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PLANTS-NUTMEG

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Classification   |    Detailed evidence-based information

Substances Included Synonyms

Therapeutic Toxic Class

    A) Nutmeg is a spice consisting of the seed of the Myristica fragrans, a tropical, dioecious evergreen tree native to the Moluccas or Spice Islands of Indonesia.

Specific Substances

    A) Myristicin
    1) 3-methoxy-4,5-methylene dioxyallylbenzene
    2) 5-allyl-1-methoxy-2,3-methylene dioxybenzene
    Elemicin
    1) 3,4,5-trimethoxyallylbenzene
    GENERAL TERM
    1) Nutmeg

Available Forms Sources

    A) FORMS
    1) Nutmeg contains 20 to 40% nutmeg butter (fixed oil), which has been externally applied for healing of sprains. Nutmeg also contains 8 to 15% essential oil and 45 to 60% cellulose containing structures (Anon, 1984; Kalbhen, 1971). The oils appear to contain the toxic ingredients.
    2) The volatile oils in nutmeg and mace are complex mixes of allylbenzene derivatives and terpines. Myristicin, elemicin and safrole make up 80% of the allylbenzene derivatives (Kalbhen, 1971). Below is a list of the components of each of these volatile oils.
    a) NUTMEG (Kalbhen, 1971)
    1) Terpene hydrocarbons
    1) a-pinene
    2) b-pinene
    3) camphene
    4) sabinene
    5) p-mentha-1,4-diene
    6) p-mentha-1,4(8)-diene
    7) p-mentha-1,8-diene
    8) p-menth-1-en-4-ol (4-terpinol)
    9) p-menth-1-en-8-ol
    2) Allylbenzene derivatives
    1) myristicin
    2) elemicin
    3) safrole
    4) methyleugenol
    5) eugenol
    6) myristic acid
    7) unidentified substances
    8) toluene
    9) p-cymene
    10) linalool
    11) genanyl acetate
    12) cineol
    13) camphor
    14) citronellol
    15) (+)-borneol
    16) methylisoeugenol (6)
    17) isoeugenol (7)
    18) isoelemicin (8)
    19) methoxyeugenol (9)
    3) MACE (Forest et al, 1972)
    ComponentPercentages
    a-pinene26.7
    camphene0.5
    b-pinene (and myrcene)20.7
    sabinene14.5
    unidentified monoterpin9.7
    limonene9.4
    B-phellandrene2.3
    p-cymene0.9
    terpinolene2.1
    unidentified0.16
    unidentified monoterpinol0.38
    linalool0.2
    terpinen-4-ol4.4
    unidentified sesquiterpen0.2
    a-terpineol0.7
    safrole1.9
    geraniol0.1
    eugenol methyl ether0.2
    eugenol0.1
    myristicin3.8
    isoeugenol0.1
    elemicin0.2

    B) SOURCES
    1) Nutmeg and mace are obtained from the tree Myristica fragrans (family Myristicacea). The tree develops a fruit somewhat like an apricot (nutmeg apple). The fruit of this plant is dried and yields nutmeg. The dried, fleshy, scarlet covering of the fruit (aril) yields mace, which has a flavor similar to nutmeg (Anon, 1984).
    2) MYRISTICIN SOURCES -
    a) Myristicin is found in many plants, but especially members of the Umbelliferae.
    b) Several parsleys (Petroselinum hortense, P. sativum) contain oils with high myristicin content, but no elemicin.
    c) Lovage oil (from Levisticum scoticum but not L. officinale) also contain myristicin, up to 1% in the rhizomes.
    d) Other plants containing small amounts are:
    1) Anethum gravoleus (common dill weed oil).
    2) Pastinaca sativa (common parsnip).
    3) Cinnamonomum glanduliferums (Nepal camphor wood).
    3) ELEMICIN SOURCES -
    a) Elemicin is a myristicin analog with the methylenedioxy group replaced by 2 methoxy groups.
    b) It is a main component of orthodon oil (Orthodon asaroniferum). It is also a positional conjugated isomer of asarone (another plant product thought to be a CNS depressant and hallucinogen) (Shulgin, 1966). Another common source of elemicin is an oil of carrot (Daucus carota) (Shulgin, 1966).
    C) USES
    1) Herbal uses of nutmeg include treatment for GI disorders and rheumatism, as a CNS depressant and stimulant, as an emmenogogue, as an abortifacient, and as a possible aphrodisiac (Anon, 1984). Nutmeg has also been used to treat psychiatric conditions and flatulence.
    2) Nutmeg has recently been tried as an antidiarrheal in calves (Anon, 1984) and for resistant diarrhea in man (Barrowman et al, 1975).
    3) Poisonings have resulted when nutmeg was tried as an abortifacient (Payne, 1963). In Indonesia, it has been used as an analgesic, aromatic stomachic, and anti-inflammatory (Ozaki et al, 1989).
    4) The essential oil of nutmeg was found to have anti-microbial properties specifically against Listeria monocytogenes (Smith-Palmer et al, 1998).

