Double Nn Image by Freepik Company S.L., 2020
Mitragyna speciosa or kratom is a Southeast Asian tropical tree related to the coffee plant whose leaves were traditionally employed to make tea or chewed and smoked to provide energy for long working hours (Generes, 2022; Smith, 2019). Today, over the last two decades, kratom is a sexual performance enhancement and pain-relieving herb (Meireles et al., 2019). In addition, it has been found to alleviate diarrhea, fevers, diabetes, and hypertension. When given recreationally, it provides a feeling of pleasure and has psychoactive effects. Furthermore, kratom is consumed as an alternative to opioids because of its lower price and easier availability since it does not require a prescription. On the contrary, there is not strong enough evidence illustrating that kratom is an effective treatment for opioid use disorder (FDA, 2018). In addition, regular kratom employment has caused cases of weight loss, dehydration, constipation, hand shaking, headaches, and hyperpigmentation in Southeast Asian countries (Garner-Wizard et al., 2017). In the West, seizures, hypothyroidism, and liver injury have occurred. Ultimately, kratom exhibits both intrinsic and idiosyncratic toxicities.
Currently, it is estimated that more than two million Americans ingest kratom annually with powder or capsules being the preferred method of administration (Smith, 2019). However, contrary to its various benefits, there are considerable risks from taking kratom, especially if concomitantly practiced (Garner-Wizard et al., 2017). When ingested in its raw form, kratom has rarely resulted in death from overdose. However, much of the employment of kratom is through pills or in conjunction with some form of drug or substance such as alcohol, sedatives, benzodiazepines, opioids or opium-containing products, caffeine or caffeine-containing products, cocaine, yohimbine, carbamazepine, theophylline, digoxin warfarin, and phenytoin (Meireles et al., 2019). It is believed that the drugs change the CYP isoenzymes in kratom and result in serious drug-drug interactions such as liver damage (Generes, 2022). For example, one patient experience serotonin syndrome and electrocardiogram abnormalities after ingesting 150mg venlafaxine (CYP2D6/3A substrate), 300mg quetiapine (CYP3A substrate), and about 90g kratom daily (Brogdon et al., 2022). Lastly, some studies indicate that the acid degradable characteristics of mitragynine, the psychoactive alkaloid in kratom, and the hydrophobicity, poor water solubility, and high variability of drug release led to the broad range of reactions, which further supports the idea that kratom has idiosyncratic toxicity (Cinosi et al., 2015).
In addition, overdoses from herbal powders can also occur. In a 2019 retrospective review of cases recorded by the National Poison Data System and New York City Office of the Chief Medical Examiner, poisoning mostly occurred at dosages more than 8g of kratom powder and can result in kidney injury, cardiotoxicity, arrhythmia, hypothyroidism, lung injury, and hepatic injury (Eastlack et al., 2020). This dose range implies a possible intrinsic toxicity to kratom in the case of powders. For example, in an anonymous internet survey, participants who ingest 5g and below of the herb experienced less harmful reactions than those who consumed 8g or more (Veltri & Grundmann, 2019). Furthermore, there is a correlation between stimulatory reactions and small doses of kratom analogous to cocaine and sedative-narcotic reactions similar to opiates from large doses (Cinosi et al., 2015). As discussed by Anna Marie Wheeler and Keira Kroin, the high dose dependency for adverse reactions in cases of anxiety, aggression, weight loss, and psychosis along with kidney, lung, and liver damage implies an intrinsic effect (Kroin, 2023; Wheeler, 2023).
Next, the FDA’s PHASE computer model indicated that chemicals in kratom cause stress responses in the brain that affect the body’s neurologic and cardiovascular function (FDA, 2018). The adverse consequences include seizures and respiratory depression. Additionally, 1-10mg/kg mitragynine was much safer than 100mg/kg doses in rats, which resulted in histopathological and hematological effects in the liver, kidney, and brain (Karunakaran et al., 2022). Lastly, in vitro studies have illustrated cytotoxic impacts of mitragynine and 7-hydroxymitragynine on human neuronal, hepatic, and cardiac myocyte cell lines (Alsarraf et al., 2019). However, in a study conducted from 2011-2017, kratom consumption only resulted in 1,800 poison control calls from adverse effects even though millions of Americans ingest kratom every year. As a result of the rarity of toxicity and the multiplicity of variables that coincide with the adverse reactions, kratom could be idiosyncratically toxic (Roth & Ganey, 2010).
In the end, kratom is a plant that has been adopted as a stimulant and treatment for illnesses such as diabetes, diarrhea, fever, and pain for centuries in countries such as Thailand, Malaysia, and Myanmar (Cinosi et al., 2015; Eastlack et al., 2020). Unfortunately, today kratom is commonly misused and dangerously consumed with drugs and other interactive substances, which have resulted in numerous toxicity reports. Additionally, kratom has a history of being adulterated. There have been cases of the herb being mixed with heavy metals (Generes, 2022). Furthermore, the FDA has discovered harmful bacteria such as salmonella in the plant (Smith, 2019). Lastly, there have been reports of the herb being intentionally modified to have higher levels of 7-OH-mitragynine, kratom’s major constituent, to have stronger effects by mixing it with chemicals such as phenylethylamine and desmethyltramadol, both of which have resulted in fatalities (Meireles et al., 2019). As emphasized by Phoenix Vetra, kratom would be a formidable herb to represent the dangers of drug-herb interactions, adulteration, and potency disparities(Vetra, 2023).
In summary, if administered properly, kratom can be beneficial in easing pain, increasing energy, and providing a sense of euphoria. However, if it is ingested above the recommended dosage or with any additional substances, it can lead to serious life-threatening adverse reactions. Ultimately, kratom does not have enough clinical trials analyzing its effects to conclusively determine whether or not it has intrinsic or idiosyncratic toxicity. There is evidence that kratom poisoning is dose dependent, but the numerous cases of concomitant use of drugs with kratom makes it difficult to come to a final judgement of its true nature.
References
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Brogdon, H. D., McPhee, M. M., Paine, M. F., Cox, E. J., & Burns, A. G. (2022). A Case of Potential Pharmacokinetic Kratom-drug Interactions Resulting in Toxicity and
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https://doi.org/10.1155/2015/968786
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