ArticleCellular and molecular neurobiology2021
Kratom Alkaloids, Natural and Semi-Synthetic, Show Less Physical Dependence and Ameliorate Opioid Withdrawal.
Article in Cellular and molecular neurobiology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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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.
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Who cites it
32 citing papers in PubMed, 55 citations in OpenAlex.
- Atypical respiration patterns of kratom alkaloids.The Journal of pharmacology and experimental therapeutics · 2026Article
- A Review of Kratom Product Evolution and Its Associated Health Outcomes.Substance abuse and rehabilitation · 2026Review
- Serotonin release mediates analgesia via opioidergic system and withdrawal symptoms in chronic kratom extract-treated mice.BMC complementary medicine and therapies · 2025Article
- Docking 14 Million Virtual Isoquinuclidines against the μ and κ Opioid Receptors Reveals Dual Antagonists-Inverse Agonists with Reduced Withdrawal Effects.ACS central science · 2025Article
- Docking 14 million virtual isoquinuclidines against the mu and kappa opioid receptors reveals dual antagonists-inverse agonists with reduced withdrawal effects.bioRxiv : the preprint server for biology · 2025Article
- Dual anti-inflammatory activities of COX-2/5-LOX driven by kratom alkaloid extracts in lipopolysaccharide-induced RAW 264.7 cells.Scientific reports · 2024Article
- Article
- An In Vitro Examination of Whether Kratom Extracts Enhance the Cytotoxicity of Low-Dose Doxorubicin against A549 Human Lung Cancer Cells.Molecules (Basel, Switzerland) · 2024Article
- Identification and Pharmacological Characterization of a Low-Liability Antinociceptive Bifunctional MOR/DOR Cyclic Peptide.Molecules (Basel, Switzerland) · 2023Article
- Structure-based discovery of conformationally selective inhibitors of the serotonin transporter.Cell · 2023Article
- Kratom's Emergence and Persistence Within the US Polydrug Epidemic.Current addiction reports · 2023Review
- Opioid signaling and design of analgesics.Progress in molecular biology and translational science · 2023Review
- Characterization of a Potential KOR/DOR Dual Agonist with No Apparent Abuse Liability via a Complementary Structure-Activity Relationship Study on Nalfurafine Analogues.ACS chemical neuroscience · 2022Article
- Interactive Effects ofThe Journal of pharmacology and experimental therapeutics · 2022Article
- An analog of [d-Trp]CJ-15,208 exhibits kappa opioid receptor antagonism following oral administration and prevents stress-induced reinstatement of extinguished morphine conditioned place preference.Pharmacology, biochemistry, and behavior · 2022Article
- Physiological dependence to mitragynine indicated by a rapid cross-dependence procedure with heroin-dependent mice.Psychopharmacology · 2022Article
- Experimental considerations for the assessment of in vivo and in vitro opioid pharmacology.Pharmacology & therapeutics · 2022Review
- Review
- Contributions of the International Narcotics Research Conference to Opioid Research Over the Past 50 years.Advances in drug and alcohol research · 2022Review
- How essential is kratom availability and use during COVID-19? Use pattern analysis based on survey and social media data.Substance abuse · 2022Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Chronic administration of opioids produces physical dependence and opioid-induced hyperalgesia. Users claim the Thai traditional tea "kratom" and component alkaloid mitragynine ameliorate opioid withdrawal without increased sensitivity to pain. Testing these claims, we assessed the combined kratom alkaloid extract (KAE) and two individual alkaloids, mitragynine (MG) and the analog mitragynine pseudoindoxyl (MP), evaluating their ability to produce physical dependence and induce hyperalgesia after chronic administration, and as treatments for withdrawal in morphine-dependent subjects. C57BL/6J mice (n = 10/drug) were administered repeated saline, or graded, escalating doses of morphine (intraperitoneal; i.p.), kratom alkaloid extract (orally, p.o.), mitragynine (p.o.), or MP (subcutaneously, s.c.) for 5 days. Mice treated chronically with morphine, KAE, or mitragynine demonstrated significant drug-induced hyperalgesia by day 5 in a 48 °C warm-water tail-withdrawal test. Mice were then administered naloxone (10 mg/kg, s.c.) and tested for opioid withdrawal signs. Kratom alkaloid extract and the two individual alkaloids demonstrated significantly fewer naloxone-precipitated withdrawal signs than morphine-treated mice. Additional C57BL/6J mice made physically dependent on morphine were then used to test the therapeutic potential of combined KAE, mitragynine, or MP given twice daily over the next 3 days at either a fixed dose or in graded, tapering descending doses. When administered naloxone, mice treated with KAE, mitragynine, or MP under either regimen demonstrated significantly fewer signs of precipitated withdrawal than control mice that continued to receive morphine. 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.
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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.