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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.

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.

There are a number of different strains of kratom, with different strains having different effects. Maeng Da is originally from Thailand, but there are also Indonesian and Malaysian strains, which can be green, red, or white in color. It is generally regarded as strong and long-lasting compared to Indo kratom from Indonesia, which is weaker in strength. The leaves of plants from Thailand contain up to 66% mitragynine, one of the active components in kratom, and as little as 12% in kratom leaves from Malaysia.² Indo strains are known to help with relaxation, pain relief, and anxiety. Bali kratom, also from Indonesia, is red in color and regarded as the most opioid-like of kratom strains. Green Malay, from Malaysia, is dark green in color and provides a sedative effect on the user in high doses. Other forms include red, green, and white Thai kratom and Borneo kratom.³

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.⁴ 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.⁵

• See also:  Underwriting Marijuana Risk: A New Era

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.⁶ 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.^4,5 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.²

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.’ Price per gram ranges from 2 to 10 euros depending on the country of purchase and the type of kratom. It can also be purchased directly from gas stations and specialist stores (for example, marijuana and CBD oil dispensaries) in the U.S.7 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.⁸ However, there have been no reported deaths to date in Southeast Asia from the traditional use of pure kratom leaf, likely because users tend to buy fresh ketum juice that has not been contaminated with other compounds.^1,2,9

So far, there have been 44 reported deaths in the U.S. as a result of kratom use; however, as nearly all the deaths involved poly-drug use, a direct causative link cannot definitively be made. The U.S. Food and Drug Administration (FDA) has reported that, in many cases, kratom was contaminated with other opioids such as hydrocodone.⁵ One such product, called Krypton, was found to contain O-desmethyltramadol, an active metabolite of the synthetic opiate tramadol, which has been implicated in nine deaths. Krypton can be bought over the internet and is consumed in many countries around the world. It is frequently sold in large quantities of up to 50 grams, even though the recommended dose is as little as ­<5g. Hence, there is a significant risk of unintentional overdose.

While kratom is not yet illegal in the U.S., the FDA is actively monitoring the sale of kratom products and has issued a number of warnings to companies for making false claims about its ability to treat opioid addiction, depression, anxiety, and even cancer. Furthermore, the FDA has issued several public warnings regarding the consumption of kratom, including warnings about product contamination from salmonella and even heavy metals. In April 2018, packages of Maeng Da Red were recalled across the U.S. after the presence of salmonella was detected in the kratom powder product.¹⁰ Between 2017 and 2018, a total of 199 people from 41 states were infected with salmonella from contaminated kratom products. Of the 81 products tested, 52% were contaminated with several types of salmonella.11 In April 2019, the FDA confirmed that test results on 30 kratom products showed the presence of heavy metals such as lead and nickel at levels considered not safe for human consumption.¹²

• See also: Marijuana - Not Just Blowing Smoke (Updated)

Prevalence of Use

The World Drug Report 2019 notes the growing importance of kratom in 2016 and 2017, with seizures of kratom reported by six countries, mainly in Southeast Asia. There has been a clear upward trend over the last decade in seizures of new plant-based psychoactive substances that replicate those under international control. ¹³

The American Kratom Association suggests that in excess of 5 million people in America are using kratom.⁷ According to the International Narcotics Control Board, U.S. authorities encountered 55 tons of kratom, equating to 50 million doses, between February 2014 and July 2016.⁸ There have been increasing numbers of calls to the American Association of Poison Control Centers (AAPCC) regarding kratom use. Between January 2010 and December 2015, poison control centers received 660 calls about exposure to kratom, with the number of calls increasing tenfold from 26 in 2010 to 263 in 2015. Two-thirds of these calls related solely to kratom. Three-quarters of users were male, with an average age of 28, and 7% of all kratom-related adverse events were classified as major and life-threatening.⁵ From 2016 to 2018, there was a sixfold increase in calls regarding kratom use, with more than 635 calls made to the AAPCC’s national hotline in 2018.^7,14

