A systematic review of (pre)clinical studies on the therapeutic potential and safety profile of kratom in humans

Abstract

Introduction: Kratom (Mitragyna speciosa) is a tropical plant traditionally used as an ethnomedicinal remedy for several conditions in South East Asia. Despite the increased interest in its therapeutical benefits in Western countries, little scientific evidence is available to support such claims, and existing data remain limited to kratom's chronic consumption.Objective: Our study aims to investigate (pre)clinical evidence on the efficacy of kratom as a therapeutic aid and its safety profile in humans. Methods: A systematic literature search using PubMed and the Medline database was conducted between April and November 2020. Results: Both preclinical (N = 57) and clinical (N = 18) studies emerged from our search. Preclinical data indicated a therapeutic value in terms of acute/chronic pain (N = 23), morphine/ethanol withdrawal, and dependence (N = 14), among other medical conditions (N = 26). Clinical data included interventional studies (N = 2) reporting reduced pain sensitivity, and observational studies (N = 9) describing the association between kratom's chronic (daily/frequent) use and safety issues, in terms of health consequences (e.g., learning impairment, high cholesterol level, dependence/withdrawal).Conclusions: Although the initial (pre)clinical evidence on kratom's therapeutic potential and its safety profile in humans is encouraging, further validation in large, controlled clinical trials is required.

Inhibition of α-Glucosidase and Pancreatic Lipase Properties of Mitragyna speciosa (Korth.) Havil. (Kratom) Leaves

“…M. speciosa or kratom contains more than 40 identified bioactive compounds including indole alkaloids, flavonoids, triterpenoids, saponins, and glycosides. These compounds have been described to have antioxidant, anti-inflammatory, antibacterial, antiproliferative, and analgesic activities by several studies [ 26 , 28 , 29 , 40 ]. In this study, the presence of phenolic, flavonoid, and alkaloid compounds in our kratom extracts were confirmed by TPC, TFC, and TAC, respectively ( Table 1 ).…”

Mitragyna Species as Pharmacological Agents: From Abuse to Promising Pharmaceutical Products

“…Because of the popularity of this plant, several studies have focused on its use, especially on the interaction of mitragynine, which has an opioid-like effect. Given the large number of cases of its abuse and the side effects caused by its use that have been reported in Europe and America, this is in stark contrast to the cases reported under its traditional use in Southeast Asia for centuries [172][173][174].…”

Narrative Review of Kratom, an Emerging Psychoactive Substance With Perianesthetic Implications

“…14,38 Most Internet kratom vendors include disclaimers that products are for research purposes and are not intended for human consumption, that kratom is addictive, and that it is not recommended for underaged consumers. 17 Information regarding other adverse effects with acute and chronic use is frequently absent on retailer websites, as are warnings μ-opioid receptor (G-protein--biased agonism) 22,26,27 Low dose: mild stimulant 6,12,18 Increase alertness and productivity 5,17,[35][36][37] Potentiation of opioid drug effects Delta and kappa opioid receptor antagonism 22,26 High dose: analgesic 6,12,26,27 and euphoric 6,38 Decrease pain, opioid withdrawal, and diarrhea 5,17,[35][36][37] Withdrawal if prolonged abstinence before anesthetic Cyclooxygenase-2 pathway inhibition 29 Anti-inflammatory 2,9,12,29 Decrease pain and inflammation 2,4 Kidney injury with concurrent nonsteroidal antiinflammatory drug use Alpha-2 adrenergic receptor agonism (postsynaptic) 30,31 Low dose: anxiolytic 2,18 Increase relaxation 6,17,[35][36]…”

“…The promotion of kratom in the lay press as a safe and effective opioid alternative has gained attention by the medical community, resulting in an increasing body of scientific publications, including expert opinions and comprehensive reviews of potential therapeutic benefits as well as risk for harms. 9,10,12 A search of the United States National Library of Medicine PubMed database in December 2021 with keywords “kratom” or “ Mitragyna speciosa ” resulted in 590 articles, more than 70% of which were published in past 10 years. A considerable number of studies have been dedicated to mechanistic effects, metabolism, quantification of components in kratom products (preconsumption), and identification of metabolic products in serum and urine (postconsumption).…”