Evidence map›Paper›PMID 33154449›Full record

ArticleScientific reports2020

Chemical composition and biological effects of kratom (Mitragyna speciosa): In vitro studies with implications for efficacy and drug interactions.

D A Todd, J J Kellogg, E D Wallace, M Khin, L Flores-Bocanegra, R S Tanna, S McIntosh, H A Raja, T N Graf, S E Hemby and 3 more

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
66citing papers in PubMed, 1 pooled it
12.2field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

66 citing papers in PubMed, 1 synthesis or guideline pooled it, 119 citations in OpenAlex.

  1. Pooled it
  2. Trial
  3. Article
  4. Review
  5. Article
  6. Identification and Characterization of Mitragynine or 7-Hydroxymitraynine Oral Dosage Form Products That Appeal to Children.The journal of pediatric pharmacology and therapeutics : JPPT : the official journal of PPAG · 2026
    Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Mitragynine and 7-hydroxymitragynine: Bidirectional effects on breathing in rats.The Journal of pharmacology and experimental therapeutics · 2025
    Article
  14. Article
  15. Evaluating the drug interactions in kratom usage: clinical application.Expert opinion on drug metabolism & toxicology · 2025
    Review
  16. Article
  17. Article
  18. Article
  19. Article
  20. Review

6 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors at 3 institutions in 1 country.

D A ToddDepartment of Chemistry and Biochemistry, The University of North Carolina Greensboro, 435 Sullivan Bldg., 301 McIver St., Greensboro, NC, 27402, USA.
J J KelloggDepartment of Chemistry and Biochemistry, The University of North Carolina Greensboro, 435 Sullivan Bldg., 301 McIver St., Greensboro, NC, 27402, USA.
E D WallaceDepartment of Chemistry and Biochemistry, The University of North Carolina Greensboro, 435 Sullivan Bldg., 301 McIver St., Greensboro, NC, 27402, USA.
M KhinDepartment of Chemistry and Biochemistry, The University of North Carolina Greensboro, 435 Sullivan Bldg., 301 McIver St., Greensboro, NC, 27402, USA.
L Flores-BocanegraDepartment of Chemistry and Biochemistry, The University of North Carolina Greensboro, 435 Sullivan Bldg., 301 McIver St., Greensboro, NC, 27402, USA.
R S TannaDepartment of Pharmaceutical Sciences, Washington State University, Spokane, WA, 99202, USA.
S McIntoshDepartment of Basic Pharmaceutical Sciences, High Point University, High Point, NC, 27268, USA.
H A RajaDepartment of Chemistry and Biochemistry, The University of North Carolina Greensboro, 435 Sullivan Bldg., 301 McIver St., Greensboro, NC, 27402, USA.
T N GrafDepartment of Chemistry and Biochemistry, The University of North Carolina Greensboro, 435 Sullivan Bldg., 301 McIver St., Greensboro, NC, 27402, USA.
S E HembyDepartment of Basic Pharmaceutical Sciences, High Point University, High Point, NC, 27268, USA.
M F PaineDepartment of Pharmaceutical Sciences, Washington State University, Spokane, WA, 99202, USA.
N H OberliesDepartment of Chemistry and Biochemistry, The University of North Carolina Greensboro, 435 Sullivan Bldg., 301 McIver St., Greensboro, NC, 27402, USA.
N B CechDepartment of Chemistry and Biochemistry, The University of North Carolina Greensboro, 435 Sullivan Bldg., 301 McIver St., Greensboro, NC, 27402, USA. nadja_cech@uncg.edu.
University of North Carolina at Greensboro · USHigh Point University · USWashington State University Spokane · US

Funding

Pharmacology CoreU54AT008909 · NCCIH · WASHINGTON STATE UNIVERSITY · PI BOYCE, RICHARD DAVID · 2015 to 2024
$22.4M
Pilot Project ProgramP30GM122733 · NIGMS · UNIVERSITY OF MISSISSIPPI · PI WILLETT, KRISTINE L · 2018 to 2022
$5.3M
The Whole is Greater than the Sum of its Parts: Identifying Active Mixture Components, and Evaluating their Combined EfficacyF32AT009816 · NCCIH · UNIVERSITY OF NORTH CAROLINA GREENSBORO · PI KELLOGG, JOSHUA · 2018 to 2018
$61k
NCCIH NIH HHS F32 AT009816NCCIH NIH HHS U54 AT008909NIGMS NIH HHS P30 GM122733NIH HHS P30 GM122733NIH HHS U54 AT008909
6 · The paper itself

Abstract

The safety and efficacy of kratom (Mitragyna speciosa) for treatment of pain is highly controversial. Kratom produces more than 40 structurally related alkaloids, but most studies have focused on just two of these, mitragynine and 7-hydroxymitragynine. Here, we profiled 53 commercial kratom products using untargeted LC-MS metabolomics, revealing two distinct chemotypes that contain different levels of the alkaloid speciofoline. Both chemotypes were confirmed with DNA barcoding to be M. speciosa. To evaluate the biological relevance of variable speciofoline levels in kratom, we compared the opioid receptor binding activity of speciofoline, mitragynine, and 7-hydroxymitragynine. Mitragynine and 7-hydroxymitragynine function as partial agonists of the human µ-opioid receptor, while speciofoline does not exhibit measurable binding affinity at the µ-, δ- or ƙ-opioid receptors. Importantly, mitragynine and 7-hydroxymitragynine demonstrate functional selectivity for G-protein signaling, with no measurable recruitment of β-arrestin. Overall, the study demonstrates the unique binding and functional profiles of the kratom alkaloids, suggesting potential utility for managing pain, but further studies are needed to follow up on these in vitro findings. 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.

Indexed as

AnalgesicsChromatography, LiquidHumansMetabolomicsMicrosomes, LiverMitragynaPlant ExtractsReceptors, Opioid, muSecologanin Tryptamine AlkaloidsTandem Mass Spectrometry7-hydroxymitragynineAnalgesicsmitragyninePlant ExtractsReceptors, Opioid, muSecologanin Tryptamine Alkaloids

Identifiers

PMID33154449
PMCPMC7645423
OpenAlexW3096192104

What OpenQuestion holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.