Overview

Life Support

    A) This overview assumes that basic life support measures have been instituted.

Clinical Effects

    0.2.1) SUMMARY OF EXPOSURE
    A) USES: Nutmeg is used in cooking. It is also abused for its sedative and possible hallucinogenic effects.
    B) PHARMACOLOGY: Myristicin is the main active ingredient in nutmeg oil. The exact mechanism of action is not known. It is thought that myristicin has an indol-like structure similar to reserpine and can act as a serotonin antagonist (responsible for the CNS effects observed). Myristicin is also a weak inhibitor of monoamine oxidase, which may contribute to its cardiovascular effects. It has been speculated that myristicin may be metabolized to 3-methoxy-4,5-methylenedioxyamphetamine (MMDA).
    C) EPIDEMIOLOGY: Exposures are uncommon and toxicity (other than GI effects) is rare.
    D) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: CNS symptoms predominate in nutmeg overdose. Patients may present with a syndrome similar to anticholinergic toxicity (tachycardia, dry mouth) save for a lack of mydriasis. Miosis is likely to be present due to myristicin. CNS depression may occur. Abdominal pain has been reported frequently. Nausea and vomiting appear to occur more frequently with coingestants, but have been observed following ingestions of nutmeg alone.
    2) SEVERE TOXICITY: Agitation and hallucinations or CNS depression may develop.
    0.2.4) HEENT
    A) Dry mouth, blurred vision, headache, thirst, flushing and miosis or mydriasis have been seen.
    0.2.17) METABOLISM
    A) Animal studies indicate nutmeg has mild monoamine oxidase inhibitory properties.
    0.2.20) REPRODUCTIVE
    A) Nutmeg is in pregnancy category C. A 29-year-old woman who ingested 1 tablespoonful of nutmeg at 30 weeks gestation developed signs of anticholinergic intoxication. The fetal heart beat was increased for 12 hours.

Laboratory Monitoring

    A) Monitor vital signs and mental status.
    B) No routine laboratory tests are needed.
    C) Monitor serum electrolytes, glucose, liver enzymes, acetaminophen and salicylates concentrations if the diagnosis is in question or self harm is suspected.
    D) Myristicin can be detected in the blood, but concentrations are not routinely available and do not correlate well with toxicity.

Treatment Overview

    0.4.2) ORAL/PARENTERAL EXPOSURE
    A) MANAGEMENT OF MILD TO MODERATE TOXICITY
    1) Supportive care is the mainstay of therapy. Consider benzodiazepines for psychomotor agitation.
    B) MANAGEMENT OF SEVERE TOXICITY
    1) Supportive care is the mainstay of therapy.
    C) DECONTAMINATION
    1) PREHOSPITAL: Not indicated due to somnolence and low likelihood of benefit.
    2) HOSPITAL: Given the propensity to cause CNS depression and vomiting, and the low likelihood of severe life-threatening toxicity, charcoal should not be used routinely in the absence of coingestants.
    D) AIRWAY MANAGEMENT
    1) Patients with coingestants that also cause CNS depression may require intubation for airway protection.
    E) ENHANCED ELIMINATION
    1) Not indicated.
    F) PATIENT DISPOSITION
    1) HOME CRITERIA: Patients that are not intentionally abusing nutmeg are unlikely to develop symptoms and can be observed at home.
    2) OBSERVATION CRITERIA: Patients with CNS symptoms, persistent vomiting, those with deliberate abuse or self harm ingestions should be referred to a healthcare facility. Patients should be observed until symptoms of intoxication resolve.
    3) ADMISSION CRITERIA: Patients with profound CNS depression or agitation, or persistent hallucinations or vomiting should be admitted, because symptoms can last for greater than 24 hours.
    4) CONSULT CRITERIA: A medical toxicologist or poison center should be consulted for patients with CNS symptoms or severe anticholinergic symptoms. Patients should be referred for substance abuse counseling as appropriate.
    G) TOXICOLOGIC MECHANISM
    1) CNS toxicity may result from monoamine oxidase inhibition causing increased serotonin concentrations in the brain. There is a theoretical risk of serotonin syndrome when nutmeg is used in conjunction with another serotonergic medication. Experimental data suggests a myristicin metabolite may have amphetamine-like activity. This may explain the euphoric effects reported with nutmeg abuse. Liver steatosis has also been shown to occur in animals.
    H) PREDISPOSING CONDITIONS
    1) Use of monoamine oxidase inhibitors, serotonin reuptake inhibitors, or other serotonergic medications may predispose patients to nutmeg toxicity.
    I) DIFFERENTIAL DIAGNOSIS
    1) Anticholinergic toxidrome, serotonin syndrome, hallucinogen use or acute psychosis.

