A complex, poorly understood plant product, kratom, or Mitragyna speciosa, has recently burst onto the American stage in a big way and gained the attention of the US Food and Drug Administration (FDA), as well as the Drug Enforcement Administration (DEA). Mitragynine, the dominant alkaloid in the compound, has been found to have some opioid-like activity and some argue that it is useful in assisting patients who are withdrawing from either licit or illicit narcotic use. The debate about potential DEA regulation of this compound is, more than likely, just beginning.

Background

Kratom grows naturally in much of southeast Asia, more specifically, in Malaysia.1 This evergreen tree can reach a height of more than 80 feet with a trunk diameter of 3 feet.1 The large, dark glossy green leaves yield the extract that is the active component of the tree.

Kratom has been used in its native environment for centuries for purposes ranging from religious ceremonies to wound healing. Its action as an opium substitute, however, was reported in 1836.2 Official notation of this plant and its action was first made by Dutch botanist Pieter Korthals in 1839.3 Despite centuries of use in Malaysia, the compound has been relatively slow to develop a following in the United States, but that appears to be changing.

Science

The main mechanism of action of kratom is due largely to one of the more than 25 alkaloids found in its extract.4 Mitragynine, the dominant alkaloid, has been found to exert somewhat selective μ-opioid receptor activity, especially when used in moderation.5 Proponents of this chemical argue that it is useful in assisting patients who are withdrawing from either licit or illicit narcotic use. Those against the use of kratom take the stance that, since its action is basically opioid in nature, nothing is gained.

There are no clinical trials in humans to determine either the safety or efficacy of kratom. However, a growing body of laboratory data shows some very intriguing actions of the extract. One study demonstrated both adrenergic and serotonergic actions, as well as actual opioid antagonistic functions.6 These activities are seen as promising means to ease withdrawal from narcotic dependence.

In the absence of human clinical trials based in the United States, we are forced to depend largely upon pharmacokinetic data and foreign trials. One case report highlights the differing actions of kratom based on total daily dose.7 In this report, a man in his early 40s was using escalating doses of prescribed hydromorphone for a chronic pain condition. Due to a sudden change in his personal life, he was forced to abruptly cease use of this potent drug. In order to manage his intense symptoms of withdrawal, he began ingesting a kratom tea four times a day. He found that the tea greatly alleviated his physical pain without the typical sedation from prescription medication.7  

In a survey in Malaysia, researchers sought to determine the demographics and substance use habits of self-treated kratom users.8 Nearly 77% of participants reported histories of prior drug use, often heroin. At the time of the survey, more than 45% of participants were still using at least one other psychoactive substance. However, all participants reported greater productivity, better appetites, and reduced dependence on other drugs before beginning kratom use.8

Safety, interactions, side effects

The safety of this product is definitely in question. Due to its known opioid action, addiction and overdose are easily possible. In August 2016, the DEA published a notice of intent to classify this compound as a schedule I drug.9 Due to a huge public response, however, a formal retraction of that intent was published in October 2016, pending further review.9

Regardless of regulation, kratom should be considered an opioid compound and, as such, possess all of the potential side effects and interactions of the class. Until such studies are conducted that more clearly show safety and efficacy for specific uses, there is no current indication for this compound.

Kratom powder is a commonly used form in the United States

 

How supplied, dose, cost

Kratom is widely available in the United States either online or in most ‘head shops.’ It is available in a variety of forms including extract, powder, or capsule. Due to the lack of any quality control, there is no way to establish a ‘recommended dose.’ Also, the concentration of the active ingredient, mitragynine, varies widely based on the form of the product. Extracts tend to be more concentrated, while powders and capsules are weaker.

Those who report sporadic use for anxiety or other episodic concerns may only use 1 to 2 g at a time, whereas daily users managing chronic pain or intense withdrawal from other opiates report using as much as 15 to 20 g or more per day. The type of product and the amount used dictate cost, with an average cost per ounce of about $30.

Summary

With the abundance of approved medications at the disposal of healthcare providers, the use of an unproven and potentially dangerous product such as kratom is not justified. However, providers must be aware of the growing use of this compound in the United States and, when opioid use is either ongoing or newly initiated, screen for use of this product.

References

  1. Rech MA, Donahey E, Dziedzic JMC, Oh L, Greenhalgh E. New drugs of abuse. Pharmacotherapy. 2015;35:189-197.
  2. Assanangkornchai S, Muekthong A, Sam-Angsri N, Pattanasattayawong U. The use of Mitragynine speciosa (“Krathom”), an addictive plant, in Thailand. Subst Use Misuse. 2007;42:2145-2157.
  3. Raffa RB, ed. Kratom and Other Mitragynines: The Chemistry and Pharmacology of Opioids from a Non-Opium Source. Boca Raton, FL: CRC Press; 2014.
  4. León F, Habib E, Adkins JE, Furr EB, McCurdy CR, Cutler SJ. Phytochemical characterization of the leaves of Mitragyna speciosa grown in the USA. Nat Prod Commun. 2009;4:907-910.
  5. Adkins JE, Boyer EW, McCurdy CR. Mitragyna speciosa, a psychoactive tree from Southeast Asia with opioid activity. Curr Top Med Chem. 2011;11:1165-1175.
  6. Suhaimi FW, Yusoff NH, Hassan R, et al. Neurobiology of Kratom and its main alkaloid mitragynine. Brain Res Bull. 2016 Sep;126(Pt 1):29-40.
  7. Boyer EW, Babu KM, Adkins JE, McCurdy CR, Halpern JH. Self-treatment of opioid withdrawal using kratom (Mitragynia speciosa korth). Addiction. 2008;103:1048-1050.
  8. Vicknasingam B, Narayanan S, Beng GT, Mansor SM. The informal use of ketum (Mitragyna speciosa) for opioid withdrawal in the northern states of peninsular Malaysia and implications for drug substitution therapy. Int J Drug Policy. 2010. 21: 283-288.
  9. US Drug Enforcement Administration. Federal Register. Withdrawal of notice of intent to temporarily place mitragynine and 7-hydroxymitragynine into schedule I. https://www.federalregister.gov/d/2016-24659. Published October 13, 2016. Accessed December 9, 2016.