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Kratom

Medically reviewed on Oct 06, 2016 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 January, 2016, FDA seized nearly 90,000 bottles of dietary supplements labeled as containing kratom. The product was marketed under the brand name RelaKzpro and worth more than $400,000. In a review of poison control records in 2016, the DEA also noted various levels of toxicity with kratom use, from minor to moderate to death. As of September 2016, the DEA notes that they are aware of 15 deaths related to kratom use since 2014.

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 planned to place kratom in Schedule I, the most restrictive classification of the Controlled Substances Act. Its two primary active ingredients, mitragynine and 7-hydroxymitragynine, 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. However, DEA did not solicit public comments on this federal rule, as is normally done.

The scheduling of kratom did not occur on September 30th, as previously thought. It seems 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. According to Medscape Medical News, DEA spokesman Russ Baer says the DEA still plans on scheduling kratom, but the addition of public commenting on the ban is still up in the air.

Kratom Pharmacology

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. Mitragynine is classified as a kappa-opioid receptor agonist and is roughly 13 times more potent than morphine. Mitragynine, structurally similar to yohimbine, is thought to be responsible for the opioid-like effects, as well as 7-hydroxymitragynine, which is even more potent than mitragynine.

Kratom, due to its opioid-like action, has been used for treatment of pain and opioid withdrawal but structurally it is not the same as the common opioids morphine or codeine. 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. 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.

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.

Effects are dose-dependent and occur rapidly, reportedly beginning within 10 minutes after consumption and lasting from one to five hours.

Beside pain, other 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.

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.

Kratom Doses

Doses at the lower end of the range, roughly 1 to 5 grams of the leaves, are said to produce mild stimulant effects or anxiety, while higher doses (5 to 15 grams) produce euphoria effects more in-line with opioids. Doses exceeding 15 grams can lead to a state of excessive sedation and stupor. Effects can vary from patient to patient, and a reaction from a low dose or high dose may not be the same in all people.

While some people may use kratom for recreational use, others may be using it for pain relief or opioid withdrawal. However, it is important to note that these anecdotal doses have not been substantiated or shown in clinical trials to be safe or effective.

Extent of Kratom Use

Until fall of 2016, kratom was widely available legally on the Internet without a prescription and in retail smoke shops. The DEA placed kratom in Schedule I of the Controlled Substances Act in September of 2016, making it illegal to possess and attempting to block access by the public. On the Internet, it 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 herbal product is promoted as an alternative agent for muscle pain relief, diarrhea, and as a treatment for opiate addiction. However, its safety and effectiveness for these conditions has not been clinically determined. In addition, the DEA states that drug abuse surveys have not monitored kratom abuse in the US, so its true demographic extent of use, abuse, addiction, or toxicity is not known.

Kratom Side Effects and Health Hazards

Expected opioid-like side effects that may occur with kratom in the dose range of 5 to 15 grams include:

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

While definite side effects linked to kratom have not been determined from clinical studies, case reports describe the following adverse effects from mitragynine: 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. Tremor, anorexia and weight loss are other possible side effects with long-term use. Seizures have occurred with doses over 15 grams.

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.

As with many herbal alternatives, designer drugs, or illicit products sold on the Internet, the possibility exists that kratom may also be contaminated with illegals 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. At the very least, additive CNS depressant effects may occur when combined with other depressants.

In the treatment of acute toxicity with kratom or “krypton”, clinicians might consider airway protection, the use of naloxone for respiratory depression, and if seizures are present, titration of adequate doses of benzodiazepines. Tramadol-induced seizures may not respond to naloxone.

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.

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.

Legal Status in the U.S. and Other Countries

The DEA still plans to place kratom in Schedule I of the Controlled Substances Act blocking legal access, but that has not yet occurred as of October 6, 2016. However, in February 2014, the FDA issued an import alert that allows U.S. officials to detain imported dietary kratom products.

According to the DEA, there is no known legitimate medical use for kratom in the US. In 2014, the US FDA banned the inclusion of kratom in dietary supplements because of safety concerns.

According to a 2012 article in the Journal of Medical Toxicology, kratom is federally prohibited in Thailand, Malaysia, and Myanmar (Burma). Other countries, including Australia, have also considered or placed mitragynine in a restrictive schedule.

Bottom Line

Kratom has been associated with increasing case reports of harm. Kratom is being used to treat chronic pain and to reverse opioid withdrawal symptoms. Recreational use may be on the rise. The primary psychoactive component, mitragynine, is many times more potent than morphine. DEA lists kratom as a drug and chemical of concern, and has plans to place it into schedule I, the most restrictive classification for controlled substances. Placing kratom into schedule I would place it in the same category as heroin or marijuana, and prevent access for medical research, a concern for some experts.

Lack of quality scientific evidence confounds the evaluation of the safety of kratom. There have been cases of fatal toxicity and acute liver injury associated with kratom use when used alone or combined with other prescription drugs. The general public would not be able to identify or confirm the quality or purity of kratom from any Internet source, and should not purchase or use the product due to toxicity concerns.

The FDA is also warning consumers not to use any products labeled as containing kratom. Health care professionals and consumers should report any adverse events related to products containing kratom to the FDA’s MedWatch program.

See Also:

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Sources

  • FDA News release. January 2016. US Marshals seize dietary supplements containing Kratom. Accessed October 6, 2016.
  • 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.
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