Range Of Toxicity

    A) TOXIC DOSE: Myristicin doses of 6 to 7 mg/kg have resulted in symptoms in patients. Doses up to 80 g of nutmeg powder have been ingested without resulting in life-threatening effects. One young adult developed tonic-clonic seizures about 6 hours after ingesting 39 g (650 mg/kg [actual body weight]) of ground nutmeg and alcohol; he recovered completely following airway management and sedation. Fatality is generally not expected in nutmeg abuse.

Clinical Effects

Summary Of Exposure

    A) USES: Nutmeg is used in cooking. It is also abused for its sedative and possible hallucinogenic effects.
    B) PHARMACOLOGY: Myristicin is the main active ingredient in nutmeg oil. The exact mechanism of action is not known. It is thought that myristicin has an indol-like structure similar to reserpine and can act as a serotonin antagonist (responsible for the CNS effects observed). Myristicin is also a weak inhibitor of monoamine oxidase, which may contribute to its cardiovascular effects. It has been speculated that myristicin may be metabolized to 3-methoxy-4,5-methylenedioxyamphetamine (MMDA).
    C) EPIDEMIOLOGY: Exposures are uncommon and toxicity (other than GI effects) is rare.
    D) WITH POISONING/EXPOSURE
    1) MILD TO MODERATE TOXICITY: CNS symptoms predominate in nutmeg overdose. Patients may present with a syndrome similar to anticholinergic toxicity (tachycardia, dry mouth) save for a lack of mydriasis. Miosis is likely to be present due to myristicin. CNS depression may occur. Abdominal pain has been reported frequently. Nausea and vomiting appear to occur more frequently with coingestants, but have been observed following ingestions of nutmeg alone.
    2) SEVERE TOXICITY: Agitation and hallucinations or CNS depression may develop.

Vital Signs

    3.3.3) TEMPERATURE
    A) Hypothermia frequently occurs (Anon, 1984; Panayotopoulos & Chisholm, 1970).

Heent

    3.4.1) SUMMARY
    A) Dry mouth, blurred vision, headache, thirst, flushing and miosis or mydriasis have been seen.
    3.4.3) EYES
    A) MIOSIS has been seen early in the intoxication (Shafran, 1976) in contrast to anticholinergic poisoning. This is not a reliable sign of intoxication (Brenner et al, 1993). Miosis is more common than mydriasis (Payne, 1963).
    B) MYDRIASIS: Mild mydriasis has occurred (Ehrenpreis et al, 2014; McKenna et al, 2004; Demetriades et al, 2005; Hentschel et al, 2000; Payne, 1963).
    C) BLURRED VISION may develop (Ehrenpreis et al, 2014; Sangalli & Chiang, 2000; Venables et al, 1976).
    3.4.6) THROAT
    A) XEROSTOMIA has been reported (Lavy, 1987).
    B) DRY MOUTH may be seen (Anon, 1984; Anon, 1981).
    C) THIRST has been reported (Payne, 1963).
    D) CASE REPORT: An 18-year-old girl developed dry mouth and thirst 30 minutes after drinking 3 quarters of a milkshake containing 50 g of grated nutmeg (Demetriades et al, 2005).

