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Myristica fragrans Houtt.

1. NAME
   1.1 Scientific name
   1.2 Family
   1.3 Common name(s) and synonym(s)
2. SUMMARY
   2.1 Main risks and target organs
   2.2 Summary of clinical effects
   2.3 Diagnosis
   2.4 First-aid measures and management principles
   2.5 Poisonous parts
   2.6 Main toxins
3. CHARACTERISTICS
   3.1 Description of the plant
      3.1.1 Special identification features
      3.1.2 Habitat
      3.1.3 Distribution
   3.2 Poisonous parts of the plant
   3.3 The toxin(s)
      3.3.1 Name(s)
      3.3.2 Description, chemical structure, stability
      3.3.3 Other physico-chemical characteristics
   3.4 Other chemical contents of the plant
4. USES/CIRCUMSTANCES OF POISONING
   4.1 Uses
      4.1.1 Uses
      4.1.2 Description
   4.2 High risk circumstances
   4.3 High risk geographical areas
5. ROUTES OF EXPOSURE
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eye
   5.5 Parenteral
   5.6 Others
6. KINETICS
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life by route of exposure
   6.4 Metabolism
   6.5 Elimination and excretion
7. TOXINOLOGY
   7.1 Mode of action
   7.2 Toxicity
      7.2.1 Human data
         7.2.1.1 Adults
         7.2.1.2 Children
      7.2.2 Relevant animal data
      7.2.3 Relevant in vitro data
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
8. TOXICOLOGICAL/TOXINOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS
   8.1 Material sampling plan
      8.1.1 Sampling and specimen collection
         8.1.1.1 Toxicological analyses
         8.1.1.2 Biomedical analyses
         8.1.1.3 Arterial blood gas analysis
         8.1.1.4 Haematological analyses
         8.1.1.5 Other (unspecified) analyses
      8.1.2 Storage of laboratory samples and specimens
         8.1.2.1 Toxicological analyses
         8.1.2.2 Biomedical analyses
         8.1.2.3 Arterial blood gas analysis
         8.1.2.4 Haematological analyses
         8.1.2.5 Other (unspecified) analyses
      8.1.3 Transport of laboratory samples and specimens
         8.1.3.1 Toxicological analyses
         8.1.3.2 Biomedical analyses
         8.1.3.3 Arterial blood gas analysis
         8.1.3.4 Haematological analyses
         8.1.3.5 Other (unspecified) analyses
   8.2 Toxicological Analyses and Their Interpretation
      8.2.1 Tests on toxic ingredient(s) of material
         8.2.1.1 Simple Qualitative Test(s)
         8.2.1.2 Advanced Qualitative Confirmation Test(s)
         8.2.1.3 Simple Quantitative Method(s)
         8.2.1.4 Advanced Quantitative Method(s)
      8.2.2 Tests for biological specimens
         8.2.2.1 Simple Qualitative Test(s)
         8.2.2.2 Advanced Qualitative Confirmation Test(s)
         8.2.2.3 Simple Quantitative Method(s)
         8.2.2.4 Advanced Quantitative Method(s)
         8.2.2.5 Other Dedicated Method(s)
      8.2.3 Interpretation of toxicological analyses
   8.3 Biomedical investigations and their interpretation
      8.3.1 Biochemical analysis
         8.3.1.1 Blood, plasma or serum
         8.3.1.2 Urine
         8.3.1.3 Other fluids
      8.3.2 Arterial blood gas analyses
      8.3.3 Haematological analyses
      8.3.4 Interpretation of biomedical investigations
   8.4 Other biomedical (diagnostic) investigations and their interpretation
   8.5 Overall interpretation of all toxicological analyses and toxicological investigations
   8.6 References
9. CLINICAL EFFECTS
   9.1 Acute poisoning:
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure
      9.1.6 Other
   9.2 Chronic poisoning
      9.2.1 Ingestion
      9.2.2 Inhalation
      9.2.3 Skin exposure
      9.2.4 Eye contact
      9.2.5 Parenteral exposure
      9.2.6 Other
   9.3 Course, prognosis, cause of death
   9.4 Systematic description of clinical effects
      9.4.1 Cardiovascular
      9.4.2 Respiratory
      9.4.3 Neurological
         9.4.3.1 Central nervous system (CNS)
         9.4.3.2 Peripheral nervous system
         9.4.3.3 Autonomic nervous system
         9.4.3.4 Skeletal and smooth muscle
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary
         9.4.6.1 Renal
         9.4.6.2 Other
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eye, ear, nose, throat: local effects
      9.4.10 Haematological
      9.4.11 Immunological
      9.4.12 Metabolic
         9.4.12.1 Acid-base disturbances
         9.4.12.2 Fluid and electrolyte disturbances
         9.4.12.3 Others
      9.4.13 Allergic reactions
      9.4.14 Other clinical effects
      9.4.15 Special risks
   9.5 Other
   9.6 Summary
10. MANAGEMENT
   10.1 General principles
   10.2 Life supportive procedures and symptomatic/specific treatment
   10.3 Decontamination
   10.4 Enhanced elimination
   10.5 Antidote/antitoxin treatment
      10.5.1 Adults
      10.5.2 Children
   10.6 Management discussion
11. ILLUSTRATIVE CASES
   11.1 Case reports from literature
12. ADDITIONAL INFORMATION
   12.1 Specific preventative measures
   12.2 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES)
    MYRISTICA FRAGRANS

