Can People Overdose on Kratom?
Yes, people can overdose on kratom, though fatal overdoses from kratom alone are rare and typically occur when kratom is combined with other substances, particularly opioids like fentanyl or sedatives like benzodiazepines. 1, 2
Understanding Kratom's Overdose Risk
Mechanism of Toxicity
Kratom contains alkaloids (mitragynine and 7-hydroxymitragynine) that act as atypical opioids, targeting mu, delta, and kappa opioid receptors while also affecting adrenergic, serotonergic, and dopaminergic pathways. 3
Unlike traditional opioids, kratom carries a lower risk of respiratory depression when used alone, but this protective effect is lost when combined with other substances. 3
The Society for Perioperative Assessment and Quality Improvement explicitly warns that kratom has "opioid- and stimulant-like properties" and that "chronic use may lead to neurologic effects including seizures," with the FDA warning against its use. 1
Evidence from Fatal Overdoses
In a 2020 California coroner study of 214 opioid-associated accidental overdoses, 1.9% involved kratom (mitragynine) exposure. 2
Critically, all four kratom-positive deaths involved polysubstance use: three cases included fentanyl (75%), and one case without fentanyl involved benzodiazepines, cannabis, and psychiatric medications. 2
Among 11 deaths associated with kratom exposure reported to U.S. poison control centers from 2011-2017, only two occurred after exposure to kratom alone, while the remaining nine involved multiple substances. 4
Clinical Presentation and Severity
From 2011-2017,1,807 kratom exposures were reported to U.S. poison control centers, with 65% occurring in 2016-2017 alone, indicating rapidly increasing use. 4
Among first-ranked kratom exposures, 31.8% required admission to a healthcare facility and 51.9% resulted in serious medical outcomes. 4
Multiple-substance exposures dramatically increased risk: odds of healthcare facility admission increased 2.8-fold (OR: 2.80; 95% CI: 2.21-3.55) and serious medical outcomes increased 2.25-fold (OR: 2.25; 95% CI: 1.77-2.85) compared to kratom-only exposures. 4
The most common clinical effects in kratom-only exposures were agitation/irritability (22.9%) and tachycardia (21.4%). 4
Drug Interaction Concerns
Kratom and its alkaloids inhibit CYP2D6, CYP3A, and P-glycoprotein, which can increase systemic exposure to co-consumed drugs and precipitate adverse effects. 5
This pharmacokinetic interaction potential is particularly dangerous when kratom is combined with opioids, benzodiazepines, or other central nervous system depressants. 5, 2
Dependence and Withdrawal
Daily use of more than 5-15 grams per day can lead to withdrawal syndrome upon cessation. 1
Up to 20% of U.S. kratom users report symptoms consistent with kratom use disorder, and some individuals experience classic opioid withdrawal symptoms upon abrupt cessation. 6, 3
Kratom use disorder and withdrawal are best treated with buprenorphine. 6
Critical Clinical Pitfalls
The most dangerous scenario is combining kratom with other substances, particularly:
- Fentanyl or other opioids (present in 75% of kratom-related deaths) 2
- Benzodiazepines 2, 4
- Alcohol (which increases respiratory depression risk with any opioid-like substance) 7
Do not assume kratom is safe because it is "natural" or legally available as a dietary supplement—the FDA explicitly warns against its use, and it carries real overdose risk, especially in polysubstance scenarios. 1, 3