ArticlePloS one2020
Evaluating kratom alkaloids using PHASE.
Article in PloS one, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 57 citations in OpenAlex.
- Decoding kratom: molecular mechanisms and epigenetic factors in use and dependence.Translational psychiatry · 2026Pooled it
- Article
- Mitragynine and Morphine Stabilize Different Conformations of the μ‑Opioid Receptor as Revealed by Molecular Dynamics Simulation Studies.ACS omega · 2026Article
- Multifaceted modulation of human opioid receptors by kratom alkaloids: binding affinity, functional selectivity, and allosteric activity.Frontiers in pharmacology · 2026Article
- Assessment of In Vitro Antioxidant Activity and Subacute Toxicity and Safety of Tetrahydroserpentine in Hyperglycemic Mice.Chemistry & biodiversity · 2026Article
- Disulfide-rich polysulfur alkaloids target vascular endothelial growth factor A through electronic duality and shape-responsive recognition.Scientific reports · 2025Article
- Exploring the Therapeutic Potential of Mitragynine and Corynoxeine: Kratom-Derived Indole and Oxindole Alkaloids for Pain Management.Pharmaceuticals (Basel, Switzerland) · 2025Review
- The Mitragyna speciosa (kratom) alkaloid mitragynine: Analysis of adrenergic αEuropean journal of pharmacology · 2024Article
- Controversies in Assessment, Diagnosis, and Treatment of Kratom Use Disorder.Current psychiatry reports · 2024Review
- A Critical Review of the Neuropharmacological Effects of Kratom: An Insight from the Functional Array of Identified Natural Compounds.Molecules (Basel, Switzerland) · 2023Review
- Modified Akuamma Alkaloids with Increased Potency at the Mu-opioid Receptor.Journal of medicinal chemistry · 2023Article
- Interactive Effects ofThe Journal of pharmacology and experimental therapeutics · 2022Article
- Current and emerging pharmacotherapies for opioid dependence treatments in adults: a comprehensive update.Expert opinion on pharmacotherapy · 2022Review
- Kratom (Mitragyna speciosa) Validation: Quantitative Analysis of Indole and Oxindole Alkaloids Reveals Chemotypes of Plants and Products.Planta medica · 2022Article
- Metabolism of Speciociliatine, an Overlooked Kratom Alkaloid for its Potential Pharmacological Effects.The AAPS journal · 2022Article
- The Lack of Contribution of 7-Hydroxymitragynine to the Antinociceptive Effects of Mitragynine in Mice: A Pharmacokinetic and Pharmacodynamic Study.Drug metabolism and disposition: the biological fate of chemicals · 2022Article
- Exploring of cardiac autonomic activity with heart rate variability in long-term kratom (PeerJ · 2022Article
- New science, drug regulation, and emergent public health issues: The work of FDA's division of applied regulatory science.Frontiers in medicine · 2022Review
- The Chemical and Pharmacological Properties of Mitragynine and Its Diastereomers: An Insight Review.Frontiers in pharmacology · 2022Review
- Oxidative Metabolism as a Modulator of Kratom's Biological Actions.Journal of medicinal chemistry · 2021Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Kratom is a botanical substance that is marketed and promoted in the US for pharmaceutical opioid indications despite having no US Food and Drug Administration approved uses. Kratom contains over forty alkaloids including two partial agonists at the mu opioid receptor, mitragynine and 7-hydroxymitragynine, that have been subjected to the FDA's scientific and medical evaluation. However, pharmacological and toxicological data for the remaining alkaloids are limited. Therefore, we applied the Public Health Assessment via Structural Evaluation (PHASE) protocol to generate in silico binding profiles for 25 kratom alkaloids to facilitate the risk evaluation of kratom. PHASE demonstrates that kratom alkaloids share structural features with controlled opioids, indicates that several alkaloids bind to the opioid, adrenergic, and serotonin receptors, and suggests that mitragynine and 7-hydroxymitragynine are the strongest binders at the mu opioid receptor. Subsequently, the in silico binding profiles of a subset of the alkaloids were experimentally verified at the opioid, adrenergic, and serotonin receptors using radioligand binding assays. 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.
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Registered trials
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.