    International Programme on Chemical Safety
    Poisons Information Monograph 355
    Plant

    1.  NAME

        1.1  Scientific name

             Myristica fragrans Houtt.

        1.2  Family

             Myristicaceae

        1.3  Common name(s) and synonym(s)

             mace (UK); muscadier (France); Muskatbaum
             (Germany); myristica; nuez moscada (Uruguay, Spain);
             nutmeg (UK); nutmeg tree (UK); nux moschata;
             Myristica officinalis L.

    2.  SUMMARY

        2.1  Main risks and target organs

             -transient psychosis
    
             -possibility of fatty liver and hepatic necrosis
    
             -transient renal toxicity
    
             -possible carcinogen and teratogen
    
             -possibility of death occurring

        2.2  Summary of clinical effects

             Nutmeg intoxication resembles anticholinergic
             intoxication, e.g. profuse sweating, flushed face, delirium,
             dry throat etc.  There is always an altered state of mind,
             e.g. hallucinations, confusion and an impending sense of
             doom.  Clinical symptoms may be contradictory depending on
             the length of time lapsed after ingesting the toxin. 
             Symptoms also vary according to the dose taken and the
             variability between different samples of nutmegs.

        2.3  Diagnosis

             Blood: for electrolytes, liver enzymes and renal
             function tests; plus urinalysis.

        2.4  First-aid measures and management principles

             Management
    
             Treatment is symptomatic and supportive.  The use of
             cathartics, gastric lavage or ipecac may be beneficial if
             they are not contraindicated.  A sedative and anticonvulsant
             may be administered to calm the patient and combat seizures
             should they occur.  A liquid diet high in protein and
             carbohydrate, but low in fat, is recommended.

        2.5  Poisonous parts

             The seeds (nutmeg) and, to a lesser extent, the aril
             (mace).

        2.6  Main toxins

             Myristicin and elemicin, but intoxication is not thought
             to be due to these alone.

    3.  CHARACTERISTICS

        3.1  Description of the plant

             3.1.1  Special identification features

                    M. fragrans is a spreading aromatic evergreen
                    tree usually growing to around 5 to 13 metres high,
                    occasionally 20 metres.  The bark contains watery pink
                    or red sap.  The pointed dark green leaves (5 to 15 cm
                     2 to 7 cm) are arranged alternately along the
                    branches and are borne on leaf stems about 1 cm long. 
                    Upper leaf surfaces are shiny.  Flowers are usually
                    single sexed; occasionally male and female flowers are
                    found on the same tree.  Female flowers arise in
                    groups of 1 to 3; males in groups of 1 to 10.  Flowers
                    are pale yellow, waxy, fleshy and bell-shaped.  Male
                    flowers are 5 to 7 mm long; female flowers are up to
                    1 cm long.  The fruits are fleshy, drooping, yellow,
                    smooth, 6 to 9 cm long with a longitudinal ridge. 
                    When ripe, the succulent yellow fruit coat splits into
                    2 valves revealing a purplish-brown, shiny seed
                    (nutmeg) surrounded by a red aril (mace).  Seeds
                    (nutmegs) are broadly ovoid (2 to 3 cm long), firm,
                    fleshy, whitish and transversed by red-brown veins. 
                    When fresh, the aril (mace) is bright scarlet becoming
                    more horny, brittle and a yellowish-brown colour when
                    dried (Purseglove, 1968).
    

