Diagnostic Ambiguities and Underuse of Clinical Assessment Tools: A Systematic Review of Case Reports on Kratom Addiction and Physical Dependence

Smith, Kirsten E.; Feldman, Jeffrey D.; Schriefer, Destiny; Weiss, Stephanie T.; Grundmann, Oliver; Dunn, Kelly E.; Singh, Darshan; McCurdy, Christopher R.; Butera, Gisela; Epstein, David H.

doi:10.1007/s40429-023-00474-7

Cited by 9 publications

(6 citation statements)

References 61 publications

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“…More recently, the findings of a global forum that included at least one representative of most of the research centers that conducted kratom withdrawal and abuse potential studies since 2018 were published (Henningfield et al, 2023). They concurred that KUD and withdrawal profiles are not identical to opioid or other substance disorders in animal or human studies and were overall of lower severity when they did occur (Henningfield et al, 2023; see also Smith et al, 2023b;Smith et al, 2024). As concluded by Henningfield et al (2023), more research is needed to better inform potential diagnostic listings in the DSM and ICD.…”

Section: Clinical and Nonclinical Evidence Related To Kratom Use Diso...mentioning

confidence: 93%

“…As concluded by Henningfield et al (2023), more research is needed to better inform potential diagnostic listings in the DSM and ICD. Several studies published since that forum also add to the following summary of the state of the science at this writing (see Smith et al, 2023b).…”

Section: Clinical and Nonclinical Evidence Related To Kratom Use Diso...mentioning

confidence: 99%

“…It is important to understand the prevalence of KUD and kratom withdrawal at the population-level. Although US surveys which evaluated KUD suggest that many kratom consumers do not meet criteria for KUD, or if they do it is of mild severity, and do not seek assistance for KUD or withdrawal, some reported “addiction” or withdrawal and seek medical assistance to manage withdrawal, or to aid cessation of kratom use (e.g., Singh et al, 2016 ; Grundmann, 2017 ; Singh et al, 2018 ; Swogger and Walsh, 2018 ; Coe et al, 2019 ; Garcia-Romeu et al, 2020 ; Smith et al, 2021 ; Smith et al, 2023b ; Smith et al, 2024 ). A recently conducted EMA study of kratom consumers found that greater frequency of use was modestly associated with a greater number of KUD symptoms and taking kratom to avoid kratom-related withdrawal, but that irrespective of frequency, the mean number of KUD symptoms was less than four across the sample ( Smith et al, 2024 ).…”

Section: Kratom Use Disorder Withdrawal and Addictionmentioning

confidence: 99%

“…Published case report data indicate that such events do occur (e.g., Grundmann, 2017 ; Garcia-Romeu et al, 2020 ). However, the apparent low rates of KUD or kratom withdrawal treatment seeking in the United States or globally suggest that kratom’s “addiction” related risks are lower than those associated with many controlled substances such as amphetamine, cocaine, and morphine-like opioids ( Smith et al, 2023b ). Taken together, (e.g., Grundmann, 2017 ; Garcia-Romeu et al, 2020 ), these findings and those from a recent EMA study indicate that some users with KUD may experience withdrawal ( Smith et al, 2024 ).…”

Section: Kratom Use Disorder Withdrawal and Addictionmentioning

confidence: 99%

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Kratom safety and toxicology in the public health context: research needs to better inform regulation

Henningfield,

Grundmann,

Huestis

et al. 2024

Front. Pharmacol.

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Although kratom use has been part of life for centuries in Southeast Asia, the availability and use of kratom in the United States (US) increased substantially since the early 2000s when there was little information on kratom pharmacology, use patterns, and effects, all critical to guiding regulation and policy. Here we provide a synthesis of research with several hundred English-language papers published in the past 5 years drawing from basic research, epidemiological and surveillance data, and recent clinical research. This review of available literature aims to provide an integrated update regarding our current understanding of kratom’s benefits, risks, pharmacology, and epidemiology, which may inform United States-based kratom regulation. Recent surveillance indicates there are likely several million past-year kratom consumers, though estimates vary widely. Even without precise prevalence data, kratom use is no longer a niche, with millions of United States adults using it for myriad reasons. Despite its botanical origins in the coffee tree family and its polypharmacy, kratom is popularly characterized as an opioid with presumed opioid-system-based risks for addiction or overdose. Neuropharmacology, toxicology, and epidemiology studies show that kratom is more accurately characterized as a substance with diverse and complex pharmacology. Taken together the work reviewed here provides a foundation for future scientific studies, as well as a guide for ongoing efforts to regulate kratom. This work also informs much-needed federal oversight, including by the United States Food and Drug Administration. We conclude with recommendations for kratom regulation and research priorities needed to address current policy and knowledge gaps around this increasingly used botanical product.

