View Original Article https://www.drugs.com/illicit/kratom.html
Medically reviewed on Jan 10, 2017 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, the herbal product has been used as an alternative agent for muscle pain relief, diarrhea, and as a treatment for opiate addiction and withdrawal. Patients with PTSD have reported positive effects. However, its safety and effectiveness for these conditions has not been clinically determined.
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, 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.
According to the American Kratom Association, kratom is legal in 44 states. State laws have restricted its use in six states – Indiana, Tennessee, Wisconsin, Vermont, Arkansas and Alabama. These states classify kratom as a schedule I substance. Kratom is also noted as being banned in Sarasota County, Florida and San Diego County, California.
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.
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.
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
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. According to Susan Ash, founder, American Kratom Association, “kratom is a natural botanical product consumed by millions of Americans daily”, but the exact numbers of kratom users are officially 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:
- Dry mouth
- Increased urination
- Loss of appetite
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 been reported when kratom was combined with modafinil in at least one case report.
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.
According to Dr. Henningfield in his report for the the American Kratom Association, no “there have been no reports of fatal overdose from kratom per se”, as of August 2015. However, in September 2016 the DEA noted that they were aware of 15 deaths related to kratom use since 2014, but whether those deaths involved other substances was not reported.
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 by wary of 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.
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.
Kratom, an herbal product that originated in Southeast Asia, is being used in the US to treat chronic pain and to reverse opioid withdrawal symptoms, and often purchased over the Internet. However, recreational use may be on the rise, too. 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. Putting kratom into schedule I would place it in the same category as heroin 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. There have been cases of fatal toxicity and acute liver injury associated with kratom. Concerns exists that the general public would not be able to identify or confirm the quality or purity of kratom from any Internet source.
Advocates of kratom report its beneficial effects for pain and opioid withdrawal effects, and one researcher has reported that kratom’s potential for abuse may be as low as that with “nutmeg and St. John’s Wort”.
However, the FDA has warned 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.
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