Kratom: Therapy or Threat?

Gayle Nicholas Scott, PharmD

Disclosures

October 22, 2015

Question

What is kratom, and is it a helpful remedy or a harmful drug?

Gayle Nicholas Scott, PharmD
Assistant Professor, Eastern Virginia Medical School, Norfolk, Virginia

Kratom (Mitragyna speciosa) is a tree-like plant in the same botanical family as the coffee tree and gardenia (Rubiaceae), and is native to Southeast Asia. Other names for kratom are ketum, thang, icthang, kakuam, kraton, thom, and biak-biak.

Kratom has been used for centuries in Thailand, Malaysia, and Indonesia to combat fatigue and, empirically, to treat pain and opioid withdrawal symptoms.[1,2] It is most commonly used orally, as fresh leaves that are chewed or that have been prepared as an extract, or as dried plant material brewed as a tea or ingested in gelatin capsules. Less frequently, kratom is smoked.[1,2]

Effects are reported to be dose-dependent. Doses of 1-5 g have a stimulant effect and increase energy. Moderate to high doses (5-15 g) have opioid-like effects, including euphoria. Doses > 15 g can cause extreme sedation and stupor, similar to opioids.

The indole alkaloid mitragynine appears to be responsible for the opioid-like effects of kratom. Mitragynine has high affinity for mu-opioid receptors, but less than morphine. Affinity for delta- and kappa-opioid receptors are lower than for mu, but higher than the affinity of morphine for delta and kappa.

Animal research suggests that kratom has analgesic effects that are reversed by naloxone, and that kratom may have anti-inflammatory and anorexic effects. Some effects of mitragynine appear to be independent of opioid receptor activity and may involve noradrenergic and serotonergic mechanisms.[1]

Animal research suggests that kratom can be addictive, and observational research in chronic kratom users in Malaysia suggests that kratom can lead to dependence, although social functioning does not appear to be impaired.[3,4]

Despite its potentially addictive properties, kratom is currently legal in most states. Kratom is regulated in the United States as a dietary supplement and can be purchased in smoke shops and on the Internet. Recently, however, the US Food and Drug Administration (FDA) moved to ban the importation of kratom, calling it a "new dietary ingredient," on the basis of lack of marketing documentation in the United States before the enactment of the Dietary Supplement Health and Education Act of 1994. The FDA also cited the absence of established safety and potential toxicity.[5,6]

Acute adverse effects of kratom include anxiety, irritability, and aggression, as well as opioid-like effects, such as sedation, nausea, constipation, and itching. Chronic high-dose use has been associated with hyperpigmentation of the cheeks, tremor, weight loss, and psychosis.[1,2]

Cases of both overdose and withdrawal have been reported by poison control centers. Common presentations of overdose include palpitations and seizures. Withdrawal symptoms include myalgia, insomnia, fatigue, and chest discomfort. Withdrawal symptoms have even occurred in the infant of a chronic kratom-using mother.[7,8] Fatalities possibly attributed to kratom, usually in combination with other drugs, have been reported.[9,10,11]

Kratom appears to have a strong drug interaction potential. Kratom extracts inhibit CYP2C9, CYP2D6, and CYP3A4 in vitro.[12,13] Kratom is sometimes combined with O-desmethyltramadol, a tramadol (Ultram®) metabolite, in a product called "krypton."[9] Additive depressant effects on the central nervous system, along with potential metabolic drug interactions, in theory may increase its opioid-like effects.

Kratom use appears to be increasing in the United States and worldwide.[7,8] Routine toxicologic screens do not detect kratom.[14] Healthcare providers caring for patients who present for emergency treatment should be aware that kratom use may be responsible for otherwise unexplained stimulant or depressive symptoms.

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