What to know about the kratom-related drugs found near the late Ole Miss students

By Kristen Rogers, CNN

(CNN) — The drug products found near two University of Mississippi students who died on September 21 contained three kratom-related compounds, according to court documents reviewed by CNN and law enforcement.

The substances aren’t natural kratom — as was suspected due to earlier law enforcement reports — which is an herb from the leaves of the tropical tree Mitragyna speciosa native to Southeast Asia. Having both stimulant and sedative effects, the herb carries a risk for addiction due to how it interacts with the brain, researchers told CNN in a previous story. What’s in the packaged tablets that law enforcement discovered when investigating those deaths are mitragynine pseudoindoxyl, MGM-15 and 7-OH, which are semisynthetic, concentrated and potent derivatives of certain components of kratom.

Two of those substances, MGM-15 and mitragynine pseudoindoxyl, were banned in August by the US Department of Justice, which includes the US Drug Enforcement Administration, as the agencies classified them as Schedule I controlled substances for two years on an emergency basis. That’s the category the government uses for illicit substances with no currently accepted medical use and a high potential for abuse.” The Schedule I list also includes heroin, LSD and cannabis.

The compounds have not been confirmed to have caused or contributed to the deaths, as the autopsies and toxicology reports have not yet been released. But reports of poisonings, mild to severe addictions, or deaths from kratom or semisynthetic derivatives, have been growing — though data documentation limits mean it’s not always clear how many of those reports are due to natural kratom versus semisynthetic derivatives.

Scientists at the National Institute on Drug Abuse are “very concerned” about how easily accessible certain kratom products are, as well as other substances that also have strong opioid effects, NIDA Director Dr. Nora Volkow said in a Tuesday briefing for journalists.

In states that haven’t banned the substance, it’s sold at gas stations, smoke shops and convenience, grocery and health food stores in various forms, including powders, loose-leaf teas, capsules, tablets and concentrates.

What makes kratom psychoactive are its alkaloids, which naturally occur in many flowering plants, contain nitrogen and have pronounced physiological effects on humans. Mitragynine is one of the most abundant alkaloids in kratom, and when it’s metabolized in the body or dried in the manufacturing process, it turns into 7-hydroxymitragynine, commonly called 7-OH. That resulting compound is typically up to 1% to 2% of the total content of natural leaf kratom products and some kratom extracts. Then 7-OH metabolizes into mitragynine pseudoindoxyl.

These compounds, especially 7-OH, bind to the brain’s mu opioid receptors, which help regulate pain, breathing, gastrointestinal activity and more. That binding — along with effects similar to opioid drugs such as heroin, oxycodone or fentanyl — makes kratom an opioid-like drug, though its biological effects are weaker than those of typical opioids.

While natural kratom has been used in the United States since 1990 and increasingly over the past decade, the semisynthetic products have been available in the United States consumer market — though not regulated or verified — for about three years, said Dr. Kim Aldy, director of the ToxIC (Toxicology Investigators Consortium) program at the American College of Medical Toxicology. They are more potent since they’re isolated, which can amplify the opioid-like abilities and effects that can lead to dependency and overdose via slowed breathing and stimulant toxicity, Aldy added.

Some patients are experiencing “withdrawal syndromes that are similar to what we see with heroin or fentanyl,” Aldy said.

Semisynthetic 7-OH has not been federally restricted as the government had extended the period for public comment on a proposed threshold for 7-OH scheduling under the Controlled Substances Act through September 10. Some states have already banned or otherwise restricted the compound, including Florida, Ohio, Kentucky and California.

Kratom isn’t federally regulated and thus isn’t “lawfully marketed in the U.S. as a drug product, a dietary supplement, or a food additive in conventional food,” according to the US Food and Drug Administration. Natural kratom is regulated in some way in at least 30 states and has been banned in nine of those states, including Alabama, Connecticut, Louisiana and Vermont.

Signs of poisoning by kratom or its derivatives can include high blood pressure, vomiting, heart attack, tremors, seizures, delusions, hallucinations, liver damage and an increased heart rate, known as tachycardia. That can cause heart palpitations, dizziness or lightheadedness, shortness of breath, fainting and chest pain.

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