                    The tree does not flower until around 9 years old,
                    when it fruits; it can continue to do so for a further
                    75 years.  The tree bears 2 to 3 crops a year.  The
                    seeds (nutmegs) need 3 to 6 weeks to dry before they
                    are ready for use.

             3.1.2  Habitat

                    Grows wild on rich volcanic soils in lowland
                    tropical rain forests.  Its cultivation as a crop is
                    largely confined to islands in the hot, humid tropics
                    at altitudes up to 4,500 metres (Purseglove,
                    1968).

             3.1.3  Distribution

                    Indigenous to the Moluccas and Banda Islands in
                    the South Pacific although it is seldom found truly
                    wild.  It is now cultivated in tropical regions,
                    especially Indonesia, Grenada in the West Indies and
                    Sri Lanka (Purseglove, 1968; Bown, 1995).

        3.2  Poisonous parts of the plant

             Seeds (nutmegs) and to a lesser extent the aril
             (mace).
    
             Nutmeg oil:
    
             Nutmeg oil is also known as oleum myristicae, ol. myrist.,
             myristica oil, essence de muscade, atheririsches muskatol,
             essencia de moscada and essencia de nuez moscada.  It is a
             volatile oil obtained by steam distillation from the seed. 
             It is a colourless or pale yellow liquid with an odour and
             taste of nutmeg.  It is scarcely distinguishable from the
             volatile oil of mace and frequently no commercial distinction
             is made between the two.  There are two types of nutmeg oil,
             mainly East Indian Nutmeg Oil and West Indian Nutmeg Oil. 
             The East Indian Nutmeg Oil has a weight of 0.885 to 0.915
             g/mL and is soluble in 90% alcohol at a ratio of 1 part oil
             to 3 parts alcohol.  West Indian Nutmeg Oil has a weight of
             0.86-0.88 g/mL and is soluble in 90% alcohol at a ratio of 1
             part oil to 4 parts alcohol.  Nutmeg oil should be stored in
             a cool place in well filled airtight containers and protected
             from light.
    
             Nutmeg Butter:
    
             Nutmeg butter, also known as balsam of nutmegs, oil of mace,
             butter of mace, Banda soap and oleum myristicae expressum is
             the fixed oil component of the seed (nutmeg).  It accounts
             for 25 to 40% of the nutmeg's weight and it is a solid at

             room temperature.  Sometimes it occurs in the form of
             prismatic crystals.  It is obtained by exposing the nuts to
             hydraulic pressure and heat.
    
             Pharmacologically active parts of the plant:
    
             The most important part of the plant in terms of its
             pharmacological activity and also in commerce, is of course
             the dried kernel (seed), the nutmeg.  Intoxication from the
             use of the aril of the fruit (seed case), generally known as
             mace, has also been reported, but only rarely.  The oil of
             nutmeg has also been used for medicinal purposes and it is
             this fraction of the nutmeg which is strongly suspected of
             harbouring the pharmacologically active components of
             nutmeg.

        3.3  The toxin(s)

             No single component of the nutmeg has been identified as
             responsible for all the symptoms seen during intoxication. 
             It is widely believed that myristicin is the major component
             responsible, however, it alone cannot reproduce all the
             symptoms.  Shulgin (1966) suggests that myristicin and
             elemicin may not be the active ingredients but they may be
             metabolized in the body to 3-methoxy-4,5-methylenedioxy
             amphetamine (MMDA) and elemicine, an ether analogous to
             myristicin, 3,4,5-trimethoxy amphetamine (TMA).

             3.3.1  Name(s)

                    Myristicin:
                    CAS number:   607-91-0
                    Molecular formula: C11H12O3
                    Molecular weight: 192.21
    
                    Elemicin:
                    CAS number:  487-11-6
                    Molecular formula:  C12H16O3
                    Molecular weight: 208.26
                    (Harborne & Baxter, 1996).

