Update on the Pharmacology and Legal Status of Kratom

Prozialeck, Walter C.

doi:10.7556/jaoa.2016.156

Cited by 69 publications

(96 citation statements)

References 37 publications

(41 reference statements)

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“…Kratom use appears to be increasing in the United States (Warner et al, 2016), especially for selfmanagement of opioid withdrawal and pain relief (Grundmann, 2017;Prozialeck, 2016). Pain relief appears to be the most common reason, closely followed by emotional/mental conditions such as anxiety, depression and Post Traumatic Stress Disorder (PTSD), followed by drug dependency (Grundmann, 2017).…”

Section: Epidemiologymentioning

confidence: 99%

Characteristics of deaths associated with kratom use

Corkery

Streete²,

Claridge

et al. 2019

J Psychopharmacol

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Background: Kratom ( Mitragyna speciosa Korth) use has increased in Western countries, with a rising number of associated deaths. There is growing debate about the involvement of kratom in these events. Aims: This study details the characteristics of such fatalities and provides a ‘state-of-the-art’ review. Methods: UK cases were identified from mortality registers by searching with the terms ‘kratom’, ‘mitragynine’, etc. Databases and online media were searched using these terms and ‘death’, ‘fatal*’, ‘overdose’, ‘poisoning’, etc. to identify additional cases; details were obtained from relevant officials. Case characteristics were extracted into an Excel spreadsheet, and analysed employing descriptive statistics and thematic analysis. Results: Typical case characteristics ( n = 156): male (80%), mean age 32.3 years, White (100%), drug abuse history (95%); reasons for use included self-medication, recreation, relaxation, bodybuilding, and avoiding positive drug tests. Mitragynine alone was identified/implicated in 23% of cases. Poly substance use was common (87%), typically controlled/recreational drugs, therapeutic drugs, and alcohol. Death cause(s) included toxic effects of kratom ± other substances; underlying health issues. Conclusions: These findings add substantially to the knowledge base on kratom-associated deaths; these need systematic, accurate recording. Kratom’s safety profile remains only partially understood; toxic and fatal levels require quantification.

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Section: Epidemiologymentioning

confidence: 99%

Characteristics of deaths associated with kratom use

Corkery

Streete²,

Claridge

et al. 2019

J Psychopharmacol

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“…Despite these perceived benefits, increasing rates of kratom use have led to concomitant increases in reports of adverse effects following consumption, although to date, no fatal overdoses have been attributed to kratom use alone (Cinosi et al, 2015;Kruegel & Grundmann, 2017). While the Drug Enforcement Administration recently decided to withhold its decision on classifying kratom as a Schedule I drug (Griffin & Webb, 2018;Grundmann, Brown, Henningfield, Swogger, & Walsh, 2018), reservations about the safety of kratom remain, leading to increased scrutiny of its current legal status in the United States (Henningfield, Fant, & Wang, 2018;Prozialeck, 2016).…”

Section: Introductionmentioning

confidence: 99%

G protein‐biased kratom‐alkaloids and synthetic carfentanil‐amide opioids as potential treatments for alcohol use disorder

Gutridge

Robins

Cassell

et al. 2020

British J Pharmacology

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Background and Purpose Mitragyna speciosa, more commonly known as kratom, is a plant that contains opioidergic alkaloids but is unregulated in most countries. Kratom is used in the self‐medication of chronic pain and to reduce illicit and prescription opioid dependence. Kratom may be less dangerous than typical opioids because of the stronger preference of kratom alkaloids to induce receptor interaction with G proteins over β‐arrestin proteins. We hypothesized that kratom (alkaloids) can also reduce alcohol intake. Experimental Approach We pharmacologically characterized kratom extracts, kratom alkaloids (mitragynine, 7‐hydroxymitragynine, paynantheine, and speciogynine) and synthetic carfentanil‐amide opioids for their ability to interact with G proteins and β‐arrestin at μ, δ, and κ opioid receptors in vitro. We used C57BL/6 mice to assess to which degree these opioids could reduce alcohol intake and whether they had rewarding properties. Key Results Kratom alkaloids were strongly G protein‐biased at all three opioid receptors and reduced alcohol intake, but kratom and 7‐hydroxymitragynine were rewarding. Several results indicated a key role for δ opioid receptors, including that the synthetic carfentanil‐amide opioid MP102—a G protein‐biased agonist with modest selectivity for δ opioid receptors—reduced alcohol intake, whereas the G protein‐biased μ opioid agonist TRV130 did not. Conclusion and Implications Our results suggest that kratom extracts can decrease alcohol intake but still carry significant risk upon prolonged use. Development of more δ opioid‐selective synthetic opioids may provide a safer option than kratom to treat alcohol use disorder with fewer side effects.

