Mitragyna speciosa is a tropical plant whose leaves, known as kratom, have been used for centuries in Southeast Asia for a variety of purposes. How is it that kratom is currently one of the most widely used new psychoactive substances in the Western world?
About the plant
Mitragyna speciosa is a tropical tree up to 15 m tall. It grows in tropical and subtropical areas of Southeast Asia: Thailand, Malaysia, the Philippines, Burma. It belongs to the family Rubiaceae, which, among others, includes plants from the genera Coffea (source of coffee) and Cinchona (source of antimalarial quinine). It has large oval dark green leaves – they are the dried herbal drug of interesting effects.
Kratom is most commonly taken by chewing the leaves, crushed into a powder, as a hot tea or in the form of gel kratom capsules. In the traditional medicine of the native lands, it was used for the treatment of diabetes, diarrhea, fever and pain. Due to its stimulating effect, it has been taken for centuries by manual workers, especially those on rubber plantations or by sailors and fishermen. In addition, in the 1940s, its use was recorded in Malaysia and Thailand for the purpose of replacing opium intake or as a therapy for withdrawal symptoms (abstinence syndrome).
What does it contain and how does it work?
Kratom contains more than 25 alkaloids, of which the most active are mitraginine and 7-hydroxymitraginine (there are 60% and 2% of them). It is they who are responsible for the characteristic effects of kratom. Although less abundant, 7-hydroxymitraginine is more potent due to the presence of a hydroxyl group on the C-7 atom. Less significant, but quantitatively represented are paniantein, speciocialitin and specioginin. Mitraginine is an alkaloid that contains an indole ring, such as yohimbine and voacangine.
The effect of kratom capsules is complex. In low doses it has a primary stimulatory effect, and in high doses its opioid effect is more pronounced. Different varieties have differences in action. Plants from Bali have more pronounced analgesic properties, while those from Malaysia have stronger stimulating effects. In principle, a dose of 1 to 5 grams has mild stimulant effects, and so it is used by workers. Effects include greater sociability, caution, increased sexual desire, blush, contracted pupils, anxiety, and agitation. At a dose of 5 to 15 grams, opioid properties predominate: analgesic and antinociceptic properties are expressed, as well as euphoria, but to a lesser extent than with more frequently used opioid drugs such as heroin. In overdoses it can cause stupor, sweating, dizziness and nausea. Tremors, anorexia, development of addiction, weight loss, epileptic seizures, and psychosis have been reported in chronic users.
Mitraginine and 7-hydroxymitraginine (7-HMG) are selective and complete agonists of opioid μ-receptors. Mitraginine is active at the supraspinal μ- and δ-receptors. Inhibits neurotransmitter release by Cacijom channel obstruction. The stimulatory effect is manifested in the blocked stimulation of serotonergic 5-HT2A receptors and in the stimulation of postsynaptic ɑ-2-adrenergic receptors. 7-HMG is known to have enhanced activity, but it is not fully understood why and exactly how it works. Mitraginine also has an anti-inflammatory effect: it suppresses the production of prostaglandin E2.
How dangerous is it and is it legal?
The full effect is manifested 30-60 minutes after ingestion, and lasts 5 to 7 hours. Kratoma extracts inhibit various CYP enzymes, leading to potential dangers of harmful interactions with other drugs. Kratom is dangerous to take with carisoprodol, modafinil, propylhexedrine, Datura stramonium extract, fentanyl, diphenhydramine, caffeine, morphine and O-desmethyltramadol. Just a few deaths in the last few years, mostly in the US, have been attributed to a combination of kratom with any of the listed substances. Gaining media attention, these cases were followed by attempts by various authorities to regulate both mitraginine and 7-hydroxymitraginine.
The legal status of kratom varies, and is subject to various recent changes, especially because, along with khat and Salvia, divinorum is one of the most widely used novel psychoactive substances. In Thailand and Malaysia, it was briefly banned in the 1970s, but it is still widely used. Legal status in the U.S. varies from state to state, and there are specific cities and municipalities that have chosen to strictly regulate or ban it, most often after a highly publicized death case related to its use. In the EU, 6 Member States (Denmark, Latvia, Lithuania, Poland, Romania, Sweden) have initiated the process of regulating and limiting chratome and its alkaloids. It is usually procured over the internet, but there are also companies that import and market a variety of kratom products on the physical market. These products come in different forms: dried whole leaves, powder, capsules, tablets, concentrated extracts, etc.
Kratom cannot be detected by conventional drug tests – analytical methods such as HPLC or mass spectrometry are needed to identify its metabolites. An additional clinical danger is that the effect of some secondary alkaloids (paniantein, speciocialitin, specioginine) cannot be inhibited by naloxone, which poses an additional challenge in cases of acute overdose.
Why is it becoming popular?
Its use, especially in the United States, is different from that in its native Southeast Asia. Although there are people who use it only recreationally, most of the use is attributed to people affected by the so-called. opioid epidemic. It is about the emergence of extensive overuse of opioid drugs – and their over-prescribing and procurement from illegal sources. Thus, patients often use kratom in self-medication, to relieve pain and suppress the symptoms of withdrawal syndrome, after stopping the use of opioids such as heroin, methadone and buprenorphine.
However, it has been growing in popularity and use in Southeast Asia as well: its use has traditionally not been taboo as for amphetamines or heroin, and is the most widely used drug in the younger population, along with cannabis. However, its use is expanding in the form of 4 × 100 cocktails, in the form of a drink that is a mixture of kratom leaves, cough syrup, Coca-Cola and ice. Since synthetic impurities are often used in its production, calls for its stricter control are growing in Southeast Asia as well.
What don’t we know yet?
Officially, the FDA (Food and Drug Administration) warns people not to use kratom, arguing that there is no scientific basis on which it could be used for health purposes. They also point out the danger of creating addiction and tolerance, as well as the harmful effects that can occur if combined with other drugs and medications.
As this is a relatively new phenomenon in the Western world, there are not many scientific papers on the use of kratom and many doubts and unknowns remain. Most toxicity studies were performed in animals only. Individual studies have established an association between the use of large amounts of kratom and hepatotoxicity, specifically in the form of intrahepatic cholestasis. An association with hypertension and nephrotoxic effects has also been established.
There are many more things that are not clear about kratom, but it is clear that with every potential therapeutic effect, there are worrying negative aspects. In addition to studying its therapeutic and pharmacological aspects, it is necessary to keep in mind the social factors that lead to its growing popularity.