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Kratom

Medically reviewed on Feb 21, 2018 by L. Anderson, PharmD.

Common or Street Names: Thang, Krypton, Kakuam, Thom, Ketum, Biak-Biak (common name in Thailand)

What is Kratom?

Kratom (Mitragyna speciosa) is a tropical evergreen tree from Southeast Asia and is native to Thailand, Malaysia, Indonesia and Papua New Guinea. Kratom, the original name used in Thailand, is a member of the Rubiaceae family. Other members of the Rubiaceae family include coffee and gardenia. The leaves of kratom are consumed either by chewing, or by drying and smoking, putting into capsules, tablets or extract, or by boiling into a tea. The effects are unique in that stimulation occurs at low doses and opioid-like depressant and euphoric effects occur at higher doses. Common uses include treatment of pain, to help prevent withdrawal from opiates (such as prescription narcotics or heroin), and for mild stimulation.

Traditionally, kratom leaves have been used by Thai and Malaysian natives and workers for centuries. The stimulant effect was used by workers in Southeast Asia to increase energy, stamina, and limit fatigue. However, some Southeast Asian countries now outlaw its use.

In the US, this herbal product has been used as an alternative agent for muscle pain relief, diarrhea, and as a treatment for opiate addiction and withdrawal. However, its safety and effectiveness for these conditions has not been clinically determined, and the FDA has raised serious concerns about toxicity and possible death with use of kratom.

As published on February 6, 2018, the FDA notes it has no scientific data that would support the use of kratom for medical purposes. In addition, the FDA states that kratom should not be used as an alternative to prescription opioids, even if using it for opioid withdrawal symptoms. As noted by the FDA, effective, FDA-approved prescription medications, including buprenorphine, methadone, and naltrexone, are available from a health care provider, to be used in conjunction with counseling, for opioid withdrawal. Also, they state there are also safer, non-opioid options for the treatment of pain.

On February 20, 2018 the US Centers for Disease Control and Prevention (CDC) reported it was investigating a multistate outbreak of 28 salmonella infections in 20 states linked to kratom use. They noted that 11 people had been hospitalized with salmonella illness linked to kratom, but no deaths were reported. Those who fell ill consumed kratom in pills, powder or tea, but no common distributors has been identified.

Learn More: Herbal Drug Kratom Contains Opioids, FDA Says

DEA Scheduling of Kratom

Kratom was on the DEA’s list of drugs and chemicals of concern for several years. On August 31, 2016, the DEA published a notice that it was planning to place kratom in Schedule I, the most restrictive classification of the Controlled Substances Act. Its two primary active ingredients, mitragynine and 7-hydroxymitragynine (7-HMG), would be temporarily placed onto Schedule I on September 30, according to a filing by the DEA. The DEA reasoning was "to avoid an imminent hazard to public safety. The DEA did not solicit public comments on this federal rule, as is normally done.

However, the scheduling of kratom did not occur on September 30th, 2016. Dozens of members of Congress, as well as researchers and kratom advocates have expressed an outcry over the scheduling of kratom and the lack of public commenting. The DEA withheld scheduling at that time and opened the docket for public comments.

Over 23,000 public comments were collected before the closing date of December 1, 2016, according to the American Kratom Association. The American Kratom Association is a lobbying and advocacy group in support of kratom use. The American Kratom Association reports that there are a "number of misconceptions, misunderstandings and lies floating around about Kratom."

As reported by the Washington Post in December 2016, Jack Henningfield, an addiction specialist from Johns Hopkins University and Vice President, Research, Health Policy, and Abuse Liability at Pinney Associates, was contracted by the American Kratom Association to research the kratom's effects. In Henningfield's 127 page report he suggested that kratom should be regulated as a natural supplement, such as St. Johns Wort or Valerian, under the FDA's Food, Drug and Cosmetic Act. The American Kratom Association then submitted this report to the DEA during the public comment period.

