Chapter 9
NUTMEG
(Myristica fragrans Houtt.)
HISTORY
Nutmeg probably was imported into Europe during the
12th century by Arab merchants. For many years, this
spice has been used as an aromatic stimulant, abortifa-
cient, antiflatulent and as a means to induce menses.1
The Portuguese discovered the nutmeg tree on the
Banda Islands of Indonesia (Spice Islands) in 1512. In
1576, de Lobel reported the first case of nutmeg intoxi-
cation in a pregnant English woman, who ingested 10–12
nutmeg nuts.2 Beginning in the 17th century, the Dutch
controlled the Spice Islands, and they monopolized the
spice trade until the British obtained nutmeg seedlings
from the Banda Islands at the end of the 18th century.
References to the central nervous system effects of
nutmeg appeared in the first part of the 19th century
when Purkinje developed lethargy after consuming
three nutmeg nuts.1 Because of the alleged hallucino-
genic and euphoria-inducing properties of nutmeg,
abuse of this spice has occurred for many years, particu-
larly in persons with limited access to other drugs. The
autobiography of Malcolm X contains accounts of his
use of nutmeg while incarcerated.3
BOTANICAL DESCRIPTION
Common Name: Nutmeg
Scientific Name: Myristica fragrans Houtt.
Botanical Family: Myristicaceae (nutmeg)
Physical Description: This aromatic evergreen tree
grows 9–12 m (30–39 ft) high with spreading
branches and a yellow fleshy fruit similar in appear-
Medical Toxicology of Natural Substances, by Donald G. Barceloux, MD
Copyright © 2008 John Wiley & Sons, Inc.
ance to an apricot or peach. The ripe fruit splits to
expose a single glossy brown nut enclosed by a
scarlet aril. The tree produces fruit year round, but
the harvest usually occurs in April and November.
Distribution and Ecology: The nutmeg tree is indig-
enous to the Maluku Province of Indonesia, for-
merly known as the Spice Islands. The nutmeg tree
is grown commercially on the Caribbean islands
of Grenada and Trinidad as well as in Central and
East Java.
EXPOSURE
Traditional uses of nutmeg include the treatment of
rheumatism, cholera, psychosis, stomach cramps, nausea,
diarrhea, flatulence, and anxiety in addition to use as an
aphrodisiac and an abortifacient. Nutmeg is not used as
a narcotic or hallucinogen in traditional Indonesian
culture.4 Although a case report associated the resolu-
tion of diarrhea secondary to thyroid medullary carci-
noma with the use of nutmeg,5 there are no approved
medical indications for this spice. Nutmeg is a substitute
psychotomimetic substance of abuse, particularly for
adolescents, students, and prisoners with limited access
to other psychotomimetic agents. The unpleasant taste,
large doses required for effect, frequent adverse effects,
and relative lack of potency as a hallucinogen limit the
abuse of nutmeg.6
The mature fruit from the nutmeg tree contains a
2.5 cm (1 in.) nut with a bright red, fleshy covering
(scarlet aril). Nutmeg is the nut, whereas the dried
scarlet aril is called mace. The nut and mace are dried
67
PART 1 FOODBORNE and MICROBIAL TOXINS
and processed separately. Mace is also a spice, and this
spice has been used as an aphrodisiac by physicians in
the Near East. There are relatively few reports of poi-
soning following the ingestion of mace.
PRINCIPAL TOXINS
Structure and Properties
The concentration of active components depends on the
botanical source, environmental conditions, storage, and
analytical methods. The two oils of nutmeg are fixed oil
(expressed oil, nutmeg butter) and essential oil. The
fixed oil is an orange, butter-like material obtained by
applying heat and hydraulic pressure to nutmeg. This oil
contains primarily trimyristin, and the product has no
culinary value. Essential oil of nutmeg is a steam distil-
late that appears as a pale-yellow, nearly colorless liquid
with the characteristic odor of spice. Table 9.1 lists some
properties of myristicin, which is the main psychoactive
constituent of nutmeg. This compound is structurally
similar to kawain and related psychoactive constituents
of kava (Piper methysticum Forst.). Myristicin is also the
major component of the aromatic ether fraction of
essential oil of mace.7 Figure 9.1 displays the chemical
structure of myristicin.
