Answer

3 – Mitragynine from Mitragyna speciosa also known as Kratom

What is Kratom? [1-6]

• Kratom is an herbal product that derives from the tree Mitragyna speciosa, native to Southeast Asia, where it has been historically used as a stimulant.
• Recently it has grown in popularity in western countries for its opioid activity, primarily used to self-treat opioid withdrawal and chronic pain.
• It is sold in several forms including leaves, powder, capsules, gum, and extract.
• The active compound, mitragynine, may cause nausea, vomiting, hallucinations, and opioid-like Deaths have been reported.
• There are currently no FDA-approved uses for kratom and its legal status is evolving, most recently classified by the DEA as a Drug and Chemical of Concern. The FDA continues to warn consumers not to use any products labeled as containing the botanical substance kratom or its psychoactive compounds, mitragynine, and 7-hydroxymitragynine.

What is the clinical presentation of kratom toxicity? [1,3,5,7]

• Kratom contains over 40 alkaloids, including mitragynine. Mitragynine is primarily a mu-opioid receptor agonist but also has activity at postsynaptic α-2, serotonin, dopamine, adenosine, and additional opioid receptors.
• Kratom’s neuropsychiatric effects occur rapidly after ingestion and may last 4-6 hours after the exposure.
• At lower ingestions (approximately 2-6 grams) kratom acts as a stimulant, while larger ingestions predominantly result in sedation and other opioid effects.
• The dose-dependent effects of kratom are thought to be due to the dual binding of α adrenergic receptors leading to stimulation and μ opioid receptors causing sedation.
• Gastrointestinal symptoms including nausea, vomiting, and constipation
• Cardiovascular symptoms such as tachycardia and hypertension
• Neurologic symptoms including seizures, hallucinations, agitation, psychosis, and coma
• Respiratory depression can occur
• Substance use disorder and withdrawal are reported with symptoms similar to other opioids.

How do you manage kratom toxicity? [1, 3]

• Minor symptoms generally require only supportive care
• Naloxone can reverse opioid effects
• Benzodiazepines can be used to treat patients with seizures, tachycardia, hypertension, and agitation.
• Withdrawal and substance use disorder may be managed similarly to other opioids.

Bedside pearls

• Kratom use is increasingly popular in the United States, often for self-treatment of chronic pain or opioid use disorder.
• Kratom acts on many different receptors, including the μ, κ, and δ opioid receptors, which contributes to potential withdrawal symptoms and substance use disorders
• Toxicity can lead to life-threatening symptoms such as respiratory depression, seizure, and coma
• Withdrawal presents similarly to opioid withdrawal and should be managed similarly