Next steps include review by the DEA of the public comments in the kratom docket, review of recommendations from the FDA on scheduling, and determination of additional analysis. Possible outcomes could include emergency scheduling and immediate placement of kratom into the most restrictive Schedule I; routine DEA scheduling in schedule 2 through 5 with more public commenting; or no scheduling at all. The timing for the determination of any of these events is unknown.

State laws have banned kratom use in several states including, Indiana, Tennessee, Wisconsin, Vermont, Arkansas, Alabama and the District of Columbia. These states classify kratom as a schedule I substance. Kratom is also noted as being banned in Sarasota County, Florida, San Diego County, California, and Denver, Colorado. The FDA's analysis from February 2018 included 44 reported deaths associated with the use of kratom. According to Governing.com, legislation was considered last year in at least six other states — Florida, Kentucky, New Hampshire, New Jersey, New York and North Carolina.

What is the Pharmacology of Kratom?

As reported in February 2018, the FDA has confirmed from analysis that kratom has opioid properties. More than 20 alkaloids in kratom have been identified in the laboratory, including those responsible for the majority of the pain-relieving action, the indole alkaloid mitragynine, structurally related to yohimbine. Mitragynine is classified as a kappa-opioid receptor agonist and is roughly 13 times more potent than morphine. Mitragynine is thought to be responsible for the opioid-like effects.

Kratom, due to its opioid-like action, has been used for treatment of pain and opioid withdrawal. Animal studies suggest that the primary mitragynine pharmacologic action occurs at the mu and delta-opioid receptors, as well as serotonergic and noradrenergic pathways in the spinal cord. Stimulation at post-synaptic alpha-2 adrenergic receptors, and receptor blocking at 5-hydroxytryptamine 2A may also occur. The 7-hydroxymitragynine may have a higher affinity for the opioid receptors. Partial agonist activity may be involved.

Additional animals studies show that these opioid-receptor effects are reversible with the opioid antagonist naloxone.

Time to peak concentration in animal studies is reported to be 1.26 hours, and elimination half-life is 3.85 hours. Effects are dose-dependent and occur rapidly, reportedly beginning within 10 minutes after consumption and lasting from one to five hours.

Kratom Effects and Actions

Most of the psychoactive effects of kratom have evolved from anecdotal and case reports. Kratom has an unusual action of producing both stimulant effects at lower doses and more CNS depressant side effects at higher doses. Stimulant effects manifest as increased alertness, boosted physical energy, talkativeness, and a more social behavior. At higher doses, the opioid and CNS depressant effects predominate, but effects can be variable and unpredictable.

Consumers who use kratom anecdotally report lessened anxiety and stress, lessened fatigue, pain relief, sharpened focus, relief of withdrawal symptoms, 

Beside pain, other anecdotal uses include as an anti-inflammatory, antipyretic (to lower fever), antitussive (cough suppressant), antihypertensive (to lower blood pressure), as a local anesthetic, to lower blood sugar, and as an antidiarrheal. It has also been promoted to enhance sexual function. None of the uses have been studied clinically or are proven to be safe or effective.

In addition, it has been reported that opioid-addicted individuals use kratom to help avoid narcotic-like withdrawal side effects when other opioids are not available. Kratom withdrawal side effects may include irritability, anxiety, craving, yawning, runny nose, stomach cramps, sweating and diarrhea; all similar to opioid withdrawal.

Deaths reported by the FDA have involved one person who had no historical or toxicologic evidence of opioid use, except for kratom. In addition, reports suggest kratom may be used in combination with other drugs that have action in the brain, including illicit drugs, prescription opioids, benzodiazepines and over-the-counter medications, like the anti-diarrheal medicine, loperamide (Imodium AD). Mixing kratom, other opioids, and other types of medication can be dangerous. Kratom has been shown to have opioid receptor activity, and mixing prescription opioids, or even over-the-counter medications such as loperamide, with kratom may lead to serious side effects.

Extent of Kratom Use

On the Internet, kratom is marketed in a variety of forms: raw leaf, powder, gum, dried in capsules, pressed into tablets, and as a concentrated extract. In the US and Europe, it appears its use is expanding, and recent reports note increasing use by the college-aged population.

