Kratom (Mitragyna speciosa Korth.) Psychological Withdrawal Symptoms (opens in a new tab)

     Singh D, Narayanan S, Müller CP, Swogger MT, Rahim AA, Leong Bin Abdullah MFI et al. · J Psychoactive Drugs

     Those who consumed higher quantities of kratom tea daily (≥4 glasses) had higher odds of reporting longer duration of kratom use history (OR = 4.8, 95% CI 2.3 -10.1, p < 0.001), higher frequency of daily kratom use (≥4 times) (OR = 72, CI 9.5- 543.1, p < 0.001), and were more likely to experience moderate symptoms o…

245. Reviews · 2018 · Open access

     The abuse potential of kratom according the 8 factors of the controlled substances act: implications for regulation and research (opens in a new tab)

     Henningfield JE, Fant RV, Wang DW · Psychopharmacology (Berl)

     Although kratom appears to have pharmacological properties that support some level of scheduling, if it was an approved drug, placing it into Schedule I, thus banning it, risks creating public health problems that do not presently exist.

246. Case reports · 2018

     Treatment of Kratom Withdrawal and Addiction With Buprenorphine (opens in a new tab)

     Khazaeli A, Jerry JM, Vazirian M · J Addict Med

     Her kratom-related withdrawal symptoms responded to a trial of buprenorphine-naloxone. Subsequently, she was maintained on this medication.

247. Human studies · 2017 · Open access

     Association between concurrent use of prescription opioids and benzodiazepines and overdose: retrospective analysis (opens in a new tab)

     Sun EC, Dixit A, Humphreys K, Darnall BD, Baker LC, Mackey S · BMJ

     If this association is causal, elimination of concurrent benzodiazepine/opioid use could reduce the risk of emergency room visits related to opioid use and inpatient admissions for opioid overdose by an estimated 15% (95% confidence interval 14 to 16).Conclusions From 2001 to ...

248. Reviews · 2017 · Open access

     Biochemical Benefits, Diagnosis, and Clinical Risks Evaluation of Kratom (opens in a new tab)

     Fluyau D, Revadigar N · Front Psychiatry

     Our data analysis has not determined if biochemical benefits of kratom may prove to outweigh its toxicity and risks.

249. Reviews · 2017 · Open access

     Changing trends in the use of kratom (Mitragyna speciosa) in Southeast Asia (opens in a new tab)

     Singh D, Narayanan S, Vicknasingam B, Corazza O, Santacroce R, Roman-Urrestarazu A · Hum Psychopharmacol

     Legal sanctions appear to have preceded serious scientific investigations into the claimed benefits of ketum.

250. Human studies · 2017

     Patterns of Kratom use and health impact in the US-Results from an online survey (opens in a new tab)

     Grundmann O · Drug Alcohol Depend

     Kratom shows a dose-dependent opioid-like effect providing self-reported perceived beneficial effects in alleviating pain and relieving mood disorders.

251. Reviews · 2016

     A systematic review of adverse events arising from the use of synthetic cannabinoids and their associated treatment (opens in a new tab)

     Tait RJ, Caldicott D, Mountain D, Hill SL, Lenton S · Clin Toxicol (Phila)

     Precise estimates of their incidence are difficult to calculate due to the lack of widely available, rapid laboratory confirmation, the variety of SC compounds and the unknown number of exposed individuals. Long-term consequences of SCs use are currently unknown.

252. Reviews · 2016

     Biomarkers in the diagnosis and study of psychogenic nonepileptic seizures: A systematic review (opens in a new tab)

     Sundararajan T, Tesar GE, Jimenez XF · Seizure

     Future investigational and clinical imperatives are discussed.

253. Surveillance · 2016 · Open access

     CDC MMWR 2016 Notes from the Field Kratom Exposures (opens in a new tab)

     CDC · Agency / organization document

     Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.

254. Product testing · 2016

     Drug discrimination: A versatile tool for characterization of CNS safety pharmacology and potential for drug abuse (opens in a new tab)

     Swedberg MD · J Pharmacol Toxicol Methods

     These and other findings will be discussed, and the application of drug discrimination procedures beyond the typical standard application of testing novel compounds against known and well characterized reference drugs will be addressed.

255. Human studies · 2016

     Factor Analytical Investigation of Krathom (Mitragyna speciosa Korth.) Withdrawal Syndrome in Thailand (opens in a new tab)

     Saingam D, Assanangkornchai S, Geater AF, Lerkiatbundit S · J Psychoactive Drugs

     The krathom withdrawal intensity is predicted by duration of krathom use, frequency, and daily amount of krathom use.

