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Kratom: A Primer for Clinicians
Kratom (Mitagyna speciose) is a tropical evergreen tree in the coffee family whose leaves have been used for centuries in South Asian countries as a stimulant and pain reliever. Recently, kratom has entered US and European markets and is now sold in various forms, both online and at local head shops.
Because kratom possesses opioid-like properties, both the federal Drug Enforcement Administration (DEA) and various state authorities have either banned or considered banning the substance. Currently, kratom is legal to purchase in all but six US states. In 2014, the Food and Drug Administration (FDA) banned import of kratom into the US, but kratom still manages to find its way into the country, and it is easy to obtain.
The following jurisdictions have banned the sale of kratom: Alabama, Arkansas, Indiana, Tennessee, Vermont, Wisconsin, and the local communities of Sarasota, Florida, and Jerseyville, Illinois. There is a handy state-by-state map at http://speciosa.org/home/kratom-legality-map, which will help you keep on top of the latest legislation around kratom.
The DEA attempted last year to ban kratom by making it a Schedule I controlled substance. The DEA reported in a 2016 press release that it is aware of 15 kratom-related deaths between 2014 and 2016. However, it then reversed its decision to ban the substance—some feel the about-face was because of pressure from a growing brigade of kratom users.
From a clinical standpoint, you will increasingly have to field questions from patients about kratom. Online forums are replete with glowing testimonials from users, who report various putative benefits of the herb. Many people with either current or former opioid use disorder believe that kratom has helped them end their addiction or manage their cravings more effectively. Other consumers maintain that kratom helps them manage various ailments, such as restless leg syndrome, anxiety disorders, insomnia, and chronic pain. Still others blatantly praise the substance as a great legal high—as good as prescription narcotics for those who are seeking chemically induced euphoria.
With little or no clinical research available to draw on, how do you respond to your patients’ questions? Here are some frequently asked questions, along with our best attempt at answers.
How is kratom used?
Kratom, which has a very bitter taste, comes in various forms, including a powder that is dissolved in tea or another clear liquid, tablets, liquids, gum/resin, concentrated extracts, and a drug patch. Currently, no national retailers that sell other supplements or herbal remedies are stocking kratom, so it remains almost an “underground” substance for those who wish to purchase it.
There are many strains that are advertised as having different psychotropic effects and potencies, with the strains typically given “druggy” sounding names based on geographic origin such as “Borneo Green” or “Red Vein Sumatra.” Since there are no regulations or quality controls in place, it’s impossible for those who purchase kratom to determine its components, strength, or purity.
Is kratom actually an opiate?
There is debate over this question. Opioids are technically substances that are derived from the opium poppy or are synthesized in laboratories based on the chemical compositions of opiates. Kratom leaves contain alkaloid ingredients, with mitragynine being the most prominent. Overall, more than 20 alkaloid ingredients were isolated in kratom as part of one study on mice to show that these compounds do have pharmacologic effects (Adkins JE et al, Curr Top Med Chem 2011;11(9):1165–1175).
Another study in rats showed that mitragynine, as well as the alkaloid 7-hydroxymitragynine, had an influence on opioid receptors, acting as partial agonists with mu-opioid receptors (Kruegel AC and Grundmann O, Neuropharmacology 2017. doi:/10.1016/j.neuropharm.2017.08.026).
Can kratom be helpful for opioid withdrawal or treatment?
There are no credible human studies or clinical trials for kratom. Almost all the “evidence” for its usefulness in opioid addiction treatment is anecdotal, mainly from online user-forum testimonials. There was one trial at the University of Mississippi conducted with mice, which showed kratom to be effective in an animal model of opioid withdrawal. In that study, researchers fed mice morphine, causing them to become habituated to the substance. They then randomized the mice to withdrawal using tapering doses of methadone vs using kratom tea. The withdrawal symptoms were less severe in the methadone group, casting doubt on claims of kratom’s efficacy in opioid withdrawal—though non-human trials are not clearly relevant (Adkins JE et al, Current Top Medicinal Chemistry 2011;11(9):1165–1175).
Is kratom addictive?
Kratom is almost certainly addictive for its users, though whether it is as dangerously addictive as opioids is not yet clear.
One study of 293 regular kratom users that was conducted in Malaysia found that more than half of regular users (who used for more than 6 months) developed severe kratom dependence, while 45% showed moderate kratom dependence (Darshan S, Drug Alcohol Depend 2014;139(6):132–137). Those who used more than three doses of kratom per day had higher odds of developing severe dependence, which included withdrawal symptoms and inability to control their kratom cravings.
Is there a kratom withdrawal syndrome?
Yes. Stopping kratom use after dependence can produce physical withdrawal symptoms that are similar to opioid withdrawal, such as muscle spasms, insomnia, watery eyes, runny nose, nausea, vomiting, and decreased appetite. Psychological withdrawal symptoms, including restlessness, tension, anger, and depression, have also been reported (Preely VR. Neuropathology of Drug Addictions and Substance Misuse, Volume 3. Cambridge, MA: Academic Press; 2016).
Does kratom use cause dangerous side effects?
The Centers for Disease Control & Prevention (CDC) reports that kratom abuse can lead to agitation, irritability, tachycardia, nausea, drowsiness, and hypertension. On user forums, the most common reported side effects are nausea and vomiting, which appear most commonly in kratom-naïve users who are trying high doses for the first time.
Final treatment recommendations for patients
You should tell patients that the evidence so far indicates that kratom is very similar to opioids, can lead to a similar addiction syndrome, and can cause withdrawal problems that are very similar to opioid withdrawal. Whether it has any usefulness for helping patients withdraw from opioids is an unresolved question. Similarly, we still aren’t certain just how dangerous kratom is in terms of the risk for overdose and death. But anyone who orders the herb online or buys it at a head shop has no idea exactly what they are getting, so they are definitely playing with fire.