Cardiovascular

    3.5.2) CLINICAL EFFECTS
    A) TACHYARRHYTHMIA
    1) WITH POISONING/EXPOSURE
    a) Common cardiovascular effects include weak pulse, feeling of pressure in the chest, and tachycardia (Hentschel et al, 2000; Anon, 1984; Shafran, 1976). Palpitations have also been noted (McKenna et al, 2004; Quin et al, 1998; Demetriades et al, 2005; Lavy, 1987).
    b) CASE SERIES: In a review of the Illinois Poison Center data from January 2001 to December 2011, a total of 32 cases (intentional (n=15); unintentional (n=17)) of nutmeg exposure were identified. Tachycardia was reported in 3 (n=15; 10%) patients following an intentional exposure; no cases were reported following unintentional nutmeg exposure (Ehrenpreis et al, 2014).
    c) CASE SERIES: In a retrospective review by the California Poison Control System during 1997 to 2008, 119 cases of nutmeg exposure were identified, and 86 of these were deliberate. Among patients that abused nutmeg, tachycardia developed in 27% and agitation in 17% compared to 3% of patients with unintentional exposures (Carstairs & Cantrell, 2011).
    d) CASE REPORT: A 20-year-old man ingested 4 whole nutmegs and half of a liter of vodka and developed tingling in his hands and feet, dry mouth, nausea, palpitations and dizziness about 5 hours later. At presentation some 14 hours later, the patient had become highly agitated with flushing, tachycardia (130 bpm), dilated pupils and hyper-reflexia of the upper and lower limbs. Laboratory studies were normal. He was admitted for observation and his altered mental status persisted for 32 hours and sinus tachycardia resolved after 20 hours. The patient was discharged 3 days after admission following psychiatric evaluation (Quin et al, 1998).
    e) CASE REPORT: A 16-year-old healthy teenager ingested 25 g of powered nutmeg and woke up with complaints of right-sided facial weakness, right arm paresis, paresthesia and palpitations. Upon admission he was found to be lethargic with a slow affect and sluggish pupils. Heart rate was tachycardic (121 bpm) with a normal BP. ECG showed non-specific T-wave inversion in leads II, III and aVF and cardiac enzymes were normal. His tachycardia resolved 4 hours after being admitted for observation. All symptoms spontaneously resolved within 24 hours of admission (McKenna et al, 2004).
    f) CASE REPORT: An 18-year-old girl developed palpitations and tachycardia (102/min) after drinking 3 quarters of a milkshake containing 50 g of grated nutmeg. A 12 lead ECG revealed a fast sinus dysrhythmia (rate 95 to 110/min) with no ischemic or hypertrophic changes. She recovered completely following supportive therapy (Demetriades et al, 2005).
    g) CASE REPORT: A 23-year-old man ingested 28 g of nutmeg, in an attempt to get "high", and experienced tachycardia, severe anxiety, and hallucinations. After oral administration of charcoal and supportive treatment, the patient's symptoms resolved gradually over the next 12 hours (Abernathy & Becker, 1992).
    B) HYPOTENSIVE EPISODE
    1) WITH POISONING/EXPOSURE
    a) There may be a slight increase in blood pressure, but a more serious reaction of marked hypotension with cyanosis and shock has been reported (Green, 1959).

Neurologic

    3.7.2) CLINICAL EFFECTS
    A) CENTRAL STIMULANT ADVERSE REACTION
    1) WITH POISONING/EXPOSURE
    a) Initial effects are those of giddiness, CNS "excitation", tingling, dizziness, apprehension, and anxiety (Anon, 1984; Venables et al, 1976; Painter et al, 1971). Severe agitation may follow an initial period of tingling and euphoria (Quin et al, 1998).
    b) CASE SERIES: In a retrospective review by the California Poison Control System during 1997 to 2008, 119 cases of nutmeg exposure were identified, and 86 of these were deliberate. Among patients that abused nutmeg, tachycardia developed in 27% and agitation in 17% compared to 3% of patients with unintentional exposures. Dizziness was also reported following intentional and unintentional exposures (Carstairs & Cantrell, 2011).
    c) CASE REPORT: A 20-year-old man ingested 4 whole nutmegs and half of a liter of vodka and developed tingling in his hands and feet, dry mouth, nausea, palpitations and dizziness about 5 hours later. At presentation some 14 hours later, the patient had become highly agitated with flushing, tachycardia (130 bpm), dilated pupils and hyper-reflexia of the upper and lower limbs. Laboratory studies were normal. He was admitted for observation and his altered mental status persisted for 32 hours and sinus tachycardia resolved after 20 hours. The patient was discharged 3 days after admission following psychiatric evaluation (Quin et al, 1998).
    d) CASE REPORT: An 18-year-old girl developed drowsiness, dizziness, anxiety, restlessness, and agitation 30 minutes after drinking 3 quarters of a milkshake containing 50 g of grated nutmeg. She complained of being "in a trance state". She recovered completely following supportive therapy (Demetriades et al, 2005).
    B) PARESTHESIA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: A 16-year-old healthy teenager ingested 25 g of powered nutmeg and woke up with complaints of right-sided facial weakness, right arm paresis, paresthesia and palpitations. Upon admission he was found to be lethargic with a slow affect and sluggish pupils. Facial weakness and paresis had resolved, but paresthesia was ongoing. Heart rate was tachycardic (121 bpm). He was observed for 24 hours and all symptoms resolved spontaneously (McKenna et al, 2004).
    b) CASE REPORT: Paraesthesia in all extremities occurred in a 32-year-old man after ingesting approximately 7 g of nutmeg the previous night. Other symptoms included generalized weakness, vertigo, nausea, and anxiety. The patient was monitored overnight in the ICU and all symptoms resolved by the following day (Sjoholm et al, 1998).
    C) FEELING AGITATED
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: In a review of the Illinois Poison Center data from January 2001 to December 2011, a total of 32 cases (intentional (n=15); unintentional (n=17)) of nutmeg exposure were identified. Agitation/irritability was reported in 3 (n=15; 10%) patients following an intentional exposure and 1 (n=17) patient following an unintentional exposure (Ehrenpreis et al, 2014).
    D) DROWSY
    1) WITH POISONING/EXPOSURE
    a) Later, extreme drowsiness may occur lasting for 24 hours or longer (McKenna et al, 2004; Sangalli & Chiang, 2000; Payne, 1963; Truitt et al, 1961).
    b) CASE SERIES: In a review of the Illinois Poison Center data from January 2001 to December 2011, a total of 32 cases (intentional (n=15); unintentional (n=17)) of nutmeg exposure were identified. Drowsiness was reported in 3 (n=15; 10%) patients following an intentional exposure and 1 (n=17) patient following an unintentional exposure (Ehrenpreis et al, 2014).
    E) DIZZINESS
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: In a review of the Illinois Poison Center data from January 2001 to December 2011, a total of 32 cases (intentional (n=15); unintentional (n=17)) of nutmeg exposure were identified. Dizziness was reported in 4 (n=15; 13.3%) patients following an intentional exposure and 1 (n=17) patient following an unintentional exposure (Ehrenpreis et al, 2014).
    F) HEADACHE
    1) WITH POISONING/EXPOSURE
    a) Headache may occur (Sangalli & Chiang, 2000; Kalbhen, 1971).
    G) ATAXIA
    1) WITH POISONING/EXPOSURE
    a) CASE REPORT: Muscle weakness and ataxia were reported in a 13-year-old girl several hours after smoking marijuana and ingesting 15 to 24 g of nutmeg over a 3-hour period. The patient recovered following decontamination with 50 g of activated charcoal (Sangalli & Chiang, 2000).
    H) SEIZURE
    1) WITH POISONING/EXPOSURE
    a) CASE SERIES: In a review of the Illinois Poison Center data from January 2001 to December 2011, a total of 32 cases (intentional (n=15); unintentional (n=17)) of nutmeg exposure were identified. Seizure activity was reported in one patient with a history of seizure disorder following a nutmeg overdose (Ehrenpreis et al, 2014).
    b) CASE REPORT: A 24-year-old man with a history of autism, unmedicated ADHD, and a prior history of cannabis abuse presented to the ED approximately 4 hours after intentionally ingesting an unknown amount of ethanol and ground nutmeg. Upon admission, he was agitated and tachycardic and was treated with diazepam. Methanol, isopropanol, acetaminophen or salicylate levels were unremarkable and other laboratory studies were within normal limits. Approximately 6 hours after ingestion, transient generalized tonic-clonic seizures occurred with desaturation and laryngospasm requiring intubation. No further seizures were observed with sedation. The patient was successfully extubated the following day. He had no prior history of seizures and reported that he impulsively consumed 39 g (650 mg/kg) of ground nutmeg and 0.75 liters of vodka with 6 bottles of beer or cider (Flam et al, 2015).