Prevalence of lifetime kratom use (ages 12 to 65) in Thailand in 2007 was 2.3%, significantly higher than for marijuana use, with up to 9.4% of adolescents between the ages of 13 and 16 reporting kratom use in the last 30 days. The 2008 national survey found that up to 70% of the male Thai population used kratom on a daily basis in parts of southern Thailand.4 While information on the prevalence of kratom use in other countries outside of Southeast Asia is not available, evidence to date indicates that more and more people in the U.S. and in Europe are using kratom for the treatment of pain and symptoms of opioid withdrawal.⁹

Surveys by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) in 2008 showed that kratom was one of the most widely promoted ‘legal highs’ in 44% of the 27 online shops investigated. By July 2011, kratom was the most widely offered product, with 128 out of 631 online retailers sending it to at least one EU member state, most commonly to the U.K.²

• See also: Lifestyle-Related Behaviors and Mortality: A Comparison of Physical Inactivity and Smoking

Consumption

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.4,5 These homemade cocktails are becoming increasingly popular among young Muslim people as they can mimic the effects of alcoholic drinks.²

A recently reported case of kratom overdose in the U.S. involved an unresponsive male who was admitted to the hospital with significant tachycardia and hypotension after consuming more than 500g of kratom the previous day.15 There is also a high likelihood that the product may be contaminated with other synthetic drugs or that the concentrations of O-desmethyltramadol in the preparation may be higher than recommended (O-desmethyltramadol is twice as potent as its parent drug tramadol and has been linked to a number of cases of drug poisoning in Sweden).¹⁶

Research to date would appear to support the fact that in pure herbal form of doses of less than 5g, kratom is far less hazardous than classic opioids. In Malaysia, kratom is commonly consumed as a juice, with 42% of consumers drinking two to three glasses a day and 44% consuming more than three glasses a day. One glass measures approximately 350mL of kratom juice, but it is often mixed with caffeinated soda, dextromethorphan, or nimetazepam (a benzodiazepine). The kratom cocktail (4 x 100) is becoming an increasingly popular method of kratom consumption, which is far riskier than ingesting pure leaf kratom.⁵

• For more on this topic, see also:  Chronic Pain and Best Practices in Claims Management
  

Legislation

Kratom is illegal in Germany, Ireland, Italy, Latvia, Lithuania, Poland, Romania, Russia, Sweden, and Turkey but can be bought in Denmark, Finland, and Norway with a valid medical prescription. The legal status of kratom in the U.K. is complicated as it is defined as a psychoactive substance, although the plant M. speciosa is not a Schedule I controlled substance. In the U.K., it is currently the second most commonly used drug, behind Salvia divinorum (a plant species with psychoactive properties) to obtain a legal high.¹ It was listed as a controlled substance in Australia in 2003, and many Southeast Asian countries also state that kratom is an illegal substance. It is currently illegal in Malaysia under the Poisons Act 1952, but the use, possession, and production of kratom have been legal in Thailand since 2018 if used for medicinal purposes. It is illegal in South Korea and Japan, but the legal status of kratom in China is quite unclear. It remains legal in India and South Africa and most parts of South America, with the exception of Brazil. Health Canada has not authorized the sale of any product in Canada containing kratom. It is legal to sell capsules and powder containing kratom, as long as the intention is not for ingestion.^{17, 18}

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.^9,19,20

To date, there are no FDA-approved uses for kratom; in fact, the FDA advises against using kratom in any form and clearly states that there is no reliable evidence to show that it is a safe and reliable treatment for opioid use disorder.¹⁹ Despite the conclusion by the DEA, with support from the FDA and the National Institute on Drug Abuse (NIDA) that kratom did not appear to be a public health threat, the FDA issued an import ban in June 2019 on kratom products or products containing Mitragyna speciosa. It applies to products marketed as dietary supplements and bulk dietary ingredients from numerous companies in Canada, Indonesia, Malaysia, the Philippines, and the U.S. based on inadequate information providing reasonable assurance that the ingredients do not present a risk of illness or injury.^{21, 22}