256. In vitro · 2016

     Mitragynine and its potential blocking effects on specific cardiac potassium channels (opens in a new tab)

     Tay YL, Teah YF, Chong YM, Jamil MFA, Kollert S, Adenan MI et al. · Toxicol Appl Pharmacol

     Blocking of both hERG and GIRK channels may cause additive cardiotoxicity risks.

257. In vitro · 2016 · Open access

     Mitragynine/Corynantheidine Pseudoindoxyls As Opioid Analgesics with Mu Agonism and Delta Antagonism, Which Do Not Recruit β-Arrestin-2 (opens in a new tab)

     Váradi A, Marrone GF, Palmer TC, Narayan A, Szabó MR, Le Rouzic V et al. · J Med Chem

     Additionally, 3 developed analgesic tolerance more slowly than morphine, showed limited physical dependence, respiratory depression, constipation, and displayed no reward or aversion in CPP/CPA assays, suggesting that analogs might represent a promising new generation of novel...

258. Surveillance · 2016 · Open access

     Notes from the Field: Kratom (Mitragyna speciosa) Exposures Reported to Poison Centers - United States, 2010-2015 (opens in a new tab)

     Anwar M, Law R, Schier J · MMWR Morb Mortal Wkly Rep

     NPDS case records are the result of call reports made by the public and health care providers.

259. Product testing · 2016 · Open access

     Suspected Adulteration of Commercial Kratom Products with 7-Hydroxymitragynine (opens in a new tab)

     Lydecker AG, Sharma A, McCurdy CR, Avery BA, Babu KM, Boyer EW · J Med Toxicol

     We have found multiple packaged commercial Kratom products likely to contain artificially elevated concentrations of 7-hydroxymitragynine, the alkaloid responsible for M. speciosa's concerning mechanistic and side effect profile.

260. In vitro · 2016 · Open access

     Synthetic and Receptor Signaling Explorations of the Mitragyna Alkaloids: Mitragynine as an Atypical Molecular Framework for Opioid Receptor Modulators (opens in a new tab)

     Kruegel AC, Gassaway MM, Kapoor A, Váradi A, Majumdar S, Filizola M et al. · J Am Chem Soc

     Molecular docking studies, in combination with the observed chemical SAR, suggest that Mitragyna alkaloids adopt a binding pose at the mu-opioid receptor that is distinct from that of classical opioids.

261. Reviews · 2016

     Traditional and non-traditional uses of Mitragynine (Kratom): A survey of the literature (opens in a new tab)

     Singh D, Narayanan S, Vicknasingam B · Brain Res Bull

     Despite its addictive properties, reported side-effects and its tendency to be used a recreational drug, more scientific clinical human studies are necessary to determine its potential therapeutic value.

262. Animal · 2015 · Open access

     Discriminative stimulus properties of mitragynine (kratom) in rats (opens in a new tab)

     Harun N, Hassan Z, Navaratnam V, Mansor SM, Shoaib M · Psychopharmacology (Berl)

     The present study demonstrates that the discriminative stimulus effect of MG possesses both opioid- and psychostimulant-like subjective effects.

263. Reviews · 2015 · Open access

     Following "the Roots" of Kratom (Mitragyna speciosa): 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 (opens in a new tab)

     Cinosi E, Martinotti G, Simonato P, Singh D, Demetrovics Z, Roman-Urrestarazu A et al. · Biomed Res Int

     Finally, it concludes that the use of kratom is not negligible, especially for self-medication, and more clinical, pharmacological, and socioanthropological studies as well as a better international collaboration are needed to tackle this marginally explored phenomenon.

264. Human studies · 2015 · Open access

     Pharmacokinetics of mitragynine in man (opens in a new tab)

     Trakulsrichai S, Sathirakul K, Auparakkitanon S, Krongvorakul J, Sueajai J, Noumjad N et al. · Drug Des Devel Ther

     This was the first pharmacokinetic study in humans, which demonstrated linearity and was consistent with the oral two-compartment model with a terminal half-life of about 1 day.

265. Case reports · 2014

     An accidental poisoning with mitragynine (opens in a new tab)

     Karinen R, Fosen JT, Rogde S, Vindenes V · Forensic Sci Int

     We recommend that both mitragynine and 7-hydroxymitragynine are analyzed for in cases with suspected Kratom intoxication.