Gastrointestinal

    3.8.2) CLINICAL EFFECTS
    A) NAUSEA AND VOMITING
    1) WITH POISONING/EXPOSURE
    a) Nausea, vomiting and a burning epigastric pain are commonly reported symptoms (Quin et al, 1998; McKenna et al, 2004; Sjoholm et al, 1998; Hentschel et al, 2000; Sangalli & Chiang, 2000; Painter et al, 1971).
    b) CASE SERIES: In a retrospective review by the California Poison Control System during 1997 to 2008, 119 cases of nutmeg exposure were identified. Vomiting, abdominal pain and nausea were among the most common adverse effects reported following nutmeg exposure (Carstairs & Cantrell, 2011).
    c) CASE REPORT: An 18-year-old girl developed nausea 30 minutes after drinking 3 quarters of a milkshake containing 50 g of grated nutmeg (Demetriades et al, 2005).
    B) APTYALISM
    1) WITH POISONING/EXPOSURE
    a) Dry mouth may be seen (Anon, 1984).
    b) CASE REPORT: An 18-year-old girl developed dry mouth 30 minutes after drinking 3 quarters of a milkshake containing 50 g of grated nutmeg (Demetriades et al, 2005).
    C) DRUG-INDUCED ILEUS
    1) WITH POISONING/EXPOSURE
    a) Gastrointestinal hypomotility has occurred (Lavy, 1987).

Genitourinary

    3.10.2) CLINICAL EFFECTS
    A) RETENTION OF URINE
    1) WITH POISONING/EXPOSURE
    a) Urinary retention has occurred (Lavy, 1987).

Dermatologic

    3.14.2) CLINICAL EFFECTS
    A) FLUSHING
    1) WITH POISONING/EXPOSURE
    a) Cutaneous flushing may occur (Quin et al, 1998; Shafran, 1976).
    B) URTICARIA
    1) WITH POISONING/EXPOSURE
    a) Hives have been seen (Anon, 1984).
    C) DRY SKIN
    1) Dry skin, similar to other drugs with anticholinergic properties, may occur (Lavy, 1987).
    D) EXCESSIVE SWEATING
    1) WITH POISONING/EXPOSURE
    a) Sweating has been reported in several cases (Faguet & Rowland, 1978).
    E) CONTACT DERMATITIS
    1) WITH POISONING/EXPOSURE
    a) In 103 patients with suspected contact allergy, the highest number of reactions elicited by patch testing were to nutmeg (28%) (van den Akker et al, 1990).