             3.3.2  Description, chemical structure, stability

                    Components of nutmeg
    
                    The major components in M. fragrans are terpenes,
                    terpene alcohols and phenolic ethers.  The major
                    phenolic ether is myristicin (4-methoxy-6-(2-
                    propenyl)-1,3-benzadioxole) accompanied by safrole
                    (5-(2-propenyl)-3-benzodioxole) and eugenol methyl
                    ether (3,4,-dimethoxy-(2-propenyl)-benzene). 
                    Myristicin accounts for about 2.12 to 2.88% of the
                    total weight of the nutmeg where as safrole accounts

                    for 0.27 to 0.39%.  The volatile oil content of nutmeg
                    depends on the geographical origin and length of
                    storage.  Chemical analysis has shown that even though
                    there is a real variability between the quality
                    (differences in composition) and quantity of nutmeg
                    oil from various samples of nutmegs oil accounts for
                    84 to 95% of the total aromatic fraction of the
                    volatile oil from all the samples tested.  In the
                    samples, myristicin, safrole and elemicin accounted
                    for 3.86 to 12.7%, 0.53 to 3.42% and 0.02 to 2.36%,
                    respectively of the nutmeg oil samples.  Early work on
                    myristicin used myristicin distilled from nutmeg oil. 
                    It has been subsequently proven that myristicin
                    extracted from nutmeg via this method is not elemicin
                    free and therefore the effects reported may be due to
                    either substances found in the extract.

             3.3.3  Other physico-chemical characteristics

                    No data available.

        3.4  Other chemical contents of the plant

             No data available.

    4.  USES/CIRCUMSTANCES OF POISONING

        4.1  Uses

             4.1.1  Uses

                    Miscellaneous pharmaceutical product
                    Other therapeutic preparation
                    Food; 
                    general
                    Beverage; general

             4.1.2  Description

                    Medicinal:
    
                    Used as an anti-diarrhoea agent for patients with
                    medullary carcinoma of the thyroid.  The effectiveness
                    of the treatment may be due to the inhibition of
                    prostaglandin synthesis in the mucosa and submucosa of
                    the colon.  The dosage given was 9 tablespoons orally
                    per day but it may vary between patients to avoid
                    toxic symptoms.
    
                    Domestic:
    
                    Used as a spice in various dishes, as components of
                    teas and soft drinks or mixed in milk and alcohol.
                    Traditional and folk medicine:
    

                    It is widely used as a traditional medicine in the
                    Middle East and Asia.
    
                    In Western medicine nutmeg is sometimes used as a
                    stomachic, stimulant, carminative as well as for
                    intestinal catarrh and colic, to stimulate appetites,
                    to control flatulence, and it has a reputation as a
                    emmenagogue and abortifacient.

        4.2  High risk circumstances

             Abuse
    
             Nutmeg has been known for its hallucinogenic properties for a
             long time.  Adults may abuse the hallucinogenic properties of
             nutmeg.  Children may be at high risk at home, since nutmeg
             may be widely available as a cooking additive.  In the course
             of its use in traditional medicine, overdose may occur.

        4.3  High risk geographical areas

             No data available.

    5.  ROUTES OF EXPOSURE

        5.1  Oral

             This is the most common method of consuming nutmeg, be
             it as a remedy, a spice or as a psychotropic drug.

        5.2  Inhalation

             Nutmeg is mixed with tobacco snuff in certain parts of
             southern India.  Intoxication through this method of
             administration is reported to be the same as for intoxication
             through oral administration, except that the onset of
             symptoms is faster.

        5.3  Dermal

             No data available.

        5.4  Eye

             No data available.

        5.5  Parenteral

             Reported only in experimental animals.  The effects are
             reported to be the same as those when given orally.

        5.6  Others

             No data available.

    6.  KINETICS

        6.1  Absorption by route of exposure

             No detailed studies are available concerning the
             absorption of the active principles involved in nutmeg
             poisoning.  Current literature states that when nutmeg powder
             is administered orally, the toxic effects begin within 1 to
             12 hours.  The effects last generally for 24 hours but may
             continue for as long as a week or more.  When taken as a tea,
             the reaction is reported to be immediate.  Snuffing nutmeg is
             reported to produce a reaction within 15 minutes.

        6.2  Distribution by route of exposure

             No data available.

        6.3  Biological half-life by route of exposure

             No data available.

        6.4  Metabolism

             3,4,5,-trimethoxy amphetamine (TMA):
    
             It has been postulated that elemicin, a major component in
             nutmeg oil, could undergo oxidation of its oleficin side
             chain in the same manner that the mentioned side chain in
             safrole is also oxidized in the body.  This would produce a
             vinyl alcohol which could under go transamination to produce
             TMA.
    
             The potency of TMA is reported to be more than that of
             mescaline as a psychotropic drug.
    
