Nutmeg – myristica fragrans

Nutmeg is a spice.  It is used in cooking and at normal quantities does no harm.  But it has gained an unjustified reputation for being ‘hallucinogenic’ and as a consequence has been taken in overdose proportions.

Metabolism

We will first take a look at how nutmeg is metabolised in the body.

Reporting in the Drug Monitor [Beyer J et al; The Drug Monitor 28 (4): 568-75 (2006)] scientists wrote that:

“Metabolites of elemicin, myristicin, and safrole were identified using gas chromatography-mass spectrometry …… and their presence in the human urine of a nutmeg abuser was confirmed. The identified metabolites indicated that elemicin, myristicin and safrole are once and twice hydroxylated at the side chain. ... myristicin and safrole are 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

Neither amphetamine derivatives nor the main nutmeg ingredients could be detected in the urine samples.”

So, no conversion takes place, if anything happens at all, it is conversion to these metabolites.

Myristicin [1-allyl-3,4-methylenedioxy-5-methoxybenzene ] is metabolised in the liver to a number of metabolites, but the major metabolite is actually , 5-allyl-1-methoxy-2,3-dihydroxybenzene.  The transformation is performed by a liver cytochrome P450 (CYP), more specifically CYP3A4 and possibly other CYP3A enzymes.  [Ref:  Yun CH et al; Toxicol Lett 137 (3): 143-50 (2003)].

It doesn’t  particularly matter which enzyme because the result is not an alkaloid, nor does it have any hallucinogenic potential.  I don’t even need to go into the chemistry because the very name ‘benzene’ should be enough to demonstrate this.

The chemicals in nutmeg

Nutmeg actually contains quite a range of chemicals.  Most of these  provide flavour and smell to the nutmeg or protect the plant against predators.  They are not alkaloids nor do they have any receptor ability.  We can divide these chemicals into three basic groups;

• Monoterpenes - A number are Monoterpenes derived from the molecular formula C₁₀H₁₆. Examples of monoterpenes in nutmeg include: sabinene, pinene, phellandrine and limonene and  shown in blue in the lists below. These act as natural insecticides

• Sesquiterpenes  - Some are Sesquiterpenes. Sesquiterpenes are found naturally in plants and insects, as semiochemicals, e.g. defensive agents or pheromones.  These are shown in red in the lists below [and above]

• Phenylpropenes -  are produced by plants as defense compounds against animals and microorganisms and as floral attractants of pollinators. Humans have used phenylpropenes since antiquity for food preservation and flavouring and as medicinal agents.  They are natural anti-bacterial agents .  Some are anti-viral and anti-inflammatory agents.  Phenylpropenes include Anethole, Chavibetol, Chavicol, Elemicin,  Estragole, Eugenol, Isoeugenol, Isosafrole, Methyl eugenol, Myristicin and  Safrole

Remember they have no receptor capability.

The actual chemical constituents vary widely according to where the plant has been grown , the soil and the climate.  It can also be affected by adulterants – in lower quality nutmeg powder, other varieties of myristica may be used – such as Papuan nutmeg M. argentea from New Guinea, and Bombay nutmeg M. malabarica from India, called jaiphal in Hindi.  These have different properties and chemicals.  So in reality you don’t know what you are getting, nor do you know in what quantities you may be getting them – this partly accounts for the widely different reports you get on sites such as EROWID.

For example, Christian Rasch [Encyclopedia  of Psychoactive plants] indicates that the essential oil of the nutmeg consists of

• 4%  - Myristicin - Myristicin is a phenylpropene, a natural organic compound present in small amounts in the essential oil of nutmeg and to a lesser extent in other spices such as parsley and dill.
• 39%   - Sabinene is one of the chemical compounds that contributes to the spiciness of black pepper and is a major constituent of carrot seed oil. It also occurs in tea tree oil at a low concentration..
• 13%  -  alpha-Pinene is found in the oils of many species of many coniferous trees, notably the pine. It is also found in the essential oil of rosemary (Rosmarinus officinalis).. The racemic mixture is present in some oils such as eucalyptus oil
• 9% - beta-Pinene (?-pinene) is soluble in alcohol, but not water. It has a woody-green pine-like smell. It occurs naturally in rosemary, parsley, dill, basil, yarrow, and rose. It is also a major constituent of hop aroma and flavor.
• 4% - alpha-Phellandrene was named after Eucalyptus phellandra,  from which it can be isolated. It is insoluble in water but can be isolated in ether.  The phellandrenes are used in fragrances because of their pleasing aromas..
• 4% - Limonene is the main odor constituent of citrus.  It is in food manufacturing, as a flavoring,  a fragrant in perfumery; and it is also used as botanical insecticide.  Limonene is increasingly being used as a solvent for cleaning purposes. It has even served as a paint stripper when applied to painted wood. Limonene is also used as a solvent in some model airplane glues
• ?% - Elemicin is a phenylpropene, a constituent of the essential oil of nutmeg and a minor constituent of the oleoresin and essential oil of Manila elemi (Canarium luzonicum).  Although Rasch mentioned it, no percentage was specified. 