Reproductive

    3.20.1) SUMMARY
    A) Nutmeg is in pregnancy category C. A 29-year-old woman who ingested 1 tablespoonful of nutmeg at 30 weeks gestation developed signs of anticholinergic intoxication. The fetal heart beat was increased for 12 hours.
    3.20.3) EFFECTS IN PREGNANCY
    A) ANTICHOLINERGIC SYNDROME
    1) A 29-year-old woman who ingested 1 tablespoonful of nutmeg at 30 weeks gestation developed signs of anticholinergic intoxication. The fetal heart beat was increased for 12 hours (Lavy, 1987).
    B) PREGNANCY CATEGORY
    NUTMEGC
    Reference: Briggs et al, 1998

Laboratory Monitoring

Monitoring Parameters Levels

    4.1.1) SUMMARY
    A) Monitor vital signs and mental status.
    B) No routine laboratory tests are needed.
    C) Monitor serum electrolytes, glucose, liver enzymes, acetaminophen and salicylates concentrations if the diagnosis is in question or self harm is suspected.
    D) Myristicin can be detected in the blood, but concentrations are not routinely available and do not correlate well with toxicity.
    4.1.2) SERUM/BLOOD
    A) BLOOD/SERUM CHEMISTRY
    1) No routine laboratory tests are needed.
    2) Monitor serum electrolytes, glucose, liver enzymes, acetaminophen and salicylates concentrations if the diagnosis is in question or self harm is suspected.

Methods

    A) CHROMATOGRAPHY
    1) Myristicin has been isolated from nutmeg using high performance liquid chromatography (Hentschel et al, 2000; Archer, 1988). Chromatographic methods can easily separate the components of nutmeg and mace from marijuana (Barceloux, 2009).

Treatment

Life Support

    A) Support respiratory and cardiovascular function.

Patient Disposition

    6.3.1) DISPOSITION/ORAL EXPOSURE
    6.3.1.1) ADMISSION CRITERIA/ORAL
    A) Patients with profound CNS depression or agitation, or persistent hallucinations or vomiting should be admitted, because symptoms can last for greater than 24 hours.
    6.3.1.2) HOME CRITERIA/ORAL
    A) Patients that are not intentionally abusing nutmeg are unlikely to develop symptoms and can be observed at home.
    6.3.1.3) CONSULT CRITERIA/ORAL
    A) A medical toxicologist or poison center should be consulted for patients with CNS symptoms or severe anticholinergic symptoms. Patients should be referred for substance abuse counseling as appropriate.
    6.3.1.5) OBSERVATION CRITERIA/ORAL
    A) Patients with CNS symptoms, persistent vomiting, those with deliberate abuse or self harm ingestions should be referred to a healthcare facility. Patients should be observed until symptoms of intoxication resolve.

Monitoring

    A) Monitor vital signs and mental status.
    B) No routine laboratory tests are needed.
    C) Monitor serum electrolytes, glucose, liver enzymes, acetaminophen and salicylates concentrations if the diagnosis is in question or self harm is suspected.
    D) Myristicin can be detected in the blood, but concentrations are not routinely available and do not correlate well with toxicity.

Oral Exposure

    6.5.1) PREVENTION OF ABSORPTION/PREHOSPITAL
    A) GI decontamination is generally not indicated due to potential for somnolence and low likelihood of benefit. Most patients with significant toxicity have spontaneous vomiting, and most patients do not present to medical care until many hours after ingestion.
    6.5.2) PREVENTION OF ABSORPTION
    A) GI decontamination is generally not indicated due to potential for somnolence and low likelihood of benefit. Most patients with significant toxicity have spontaneous vomiting, and most patients do not present to medical care until many hours after ingestion.
    6.5.3) TREATMENT
    A) HYPOTENSIVE EPISODE
    1) Hypotension, although rare, may occur, and generally responds to intravenous fluids. Pharmacologic intervention with such agents as levophed or dopamine has not been necessary.
    B) PSYCHOMOTOR AGITATION
    1) Various agents have been used to decrease agitation and anxiety. The 2 most commonly used were chlorpromazine and diazepam. The doses were titrated based on each patient's needs (Painter et al, 1971).
    C) NAUSEA AND VOMITING
    1) Antiemetics have been used (Painter et al, 1971).

Enhanced Elimination

    A) SUMMARY
    1) Not indicated.