             3-methoxy-4,5-methylenedioxy amphetamine (MMDA):
    
             It has been proposed that myristicin may be metabolized in
             the body to MMDA in a manner similar to the metabolism of
             elimicin into TMA.
    
             MMDA is reported to have a higher potency than TMA as a
             psychotropic  drug, that is, its potency is about three times
             the potency of mescaline.  It has almost the same properties
             as TMA, being both hallucinogenic and permitting total recall
             of the experience.

        6.5  Elimination and excretion

             No data available.

    7.  TOXINOLOGY

        7.1  Mode of action

             3,4,5,-trimethoxy amphetamine (TMA):

             It has been postulated that elemicin, a major component in
             nutmeg oil, could undergo oxidation of its oleficin side
             chain in the same manner that the mentioned side chain in
             safrole is also oxidized in the body.  This would produce a
             vinyl alcohol which could under go transamination to produce
             TMA.
    
             The potency of TMA is reported to be more than that or
             mescaline as a psychotropic drug.
    
             3-methoxy-4,5-methylenedioxy amphetamine (MMDA):
    
             It has been proposed that myristicin may be metabolized in
             the body to MMDA in a manner similar to the metabolism of
             elimicin into TMA.
    
             MMDA is reported to have a higher potency than TMA as a
             psychotropic  drug, that is, its potency is about three times
             the potency of mescaline.  It has almost the same properties
             as TMA, being both hallucinogenic and permitting total recall
             of the experience.
    
             Nutmeg has monoamineoxidase inhibition properties (1963). 
             Nutmeg is also known to have anti-prostaglandin synthesis
             effects.

        7.2  Toxicity

             7.2.1  Human data

                    7.2.1.1  Adults

                             The dose needed to induce
                             intoxication varies according to the quality
                             and length of storage of the nutmeg.  1 to 3
                             nutmegs (5 to 15 g) is reported as the toxic
                             dose (Haddad & Winchester, 1983).

                    7.2.1.2  Children

                             Death by nutmeg intoxication has
                             been reported by Cushny (Weil, 1964) in an 8-
                             year-old boy after consuming 2 nutmegs.

             7.2.2  Relevant animal data

                    In cats, an oral dose of 24 mg nutmeg oil per
                    kg body weight was found to be lethal.

             7.2.3  Relevant in vitro data

                    No data available.

        7.3  Carcinogenicity

             Safrole is a known mild hepatocarcinogen.  Although
             safrole itself is not carcinogenic, it is metabolized to form
             1'-hydroxysafrole which is carcinogenic.  Data are not
             available on the carcinogenicity of nutmeg itself.

        7.4  Teratogenicity

             Verrett (Wulf et al., 1978) reports that myristicin may
             be a strong teratogen.

        7.5  Mutagenicity

             No data available.

        7.6  Interactions

             Consideration should be given to possible nutmeg-ethanol
             interaction since nutmeg has hallucinogenic and MAO
             inhibition effects.

    8.  TOXICOLOGICAL/TOXINOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS

        8.1  Material sampling plan

             8.1.1  Sampling and specimen collection

                    8.1.1.1  Toxicological analyses

                    8.1.1.2  Biomedical analyses

                    8.1.1.3  Arterial blood gas analysis

                    8.1.1.4  Haematological analyses

                    8.1.1.5  Other (unspecified) analyses

             8.1.2  Storage of laboratory samples and specimens

                    8.1.2.1  Toxicological analyses

                    8.1.2.2  Biomedical analyses

                    8.1.2.3  Arterial blood gas analysis

                    8.1.2.4  Haematological analyses

                    8.1.2.5  Other (unspecified) analyses

             8.1.3  Transport of laboratory samples and specimens

                    8.1.3.1  Toxicological analyses

                    8.1.3.2  Biomedical analyses

                    8.1.3.3  Arterial blood gas analysis

                    8.1.3.4  Haematological analyses

                    8.1.3.5  Other (unspecified) analyses

        8.2  Toxicological Analyses and Their Interpretation

             8.2.1  Tests on toxic ingredient(s) of material

                    8.2.1.1  Simple Qualitative Test(s)

                    8.2.1.2  Advanced Qualitative Confirmation Test(s)

                    8.2.1.3  Simple Quantitative Method(s)

                    8.2.1.4  Advanced Quantitative Method(s)

             8.2.2  Tests for biological specimens

                    8.2.2.1  Simple Qualitative Test(s)

                    8.2.2.2  Advanced Qualitative Confirmation Test(s)

                    8.2.2.3  Simple Quantitative Method(s)

                    8.2.2.4  Advanced Quantitative Method(s)

                    8.2.2.5  Other Dedicated Method(s)

             8.2.3  Interpretation of toxicological analyses

        8.3  Biomedical investigations and their interpretation

             8.3.1  Biochemical analysis

                    8.3.1.1  Blood, plasma or serum

                             "Basic analyses"
                             "Dedicated analyses"
                             "Optional analyses"