Addiction TreatmentBecause kratom possesses opioid-like properties, both the federal Drug Enforcement Administration (DEA) and various state authorities have either banned or considered banning the substance. Currently, kratom is legal to purchase in all but six US states. In 2014, the Food and Drug Administration (FDA) banned import of kratom into the US, but kratom still manages to find its way into the country, and it is easy to obtain.
The following jurisdictions have banned the sale of kratom: Alabama, Arkansas, Indiana, Tennessee, Vermont, Wisconsin, and the local communities of Sarasota, Florida, and Jerseyville, Illinois. There is a handy state-by-state map at http://speciosa.org/home/kratom-legality-map, which will help you keep on top of the latest legislation around kratom.
The DEA attempted last year to ban kratom by making it a Schedule I controlled substance. The DEA reported in a 2016 press release that it is aware of 15 kratom-related deaths between 2014 and 2016. However, it then reversed its decision to ban the substance—some feel the about-face was because of pressure from a growing brigade of kratom users.
From a clinical standpoint, you will increasingly have to field questions from patients about kratom. Online forums are replete with glowing testimonials from users, who report various putative benefits of the herb. Many people with either current or former opioid use disorder believe that kratom has helped them end their addiction or manage their cravings more effectively. Other consumers maintain that kratom helps them manage various ailments, such as restless leg syndrome, anxiety disorders, insomnia, and chronic pain. Still others blatantly praise the substance as a great legal high—as good as prescription narcotics for those who are seeking chemically induced euphoria.
With little or no clinical research available to draw on, how do you respond to your patients’ questions? Here are some frequently asked questions, along with our best attempt at answers.
How is kratom used?
Kratom, which has a very bitter taste, comes in various forms, including a powder that is dissolved in tea or another clear liquid, tablets, liquids, gum/resin, concentrated extracts, and a drug patch. Currently, no national retailers that sell other supplements or herbal remedies are stocking kratom, so it remains almost an “underground” substance for those who wish to purchase it.
There are many strains that are advertised as having different psychotropic effects and potencies, with the strains typically given “druggy” sounding names based on geographic origin such as “Borneo Green” or “Red Vein Sumatra.” Since there are no regulations or quality controls in place, it’s impossible for those who purchase kratom to determine its components, strength, or purity.
Is kratom actually an opiate?
There is debate over this question. Opioids are technically substances that are derived from the opium poppy or are synthesized in laboratories based on the chemical compositions of opiates. Kratom leaves contain alkaloid ingredients, with mitragynine being the most prominent. Overall, more than 20 alkaloid ingredients were isolated in kratom as part of one study on mice to show that these compounds do have pharmacologic effects (Adkins JE et al, Curr Top Med Chem 2011;11(9):1165–1175).
Another study in rats showed that mitragynine, as well as the alkaloid 7-hydroxymitragynine, had an influence on opioid receptors, acting as partial agonists with mu-opioid receptors (Kruegel AC and Grundmann O, Neuropharmacology 2017. doi:/10.1016/j.neuropharm.2017.08.026).
Can kratom be helpful for opioid withdrawal or treatment?
There are no credible human studies or clinical trials for kratom. Almost all the “evidence” for its usefulness in opioid addiction treatment is anecdotal, mainly from online user-forum testimonials. There was one trial at the University of Mississippi conducted with mice, which showed kratom to be effective in an animal model of opioid withdrawal. In that study, researchers fed mice morphine, causing them to become habituated to the substance. They then randomized the mice to withdrawal using tapering doses of methadone vs using kratom tea. The withdrawal symptoms were less severe in the methadone group, casting doubt on claims of kratom’s efficacy in opioid withdrawal—though non-human trials are not clearly relevant (Adkins JE et al, Current Top Medicinal Chemistry 2011;11(9):1165–1175).
Is kratom addictive?
Kratom is almost certainly addictive for its users, though whether it is as dangerously addictive as opioids is not yet clear.
One study of 293 regular kratom users that was conducted in Malaysia found that more than half of regular users (who used for more than 6 months) developed severe kratom dependence, while 45% showed moderate kratom dependence (Darshan S, Drug Alcohol Depend 2014;139(6):132–137). Those who used more than three doses of kratom per day had higher odds of developing severe dependence, which included withdrawal symptoms and inability to control their kratom cravings.
Is there a kratom withdrawal syndrome?
Yes. Stopping kratom use after dependence can produce physical withdrawal symptoms that are similar to opioid withdrawal, such as muscle spasms, insomnia, watery eyes, runny nose, nausea, vomiting, and decreased appetite. Psychological withdrawal symptoms, including restlessness, tension, anger, and depression, have also been reported (Preely VR. Neuropathology of Drug Addictions and Substance Misuse, Volume 3. Cambridge, MA: Academic Press; 2016).
Does kratom use cause dangerous side effects?
The Centers for Disease Control & Prevention (CDC) reports that kratom abuse can lead to agitation, irritability, tachycardia, nausea, drowsiness, and hypertension. On user forums, the most common reported side effects are nausea and vomiting, which appear most commonly in kratom-naïve users who are trying high doses for the first time.
Final treatment recommendations for patients
You should tell patients that the evidence so far indicates that kratom is very similar to opioids, can lead to a similar addiction syndrome, and can cause withdrawal problems that are very similar to opioid withdrawal. Whether it has any usefulness for helping patients withdraw from opioids is an unresolved question. Similarly, we still aren’t certain just how dangerous kratom is in terms of the risk for overdose and death. But anyone who orders the herb online or buys it at a head shop has no idea exactly what they are getting, so they are definitely playing with fire.
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