Kratom Use Within the Context of the Evolving Opioid Crisis and the COVID-19 Pandemic in the United States

Prozialeck, Walter C.; Lamar, Peter C.; Krupp, Michael; Moon, Matthew; Phelps, Laura E.; Grundmann, Oliver

doi:10.3389/fphar.2021.729220

Cited by 20 publications

(12 citation statements)

References 76 publications

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“…More and better research, including wellcontrolled, prospective studies, is necessary to further elucidate kratom's potential for good and harm and the moderators of its effects" (Swogger and Walsh, 2018). The therapeutic potential of kratom based on surveys, anecdotal reports, and nonclinical research supports the plausibility of such benefits as discussed by other reviewers (Prozialeck et al, 2019;Hemby et al, 2019;Yue et al, 2018;Grundmann et al, 2018;Kruegel and Grundmann, 2018;Sharma and McCurdy, 2021;Swogger et al, 2018;Prozialeck et al, 2021).…”

Section: Public Health and Individual Benefits Of Kratommentioning

confidence: 91%

Kratom Abuse Potential 2021: An Updated Eight Factor Analysis

Henningfield¹,

Wang²,

Huestis³

2022

Front. Pharmacol.

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Drugs are regulated in the United States (US) by the Controlled Substances Act (CSA) if assessment of their abuse potential, including public health risks, show such control is warranted. An evaluation via the 8 factors of the CSA provides the comprehensive assessment required for permanent listing of new chemical entities and previously uncontrolled substances. Such an assessment was published for two kratom alkaloids in 2018 that the Food and Drug Administration (FDA) have identified as candidates for CSA listing: mitragynine (MG) and 7-hydroxymitragynine (7-OH-MG) (Henningfield et al., 2018a). That assessment concluded the abuse potential of MG was within the range of many other uncontrolled substances, that there was not evidence of an imminent risk to public health, and that a Schedule I listing (the only option for substances that are not FDA approved for therapeutic use such as kratom) carried public health risks including drug overdoses by people using kratom to abstain from opioids. The purpose of this review is to provide an updated abuse potential assessment reviewing greater than 100 studies published since January 1, 2018. These include studies of abuse potential and physical dependence/withdrawal in animals; in-vitro receptor binding; assessments of potential efficacy treating pain and substance use disorders; pharmacokinetic/pharmacodynamic studies with safety-related findings; clinical studies of long-term users with various physiological endpoints; and surveys of patterns and reasons for use and associated effects including dependence and withdrawal. Findings from these studies suggest that public health is better served by assuring continued access to kratom products by consumers and researchers. Currently, Kratom alkaloids and derivatives are in development as safer and/or more effective medicines for treating pain, substances use disorders, and mood disorders. Placing kratom in the CSA via scheduling would criminalize consumers and possession, seriously impede research, and can be predicted to have serious adverse public health consequences, including potentially thousands of drug overdose deaths. Therefore, CSA listing is not recommended. Regulation to minimize risks of contaminated, adulterated, and inappropriately marketed products is recommended.

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Section: Public Health and Individual Benefits Of Kratommentioning

confidence: 91%

Kratom Abuse Potential 2021: An Updated Eight Factor Analysis

Henningfield¹,

Wang²,

Huestis³

2022

Front. Pharmacol.

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“…There is recreational use; however, many people who use opioids recreationally report kratom as a poor substitute for producing opioid-like euphoria but do find it useful to self-manage withdrawal and discontinue opioid use (Coe et al 2019;Garcia-Romeu et al 2020;Prozialeck et al 2019;Swogger et al 2022). Estimates of incidence and prevalence of intake vary from 2 to 16 million in the United States (US) (American Kratom Association 2019; Covvey et al 2020;Henningfield et al 2021;Palamar 2021;Schimmel et al 2021) and many millions more globally, with the highest prevalence in Southeast Asia and Indonesia where kratom grows in abundance and has been widely consumed for centuries (Brown et al 2017;Cinosi et al 2015;Prozialeck et al 2021;WHO ECDD 2021;Vicknasingam et al 2010).…”

Section: Introductionmentioning

confidence: 99%

“…In October 2021, the US Department of Health and Human Services (US DHHS) announced that drug overdose prevention efforts would include a substantial increase in harm reduction efforts to reduce opioid and other drug overdose deaths (US DHHS 2021). Kratom was not mentioned in the 2021 US DHHS announcement; however, US national surveys indicated that kratom is increasingly taken as a harm reduction strategy by thousands of opioid users to reduce and/or eliminate their opioid use related to pain and/ or opioid use disorder (Grundmann 2017;Grundmann et al 2018;Coe et al 2019;Garcia-Romeu et al 2020;Prozialeck et al 2019Prozialeck et al , 2020Prozialeck et al , 2021Swogger et al 2022).…”