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Section: Clinical and Nonclinical Evidence Related To Kratom Use Diso...mentioning

confidence: 93%

Section: Clinical and Nonclinical Evidence Related To Kratom Use Diso...mentioning

confidence: 99%

Section: Kratom Use Disorder Withdrawal and Addictionmentioning

confidence: 99%

Section: Kratom Use Disorder Withdrawal and Addictionmentioning

confidence: 99%

See 2 more Smart Citations

Kratom safety and toxicology in the public health context: research needs to better inform regulation

Henningfield,

Grundmann,

Huestis

et al. 2024

Front. Pharmacol.

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“…Due to the novelty, variety, and changing nature of these products, they remain challenging areas for investigation. This has contributed to an overreliance on clinical case reports, which skew toward extreme cases likely unrepresentative of typical outcomes (Feldman et al, 2023; Smith et al, 2023; Tatum et al, 2018). The gaps in research on novel substances are sometimes addressed with survey or social media data, though both suffer from self-selection bias and can quickly become outdated (Gunderson et al, 2014; Smith, Rogers, Schriefer, & Grundmann, 2021; Swogger et al, 2015; Vandrey et al, 2012).…”

mentioning

confidence: 99%

Novel methods for the remote investigation of emerging substances: Application to kratom.

Smith¹,

Feldman²,

Dunn³

et al. 2024

Experimental and Clinical Psychopharmacology

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The botanical product commonly called "kratom" is still relatively novel to the United States. Like other natural products marketed as supplements, kratom is highly variable, both in terms of the alkaloids naturally occurring in kratom leaves and in terms of processing and formulation. Kratom products sold in the United States are not well-characterized, nor are daily use patterns among regular users. Surveys and case reports have comprised most of the literature on kratom use among humans. To advance our understanding of real-world kratom use, we developed a protocol for the remote study of regular kratom-using adults in the United States. Our study had three aspects implemented in one pool of participants nationwide: an in-depth online survey, 15 days of ecological momentary assessment (EMA) via smartphone app, and the collection and assay of the kratom products used by participants during EMA. Here, we describe these methods, which can be used to investigate myriad drugs or supplements. Recruiting, screening, and data collection occurred between July 20, 2022 and October 18, 2022. During this time, we demonstrated that these methods, while challenging from a logistical and staffing standpoint, are feasible and can produce high-quality data. The study achieved high rates of enrollment, compliance, and completion. Substances that are emerging or novel, but still largely legal, can be productively studied via nationwide EMA combined with assays of shipped product samples from participants. We discuss challenges and lessons learned so other investigators can adapt these methods. Public Health SignificanceFor this nationwide study investigating the real-world use of kratom products, we utilized a three-phase fully remote design that included an in-depth survey, ecological momentary assessment, and collection of hundreds of participants' product samples. The methods required no in-person participant interaction. These methods permitted collection of subjective self-report data that can be compared to objective chemical characterization of the products used. While labor intensive, these novel methods can be applied to studying a wide range of emerging drugs or legal supplements.

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An exploratory study of the safety profile and neurocognitive function after single doses of mitragynine in humans

Prevete,

Theunissen,

Kuypers

et al. 2024

Psychopharmacology

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Diagnostic Ambiguities and Underuse of Clinical Assessment Tools: A Systematic Review of Case Reports on Kratom Addiction and Physical Dependence

Cited by 9 publications

References 61 publications

Kratom safety and toxicology in the public health context: research needs to better inform regulation

Kratom safety and toxicology in the public health context: research needs to better inform regulation

Novel methods for the remote investigation of emerging substances: Application to kratom.

An exploratory study of the safety profile and neurocognitive function after single doses of mitragynine in humans

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