Abstracts

Case Reports

    A) ADULT
    1) A 29-year-old, primigravid woman ingested an unknown amount of cookies made with approximately 7 g of nutmeg and developed anticholinergic poisoning. Within 4 hours she was experiencing palpitations, agitation, apprehension, dry mouth, chest tightening and blurred vision. She was treated with morphine IV, magnesium citrate and activated charcoal. The patient and fetus showed complete recovery within 24 hours (Lavy, 1987).

Range Of Toxicity

Minimum Lethal Exposure

    A) ADULT
    1) CASE REPORT: Myristicin (4 mcg/mL) and flunitrazepam (0.072 mcg/mL) were found in the postmortem serum of a 55-year-old woman who died of unknown causes (Stein et al, 2001).
    B) PEDIATRIC
    1) CASE REPORT: An 8-year-old boy ate 2 nutmegs and became comatose and died 24 hours later (Cushny, 1908).

Maximum Tolerated Exposure

    A) SUMMARY
    1) One tablespoonful of ground nutmeg spice is approximately equal to 7 g or 1 grated nutmeg (Mack, 1982).
    2) One to 3 nutmegs, or 5 to 30 g of the ground nut are used for inducing psychogenic effects (Painter et al, 1971; Anon, 1984). Assuming 8% to 15% of volatile oil in nutmeg, this is 0.4 to 4.5 g of volatile oil.
    B) CASE SERIES
    1) In a review of the Illinois Poison Center data from January 2001 to December 2011, a total of 32 cases (intentional (n=15); unintentional (n=17)) of nutmeg exposure were identified. Of those patients with intentional exposures, most patients were male (n=13) and between the ages of 13 and 19 (n=10; 66.7%). Of the unintentional exposures, 10 (58.8%) were under the age of 13. A total of 10 patients needed to be hospitalized, 7 of which were patients with an intentional exposure with 4 ingesting other substances. All were between the ages of 15 and 17 years. Overall, approximately one-third of the individuals with an intentional exposure also ingested other substances (ie, cannabis, amphetamines, benzodiazepines, diphenhydramine, duloxetine, acetaminophen). Gastrointestinal events (ie, nausea (n=1) and vomiting (n=2)) and CNS events (hallucinations (n=4), agitation (n=3), drowsiness (n=3) and dizziness (n=4)) were the most common events observed in patients following an intentional overdose. Seizure activity was reported in one patient with a history of seizure disorder following an intentional exposure. Patients with unintentional exposures developed fewer symptoms which were limited to a few cases of gastrointestinal events and one case each of agitation, drowsiness and dizziness. All patients hospitalized were treated supportively and recovered completely (Ehrenpreis et al, 2014).
    2) Seven cases of intentional nutmeg ingestion for hallucinogenic purposes resulted in CNS symptoms (ie, drowsiness, restlessness, dizziness, clouding of consciousness), tachycardia, mydriasis, nausea and vomiting up to 20 hours after ingestion. The doses ranged between 20 to 80 g of nutmeg powder (approximately 280 to 1100 mg/kg). All patients recovered (Stein et al, 2001).
    C) CASE REPORTS
    1) A dose of 18.5 g produced excitement and fear of death (Venables et al, 1976).
    2) In 400 mg doses, myristicin produced mild cerebral stimulation in humans. This was much less effect than 15 g of nutmeg produced (Truitt et al, 1961).
    3) A dose of approximately 28 g produced palpitations, severe anxiety, visual hallucinations, and a sense of dread (Abernethy & Becker, 1992).
    4) CASE REPORT: A 24-year-old man with a history of autism, unmedicated ADHD, and a prior history of cannabis abuse presented to the ED approximately 4 hours after intentionally ingesting an unknown amount of ethanol and ground nutmeg. Upon admission, he was agitated and tachycardic and was treated with diazepam. Methanol, isopropanol, acetaminophen or salicylate levels were unremarkable and other laboratory studies were within normal limits. Approximately 6 hours after ingestion, transient generalized tonic-clonic seizures occurred with desaturation and laryngospasm requiring intubation. No further seizures were observed with sedation. The patient was successfully extubated the following day. He had no prior history of seizures and reported that he impulsively consumed 39 g (650 mg/kg) of ground nutmeg and 0.75 liters of vodka with 6 bottles of beer or cider (Flam et al, 2015).
    5) CASE REPORT: Repeated doses of 120 to 650 mg produced agitation, sense of impending death, vomiting, polydipsia, "uncomfortable feelings in the head" and disruptive behavior in a psychotic adult (Brenner et al, 1993).
    6) CASE REPORT: A 20-year-old man ingested 4 whole nutmegs and half of a liter of vodka and developed tingling in his hands and feet, dry mouth, nausea, palpitations and dizziness about 5 hours later. At presentation some 14 hours later, the patient had become highly agitated with flushing, tachycardia (130 bpm), dilated pupils and hyper-reflexia of the upper and lower limbs. Laboratory studies were normal. He was admitted for observation and his altered mental status persisted for 32 hours and sinus tachycardia resolved after 20 hours. The patient was discharged 3 days after admission following psychiatric evaluation (Quin et al, 1998).
    7) CASE REPORT: A 16-year-old healthy teenager ingested 25 g of powered nutmeg and woke up with complaints of right-sided facial weakness, right arm paresis, paresthesia and palpitations. Upon admission he was found to be lethargic with a slow affect and sluggish pupils. Facial weakness and paresis had resolved, but paresthesia was ongoing. Other symptoms included tachycardia (121 bpm) and non-specific ECG changes with normal cardiac enzymes. He was observed for 24 hours and all symptoms resolved spontaneously (McKenna et al, 2004).
    8) CASE REPORT: An 18-year-old girl developed palpitations, tachycardia (102 beats/min), drowsiness, nausea, dizziness, thirst, agitation, anxiety, restlessness, and dry mouth 30 minutes after drinking 3 quarters of a milkshake containing 50 g of grated nutmeg. She complained of being "in a trance state". A 12 lead ECG revealed a fast sinus dysrhythmia (rate: 95 to 110 beats/min) with no ischemic or hypertrophic changes. She recovered completely following supportive therapy (Demetriades et al, 2005).