266. In vitro · 2014

     Evaluation of in vitro absorption, distribution, metabolism, and excretion (ADME) properties of mitragynine, 7-hydroxymitragynine, and mitraphylline (opens in a new tab)

     Manda VK, Avula B, Ali Z, Khan IA, Walker LA, Khan SI · Planta Med

     These data indicate the possibility of a drug interaction if mitragynine and 7-hydroxymitragynine are coadministered with drugs that are P-glycoprotein substrates.

267. In vitro · 2014 · Open access

     Evaluation of the cardiotoxicity of mitragynine and its analogues using human induced pluripotent stem cell-derived cardiomyocytes (opens in a new tab)

     Lu J, Wei H, Wu J, Jamil MF, Tan ML, Adenan MI et al. · PLoS One

     Our study indicates that Mitragynine and its analogues may potentiate Torsade de Pointes through inhibition of IKr in human cardiomyocytes.

268. Human studies · 2014

     Kratom (Mitragyna speciosa) dependence, withdrawal symptoms and craving in regular users (opens in a new tab)

     Singh D, Müller CP, Vicknasingam BK · Drug Alcohol Depend

     The findings from this study show that regular Kratom use is associated with drug dependency, development of withdrawal symptoms, and craving.

269. In vitro · 2014 · Open access

     Orally active opioid μ/δ dual agonist MGM-16, a derivative of the indole alkaloid mitragynine, exhibits potent antiallodynic effect on neuropathic pain in mice (opens in a new tab)

     Matsumoto K, Narita M, Muramatsu N, Nakayama T, Misawa K, Kitajima M et al. · J Pharmacol Exp Ther

     These findings suggest that MGM-16 could become a class of a compound with potential therapeutic utility for treating neuropathic pain.

270. In vitro · 2011

     Uniform assessment and ranking of opioid μ receptor binding constants for selected opioid drugs (opens in a new tab)

     Volpe DA, McMahon Tobin GA, Mellon RD, Katki AG, Parker RJ, Colatsky T et al. · Regul Toxicol Pharmacol

     These data add to the understanding of the pharmacology of opioid drugs and support the development of a more consistent labeling policies regarding safe disposal.

271. Case reports · 2011

     Unintentional fatal intoxications with mitragynine and O-desmethyltramadol from the herbal blend Krypton (opens in a new tab)

     Kronstrand R, Roman M, Thelander G, Eriksson A · J Anal Toxicol

     We believe that the addition of the potent mu-receptor agonist O-desmethyltramadol to powdered leaves from Kratom contributed to the unintentional death of the nine cases presented and conclude that intake of Krypton is not as harmless as it often is described on internet webs...

272. Case reports · 2010 · Open access

     Seizure and coma following Kratom (Mitragynina speciosa Korth) exposure (opens in a new tab)

     Nelsen JL, Lapoint J, Hodgman MJ, Aldous KM · J Med Toxicol

     The proposed mechanism for this reaction is unclear but suggested mechanisms include adenosine binding or stimulation of adrenergic and/or serotonergic receptors similar to tramadol.

273. Product testing · 2009 · Open access

     Phytochemical characterization of the leaves of Mitragyna speciosa grown in U.S.A (opens in a new tab)

     León F, Habib E, Adkins JE, Furr EB, McCurdy CR, Cutler SJ · Nat Prod Commun

     Biological studies are currently underway to test these compounds for opioid activity.

274. Animal · 2008

     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 mu- and kappa-opioid agonist with potent antinociceptive and weak rewarding effects in mice (opens in a new tab)

     Matsumoto K, Takayama H, Narita M, Nakamura A, Suzuki M, Suzuki T et al. · Neuropharmacology

     Taken together, the results suggest that MGM-9 is a promising novel analgesic that has a stronger antinociceptive effect and weaker adverse effects than morphine.

275. Case reports · 2008 · Open access

     Self-treatment of opioid withdrawal using kratom (Mitragynia speciosa korth) (opens in a new tab)

     Boyer EW, Babu KM, Adkins JE, McCurdy CR, Halpern JH · Addiction

     We report the self-treatment of chronic pain and opioid withdrawal with kratom.

276. Product testing · 2007 · Open access

     Self-administration of drugs in animals and humans as a model and an investigative tool (opens in a new tab)

     Panlilio LV, Goldberg SR · Addiction

     The identification of drug use as behavior that is reinforced by drugs has contributed greatly to the understanding and treatment of addiction.