Poisonous Parts
This essential oil contains from 5–15% volatile oils com-
prised of about 80% monoterpenes (α-pinene, sabinene,
1,8-p-methadiene, β-pinene, 1,4-p-menthadiene, cam-
phene), 5% monoterpene alcohols, an aromatic ether
TABLE 9.1. Identifying Characteristics and Properties of
Myristicin
Property Value
CAS Number 607-91-0
Chemical name 1-allyl-5-methoxy-3,4-
methylenedioxybenzene
Synonyms Myristicin, methoxysafrole
Empirical formula C11H12O3
Molecular weight 192.22
Appearance Colorless oil
O CH2
O ated with tachycardia, palpitations, drowsiness, nausea,
OCH3
FIGURE 9.1. Chemical structure of myristicin.
68
fraction, and miscellaneous compounds.7 The aromatic
fraction contains myristicin, elemicin, safrole, and minor
constituents (methyleugenol, eugenol, isoeugenol,
toluene). The essential oil of nutmeg contains variable
amounts (0.1–18%) of methyleugenol, which is a poten-
tially genotoxic compound with DNA-binding potency
similar to safrole.8 Myristicin, elemicin, and safrole
account for the majority (85–95%) of the compounds in
the aromatic fraction, and myristicin represents about
4–12% of the compounds present in the essential oil.9
Myristicin is present in plants from the carrot (Umbel-
liferae) family including dill, celery, parsnip, parsley, and
carrot. This compound is also a minor constituent of oil
of black pepper (Piper nigrum). The estimated intake of
myristicin from these sources by the general population
is a few mg daily.10
Mechanism of Toxicity
Structural similarities of myristicin to classical halluci-
nogenic compounds (e.g., mescaline) suggest that myris-
ticin may act as a serotonin receptor agonist and
hallucinogenic compound. However, the acute toxicity
of myristicin is relatively low. Although myristicin com-
prises the largest fraction (i.e., about 4–8%) of com-
pounds in the aromatic fraction of nutmeg, human
studies with myristicin have not duplicated the effects
of nutmeg intoxication on the central nervous system.17
In rodent studies, myristicin and elemicin impair coor-
dination and decreased motor activity.11 Safrole, eugenol,
and isoeugenol do not have similar behavioral effects is
these animal studies.
DOSE RESPONSE
One grated nutmeg is approximately one tablespoon
and weighs about 6–7 g with typical recreational doses
ranging from 5–30 g.7 The administration of 6 g nutmeg
to students did not significantly alter performance on
neuropsychological tests.12 Symptoms do not usually
develop following the ingestion of <10 g nutmeg.7 The
ingestion of two whole nutmegs caused moderate toxic-
ity;1 the ingestion of an estimated dose of 18 g of finely
ground nutmeg powder resulted in prolonged periods
of obtundation.13 The ingestion of 25–28 g of nutmeg
powder produced tachycardia, anxiety, miosis, paresthe-
sias, palpitations, anticholinergic signs (mydriasis, diffi-
culty voiding, tachycardia), and paranoid behavior
without hallucinations.14,15 The ingestion of an estimated
dose of 37 g nutmeg blended in a milkshake was associ-
dry mouth, anxiety, restlessness, and agitation without
hallucinations.16 Variation in toxicity may result from
the loss of essential oils from the ground nutmeg.

The ingestion of a single dose 400 mg myristicin by
10 subjects was associated with alertness, a feeling of
irresponsibility, and euphoria in 2 subjects as well as an
unpleasant reaction (anxiety, fear, tremor, nausea, tachy-
cardia) in 2 subjects.17 Onset of symptoms occurred
about 1–2 hours after ingestion and resolved within 24
hours. This dose of myristicin is equivalent to the amount
of myristicin present in 40 g of nutmeg.
