Clinical evidence comparison
Three related substances. Different toxicity profiles.
The kratom debate is increasingly framed as a choice between “natural kratom” and dangerous concentrated or chemically modified derivatives. Human clinical evidence does not support that simple division.
Kratom and mitragynine have the longest human exposure record and the largest published human case literature here, including neurologic, hepatic, renal, muscular and cardiac adverse events. Concentrated 7-hydroxymitragynine (7-OH) is producing a newer, more recognizably opioid-like pattern that includes profound central nervous system depression, dependence and withdrawal. Mitragynine pseudoindoxyl (MP) is newer still; human literature is sparse, but severe opioid-like withdrawal has already been published.
What PubMed shows in humans
This table does not assign an adverse effect to 7-OH or MP merely because it has been reported with kratom. Where substance-specific human evidence is absent, it says so.
| Effect | Kratom / mitragynine | 7-OH | MP |
|---|---|---|---|
| Seizure / convulsion | 20 patients reported A 2025 systematic review identified 20 patients across 11 publications, but concluded that the available evidence was insufficient to establish that kratom causes seizures. Only one case included quantitative mitragynine confirmation. | Poison-center signal; substance-specific case literature remains limited. | Not established in human cases located. |
| Major cardiac abnormality | ≥15 PubMed-indexed human case-report papers identified. Reported findings include ventricular fibrillation, pulseless ventricular tachycardia, cardiac arrest, QTc prolongation, Brugada-pattern abnormalities, cardiomyopathy and acute right-ventricular dysfunction. The literature remains case-report based and some reports include important confounders. | ≥2 direct severe cardiac case reports. One patient had cardiopulmonary arrest after reported 7-OH use and was revived with naloxone; another developed marked QTc prolongation after a large 7-OH ingestion requiring ICU care. | Not established in published human cases located. |
| Rhabdomyolysis | ≥3 clearly indexed human case reports identified. Published cases include rhabdomyolysis with compartment syndrome, acute kidney injury, hepatic dysfunction and multiorgan injury. | 1 direct PubMed-indexed case report. A 2026 report described rhabdomyolysis, renal failure and chronic neurologic deficits after prolonged immobilization following use of a 7-OH product. | Not established in published human cases located. |
| Liver injury / failure | 32 cases of kratom-associated liver injury. A 2026 systematic review identified 32 published cases; four progressed to liver transplantation. The review also noted frequent co-exposures and inconsistent formal causality assessment across reports. | Insufficient substance-specific literature to transfer the kratom finding to concentrated 7-OH. | Not established. |
| Withdrawal / dependence | Multiple published case reports and case series. Medical treatment has included buprenorphine-based management. | Substantial emerging case literature. Among the 7-OH clinical publications identified in this search are multiple single-patient withdrawal/use-disorder reports plus a 2026 retrospective series of 9 patients treated with buprenorphine. | 1 MP-specific human case report. A 2026 case described severe early-onset opioid-like withdrawal with a COWS score of 31. |
| Respiratory depression / compromise | Reported in human toxicity literature. Interpretation is complicated in many reports by co-exposures, formulation uncertainty and incomplete analytical confirmation. | Documented severe CNS/respiratory compromise. A large 7-OH ingestion caused profound CNS depression requiring airway protection; another mixed 7-OH/nicotine withdrawal case progressed to respiratory compromise requiring intubation. | Human overdose literature remains too sparse to quantify. |
Case reports and case series establish clinical observations after reported exposure; they do not by themselves establish incidence or causation. Product composition, co-ingestants and toxicologic confirmation vary substantially. Systematic reviews can summarize those reports but do not remove the limitations of the underlying evidence.
How much human 7-OH literature is now in PubMed?
A targeted PubMed search conducted October 4, 2026 identified at least 11 human clinical case-report or case-series publications specifically involving concentrated 7-hydroxymitragynine (7-OH). Ten describe individual patients and one retrospective series describes nine patients, for at least 19 described patients. This count excludes animal studies, mechanistic papers, reviews and poison-center surveillance from the case-report total.