• See also: Prescription Opioid Use

Dependence

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).^{23, 24}

However, the study never tested to find out if the compounds actually produced opioid agonist activity in living cells or organisms. While no human trials have yet been conducted, well-controlled surveys have shown that kratom users have been successful in managing their pain and opioid use disorders. Although recent studies indicate that kratom acts in a similar way to opioids on receptors, its molecular structure is very different from well-known opioids such as morphine, and mitragynine is much less likely to cause respiratory depression than opioids.⁹

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.¹

Kratom dependence is widespread, with the number of people in Thailand admitted for treatment increasing from 1,000 in 2007 to 3,000 in 2011, accounting for 2% of all drug treatment admissions in Thailand.⁴ A study by Kittirattanapaiboon et al. looked at drug use, including the use of kratom, with concurrent mental health issues and found a statistically significant higher suicide risk.1 Kratom abuse in southern Thailand is often associated with patients who suffer from mental illness. Studies have shown that consuming more than 20 leaves per day for three to five years is associated with hallucinations (31%) and symptoms of paranoia (17.2%).25 In Singh et al.’s 2014 study of kratom used in the treatment of opioid dependence, the authors found that people who took kratom for more than six months reported withdrawal symptoms similar to opioid use, and that those who took kratom began craving it, requiring treatment similar to that required for opioid addiction.²⁶ Evidence, therefore, suggests that rather than help to treat opioid addiction, the use of kratom may actually lead to addiction.

Additional Findings from Other Studies and Surveys on the Risks of Kratom Use

There are no published human studies or clinical trials on kratom or mitragynine consumption, making it extremely difficult to understand the benefits or harms of consumption. It is impossible to understand any link between the drug and the true consequences of consumption. At present, there is no standard method to test for kratom on drug screening.⁵ Mitragynine can be detected in human urine from 1.00-500.00 ng/mL using mitraphylline as an internal standard.¹⁸

There are very few studies looking into the use and potential abuse of kratom. One study in the U.S. found that most users are between 31 and 50 years of age, cohabiting, employed with an annual household income of at least US$35,000, and had used kratom for between one and five years. Users primarily consumed kratom to relieve symptoms of acute or chronic pain and to help with mental health problems. Doses of up to 5g of kratom showed lower odds for detrimental effects than amounts of 8g or more.⁴

The Centers for Disease Control and Prevention (CDC) recently analyzed data from the State Unintentional Drug Overdose Reporting System (SUDORS) on overdose deaths that occurred between July 2016 and December 2017, of which 0.56% (152) decedents tested positive for kratom on post-mortem. Fentanyl and fentanyl analogs were the most commonly identified co-occurring substances (65.1%), followed by heroin (32.9%), benzodiazepines (22.4%), prescription opioids (19.7%), and cocaine (18.4%). Kratom was therefore identified primarily in deaths that occurred as a result of overdoses related to substance misuse and was detected in combination with other substances.²⁷

The American Kratom Association conducted a survey of nearly 3,000 users to examine the primary reason for use and found that 48% used it for pain relief; 22% for anxiety, PTSD, or depression; 10% for energy or focus; and 10% for reducing the symptoms of opioid withdrawal. Adverse reactions were noted in 13% of respondents, with symptoms reported as mostly mild and self-managed.²⁸

In 2016, a survey was conducted of 10,000 current kratom users in the U.S. Of the 8,049 completed responses, 56.59% had used kratom for between one and five years, with the most common methods of consumption being in powder form dissolved in a beverage, followed by pill form. It was primarily consumed to relieve the symptoms of pain (68%) and by those suffering from anxiety, depression, or PTSD (66.5%). One-fifth of users reported negative symptoms from kratom use; those who took 21 doses or less a week were less likely to experience symptoms of nausea, constipation, or vomiting than those who consumed higher doses. Doses of 5g taken three times per day were sufficient to meet the needs of the user in most cases.²⁹