The DEA states that drug abuse surveys have not monitored kratom use or abuse in the US, so its true demographic extent of use, abuse, addiction, or toxicity is not known. However, as reported by the DEA in 2016, there were 660 calls to U.S. poison centers related to kratom exposure from 2010 to 2015.

Kratom Side Effects and Health Hazards

Expected opioid-like side effects that may occur with kratom include:

  • Sedation
  • Nausea
  • Sweating
  • Dry mouth
  • Increased urination
  • Loss of appetite
  • Itching
  • Constipation
  • Dizziness
  • Confusion

Case reports describe the following adverse effects from kratom: addiction, withdrawal, hypothyroidism, and liver injury, aching of muscles and bones and jerky limb movements.

Kratom addiction and chronic use has led to cases of psychosis with hallucinations, delusion, and confusion. High-dose use may lead to fast heart rate (tachycardia) and low blood pressure (hypotension). Tremor, anorexia and weight loss are other possible side effects with long-term use.

Seizures have been reported when kratom was combined with modafinil in at least one case report. The DEA has also reported seizure adverse events with recreations kratom use.

A case series from Kronstad, et al. described a fatal drug interaction with kratom. A substance, dubbed “Krypton” - a mixture of mitragynine and a metabolite of tramadol - was found post-mortem in nine people in Sweden over a one year period. Tramadol, an opioid-like prescription pain drug, was most likely added to kratom to boost its narcotic-like effect.

In November 2017 and February 2018, the FDA issued a public health advisory about deadly risks associated with kratom. There have been 44 reports of Kratom-related deaths, sometimes used in combination with other illicit drugs, prescription drugs, or over-the-counter agents such as loperamide (Imodium).

As with many herbal alternatives, designer drugs, or illicit products sold on the Internet, the possibility exists that kratom may also be contaminated with illegal drugs, black market prescription medications, or even poisonous products. Consumers should avoid buying unknown drug products from the Internet. When combined with other drugs -- recreational, prescription, or alcohol -- the effects of kratom are unknown and may be dangerous.

Is Kratom Addictive?

Kratom is well-known to be addictive, as found with traditional use by natives over many years in Southeast Asian countries. Withdrawal effects similar to narcotic withdrawal and drug-seeking behaviors have been described in users in Southeast Asia. Many Southeast Asian countries have restricted the use of kratom due to the potential for abuse.

The fact that kratom is derived from a plant should not lead consumers to be believe it 100% safe and "all-natural". While certainly not all botanicals have dangerous properties, drugs with dangerous effects can come from botanicals, for example, heroin (opium poppy), cocaine (coca leaves), and nicotine (tobacco).

Will a Drug Test Identify Kratom Use?

Currently, kratom is not included in standard drug screens in the US. Kratom tests are available for screening but are not widely available.

Conclusion

Kratom, an herbal product that originated in Southeast Asia, is being used in the US to ease anxiety, treat chronic pain and to reverse opioid withdrawal symptoms; often purchased over the Internet. Recreational use may be on the rise, too. Use in coffee shops has been reported.

The primary psychoactive component, mitragynine, is many times more potent than morphine. DEA lists kratom as a drug and chemical of concern, and is in the process of evaluating kratom for placement into controlled substances scheduling.

Placing kratom into schedule I would place it in the same category as heroin, LSD or marijuana, and prevent access for medical research, a concern for many experts, consumers, and advocacy groups. Lack of quality scientific evidence confounds the evaluation of the safety of kratom. Concerns also exist that the general public would not be able to identify or confirm the quality or purity of kratom from any Internet source.

The FDA has warned consumers not to use any products labeled as containing kratom. As of February 2018, the FDA has reported on 44 related deaths linked with kratom use, often in use with other substances.

Health care professionals and consumers should report any adverse events related to products containing kratom to the FDA’s MedWatch program.