Nutmeg is actually far more complex than the list above implies – see the list below. Source:  Production, handling and processing of nutmeg and mace and their culinary uses  - FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS; Guido B. Marcelle; Grenada Produce Chemist Laboratory; FAO REGIONAL OFFICE FOR LATIN AMERICA AND THE CARIBBEAN

• Bergamotene alpha;
• Bisabolene;
• Borneol;
• Cadinene;
• Camphene;
• Camphor;
• Caryophyllene beta;
• Caryophyllene;
• Cineole or eucalyptol;
• Citronellol;
• Copanene;
• Cubebene alpha
• Cymen-8-OL;
• Eugenol;
• Ether;
• Farnesene alpha;
• Fenchol – alpha;
• Geraniol;
• Germacrene;
• Humulene;
• Linalool;
• Myrcene;
• Nerol;
• Piperitone;
• Terpinen-4-OL;
• Terpinene;
• Terpineol alpha and beta;
• Terpinolene;
• Thujene;
• And Trimyristin 

Bergamottin is a natural furanocoumarin found principally in grapefruit juice. Along with the chemically related compound 6’,7’-dihydroxybergamottin, it is believed to be responsible for the grapefruit juice effect in which the consumption of the juice affects the metabolism of a variety of pharmaceutical drugs.

Trimyristin is an ester with the chemical formula C₄₅H₈₆O₆. It is a saturated fat which is the triglyceride of myristic acid. Nutmeg oil generally consists of over eighty percent trimyristin. Trimyristin makes up between 20-25% of the overall mass of dried, ground nutmeg. It is the trimyristin that contains the myristicin.

I hope you can see from this list that there is nothing here that would give you a spiritual experience – nothing.

Nutmeg poisoning

Chronic poisoning by oral administration has also caused temporary (up to six months) psychosis in prison inmates. [Ref:  International Programme on Chemical Safety (IPCS); Poisons Information Monograph: Myristica Fragrans Houtt (PIM 355) (1991)]

The effects by inhalation are generally similar to those experienced via oral administration with the exception that onset is faster by 15 minutes. [Ref:  International Programme on Chemical Safety (IPCS); Poisons Information Monograph: Myristica Fragrans Houtt (PIM 355) (1991).One reported case of nutmeg intoxication after drinking nutmeg tea, states that the reaction is immediate.

Elemecin, in the sort of doses people subject themselves to, is genotoxic.  Genotoxicity describes a deleterious action on a cell's genetic material affecting its integrity. Genotoxic substances are all those with affinity to interact with DNA - which is not proof of their dangerousness to humans, but does render them potentially mutagenic or cancerogenic in quantity.

The overall effect of the chemicals in nutmeg such as Limonene, which will have a partly

Myristicin at high doses is cytotoxic…………………………

Apoptosis  is the process of programmed cell death.  Neuroblastoma is the most common extracranial solid cancer in childhood and the most common cancer in infancy, with an annual incidence of about 650 new cases per year in the US.  Myristicin may help with fighting cancer.

It is not just the myristicin or safrole or elemecin or limonene that causes the deleriant  reaction – all the chemicals are acting together to produce this effect.

And it must be emphasised Nutmeg poisoning can kill you, although because the problem of abuse is known and hospitals are geared up to handle it, it is rare.

According to one scientific report “ Most patients with accidental nutmeg intoxication experience an impending sense of doom after the initial excitation” [International Programme on Chemical Safety (IPCS); Poisons Information Monograph: Myristica Fragrans Houtt (PIM 355) (1991)]

Well they might.

References

1. Meyler’s Side Effects of Drugs – Elsevier publishing
2. A Modern Herbal – Mrs M Grieve
3. Medical Toxicology of Natural Substances – Foods, Fungi, Medicinal Herbs, Plants and Venomous Animals pub. Wiley
4.  http://en.hortipedia.com/wiki/Main_Page
5.  Encyclopedia of Psychoactive plants - Christian Rasch
6.  http://www.erowid.org/experiences/subs/exp_Nutmeg_General.shtml
7.  http://www.erowid.org/plants/nutmeg/nutmeg_basics.shtml
8.  http://www.erowid.org/experiences/subs/exp_Nutmeg.shtml