Abuse of nutmeg (Myristica fragrans Houtt.): studies on the metabolism and the toxicologic detection of its ingredients elemicin, myristicin, and safrole in rat and human urine using gas chromatography/mass spectrometry

Ther Drug Monit. 2006 Aug;28(4):568-75. doi: 10.1097/00007691-200608000-00013.


Seeds of nutmeg are used as spice, but they are also abused because of psychotropic effects described after ingestion of large doses. It was postulated that these effects could be attributable to metabolic formation of amphetamine derivatives from the main nutmeg ingredients elemicin (EL), myristicin (MY), and safrole (SA). In a case of a suspected nutmeg abuse, neither such amphetamine derivatives nor the main nutmeg ingredients could be detected in urine. The metabolites of EL, MY, and SA were identified using gas chromatography-mass spectrometry in rat urine and their presence in human urine of the nutmeg abuser was confirmed. The identified metabolites indicated that EL, MY, and SA were once and twice hydroxylated at the side chain. In addition, EL was O-demethylated at 2 positions followed by side chain hydroxylation. MY and SA were demethylenated and subsequently methylated. In the human urine sample, the following metabolites could be identified: O-demethyl elemicin, O-demethyl dihydroxy elemicin, demethylenyl myristicin, dihydroxy myristicin, and demethylenyl safrole. As in the human urine sample, neither amphetamine derivatives nor the main nutmeg ingredients could be detected in the rat urine samples. Finally, toxicologic detection of nutmeg abuse was possible by identification of the described metabolites of the EL, MY, and SA in urine applying the authors' systematic toxicologic analysis procedure using full-scan gas chromatography-mass spectrometry after acid hydrolysis, liquid-liquid extraction of analytes, and microwave-assisted acetylation of extracted analytes.

MeSH terms

  • Allylbenzene Derivatives
  • Animals
  • Benzyl Compounds / chemistry
  • Benzyl Compounds / metabolism
  • Benzyl Compounds / urine*
  • Dioxolanes / chemistry
  • Dioxolanes / metabolism
  • Dioxolanes / urine*
  • Drug Monitoring / methods
  • Gas Chromatography-Mass Spectrometry / methods
  • Humans
  • Molecular Structure
  • Myristica / chemistry*
  • Pyrogallol / analogs & derivatives*
  • Pyrogallol / chemistry
  • Pyrogallol / metabolism
  • Pyrogallol / urine
  • Rats
  • Rats, Wistar
  • Reproducibility of Results
  • Safrole / analysis*
  • Safrole / chemistry
  • Safrole / metabolism
  • Seeds / chemistry
  • Spectrometry, Mass, Electrospray Ionization
  • Substance Abuse Detection / methods
  • Substance-Related Disorders / urine*
  • Time Factors


  • Allylbenzene Derivatives
  • Benzyl Compounds
  • Dioxolanes
  • Pyrogallol
  • myristicin
  • elemicin
  • Safrole