A new review contends that the herbal remedy kratom has some beneficial properties and suggests that a Drug Enforcement Administration (DEA) proposal to make it illegal could bring legitimate research to a standstill.

The leaves from the kratom tree (Mitragyna speciosa), which is found in Southeast Asia, have been used for hundreds of years to treat pain and reduce fatigue, but until recently, it was more or less “a well-kept secret in that part of the world,” review author Walter Prozialeck, PhD, chairman of the Department of Pharmacology at the Chicago College of Osteopathic Medicine, Midwestern University, in Illinois, told Medscape Medical News.

Use of the product has been increasing in the United States and Europe during the past decade, in part because of increased restrictions on opioid prescribing and dissemination of information via the Internet, said Dr Prozialeck.

“It’s real important that physicians know about this stuff,” especially given that patients may be using kratom, he said. Dr Prozialeck added that he believes the substance is not as harmful as opioids, but that many questions about safety and efficacy need to be resolved.

In August 2016, the DEA proposed making kratom a Schedule I drug. It would then join the list of restricted substances that includes heroin and LSD. However, the DEA has delayed that decision.

A public comment period on the drug closes on December 1, but Dr Prozialeck said that given the many questions about the substance, he believes the agency may further put off making a final scheduling decision.

In reviews conducted in 2012 and again this year, Dr Prozialeck and colleagues found that kratom likely has some legitimate and important uses.

“There’s no question kratom compounds have complex and potentially useful pharmacologic activities, and they produce chemically different actions from opioids,” Dr Prozialeck said in a statement

In the latest review, published in the December issue of the Journal of the American Osteopathic Association, Dr Prozialeck notes that kratom differs from opioids in that it does not produce intense euphoria and does not depress respiration.

Not the Same as Opioids

He cites several studies that offer proof that the mitragynines — the active substances in kratom — have different molecular actions than opioids.

Andras Váradi, PhD, PharmD, and colleagues at Memorial Sloan Kettering Cancer Center, New York City, showed in a cell culture study that although mitragynines bind to mu opioid receptors, they only partially activate the signaling pathway, and therefore it is likely they do not have the same characteristics, such as the development of dependence or euphoria, as opioids, said Dr Prozialeck.

They also correlated results in mice, and the results showed that mitragynine compounds were as good at relieving pain as opioids but were less likely to produce dependence, and withdrawal symptoms were milder, Dr Prozialeck said.

“These animal studies were really compelling,” he told Medscape Medical News.

Another study by Dr Váradi and colleagues at Columbia University in New York City similarly found that the kratom components might represent “a novel framework for the development of functionally biased opioid modulators, which may exhibit improved therapeutic profiles.”

Dr Prozialeck said his review of various websites found thousands of user reports that kratom’s effects were subjectively quite different from those of opioids.

“As a pharmacologist, I would certainly not classify kratom or the mitragynines as opioids,” he said.

Cautionary Note

Despite his optimism that kratom may hold potential, Dr Prozialeck is urging against use of the plant, in large part because the herbal product is unregulated. This makes it hard to evaluate safety and efficacy, as well as determine dosing and purity, he said.

Recent reports have shown that some commercially available products may contain substances other than kratom or may have high doses of some of the constituent elements.

In October 2016, researchers in the Boston area who bought kratom off the shelf reported that the products contained artificially elevated concentrations of 7-hydroxymitragynine, “the alkaloid responsible for M speciosa’s concerning mechanistic and side effect profile.”

In this case, it appears that “unscrupulous vendors” were “adulterating products to enhance their activity and make them more drugs of abuse,” said Dr Prozialeck.

In another study, researchers bought and tested 15 kratom products. They found that all contained mitragynine, a stimulant, but none had any 7-hydroxymitragynine, the compound responsible for kratom’s narcotic properties.

Dr Prozialeck said he understands that the DEA’s proposed ban was due to concern about increasing reports of toxicity. But given the lack of regulation of kratom products in the United States, “it’s not clear that kratom is the culprit,” said Dr Prozialeck.

“In a perfect world, there should be some way short of a total ban to regulate, or at least provide some quality control measures over the production and sale of kratom,” he said.

Dr Prozialeck reports no relevant financial relationships.

J Am Osteopath Assoc. 2016;116:802-809. Full text