Kratom: Curse or Cure?

kratom
Kratom plant image from Prozialeck et al.

Recently, the US FDA issued a public health advisory warning the public not to use kratom, a substance purported to treat pain and opioid withdrawal. They give the following arguments: 1) There is no reliable evidence that kratom effectively treats opioid withdrawal; 2) use of kratom can lead to death; and 3) it can worsen the opioid overdose epidemic.

Let’s start with a brief description of kratom. It is a substance found on the leaves of the tropical tree Mitrogyna speciosa which mainly grows in Southeast Asia. There are two active ingredients responsible for its effects: mitrogynine and 7-hydroxymitragynine. It is either an opioid or an opioid-like compound, since it binds to the opioid receptors and exerts similar effects. People have used it for thousands of years, medically to treat pain and opioid withdrawal, and recreationally for its euphoric effects. It is not illegal in the US. Administration consists of chewing on the leaves or crushing it into powder and mixing with liquids.

Abuse, dependence, and ultimately addiction have been observed among users, especially in Southeast Asian countries. As a result, two Southeast Asian countries, Thailand and Malaysia, regulate it as a controlled substance. Kratom has both cocaine and morphine-like psychoactive effects (so it’s both a stimulant and an opioid). A number of adverse effects are associated with use of kratom, mainly sweating, dizziness, nausea, diarrhea, dysphoria, tremor, anorexia, weight loss, seizures, and psychosis. It’s contribution to risk of death is more murky. Reports to poison centers usually indicate deaths involving polysubstances. Also some kratom laced with other drugs has been sold on the market.

With regards to its therapeutic potential, discussion boards show a lot of anecdotal evidence that it helps people with opioid withdrawal symptoms and even pain. That’s logical, since it works like the opioids and provides similar effects. There may be a role for it in medication-assisted therapy. However, no company has submitted a new drug application to the FDA and ran a randomized controlled trial (a very expensive process). On a side note, one of the unfortunate things about drug development is that it is often not possible to do independent trials on new drugs. So the FDA is right on that front, there is no good reliable evidence of kratom’s effectiveness. It would be a very brave and potentially foolish medical professional to make a recommendation with the current state of evidence. But let’s not dismiss potentially useful medicine just because not enough is known yet. I’m just afraid that FDA Commissioner Scott Gottlieb’s comments will trigger a war of words that generates much smoke, but not enough light.

Clearly, like most other medicine, we need to weigh the risks and benefits. Just because something is legal doesn’t mean that it’s safe. Kratom has been associated with overdose deaths. Whether it’s the cause is unknown. And remember, the dose makes the poison. There is no uniform dose for kratom. Higher doses are probably associated with more deleterious effects. We just don’t have a good cutoff.

If we want to advance the conversation, we must seriously answer these questions: How addictive is it compared to other opioids? How dangerous is it compared to other opioids? And how helpful is it in opioid withdrawal compared to methadone, buprenorphine, and naltrexone? More research is needed.

For further reading: Prozialec WC, Jivan JK, Andurkar SV. Pharmacology of kratom: an emerging botanical agent with stimulant, analgesic and opioid-like effects. J Am Osteopath Assoc. 2012 Dec;112(12):792-9. Available at: https://www.ncbi.nlm.nih.gov/pubmed/23212430

Summary: Not enough is known yet about kratom to make a summary judgement.

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