See Also

Sources

  • Statement from FDA Commissioner Scott Gottlieb, M.D., on the agency’s scientific evidence on the presence of opioid compounds in kratom, underscoring its potential for abuse. U.S. Food and Administration (FDA). Feb. 6, 2018. Accessed Feb. 7, 2018 at https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm595622.htm
  • Statement from FDA Commissioner Scott Gottlieb, M.D. on FDA advisory about deadly risks associated with kratom. U.S. Food and Administration (FDA). Nov. 14, 2017. Accessed Feb. 7, 2018 at https://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm584970.htm
  • Herbal Drug Kratom Contains Opioids, FDA Says. Drugs.com. Feb. 7, 2018. Accessed Feb. 8, 2018 at https://www.drugs.com/news/herbal-kratom-contains-opioids-fda-says-68620.html
  • FDA News release. January 2016. US Marshals seize dietary supplements containing Kratom. Accessed October 6, 2016.
  • Gianutsos G. The DEA Changes Its Mind on Kratom. US Pharm. 2017;41(3):7-9. Accessed Feb. 8, 2018 at https://www.uspharmacist.com/article/the-dea-changes-its-mind-on-kratom
  • Rosenbaum et al. Here Today, Gone Tomorrow…and Back Again? A Review of Herbal Marijuana Alternatives (K2, Spice), Synthetic Cathinones (Bath Salts), Kratom, Salvia divinorum, Methoxetamine, and Piperazines. J Med Toxicol. 2012; 8(1):15–32.
  • Kronstrad, et al. Unintentional fatal intoxications with mitragynine and O-desmethyltramadol from the herbal blend Krypton. J Anal Toxicol. 2011; 35:242-7.
  • DEA. Micrograms Bulletin. March 2006. Accessed October 6, 2016.
  • Kapp FG, Maurer HH, Auwärter V, Winkelmann M, Hermanns-Clausen M. Intrahepatic cholestasis following abuse of powdered kratom (Mitragyna speciosa). J Med Toxicol 2011; 7: 227-31.
  • DEA. Kratom. Drug Facts Sheet. p. 29. Accessed October 6, 2016.
  • Schedules of Controlled Substances: Temporary Placement of Mitragynine and 7-Hydroxymitragynine Into Schedule I. Federal Register. Proposed Rule by the DEA, 8/31/2016. Accessed October 6, 2016.
  • Ault A. DEA Delays Kratom Ban. Medscape Medical News. October 06, 2016. Accessed October 6 2016.
  • Drugs of Abuse. A DEA Resource Guide. 2015 Edition. Drugs of Concern. Kratom. p 84. Accessed October 6, 2016.
  • Kratom seized in California by US Marshals Service. FDA news Release. August 4, 2016. Accessed January 10, 2017.
  • Ingraham, C. Drug policy experts and advocates implore DEA to keep opiate-like plant legal. The Washington Post. Dec 2, 2017. Accessed January 10, 2017. https://www.washingtonpost.com/news/wonk/wp/2016/12/02/drug-policy-experts-and-advocates-implore-dea-to-keep-opiate-like-plant-legal/
  • American Kratom Association. What happens next? December 2, 2016. Accessed January 10, 2017. http://www.americankratom.org/
  • American Kratom Association. The Facts About Kratom. Accessed January 10, 2017. http://www.americankratom.org/
  • Henningfield, J. Factors Related to the Relative Abuse Potential of Mitragyna Speciosa (Kratom) and Mitragynine in the form of VivaZen. Written Summary of Oral Testimony for the State of Wisconsin Controlled Substances Board
    August 14, 2015. Accessed January 10, 2017.
  • Analysis Shows No Basis For DEA To Restrict Herb Kratom. American Kratom Association. December 1, 2016. Accessed January 10, 2017. http://www.americankratom.org/
  • PBS News Hour. Harven M. Herbal drug kratom faces uncertain legal future, despite public outpouring. December 12, 2016. Accessed January 10, 2017 at http://www.pbs.org/newshour/updates/whats-next-kratom/
  • Greenemier L. Should Kratom Use Be Legal? Sept. 30, 2013. Accessed January 10, 2017 at https://www.scientificamerican.com/article/should-kratom-be-legal/

Further information

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