A study of 70 regular kratom users examined their cognitive function using the Cambridge Neuropsychological Test Automated Battery (CANTAB). It found deficits in function with chronic kratom consumption (more than three glasses of kratom juice taken per day) in new learning and visual episodic memory. However, the study also noted that kratom use does not appear to impair social functioning and rarely causes health problems.⁴

A survey of 135 kratom users in Malaysia who were taking it to manage drug withdrawal symptoms showed that 90% of them consumed kratom to reduce addiction to other drugs. Of those surveyed, 77% had used cannabis and 53% had used heroin prior to turning to kratom.⁵

A separate study in Malaysia in 2014 found that users who consumed more than three glasses of kratom juice per day or used kratom more than three times per day were seven and five times, respectively, more likely to report severe dependence than those who consumed less than these amounts. Further analysis of this group found that while kratom was not as socially and financially destructive as other drugs such as heroin and opium, only 18% of the group went more than three months without using kratom before relapsing.⁵

The prevalence of psychotic symptoms in kratom users in Malaysia was studied in 150 regular users. Six of the 150 users (4%) presented with symptoms of psychosis, but the study did not find any significant association with regular kratom use.³⁰

A study of 163 Malaysian male opioid and kratom users on self-reported prevalence and severity of opioid and kratom side effects found that kratom initiation was associated with decreased prevalence of respiratory depression, constipation, physical pain, insomnia, depression, loss of appetite, craving, decreased sexual performance, weight loss, and fatigue.³¹

Another study of regular kratom users in Malaysia looked at the degree of pain and sleep problems following the cessation of kratom use, and found that 84% experienced moderate pain and 45% experienced sleep problems. Those who drank four or more glasses of kratom tea/juice per day (76-115mg of mitragynine) were twice as likely (OR 2.0, CI: 1.04-3.93) to report pain and sleep problems during kratom cessation, compared to those who only consumed one to three glasses per day.³²

A 2014 review of kratom use by more than 500 traditional users in southern Thailand reported that at one-year follow-up, five users had died. Two heavy users had stomach masses of accumulated kratom fiber. The study concluded that most users were still healthy and had no serious health concerns, except for those who had swallowed its fiber.³³

Underwriting Considerations

Kratom products are usually consumed in an attempt to reduce pain, improve symptoms of anxiety and depression, increase energy, reduce fatigue, and reduce the symptoms of opioid withdrawal. It is frequently consumed in conjunction with other drugs and its availability for purchase in cannabis stores and smoke shops should alert the underwriter as to its potential use by marijuana, CBD, or supplement users, particularly those who live in the U.S. Although traditionally it has been used for centuries in parts of Southeast Asia, it is also becoming increasingly popular in Europe. Applicants who declare the use of ‘supplements’ in the management of the conditions listed above should be asked to confirm the type of supplement used and, where kratom has been disclosed, the amount and duration of use, and method of consumption. Additional disclosures including tremor, palpitations, hypertension, and/or abnormal liver function should be treated with caution. Regular use of kratom, particularly at high doses, can lead to increased tolerance and, in some cases, dependence.

Summary

Kratom is an emerging drug of abuse in the Western world. Currently, there is insufficient evidence to confirm or refute that kratom consumption is safe. Indications are that kratom products are highly likely to be contaminated with other substances that in themselves are not safe, and that product information on dosage amounts is, at best, sketchy. While it is apparent that low levels of this substance have a stimulus effect on the user and high levels have a sedative effect, long-term use in large doses can lead to withdrawal symptoms and side effects similar to that of opioids. Current research indicates that high doses consumed on a regular basis have harmful effects on the user, but clinical trials are required to better define its benefits, if any, as a therapeutic drug. Users who self-medicate with kratom should be aware of the risks associated with its consumption.