One of the two major psychoactive constituents in kratom has high abuse potential and may also increase the intake of other opiates, new research shows.

The finding contradicts claims by kratom makers that the substance has no abuse potential and supports the US Food and Drug Administration's (FDA's) view that kratom is an opioid.

Derived from the plant Mitragyna speciosa, kratom is receiving increased attention as an alternative to traditional opiates and as a replacement therapy for opiate dependence. Mitragynine (MG) and 7-hydroxymitragynine (7-HMG) are the two major psychoactive constituents of kratom. Although MG and 7-HMG share behavioral and analgesic effects with morphine, their reinforcing effects have not been fully established.

Results of a series of experiments with rats show that MG does not have abuse or addiction potential and reduces morphine intake, "desired characteristics of candidate pharmacotherapies for opiate addiction and withdrawal," Scott Hemby, PhD, Department of Basic Pharmacological Sciences, High Point University, High Point, North Carolina, and colleagues report.

In contrast, 7-HMG should be considered a kratom constituent with "high abuse potential that may also increase the intake of other opiates," the investigators note.

The study was published online June 27 in Addiction Biology.

"Intriguing" Data

"The study tells us that the most abundant alkaloid in kratom, MG, does not have abuse liability and actually decreases subsequent opiate intake. The 7-HMG data are intriguing because it does seem to have abuse liability," Hemby told Medscape Medical News.

However, he said, "it's important to remember that 7-HMG is about 2% of the alkaloid compound of the plant, whereas MG is about 60%. That's about a 30-fold difference between those two alkaloids. That suggests to me that it probably wouldn't be reinforcing if kratom were taken as a whole plant with all the alkaloids and everything else in it."

One reason this is important to study, he said, is that there is evidence that levels of 7-HMG are elevated in certain strains of kratom or certain products that are being sold. This could be the result of deliberate adulteration of the product or the way the plant is harvested.

"For instance, if you leave it out in the sun to dry after it's harvested, a fair amount of the MG will be converted into 7-HMG. So it could be the way the plant is harvested and not an intentional adulteration," said Hemby.

There is no doubt that kratom is an opioid. What the FDA said was perfectly correct. Dr Scott Hemby

It's also concerning, he said, that people are starting to recognize that higher levels of 7-HMG seem to be associated with pleasure or euphoria. "No one has sold 7-HMG on its own, but it's possible that that could happen, and so it's important to know that there is a possibility of abuse of that particular compound," said Hemby.

He emphasized that the current experiments did not assess kratom itself, only the two psychoactive compounds of the plant. "My guess is, based on the ratio of MG to 7-HMG, it would not have abuse liability, but we are undertaking studies to look at that," Hemby noted.

The FDA is cracking down on kratom. There are no FDA-approved uses for kratom, and the agency has advised against using kratom or its psychoactive compounds MG and 7-HMG in any form and from any manufacturer.

Kratom has been linked to more than 40 deaths. As previously reported by Medscape Medical News, a recent analysis of kratom by FDA scientists found that its compounds act like prescription-strength opioids. The findings led the FDA to label kratom an opioid.

"There is no doubt that kratom is an opioid. What the FDA said was perfectly correct," Hemby told Medscape Medical News.

The study was supported by funding from the Fred Wilson School of Pharmacy, High Point University, and by funding from the National Institutes of Health. The authors have no relevant disclosures.

Addiction Biol. Published online June 27, 2018. Abstract

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