Kratom: The New Opioid?

In 2016, the U.S. Drug Enforcement Administration (DEA) sought to make kratom a Schedule I drug, arguing that it offered no medical benefit and had a high potential for abuse. 

However, due to numerous complaints from members of the public challenging the action, the DEA reversed its decision and kratom remains legal in most U.S. states today. Kratom users state that the plant is an effective treatment for opioid withdrawal, chronic pain, mood disorders, and fatigue. 

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Kratom Physiology

Mitragyna speciosa Korth, more commonly known as kratom, is an evergreen tree native to Southeast Asia which is grown primarily in Indonesia, Malaysia, and Thailand. The trees can grow to 50 feet high and 15 feet wide. Kratom refers to the tree as well as the extracts and preparations made from the leaves of the plant. Historically, kratom leaves, which contain psychoactive substances, have been consumed for medical and recreational use as a mild stimulant, or as a sedative at stronger doses. The leaves are chewed or made into tea to combat fatigue, increase work productivity, and alleviate pain.1 Kratom is also known as ketum, kakuam, thang, thom, maeng da and biak. 

The main active components in kratom are mitragynine and 7-hydroxymitragynine. Products made from kratom leaves generally contain about 2% mitragynine and 0% to 0.02% 7-hydroxymitragynine. The average weight of a fresh leaf is 1.7g and a dried kratom leaf is 0.43g, with 20 leaves containing approximately 17mg of mitragynine. Once the leaves are dried and ground into a powder, they are generally compressed as 5kg bricks and shipped overseas. However, the manufacture and storage of kratom are currently unregulated, and the concentrations of 7-hydroxymitragynine can vary depending on the method of production.

Risks Associated with Kratom Use

Kratom is consumed to help with symptoms of depression and anxiety, as well as to increase energy and focus. It is also used in the suppression of inflammation and pain. The effects of kratom are generally felt within 5 to 10 minutes of consumption and can last for up to six hours. Users have also been found to take kratom to reduce symptoms of withdrawal from opioids. At low doses, kratom acts as a stimulant, but at higher doses it can have a sedative or narcotic effect. Negative effects of kratom use include nausea, tachycardia, hypertension, dizziness, constipation, confusion, tremor, and sleepiness. The use of kratom with other drugs can cause elevated creatinine and bilirubin levels, with some animal experiments reporting kidney and liver damage, as a result of elevated liver enzymes and cellular damage. Liver injury, typically cholestatic injury, has been found to occur within two to eight weeks of commencing regular use of kratom, with the consumer experiencing symptoms of fatigue, nausea, and dark urine followed by jaundice, with serum bilirubin levels rising above 20mg/dL.

Popularity, Availability, and Regulation

In recent years, kratom has grown in popularity in the U.S. and the U.K. as it is easy to purchase online and advertised as a ‘legal high’. It can also be purchased directly from gas stations and specialist stores (for example, marijuana and CBD oil dispensaries) in the U.S. There is little or no regulation of these products, hence the user cannot be assured of the purity of the contents. Kratom is usually sold as a supplement and therefore does not have to go through formal testing or clinical trials. As a result, the risk of overdose is relatively high due to the lack of product testing as well as insufficient guidance for use on product packaging.

Method of Delivery

Kratom can be consumed in different forms, such as capsules, tablets, gum, tinctures, extracts, and drinks. The fresh or dried leaves are often boiled and made into tea. Kratom leaf tends to be very bitter, so honey or sugar is usually added to make it more palatable. It can also be smoked or vaped, but this is a less common method. In the U.S., kratom is usually consumed in liquid form or by mixing the powder with food, although kratom capsules are growing in popularity.

Problems arise when the product is mixed with caffeinated drinks and cough syrup containing codeine, dextromethorphan, and diphenhydramine. The mixture is boiled to create a syrup known as “4 x 100,” to which ice cubes, a benzodiazepine, an antidepressant, or an analgesic is added to make a kratom cocktail.

The Debate Goes On

In the U.S., there has been much debate in recent years about whether the use of kratom is beneficial or harmful. It is currently not a listed substance under the Controlled Substances Act, but the DEA does not recognize any legitimate use of the substance and it remains a ‘drug of concern.’ The DEA sought to make kratom a Schedule I drug in August 2016, but due to public backlash, kratom is still legal in all U.S. states except for Arkansas, Alabama, Indiana, Rhode Island, Wisconsin, and Vermont as well as the District of Columbia, with some U.S. cities banning its use.4 The DEA based its decision to classify kratom as a Schedule I drug based on reports of adverse effects and claims that kratom causes psychotic symptoms and leads to addiction. As a Schedule I drug, it would be extremely difficult for any further research to be carried out on the safety or any clinical benefits of kratom. At present, kratom cannot be legally advertised in the U.S. as a treatment for any medical condition.

Kratom Chemisty and Effects

Mitragynine has numerous effects on multiple receptors, leading to opioid-like effects on the consumer. The compound 7-hydroxymitragynine is about 13 times stronger than morphine and 46 times more potent than mitragynine. It crosses the blood-brain barrier at a much faster rate than mitragynine. Other compounds found in kratom such as speciociliatine, paynantheine, and speciogynine may contribute to the psychoactive effects of the drug. Following scientific analysis by the FDA on 22 of the 25 compounds identified in kratom, the commission stated that kratom compounds could theoretically bind to the mu opioid receptors, affecting the body just like opioids. Mu opioid receptors facilitate positive reinforcement following direct activation (from morphine) or indirect activation (alcohol, cannabinoids, nicotine).

At doses of 1 to 5 g of raw crushed leaves, users experience mild effects such as increased energy and euphoria or adverse effects such as increased anxiety and irritability. At moderate to high doses of 5 to 15g, the sedative effects are greater than the stimulant effects, and users experience symptoms such as increased euphoria, relaxation, and analgesia. In chronic users, additional effects include depression, weight loss, and psychosis. When amounts greater than 15g of raw crushed leaves are consumed, symptoms of acute kratom overdose such as respiratory depression and hypotension can occur.