Evidence map›Paper›PMID 37286363›Full record

ReviewDrug metabolism and disposition: the biological fate of chemicals2023

Translating Kratom-Drug Interactions: From Bedside to Bench and Back.

Rakshit S Tanna, Nadja B Cech, Nicholas H Oberlies, Allan E Rettie, Kenneth E Thummel, Mary F Paine

Open access · hybridAbstract readReview
PubMed Full text at PMC Publisher
In one paragraph

Review in Drug metabolism and disposition: the biological fate of chemicals, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
5.4field-weighted citation impact, top 4% 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

8 citing papers in PubMed, 22 citations in OpenAlex.

  1. Trial
  2. Indole Alkaloids as Biased Opioid Receptor Modulators.Pharmaceuticals (Basel, Switzerland) · 2026
    Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Article
  8. Article
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

6 authors at 2 institutions in 1 country.

Rakshit S TannaDepartment of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, Washington (R.S.T., M.F.P.); Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina (N.B.C., N.H.O.); Center of Excellence for Natural Product Drug Interaction Research, Spokane, Washington (N.B.C., N.H.O., A.E.R., K.E.T., M.F.P.); Departments of Medicinal Chemistry (A.E.R.) and Pharmaceutics (K.E.T.), School of Pharmacy, University of Washington, Seattle, Washington.
Nadja B CechDepartment of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, Washington (R.S.T., M.F.P.); Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina (N.B.C., N.H.O.); Center of Excellence for Natural Product Drug Interaction Research, Spokane, Washington (N.B.C., N.H.O., A.E.R., K.E.T., M.F.P.); Departments of Medicinal Chemistry (A.E.R.) and Pharmaceutics (K.E.T.), School of Pharmacy, University of Washington, Seattle, Washington.
Nicholas H OberliesDepartment of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, Washington (R.S.T., M.F.P.); Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina (N.B.C., N.H.O.); Center of Excellence for Natural Product Drug Interaction Research, Spokane, Washington (N.B.C., N.H.O., A.E.R., K.E.T., M.F.P.); Departments of Medicinal Chemistry (A.E.R.) and Pharmaceutics (K.E.T.), School of Pharmacy, University of Washington, Seattle, Washington.
Allan E RettieDepartment of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, Washington (R.S.T., M.F.P.); Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina (N.B.C., N.H.O.); Center of Excellence for Natural Product Drug Interaction Research, Spokane, Washington (N.B.C., N.H.O., A.E.R., K.E.T., M.F.P.); Departments of Medicinal Chemistry (A.E.R.) and Pharmaceutics (K.E.T.), School of Pharmacy, University of Washington, Seattle, Washington.
Kenneth E ThummelDepartment of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, Washington (R.S.T., M.F.P.); Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina (N.B.C., N.H.O.); Center of Excellence for Natural Product Drug Interaction Research, Spokane, Washington (N.B.C., N.H.O., A.E.R., K.E.T., M.F.P.); Departments of Medicinal Chemistry (A.E.R.) and Pharmaceutics (K.E.T.), School of Pharmacy, University of Washington, Seattle, Washington.
Mary F PaineDepartment of Pharmaceutical Sciences, College of Pharmacy and Pharmaceutical Sciences, Washington State University, Spokane, Washington (R.S.T., M.F.P.); Department of Chemistry and Biochemistry, University of North Carolina at Greensboro, Greensboro, North Carolina (N.B.C., N.H.O.); Center of Excellence for Natural Product Drug Interaction Research, Spokane, Washington (N.B.C., N.H.O., A.E.R., K.E.T., M.F.P.); Departments of Medicinal Chemistry (A.E.R.) and Pharmaceutics (K.E.T.), School of Pharmacy, University of Washington, Seattle, Washington mary.paine@wsu.edu.ORCID 0000-0002-3331-1839
Washington State University Spokane · USUniversity of North Carolina at Greensboro · US

Funding

NCCIH NIH HHS U54 AT008909
6 · The paper itself

Abstract

Kratom is a botanical natural product belonging to the coffee family, with stimulant effects at low doses and opioid-like effects at higher doses. During the last two decades, kratom has been purported as a safer alternative to pharmaceutical and illicit drugs to self-manage pain and opioid withdrawal symptoms. Kratom alkaloids, typically mitragynine, have been detected in biologic samples from overdose deaths. These deaths are often observed in combination with other drugs and are suspected to result from polyintoxications. This review focuses on the potential for kratom to precipitate pharmacokinetic interactions with object drugs involved in these reported polyintoxications. The legal status, chemistry, pharmacology, and toxicology are also summarized. The aggregate in vitro and clinical data identified kratom and select kratom alkaloids as modulators of cytochrome P450 (P450) enzyme activity, notably as inhibitors of CYP2D6 and CYP3A, as well as P-glycoprotein-mediated efflux activity. These inhibitory effects could increase the systemic exposure to co-consumed object drugs, which may lead to adverse effects. Collectively, the evidence to date warrants further evaluation of potential kratom-drug interactions using an iterative approach involving additional mechanistic in vitro studies, well designed clinical studies, and physiologically based pharmacokinetic modeling and simulation. This critical information is needed to fill knowledge gaps regarding the safe and effective use of kratom, thereby addressing ongoing public health concerns. SIGNIFICANCE STATEMENT: The botanical kratom is increasingly used to self-manage pain and opioid withdrawal symptoms due to having opioid-like effects. The legal status, chemistry, pharmacology, toxicology, and drug interaction potential of kratom are reviewed. Kratom-associated polyintoxications and in vitro-in vivo extrapolations suggest that kratom can precipitate pharmacokinetic drug interactions by inhibiting CYP2D6, CYP3A, and P-glycoprotein. An iterative approach that includes clinical studies and physiologically based pharmacokinetic modeling and simulation is recommended for further evaluation of potential unwanted kratom-drug interactions.

Indexed as

MitragynaSubstance Withdrawal SyndromeAnalgesics, OpioidCytochrome P-450 CYP2D6Cytochrome P-450 CYP3AHumansPainAnalgesics, OpioidCytochrome P-450 CYP2D6Cytochrome P-450 CYP3A

Identifiers

PMID37286363
PMCPMC10353077
OpenAlexW4379619370

What Socratic 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 Socratic graph.