                    8.3.1.2  Urine

                             "Basic analyses"
                             "Dedicated analyses"
                             "Optional analyses"

                    8.3.1.3  Other fluids

             8.3.2  Arterial blood gas analyses

             8.3.3  Haematological analyses

                    "Basic analyses"
                    "Dedicated analyses"
                    "Optional analyses"

             8.3.4  Interpretation of biomedical investigations

        8.4  Other biomedical (diagnostic) investigations and their
             interpretation

        8.5  Overall interpretation of all toxicological analyses and
             toxicological investigations

        8.6  References

    9.  CLINICAL EFFECTS

        9.1  Acute poisoning:

             9.1.1  Ingestion

                    In the toxic state, the patient first feels
                    excited and may have psychedelic hallucinations.  This
                    is followed by a period of drowsiness, delirium and,
                    possibly, unconsciousness.  Thirst has been reported.  
                    Mental concentration may either be impaired or
                    enhanced;  delirium with agitation, disorientation and
                    incoherence may develop.  Prison inmates taking nutmeg
                    "trips" have compared it to alcohol, heroin and
                    marihuana and referred to it as making them feel
                    "high", relaxed and drowsy.  Some reported a sleepy
                    feeling, others, restlessness and tense.  Most
                    patients with accidental nutmeg intoxication
                    experience an impending sense of doom after the
                    initial excitation.  The effects of nutmeg are most
                    often compared to those of marihuana.  Although the
                    hallucinogenic effects of nutmeg are satisfactory, the
                    side effects often discourage its use as such an
                    agent.  One reported case of nutmeg intoxication after
                    drinking nutmeg tea, states that the reaction is
                    immediate.

             9.1.2  Inhalation

                    The effects by inhalation are generally similar
                    to those experienced via oral administration with the
                    exception that onset is faster by 15 minutes.

             9.1.3  Skin exposure

                    No data available.

             9.1.4  Eye contact

                    No data available.

             9.1.5  Parenteral exposure

                    Parenteral exposure in animals has shown to
                    produce the same general effect as that of oral
                    exposure.

             9.1.6  Other

                    No data available.

        9.2  Chronic poisoning

             9.2.1  Ingestion

                    Chronic poisoning by oral administration has
                    caused temporary (up to six months) psychosis in
                    prison inmates.

             9.2.2  Inhalation

                    No data available.

             9.2.3  Skin exposure

                    No data available.

             9.2.4  Eye contact

                    No data available.

             9.2.5  Parenteral exposure

                    No data available.

             9.2.6  Other

        9.3  Course, prognosis, cause of death

             Not all the symptoms listed below appear in every case
             of poisoning.  Contradicting symptoms may occur at different
             times during the course of intoxication.
    
             The subject initially feels excited, then drowsy before a
             delirious state sets in.  This is followed by a deep sleep. 
             During this period, cyanosis of the extremities and
             convulsions may occur.  Generally there is tachycardia and an
             increase in blood pressure.  Acidosis may set in because of
             diarrhoea and vomiting which is usually present along with
             various other gastrointestinal symptoms such as abdominal
             cramps.  The subject may or may not be hallucinating but
             usually expresses a feeling of impending doom.  Nutmeg
             intoxication usually clears by itself within 24 hours,
             however, it has been reported that psychosis may set in. 
             Transient renal toxicity has also been reported causing an
             increase in albumin and non-protein nitrogen content in the
             urine, returning to normal within 24 hours.
    
             Nutmeg has been proven to cause fatty liver in cats which
             have later died from the dose of nutmeg oil but, in the case
             of humans, this is not clear since only one death has been
             attributed to nutmeg toxicity: an 8-year-old boy who became
             comatose and later died after ingesting two nutmegs.

        9.4  Systematic description of clinical effects

             9.4.1  Cardiovascular

                    Tachycardia.
                    Hypertension or hypotension may occur.
                    Chest pains or tightness in chest.

