Wednesday, 14 March 2018

Re: Uses of Kratom in Southeast Asia and the Need for Controlled Clinical Trials to Support Its Health Uses

Kratom (Mitragyna speciosa, Rubiaceae) Therapeutic Uses Date: 02-28-2018 HC# 081734-587 Singh D, Narayanan S, Vicknasingam B, Corazza O, Santacroce R, Roman-Urrestarazu A. Changing trends in the use of kratom (Mitragyna speciosa) in Southeast Asia. Hum Psychopharmacol. 2017;32(3):e2582. doi: 10.1002/hup.2582. Kratom (ketum; Mitragyna speciosa, Rubiaceae) is a medicinal plant native to Southeast Asia. Its leaves and preparations thereof are ingested in various ways (smoking, chewing, as an herbal tea, expressed juice, etc.). Traditionally, it has been used as a recreational drink for relaxation; as a household remedy for common ailments such as fever, cough, hypertension, diabetes, pain, and anxiety; and, especially for men, as a method to combat fatigue and improve work productivity. The plant's alkaloids, including mitragynine and 7-hydroxymitragynine, are reported to produce psychostimulant and opiate‐like effects. Those effects are determined by the plant variety—distinguished by either a red vein or white vein leaf. The more potent red vein leaf is preferred in Thailand. The authors reviewed the literature to analyze the changing trends of kratom use in Southeast Asia. The authors searched ScienceDirect, Scopus, ProMed, and Google Scholar using the terms "kratom," "ketum," and "Mitragyna speciosa." Of the 25 published articles on kratom use in Southeast Asia, 19 articles were included. Eleven studies originated in Malaysia, and eight studies were conducted in Thailand. The articles included three review papers, eight in-depth qualitative interviews, four case reports, two reference texts, and two short communications. Kratom is banned in Malaysia and has been illegal in Thailand since 1943. In Malaysia, the cultivation of kratom trees is not illegal; people caught distributing kratom or processing the leaves, however, can be fined, jailed, or both. An attempt by the Malaysian government to reschedule kratom from the Poisons Act of 1952 to the Dangerous Drugs Act of 1952 was halted by legislators who were not convinced of its health dangers. In Thailand, kratom was first regulated under the 1943 Kratom Act and then rescheduled under the Thai Narcotics Act in 1979, which is less punitive than the Kratom Act. Kratom is controlled in several member states of the European Union. Reported effects of kratom use include feelings of elation and strength; heightened sexual desire and increased levels of physical activity; and alertness, sedation, and contentment. Regular kratom users, who are likely to increase their intake over time, often complain of adverse effects such as constipation, weight loss, insomnia, dryness of the mouth, frequent micturition, dehydration, tiredness, darkening of the skin, and low sexual drive. The prolonged use of kratom can lead to dependence and withdrawal problems. Physical difficulties associated with withdrawal include sleeping difficulties, decreased appetite, vomiting, muscle spasms, sweating, fever, abdominal pain, diarrhea, and headaches. Psychological problems include hostility, aggression, mental confusion, delusion, hallucinations, and persecutory ideation. The severity of withdrawal symptoms depends on how much and how often kratom is used. Consumers of three or more glasses of kratom juice daily are more likely to report severe dependence and withdrawal symptoms. Unlike alcohol or drug users, male kratom users are not discriminated against in their villages, partly because they are considered hard-working people and do not engage in activities such as bullying, hurting others, quarrelling, or fighting. Employed, married, and living with their families, most kratom users in Southeast Asia have been generally healthy since beginning their use of kratom. There is no evidence suggesting that they are more likely to engage in illicit drug use or risky or criminal behaviors, nor that kratom use acts as a gateway to illicit drug use. Preclinical information on the toxic effects of kratom use is scarce. A poison center in Thailand recorded 52 kratom exposure cases reported to its surveillance system from 2005 to 2009. Of the 52 cases, 76.9% involved kratom poisoning and 23.1% were kratom withdrawal cases. The authors of the report point out that some of the cases may have been caused by the concomitant use of other illicit substances. Future clinical studies should examine the chronic toxic effects of kratom in humans. New trends in kratom use have been seen in Southeast Asia. A Malaysian cross-sectional study reported that many illicit drug users in the northern states use kratom as a cheap alternative to reduce their dependence on illicit substances and to suppress opiate withdrawal symptoms. In both Malaysia and Thailand, urban teenagers and young adults use a concoction made of brewed kratom tea, cough syrup, and other substances such as anxiolytics, antidepressants, and analgesics for its euphoric effects. "These cocktails can become fatal and as damaging as other illicit substances that have been banned," write the authors of this review. The authors conclude that "[m]ore objective-controlled trials and experiments on humans need to be conducted to validate self-report claims by kratom users in the community." The study was funded by grants from the Higher Institution Centre of Excellence (Malaysia) and Research University (Malaysia). —Shari Henson