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“…Saidin et al recommended further study and advised that individual taking large doses of Mitragynine may be at risk of toxicity in association with heavy use of alcohol (35). Prozialeck, in Update on the Pharmacology and Legal Status of Kratom published in the Journal of the American Osteopathic Association in 2016 (48), addressed imminent key issue and limitation in the study of kratom. The author interrogated the evaluation of kratom product, its confirmation, the standardization of a product that contains different mixture of other compounds that can also be active (48).…”

Section: Discussionmentioning

confidence: 99%

“…Prozialeck, in Update on the Pharmacology and Legal Status of Kratom published in the Journal of the American Osteopathic Association in 2016 (48), addressed imminent key issue and limitation in the study of kratom. The author interrogated the evaluation of kratom product, its confirmation, the standardization of a product that contains different mixture of other compounds that can also be active (48). The author also questioned the administration of a plant material to laboratory animals so it would naturally mimic human consumption (48).…”

Section: Discussionmentioning

confidence: 99%

“…The author interrogated the evaluation of kratom product, its confirmation, the standardization of a product that contains different mixture of other compounds that can also be active (48). The author also questioned the administration of a plant material to laboratory animals so it would naturally mimic human consumption (48). A major barrier to study kratom is to accurately determine that the street sales is actually composed of kratom compounds and the origin of its extracts accurately describes similarity of structures involved in both benefits and risks mentioned in the prolific literature of Asia.…”

Section: Discussionmentioning

confidence: 99%

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Biochemical Benefits, Diagnosis, and Clinical Risks Evaluation of Kratom

Fluyau

Revadigar

2017

Front. Psychiatry

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BackgroundKratom (Mitragyna speciosa) is a tropical tree with a long history of traditional use in parts of Africa and Southeast Asia. Kratom is also known as Thom, Thang, and Biak. Its leaves and the teas brewed from them have long been used by people in that region to manage pain and opioid withdrawal and to stave off fatigue. Kratom is actually consumed throughout the world for its stimulant effects and as an opioid substitute (in form of tea, chewed, smoked, or ingested in capsules). Some case reports have associated kratom exposure with psychosis, seizures, intrahepatic cholestasis, other medical conditions, and deaths. The clinical manifestations of kratom effects are not well defined and the clinical studies are limited. Data research suggest that both stimulant and sedative dose-dependent effects do exist, in addition to antinociceptive, antidepressant activity, anxiolytic-like effects, and anorectic effects, but a growing concern for the drug’s effects and safety of use has resulted in national and international attention primarily due to an increase in hospital visits and deaths in several countries that are believed to have been caused by extracts of the plant. There is a dearth of double blind controlled studies. In this study, we aim to use existing literature to clarify both benefits and risks of kratom as well as its diagnosis evaluation as kratom misuse is an emerging trend in the Western world.MethodsLiterature review using databases such as Embase, Medline, PubMed, Cochrane Library, and Mendeley from 2007 to 2017 were evaluated by all authors to analyze current state on benefits, risks, and diagnosis evaluation of kratom (M. speciosa).ResultsData analysis suggested that kratom possesses some benefits such as stimulant and sedative effects as wells as antinociceptive effects. It seems to inhibit pro-inflammatory mediator release and vascular permeability and can enhance immunity. In addition, it may be an antidepressant and anorectic. However, kratom can cause intrahepatic cholestasis, seizure, arrhythmia, impair memory function, coma, and death. Psychological manifestations described are euphoria and feeling relaxed to severe symptoms such as aggression, hostility, and psychosis. Medical manifestations described are polyuria, dry mouth, vomiting, and jerky movements. Currently, liquid chromatography/mass spectrometry and ion mobility spectrometry (IMS) are suggested as the most promising to rapidly screen kratom products providing a positive success rate.ConclusionOur data analysis has not determined if biochemical benefits of kratom may prove to outweigh its toxicity and risks. On the contrary, it seems that its potential side effects outweigh the benefits, and severe and real health hazards can, insidiously, lead to death. Kratom clinical, psychological, and medical manifestations can be disturbing. Kratom (M. speciosa) use, among multiple compounds of the leaf, appear to be increasing in the Western world. Promising methods to accurately identify kratom compounds are still ongoing.

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Update on the Pharmacology and Legal Status of Kratom

Cited by 69 publications

References 37 publications

Characteristics of deaths associated with kratom use

Characteristics of deaths associated with kratom use

G protein‐biased kratom‐alkaloids and synthetic carfentanil‐amide opioids as potential treatments for alcohol use disorder

Biochemical Benefits, Diagnosis, and Clinical Risks Evaluation of Kratom

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