Serum Plasma Blood Concentrations

    7.5.2) TOXIC CONCENTRATIONS
    A) TOXIC CONCENTRATION LEVELS
    1) CONCENTRATION LEVEL
    a) A myristicin blood level of 2 mcg/mL was reported 8 hours after ingestion of approximately 14 to 21 g of nutmeg powder (Hentschel et al, 2000; Stein et al, 2001).
    b) Postmortem analysis of a 55-year-old woman showed a myristicin level of 4 mcg/mL following ingestion of nutmeg (the estimated dose ingested was 560 to 840 mg/kg) (Hentschel et al, 2000; Stein et al, 2001).

Toxicity Information

    7.7.1) TOXICITY VALUES
    A) LD50- (INTRAPERITONEAL)RAT:
    1) >1,500 mg/kg (Truitt et al, 1961)
    B) LD50- (ORAL)RAT:
    1) 4260 mg/kg (RTECS, 2001)

Summary

    A) TOXIC DOSE: Myristicin doses of 6 to 7 mg/kg have resulted in symptoms in patients. Doses up to 80 g of nutmeg powder have been ingested without resulting in life-threatening effects. One young adult developed tonic-clonic seizures about 6 hours after ingesting 39 g (650 mg/kg [actual body weight]) of ground nutmeg and alcohol; he recovered completely following airway management and sedation. Fatality is generally not expected in nutmeg abuse.

Therapeutic Dose

    7.2.1) ADULT
    A) GENERAL
    1) Nutmeg has been used to control diarrhea associated with medullary carcinoma in man in doses of 9 teaspoonfuls per day (Venables et al, 1976). This dose has produced toxic symptoms.

Pharmacology Toxicology

Toxicologic Mechanism

    A) The exact mechanism of action is not known. It is thought that myristicin has an indol-like structure similar to reserpine and can act as a serotonin antagonist (responsible for the CNS effects observed). Myristicin is also a weak inhibitor of monoamine oxidase, which may contribute to the cardiovascular effects (Sjoholm et al, 1998). Nutmeg (and synthetic myristicin) inhibits monoamine oxidase (MAO) in animals. The potency of myristicin is approximately half that of tranylcypromine (Anon, 1984)
    B) The acute toxicity of myristicin is considered to be relatively low (Barceloux, 2009).
    C) There is some speculation that myristicin and elemicin may be changed to their amino derivatives upon metabolism.
    1) A probable derivative of myristicin is MMDA (3-methoxy-4,5,dimethylenedioxamphetamine) and of elemicin is TMA (3,4,5-trimethoxyamphetamine) both of which are psychoactive compounds related to amphetamine, with effects similar to LSD (Mack, 1982).
    2) The percentage of these produced during metabolism is unknown (Anon, 1984).
    D) Nutmeg's antidiarrheal effect may be due to inhibition of the synthesis and activity of prostaglandins in the colonic mucosa (Dietz & Stewart, 1976).
    E) Myristicin, in studies done on carrageen-induced edema in rats and acetic acid-induced vascular permeability in mice, was shown to have anti-inflammatory properties approximately equal to indomethacin (10 mg/kg) (Ozaki et al, 1989).
    F) Mace, derived from the red, net-like skin covering Myristica fragrans seeds is known to contain antimicrobials (Orabi et al, 1991).

Physicochemical

Physical Characteristics

    A) Myristicin is a clear, colorless oil.

Molecular Weight

    A) Varies

References

General Bibliography

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