277. Animal · 2006

     Involvement of mu-opioid receptors in antinociception and inhibition of gastrointestinal transit induced by 7-hydroxymitragynine, isolated from Thai herbal medicine Mitragyna speciosa (opens in a new tab)

     Matsumoto K, Hatori Y, Murayama T, Tashima K, Wongseripipatana S, Misawa K et al. · Eur J Pharmacol

     This compound induced more potent antinociceptive effects and was less constipating than morphine.

278. Animal · 2006

     Using drug-discrimination techniques to study the abuse-related effects of psychoactive drugs in rats (opens in a new tab)

     Solinas M, Panlilio LV, Justinova Z, Yasar S, Goldberg SR · Nat Protoc

     Although training can be lengthy (up to several months), the pharmacological specificity of DD procedures make them a perfect complement to other techniques used to study drug-abuse phenomena, such as intravenous self-administration and conditioned place-preference procedures.

279. Animal · 2005

     Antinociception, tolerance and withdrawal symptoms induced by 7-hydroxymitragynine, an alkaloid from the Thai medicinal herb Mitragyna speciosa (opens in a new tab)

     Matsumoto K, Horie S, Takayama H, Ishikawa H, Aimi N, Ponglux D et al. · Life Sci

     These interesting characters of 7-hydroxymitragynine promote further investigation of it as a novel lead compound for opioid studies.

280. Reviews · 2005

     Use of serum prolactin in diagnosing epileptic seizures: report of the Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology (opens in a new tab)

     Chen DK, So YT, Fisher RS, Therapeutics and Technology Assessment Subcommittee of the American Academy of Neurology · Neurology

     The use of serum PRL assay has not been established in the evaluation of status epilepticus, repetitive seizures, and neonatal seizures (Level U).

281. In vitro · 2004

     Antinociceptive effect of 7-hydroxymitragynine in mice: Discovery of an orally active opioid analgesic from the Thai medicinal herb Mitragyna speciosa (opens in a new tab)

     Matsumoto K, Horie S, Ishikawa H, Takayama H, Aimi N, Ponglux D et al. · Life Sci

     It was found that 7-hydroxymitragynine is a novel opioid agonist that is structurally different from the other opioid agonists, and has potent analgesic activity when orally administered.

282. Reviews · 2003

     Guidelines and methodological reviews concerning drug abuse liability assessment (opens in a new tab)

     Balster RL, Bigelow GE · Drug Alcohol Depend

     Thus, another goal of this review has been to identify areas where critical thinking and new guideline development are needed.

283. Reviews · 2003

     Principles of drug abuse liability assessment in laboratory animals (opens in a new tab)

     Ator NA, Griffiths RR · Drug Alcohol Depend

     A key consideration for cross-cutting and specific methodological issues is that choices made enable confident interpretation of both positive and negative results.

284. In vitro · 2002 · Open access

     Studies on the synthesis and opioid agonistic activities of mitragynine-related indole alkaloids: discovery of opioid agonists structurally different from other opioid ligands (opens in a new tab)

     Takayama H, Ishikawa H, Kurihara M, Kitajima M, Aimi N, Ponglux D et al. · J Med Chem

     Synthetic-chemistry paper (link only; omitted from summary).

285. In vitro · 1999

     Opioid receptor agonistic characteristics of mitragynine pseudoindoxyl in comparison with mitragynine derived from Thai medicinal plant Mitragyna speciosa (opens in a new tab)

     Yamamoto LT, Horie S, Takayama H, Aimi N, Sakai S, Yano S et al. · Gen Pharmacol

     The present study demonstrates that mitragynine pseudoindoxyl, a novel alkaloid structurally different from other opioid agonists, acts on opioid receptors, leading to a potent inhibition of electrically stimulated contraction in the ileum through the micro-receptors and in mo...

286. Product testing · 1994

     A New Indole Alkaloid, 7 alpha-Hydroxy-7H-mitragynine, from Mitragyna speciosa in Thailand (opens in a new tab)

     Ponglux D, Wongseripipatana S, Takayama H, Kikuchi M, Kurihara M, Kitajima M et al. · Planta Med

     Abstract not available in PubMed; see link.

287. Human studies · 1975

     A study of kratom eaters in Thailand (opens in a new tab)

     Suwanlert S · Bull Narc

     Abstract not available in PubMed; see link.

288. Agency documents · Open access

     DEA Drug Fact Sheet Kratom (opens in a new tab)

     DEA · Agency / organization document

     Government / professional-society / agency document on 7-OH or kratom (alert, advisory, statement, fact sheet or data); see link.