Kratom’s potential and pitfalls

On the Shelf

Mickie Cathers

Millions of Americans use kratom to treat chronic pain, fatigue, depression, or anxiety, despite limited clinical evidence supporting its use. Anecdotal benefits of mood enhancement, pain relief, and increased energy are overshadowed by growing concerns about addiction and dependence. As kratom’s popularity remains high, pharmacists are increasingly at the forefront of navigating its risks and potential benefits.

Background

Kratom is a tropical tree in the coffee family found in South Asian countries, including Thailand and Malaysia. There are two compounds in kratom leaves, mitragynine and 7-hydroxymitragynine (7-OH), which interact with opioid receptors in the brain.

Extracts from kratom’s leaves create a stimulant or sedative effect similar to opioids. At low doses, kratom acts as a stimulant, potentially enhancing alertness and sociability. Higher doses of 10 to 25 grams produce sedative effects, offering calmness and euphoria that could last up to 6 hours.

Kratom’s main alkaloid, mitragynine, and its psychoactive metabolite, 7-OH, act on μ- and k-opioid receptors. These compounds also influence adrenergic and serotonergic systems, contributing to their antidepressant effects.

7-OH demonstrates greater μ-opioid receptor potency than other opioids such as morphine, codeine, and heroin. While not classified as an opioid, kratom’s ability to bind to opioid receptors in the brain presents both therapeutic potential and risks.

Is there a benefit?

Preclinical evidence suggests a range of potential therapeutic applications for kratom’s use as a painkiller.

“The use of kratom can have benefits, especially for those with chronic pain or who do not wish to take opioids,” said Oliver Grundmann, PhD, assistant dean for lifelong learning at the University of Florida College of Pharmacy. “However, what product is being taken is important since it has different potential for drug interactions and adverse effects, including dependence.”

A narrative review published in May 2022 in Substance Abuse by Striley and colleagues supports kratom’s potential value as an analgesic. Studies in nonclinical samples of long-term users indicate kratom’s therapeutic benefit in managing SUD symptoms such as cravings and withdrawal for alcohol, opioids, and other illicit drugs.

Adverse effects can include constipation, loss of appetite, severe weight loss, insomnia, and elevated BP along with other risks to cardiovascular health. Adverse effects can also be severe and include liver toxicity, seizures, and SUD. Kratom’s interaction with other substances, such as alcohol, may lead to life-threatening complications. Newborns exposed to kratom prior to birth may show withdrawal symptoms such as jitteriness and irritability.

“Kratom is being used by an estimated 15 to 25 million U.S. adults,” said Grundmann. “It’s important for pharmacists to inquire about the use of kratom, the specific kratom product, the amount and frequency of use and how this may impact other drugs that are taken.”

Reports of kratom-related intoxications, often due to the adulteration and contamination of products sold online or outside clinical settings, have raised concern. Though legal in the United States, kratom is illegal in various countries, including Australia and Denmark. FDA has taken steps to limit access and issue warnings, highlighting ongoing health concerns regarding kratom use.

 “There are several states now that have laws in place related to labeling, manufacturing, and quality control of kratom products and a recent announcement by the FDA seeks to ban 7-hydroxymitragynine products,” said Grundmann.

Dosage and availability

Kratom is available at gas stations, vape shops, and online in various forms, such as drinks, powders, pastes, capsules, tablets, or dried leaves for tea. Extracts are significantly more potent than powders, posing higher risks.

A 2017 study by Grundmann published in Drug and Alcohol Dependence revealed insights into kratom usage. Based on a survey of 8,049 people who use kratom, most users reported that a dose of up to 5 grams of powder taken up to three times per day was sufficient to feel effects. 

What to tell patients

Counsel patients to exercise caution with kratom use.  Increased dosage and frequency of use can escalate health risks, particularly in patients with a prior history of SUDs.

“Make patients aware that kratom may interfere with their OTC and prescription drugs and that it can be addictive/cause a dependence,” said Grundmann. “Monitoring what product is taken (native kratom leaf vs. extracts vs. isolates) is also helpful as concentrates and isolates are much more potent, causing drug interactions, dependence, and adverse effects. Anybody with a pre-existing medical condition should be careful.”

Understanding the balance between kratom’s advantages and its risks is crucial. Pharmacists can play a key role in monitoring patient use and guiding safe practices, staying informed on the latest developments to educate patients accordingly.

“Consumers and patients need to be aware about the safe use. This means that pharmacists as the most accessible health care professionals need to educate themselves on kratom. A number of educational institutions offer CPE for pharmacists to understand kratom and counsel patients on its use,” said Grundmann. ■

FDA targets 7-OH regulation

FDA is taking steps to regulate 7-hydroxymitragynine (7-OH) products under the Controlled Substances Act. 7-OH is a concentrated, potent derivative of the kratom plant that binds to opioid receptors and poses a risk for misuse. FDA’s aim to rein in synthetic products with high, dangerous concentrations follows the widespread availability, appeals to younger consumers, and public health incidents reported from poison control centers and AERS showing an increase in serious health issues including opioid-like addiction, overdose, and withdrawal symptoms.

“7-OH is an opioid that can be more potent than morphine,” said Marty Makary, MD, FDA commissioner, in an FDA news release. He emphasized the need for regulation and public education to avert another wave of the opioid epidemic.

Products such as gummies, drink mixes, and tablets containing 7-OH are easily accessible in various retail and online outlets. Without regulation, 7-OH could contribute to the ongoing opioid crisis. DEA is reviewing FDA’s recommendation on 7-OH scheduling, which follows FDA’s previous actions like issuing warning letters and releasing public educational materials. ■