Section: Introductionmentioning

confidence: 99%

Respiratory effects of oral mitragynine and oxycodone in a rodent model

Henningfield

Rodricks

Magnuson³

et al. 2022

Psychopharmacology

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Rationale Kratom derives from Mitragyna speciosa (Korth.), a tropical tree in the genus Mitragyna (Rubiaceae) that also includes the coffee tree. Kratom leaf powders, tea-like decoctions, and commercial extracts are taken orally, primarily for health and well-being by millions of people globally. Others take kratom to eliminate opioid use for analgesia and manage opioid withdrawal and use disorder. There is debate over the possible respiratory depressant overdose risk of the primary active alkaloid, mitragynine, a partial μ-opioid receptor agonist, that does not signal through ß-arrestin, the primary opioid respiratory depressant pathway. Objectives Compare the respiratory effects of oral mitragynine to oral oxycodone in rats with the study design previously published by US Food and Drug Administration (FDA) scientists for evaluating the respiratory effects of opioids (Xu et al., Toxicol Rep 7:188–197, 2020). Methods Blood gases, observable signs, and mitragynine pharmacokinetics were assessed for 12 h after 20, 40, 80, 240, and 400 mg/kg oral mitragynine isolate and 6.75, 60, and 150 mg/kg oral oxycodone hydrochloride. Findings Oxycodone administration produced significant dose-related respiratory depressant effects and pronounced sedation with one death each at 60 and 150 mg/kg. Mitragynine did not yield significant dose-related respiratory depressant or life-threatening effects. Sedative-like effects, milder than produced by oxycodone, were evident at the highest mitragynine dose. Maximum oxycodone and mitragynine plasma concentrations were dose related. Conclusions Consistent with mitragynine’s pharmacology that includes partial µ-opioid receptor agonism with little recruitment of the respiratory depressant activating β-arrestin pathway, mitragynine produced no evidence of respiratory depression at doses many times higher than known to be taken by humans.

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“…Kratom ( Mitragyna speciosa ), a native plant in Southeast Asia, 1 has received public, scientific, and political attention in recent years. 2 - 4 In 2021, the World Health Organization (WHO) Expert Committee on Drug Dependence (ECDD) decided against recommending a critical review of kratom, electing instead to continue surveillance of this herb. 5 Although the United States (U.S.) Food and Drug Administration (FDA) does not report any FDA-approved uses for kratom, 6 the National Institute on Drug Abuse (NIDA) is funding numerous projects related to kratom and its alkaloids.…”

Section: Introductionmentioning

confidence: 99%

Health Effects Associated With Kratom (Mitragyna speciosa) and Polysubstance Use: A Narrative Review

et al. 2022

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Background: Kratom ( Mitragyna speciosa) consumption and associated health effects have raised debates in the United States. Although most people using this herb do not experience adverse health effects associated with kratom use, medical providers should be knowledgeable of emerging substances and concurrent, sequential, or simultaneous use of other drugs which may impact healthcare recommendations and prescribing practices. Methods: The objective of this narrative review was to elucidate selected health effects associated with using kratom—either alone or with other substances. Since scientifically controlled human subjects research on kratom use is still limited, relevant case reports were also described. Results: Cardiovascular, gastrointestinal, neurological, and psychiatric effects associated with kratom use were especially notable, and in-utero exposure accompanied concern regarding a neonate’s risk for developing neonatal abstinence syndrome. Our ability to identify and understand the role of this herb in kratom-associated fatalities is complicated since kratom is not routinely screened for in standard forensic toxicology. If a screening is performed, it is usually for the major alkaloid, mitragynine, as a surrogate for kratom use. In addition to lacking a standard practice of screening decedents for kratom alkaloids, the association between mortality and kratom use may be confounded by polysubstance use, adulteration of kratom products, and drug-herb interactions. Conclusions: Increasing medical awareness of this herb is vital to ensuring prompt administration of best-practice medical advice or treatment for people seeking information related to kratom use or for patients experiencing an adverse health effect that may be associated with using or withdrawing from kratom. Knowledge gained from continued surveillance and study of kratom and its associated health effects may assist in guiding clinical decision-making and preventing development of adverse health effects among people using kratom.

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Kratom Use Within the Context of the Evolving Opioid Crisis and the COVID-19 Pandemic in the United States

Cited by 20 publications

References 76 publications

Kratom Abuse Potential 2021: An Updated Eight Factor Analysis

Kratom Abuse Potential 2021: An Updated Eight Factor Analysis

Respiratory effects of oral mitragynine and oxycodone in a rodent model

Health Effects Associated With Kratom (Mitragyna speciosa) and Polysubstance Use: A Narrative Review

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