TOXICOKINETICS
In the 1970s, an in vitro study suggested that psychoac-
tive amphetamine derivatives (e.g., 3-methoxy-4,5-
methylenedioxyamphetamine, MMDA) are potential
metabolites of myristicin.18 Although the alkeneben-
zene derivatives, myristicin, elemicin, safrole, are exten-
sively metabolized following ingestion, subsequent
studies have not confirmed the presence of amphet-
amine metabolites. Limited toxicokinetic studies indi-
cate that these alkenebenzene undergo hydroxylation
of the side chain, and elemicin undergoes O-demethyl-
ation prior to hydroxylation. Metabolites detected in
the urine of rats fed these compounds include O-
demethyl elemicin, O-demethyl dihydroxy elemicin,
demethylenyl myristicin, dihydroxy myristicin, and
demethylenyl safrole.19 In vivo animal studies suggest
that enzymatic hydrolysis of myristicin produces at least
two metabolites (5-allyl-1-methoxy-2,3-dihydroxyben-
zene, 1′-hydroxymyristicin) that are conjugated and
excreted in the urine.20,21 Amphetamine derivatives were
not detected in these two studies.
CLINICAL RESPONSE
The clinical features of nutmeg intoxication resemble
belladonna (anticholinergic) toxicity manifest by facial
flushing, tachycardia, hypertension, dry mouth, blurred
vision, and delirium.22,23 However, mydriasis is uncom-
mon. Symptoms usually begin about 3–6 hours after
ingestion and resolve by 24–36 hours.6,7 Initially, these
symptoms include nausea, vomiting, abdominal pain,
chest pain, restlessness, agitation, tremor, ataxia, nystag-
mus, vertigo, and a feeling of doom. These symptoms
occur with alternating periods of lethargy and delir-
ium.13,24 Other effects of nutmeg intoxication docu-
mented in case reports include the sensation of warmth
and coldness of the extremities, distortion of space and
colors, auditory and tactile hallucinations, headache, and
generalized weakness.25 Patients usually recover without
sequelae.1 The medical literature does not contain any
fatalities solely related to nutmeg intoxication since the
first decade of the 20th century.2 There are few data on
the reproductive effects of nutmeg. A 29-year old
woman, who developed signs of nutmeg intoxication at
9 NUTMEG
30 weeks gestation, delivered a healthy infant at
term.22
The processing of nutmeg does not usually produce
irritative symptoms in spice workers.26 However, aller-
gic contact dermatitis may develop in workers sensi-
tized to allergens (e.g., isoprenyl myristate) in nutmeg.27
Occupational asthma may also occur in workers sensi-
tized to spices including mace.28
DIAGNOSTIC TESTING
Chromatographic methods easily separate marijuana
and the components of nutmeg and mace.29 Human
metabolites of the constituents in nutmeg are detect-
able by the use of gas chromatography mass spectrom-
etry after acid hydrolysis, liquid-liquid extraction of
analytes, and microwave-assisted acetylation of
extracted analytes.19 These metabolites include O-
demethyl elemicin, O-demethyl dihydroxy elemicin,
demethylenyl myristicin, dihydroxy myristicin, and
demethylenyl safrole. Developing biomarkers for
nutmeg intoxication is complicated by limited data on
the toxic constituents of nutmeg. Six hours after inges-
tion 14–21 g nutmeg powder, a 16-year-old adolescent
developed tachycardia, drowsiness, dry mouth, warm
skin, and mydriasis.30 The myristicin concentration in a
blood sample drawn 8 hours after ingestion was 2 μg/
mL. The postmortem blood from a 55-year-old woman
contained 4 μg/mL of myristicin and 0.072 μg/mL of
flunitrazepam.30 Death was attributed to the combina-
tion of the two substances. However, myristicin does
not necessarily account for the toxic effects of nutmeg,
and the contribution of myristicin and nutmeg to this
death remains speculative. Routine laboratory tests
during nutmeg intoxication are usually normal.24 The
ingestion of nutmeg does not produce positive urine
drug screens.14
TREATMENT
Management is usually supportive. The presence of
hemodynamic instability suggests the presence of other
toxins or illnesses. Decontamination measures are
usually unnecessary because of the presence of vomit-
ing or delayed contact (i.e., >1–2 hours after ingestion)
with the health care facility. There are no clinical data
to guide management of nutmeg intoxication. The use
of standard antiemetics (prochlorperazine, trimetho-
benzamide, odansetron, metoclopramide) and intrave-
nous fluids may be required to treat protracted nausea
and vomiting. Sedatives (diazepam, haloperidol)
should be used with caution because of alternating
periods of delirium and obtundation during nutmeg
intoxication.
69
PART 1 FOODBORNE and MICROBIAL TOXINS
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