Kratom - Acetaminophen, Caffeine, Dihydrocodeine Interaction

Interaction Details

Acetaminophen, Caffeine, Dihydrocodeine is classified as belonging to the following category: Cns Depressants

Theoretically, concomitant use might increase the risk for adverse CNS depressant effects.
Kratom contains mitragynine, a mu-receptor agonist that may cause respiratory depression. Although results from animal research suggest that mitragynine causes less respiratory depression than the CNS depressant codeine, fatalities have been reported for patients who ingested a combination of kratom and O-desmethyltramadol, another mu-receptor agonist. Additionally, observational research suggests that adverse effects such as drowsiness and coma are more likely to occur in individuals taking kratom in combination with agents such as opioids and sedatives. Theoretically, ingesting kratom along with other CNS depressants can increase the risk of adverse effects, including drowsiness, coma, and/or severe or fatal respiratory depression.

Interaction Rating

Likelihood of Occurrence

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists

References

• Backstrom BG, Classon G, Lowenhielm P, Thelander G. [Krypton--new, deadly Internet drug. Since October 2009 have nine young persons died in Sweden]. Lakartidningen 2010;107(50):3196-3197.
• Kronstrand R, Roman M, Thelander G, Eriksson A. Unintentional fatal intoxications with mitragynine and O-desmethyltramadol from the herbal blend Krypton. J Anal Toxicol 2011;35(4):242-247.
• Jansen KL, Prast CJ. Ethnopharmacology of kratom and the Mitragyna alkaloids. J Ethnopharmacol 1988;23(1):115-119.
• Davidson C, Cao D, King T, et al. A comparative analysis of kratom exposure cases in Thailand and the United States from 2010-2017. Am J Drug Alcohol Abuse. 2020:1-10.

Interaction Details

Acetaminophen, Caffeine, Dihydrocodeine is classified as belonging to the following category: Cytochrome P450 2D6 (Cyp2D6) Substrates

Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP2D6.
In vitro research suggests that kratom extract inhibits CYP2D6 enzyme activity.

Interaction Rating

Likelihood of Occurrence

Interaction has not been documented in well-controlled studies, however, the interaction has been demonstrated in some small human studies or in controlled animal studies in conjunction with multiple case reports.

References

• Kong WM, Chik Z, Ramachandra M, et al. Evaluation of the effects of Mitragyna speciosa alkaloid extract on cytochrome P450 enzymes using a high throughput assay. Molecules. 2011;16(9):7344-7356.

Interaction Details

Acetaminophen, Caffeine, Dihydrocodeine is classified as belonging to the following category: Cytochrome P450 1A2 (Cyp1A2) Substrates

Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP1A2.
In vitro research suggests that kratom extract inhibits the activity of CYP1A2.

Interaction Rating

Likelihood of Occurrence

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists

References

• Kong WM, Chik Z, Ramachandra M, et al. Evaluation of the effects of Mitragyna speciosa alkaloid extract on cytochrome P450 enzymes using a high throughput assay. Molecules. 2011;16(9):7344-7356.

Interaction Details

Acetaminophen, Caffeine, Dihydrocodeine is classified as belonging to the following category: Cytochrome P450 3A4 (Cyp3A4) Substrates

Theoretically, kratom might increase the levels and clinical effects of drugs metabolized by CYP3A4.
In vitro research shows that kratom extract inhibits CYP3A4 enzyme activity. Additionally, there is one case report of a 27-year-old male who died from neuroleptic malignant-like symptoms after concomitant use of kratom and quetiapine, a CYP3A4 substrate. Although it did not appear that the patient had consumed large quantities of quetiapine, postmortem plasma levels were in the lethal range, indicating possible inhibition of CYP3A4 by kratom.

Interaction Rating

Likelihood of Occurrence

Interaction has been documented in animal or in lab research, or the interaction has been documented in humans but is limited to case reports or conflicting clinical research exists

References

• Kong WM, Chik Z, Ramachandra M, et al. Evaluation of the effects of Mitragyna speciosa alkaloid extract on cytochrome P450 enzymes using a high throughput assay. Molecules. 2011;16(9):7344-7356.
• Hughes RL. Fatal combination of mitragynine and quetiapine - a case report with discussion of a potential herb-drug interaction. Forensic Sci Med Pathol. 2019 Mar;15(1):110-113.

Kratom - More Interactions

Kratom interacts with 877 drugs

Interaction Rating Key

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