| 7-OH clinical literature | PubMed count identified | What has been reported |
|---|---|---|
| All clinical case-report / case-series publications | ≥11 publications ≥19 patients | Acute intoxication, cardiopulmonary arrest, QTc prolongation, rhabdomyolysis/renal failure, substance use disorder, dependence and withdrawal. |
| Severe cardiac toxicity | ≥2 patients | Cardiopulmonary arrest after reported 7-OH use; marked QTc prolongation after a large intentional 7-OH ingestion. |
| Rhabdomyolysis / renal failure | 1 patient | Rhabdomyolysis and renal failure after prolonged immobilization following use of a 7-OH product. |
| Withdrawal / use disorder | Multiple single-patient reports + 9-patient series | Opioid-like withdrawal, rapid tolerance/dependence, and treatment with buprenorphine or methadone-to-buprenorphine strategies. |
| Respiratory / profound CNS depression | Published severe cases | Profound CNS depression requiring airway protection; respiratory compromise requiring intubation in a mixed 7-OH/nicotine withdrawal case. |
PubMed search method. Kratom cardiac search: (kratom OR "Mitragyna speciosa" OR mitragynine) AND (cardiac OR cardiovascular OR arrhythmia OR ventricular OR "cardiac arrest" OR QT OR QTc OR Brugada OR cardiomyopathy OR "heart failure"). 7-OH search: ("7-hydroxymitragynine" OR "7-HMG" OR "7-OH") AND (case OR "case report" OR "case series" OR intoxication OR toxicity OR withdrawal OR arrest OR rhabdomyolysis OR respiratory OR QT). Counts were manually restricted to human clinical case reports/case series and therefore should be read as a reproducible minimum, not a permanent lifetime total.
FDA adverse-event reports: the same endpoints, a much larger signal
The downloaded FDA line listing contains 1,708 case rows. The table was calculated directly from its suspect active ingredient, reaction and outcome fields.
| FDA measure | Kratom / mitragynine | 7-OH | MP |
|---|---|---|---|
| Cases | 1540 | 166 | 6 |
| Seizure | 113 | 8 | 0 |
| Cardiac abnormality | 157 | 11 | 0 |
| Rhabdomyolysis | 7 | 0 | 0 |
| Liver injury / failure | 57 | 3 | 0 |
| Withdrawal | 188 | 73 | 1 |
| Respiratory depression / compromise | 44 | 7 | 0 |
| Hospitalized | 401 | 61 | 2 |
| Died | 740 | 19 | 2 |
Counting rule: the mitragynine column excludes rows explicitly containing “7-hydroxy” or “pseudoindoxyl.” Ingredient categories may otherwise overlap. Reaction categories were keyword-matched to the reaction field. A case may contain multiple reactions and outcomes.
FDA reports are signals, not causation findings. “Died” means death was recorded as an outcome in the report; it does not establish that FDA determined the suspect product caused the death. Spontaneous reports are affected by incomplete information, concomitant drugs, duplicates and reporting bias.
Poison Centers show how quickly 7-OH is changing the picture
America's Poison Centers reported 3,803 kratom or kratom-derivative exposures in 2025 and 3,190 through June 30, 2026. Among single-substance kratom/derivative exposures, 44.5% had serious health problems and 25.9% were hospitalized.
For 7-OH specifically, Poison Centers recorded 593 exposures in 2025 and 901 in only the first six months of 2026. Among 7-OH-only exposures, 38.8% had serious health problems and 20.5% were hospitalized.
| Measure | Kratom / derivatives | 7-OH | MP |
|---|---|---|---|
| 2025 exposures | 3,803 | 593 | Not separately reported |
| Jan–Jun 2026 | 3,190 | 901 | Not separately reported |
| Serious outcome, single substance | 44.5% | 38.8% | Not available |
| Hospitalized, single substance | 25.9% | 20.5% | Not available |
MP's empty column is not evidence of safety. It means an equivalent national public MP category is not yet available for a clean comparison.
Thebaine: nature is not a toxicology classification
The opium poppy provides a useful warning against treating “natural” and “synthetic” as synonyms for safe and dangerous.
Thebaine is a naturally occurring opium-poppy alkaloid. In a cluster of 40 human poisonings from thebaine-contaminated poppy seeds, analytically confirmed cases developed muscle spasms, rigidity and convulsions. Five developed rhabdomyolysis, acute kidney injury and metabolic acidosis; two suffered cardiac arrest and one died.
Thebaine is also an important pharmaceutical starting material. Chemical transformation can produce hydrocodone. Hydrocodone does not share thebaine's characteristic strychnine-like neuromuscular toxicity profile; it is a clinically useful opioid whose principal life-threatening overdose hazard is opioid-induced respiratory depression.
Thebaine can produce convulsions, rhabdomyolysis and cardiac arrest. Hydrocodone's defining overdose danger is respiratory depression. Likewise, evidence of opioid-like toxicity from 7-OH or MP does not erase the independent neurologic, hepatic, cardiac and muscular toxicity reported with kratom.
Nature is a source of molecules. It is not a certificate of safety.
References
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- America's Poison Centers. “Health Advisory: Serious Illnesses Associated with Kratom and 7-OH Products.” July 8, 2026.
- Isoardi KZ, Roberts DM, Holford AG, et al. “A cluster of acute thebaine poisonings from non-food grade poppy seeds in the Australian food supply.” Clin Toxicol (Phila). 2023;61(9):639-643. PMID 37855308. DOI 10.1080/15563650.2023.2265053.
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This page distinguishes case reports, systematic reviews, spontaneous FDA adverse-event reports and poison-center surveillance. Those evidence types answer different questions and should not be treated as interchangeable measures of incidence or causation.