21 October 2019

Nutmeg - The dose makes a Toxin


is a lovely spice when enjoyed in minute doses.

However, higher amounts of nutmeg cause severe intoxication including halucinations. This is mostly due to the toxic phenolic compound myristicin. Be careful about calling something right-out toxic – it may be pleasurable at a different dose.

As a toxicologist, I find myself quite often arguing for the bare definition of toxicity: it is dangerous calling something toxic, without having information on the dose. The dose (the amount of a chemical that enters the body) however, is the “single most important factor which determines whether a chemical will cause poisoning”1. That means, the same compound can cause severe intoxication when consumed above a threshold (e.g. in the case of water: about 6 L in a short time), but may be also very beneficial or even necessary for life in low/moderate amounts1. Besides water, prime examples are vitamins or metals that are necessary for life in minute amounts but may cause severe illness or poisoning when consumed in larger amounts. Another example I want to talk about today is nutmeg.

Nutmeg (lat. Myristica fragrans) is used as a precious spice in many dishes. For cooking purposes, the minute amounts of the ground seed (the nutmeg) are used. However, if extracted into hot water or oil in sufficient amounts, the nutmeg is also a potent hallucinogen. This is because of the toxic phenylpropene myristicin (methoxysafrole), contained in the nutmeg fruit and seed. Since it is a lipophilic compound, it is concentrated in nutmeg essential oil.

Naturally, myristicin serves the plants as protection against insects, ticks and mites (insecticide and acaricide)2. In human, the psychoactive effects are probably due to metabolisation of the toxin to an amphetamine-like compound, which then acts on dopaminergic neurons – those that are linked to the reinforcing and rewarding system and euphoria3,4. Together with other constituents of nutmeg essential oil, like elemicin, that act on other steps dopamine-signaling, the response is intensified and hallucinations may occur4.

While nutmeg is perceived as a cheap psychoactive drug, its biological action may often not be very pleasant: in parallel to the dopamine signaling, other constituents of nutmeg and its essential oil act on serotonin signaling and often induce feelings of anxiety and fear4.

Taken together, this demonstrates that while a well-tasting dinner or desert may be enriched by a hint of nutmeg, excessive usage and a consumption of a higher dose may have significant unpleasant effects.

  1. What Makes Chemicals Poisonous : OSH Answers. Available at: https://www.ccohs.ca/oshanswers/chemicals/poisonou.html. (Accessed: 7th October 2019)
  2. Human Metabolome Database: Showing metabocard for Myristicin (HMDB0035873). Available at: http://www.hmdb.ca/metabolites/HMDB0035873. (Accessed: 7th October 2019)
  3. Calipari, E. S. & Ferris, M. J. Amphetamine Mechanisms and Actions at the Dopamine Terminal Revisited. J. Neurosci. 33, 8923 (2013).
  4. Demetriades, A. K., Wallman, P. D., McGuiness, A. & Gavalas, M. C. Low cost, high risk: accidental nutmeg intoxication. Emerg. Med. J. 22, 223–5 (2005).



Canonical SMILES: COC1=CC(=CC2=C1OCO2)CC=C

Picture references:
1: Image by Nandhu Kumar from https://pixabay.com
Photo by eran Menashri from https://freeimages.com/
3: Image by My_Rika from https://pixabay.com
4: Image by rahmatika from https://pixabay.com