Toxicological evaluation of myristicin

Abstract

Myristicin, or methoxysafrole, is the principal aromatic constituent of the volatile oil of nutmeg, the dried ripe seed of Myristica fragrans. Myristicin is also found in several members of the carrot family (Umbelliferae). Several intoxications have been reported after an ingestion of approximately 5 g of nutmeg, corresponding to 1-2 mg myristicin/kg body weight (b.w.). Although these intoxications may be ascribed to the actions of myristicin, it is likely that other components of nutmeg may also be involved. The metabolism of myristicin resembles that of safrole. No information is available, however, concerning the quantitative importance of the different metabolic pathways. The acute toxicity of myristicin appears to be low. No toxic effects were observed in rats administered myristicin perorally at a dose of 10 mg/kg b.w., while 6-7 mg/kg b.w. may be enough to cause psychopharmacological effects in man. A weak DNA-binding capacity has been demonstrated, but there are no indications that myristicin exerts carcinogenic activity in short-term assays using mice. Intake estimations indicate that nonalcoholic drinks may be the most important single source of myristicin intake. Based on available data, it seems unlikely that the intake of myristicin from essential oils and spices in food, estimated to a few mg per person and day in this report, would cause adverse effects in humans. It is, however, at present not possible to make a complete risk assessment, as studies regarding genotoxicity and chronic toxicity, including reproductive toxicity and carcinogenicity, are still lacking. Nat.

Effect of leaf essential oil from Piper solmsianum C.DC. in mice behaviour

“…These results are in agreement to those psychopharmalogical effects published for myristicin, an analogue of sarisan (Shulgin 1966, Hallstrom & Thuvander 1997. It has been demonstrated that myristicin promotes CNS depressant effect besides an induction of the cytochrome P-450 system (Hallstrom & Thuvander 1997).…”

“…It has been demonstrated that myristicin promotes CNS depressant effect besides an induction of the cytochrome P-450 system (Hallstrom & Thuvander 1997). Previous investigation with eugenol and safrole, arylpropanoid derivatives, showed that these compounds intervene in the cytochrome P-450 functions (Nagababu & Lakshmaiah 1994, Janiaud et al 1997.…”

“…Previous essential oil analyses from leaves of P. solmsianum (Moreira et al 1998) revealed the presence of monoterpenes, sesquiterpenes and as major compound an arylpropanoid derivative (sarisan -39.23%). Toxicological effects, including weak pulse, hypothermia, delirium, vertigo and nausea, associated to ingestion of about 5-15 g of nutmeg (Myristica fragrans), rich in the arylpropanoid derivative myristicin, has been reported (Shulgin 1966, Hallstrom & Thuvander 1997. The structure similarities of myristicin and of sarisan, the main constituent of P. solmsianum essential oil, encouraged us to perform some pharmacological studies on mice behaviour.…”

Development of Advance Extraction Methods for the Extraction of Myristicin from Myristica fragrans

“…1-4. Myristicin concentration found in GN4 is close to maximum reported concentration (Hallström and Thuvander 1997), and on this basis, it can be stated that GN4 is a high-quality spice. Moreover, it was noticed that the results somehow correspond with relations of people abusing nutmeg, published on the Internet (see Supplementary material, section 2), as nutmeg from producers 4, 3 and sometimes 2 are recommended for giving the best psychoactive effects.…”

“…Myristicin content in plant organs varies, depending on both growing and storage condition, and it can amount up to 13 mg per 1 g in the high-quality M. fragrans nut (nutmeg); it is also abundant in aril of the nut (mace) (Hallström and Thuvander 1997) and its pericarp (Choo et al 1999). Psychoactive effects usually develop after administration of at least 10 g of grounded nutmeg and include amphetamine-like effects and hallucinations (Ehrenpreis et al 2014).…”