Depressants, CYP3A medicines, antidepressants, stimulants, and other combinations by evidence basis.
Editorially reviewedModerate, heterogeneous evidenceReviewed 30 July 2026
Interactions
Show the evidence basis and warning signs
Most combinations lack controlled human studies. The classification separates direct human findings, case-report signals, and pharmacologically grounded caution. “No data” does not mean “no interaction.”
Opioids, benzodiazepines/Z-drugs, alcohol, GHB/GBL, gabapentinoids, and other strong depressants
particularly riskycase reports + pharmacology
Additive sedation, loss of consciousness, vomiting/aspiration, and breathing problems are plausible; severe kratom cases are often confounded by co-use. Treat the combination as particularly risky.
Warning signs: Cannot be woken, slow or irregular breathing, blue lips, gurgling sounds.
In twelve healthy participants, a low kratom-tea exposure moderately increased midazolam exposure, consistent with intestinal CYP3A inhibition. The result cannot clear other exposures, extracts, or narrow-therapeutic-index medicines.
Warning signs: Unexpectedly strong or prolonged medicine effects, drowsiness, circulatory symptoms.
Antidepressants, MAO inhibitors, and serotonergic mixtures
relevant, uncertainpharmacological caution
Evidence is insufficient for a blanket statement about SSRIs, SNRIs, or tricyclic antidepressants. Enzyme inhibition, additive adverse effects, and case reports support caution; uncertainty is especially high with MAO inhibitors and warrants professional review.
Warning signs: Severe agitation, confusion, fever, muscle rigidity or jerking, pronounced diarrhoea.
Heart rate, blood pressure, agitation, sleep deprivation, and overheating may compound. Kratom can subjectively mask overstimulation without removing physiological strain.
Warning signs: Chest pain, very rapid or irregular pulse, overheating, severe agitation.
Drowsiness, dizziness, vomiting, disorientation, and accident risk may increase. Sedating antihistamines are not a reliable self-treatment for kratom adverse effects.
Warning signs: Collapse, repeated vomiting, inability to walk or communicate safely.
Potentially hepatotoxic medicines or existing liver disease
elevated riskcase reports + pharmacology
Kratom has been associated with clinically significant, sometimes cholestatic liver injury. Additive risk from combinations is unquantified; medical review is especially important.
Warning signs: Yellow skin or eyes, dark urine, pale stool, severe itching, right upper abdominal pain.
•blue/grey lips, gurgling sounds, or vomiting with impaired consciousness
•seizure, chest pain, or severe overheating
Call 112 immediately, check breathing, do not leave the person alone, and follow dispatcher instructions. If breathing, use the recovery position; if not breathing normally, start resuscitation as directed.
For an opioid-type emergency, naloxone may be used if available and the responder knows how. Case reports describe improvement after naloxone, but response in kratom toxicity is not guaranteed. Naloxone never replaces calling 112 or ventilation/resuscitation and cannot reverse every co-ingestant hazard.