             9.4.2  Respiratory

                    No data available.

             9.4.3  Neurological

                    9.4.3.1  Central nervous system (CNS)

                             Severe headaches.
                             Drowsiness several hours after taking nutmeg.
                             Fitful sleep/convulsions.
                             Hallucinations (predominantly visual). Colour
                             distortion may also occur.
                             Delirium.
                             Unconsciousness/coma.
                             Agitation.
                             Disorientation.
                             Incoherence.
    

                             Sedation.
                             Euphoria.
                             Concentration may be impaired or improved.
                             Excitation resembling that caused by
                             anticholinergic intoxication.
                             Florid paranoia.
                             Belligerence.
                             Vertigo.
                             Stupor.
                             Feeling of impending doom.
    
                             Sometimes unusual behaviour occurs during
                             intoxication such as hysteria and wild
                             trashing of limbs, and behaviour resembling
                             that of a snarling dog.

                    9.4.3.2  Peripheral nervous system

                             Initial stimulation after
                             administration.
                             Strong tingling in the fingers and toes
                             shortly after snuffing some nutmeg.
                             Numbness in hand and feet half an hour after
                             snuffing nutmeg.
                             Absent limb reflexes.

                    9.4.3.3  Autonomic nervous system

                             Profuse sweating several hours after
                             administration possibly reflecting
                             amphetamine-type reaction.
                             Absence of salivation.

                    9.4.3.4  Skeletal and smooth muscle

                             Muscular excitation several hours
                             after administration.

             9.4.4  Gastrointestinal

                    Nausea.
                    Vomiting.
                    Diarrhoea.
                    Abdominal pain.

             9.4.5  Hepatic

                    Hepatic necrosis in heavy poisoning.
                    Fatty degradation of liver.

             9.4.6 Urinary

                    9.4.6.1  Renal

                             Transient renal toxicity producing
                             albuminuria.  Non-protein nitrogen content in
                             urine which returns to normal within 24
                             hours.

                    9.4.6.2  Other

                             No data available.

             9.4.7  Endocrine and reproductive systems

                    No data available.

             9.4.8  Dermatological

                    Flushed skin.

             9.4.9  Eye, ear, nose, throat:  local effects

                    Eyes: A drawing sensation over the eyes after
                    snuffing.
                    Miosis (initially or it may not occur)
                    Mydriasis (occurs less often than miosis)
    
                    Throat: Epigastric pain

             9.4.10 Haematological

                    No data available.

             9.4.11 Immunological

                    No data available.

             9.4.12 Metabolic

                    9.4.12.1 Acid-base disturbances

                             Acidosis may be attributed to
                             excessive diarrhoea and vomiting.

                    9.4.12.2 Fluid and electrolyte disturbances

                             Fluid and electrolyte disturbance
                             may develop because of diarrhoea and
                             vomiting.

                    9.4.12.3 Others

                             Hypothermia/hyperthermia.

             9.4.13 Allergic reactions

                    Oedema of eyelids.
                    Possible elevation in body temperature.
                    Marked flushing and itching of face.
                    Allergic reactions tend to subside quickly.

             9.4.14 Other clinical effects

                    Severe thirst.

             9.4.15 Special risks

                    Nutmeg has been used as an abortifacient but
                    there are no confirmed clinical accounts.

        9.5  Other

             No data available.

        9.6  Summary

    10. MANAGEMENT

        10.1 General principles

             Treatment is supportive.  Decontamination procedures,
             such as gastric lavage and cathartics, are theoretically
             beneficial within the first few hours but be aware of any
             contraindications before their administration.  Syrup of
             ipecac is not advisable because it may precipitate
             convulsions.  Milk or a demulcent may be given to alleviate
             gastric irritation.

        10.2 Life supportive procedures and symptomatic/specific treatment

             Nasal oxygen may be administered to patients suffering
             from vertigo.  Barbiturates or diazepam may be given for
             convulsions and analeptics such as chlorpromazine  (25 mg
             every 4 hours) for severe agitation.  Sedatives should be
             administered with caution since the patient goes through
             alternating periods of delirium and lethargy.  A liquid diet
             is recommended, high in protein and carbohydrate and low in
             fat.  Wash eyes if they are physically contaminated by nutmeg
             powder.  Monitor cardiac function and blood pressure and
             treat as necessary.

        10.3 Decontamination

             Decontamination procedures such as gastric lavage and
             cathartics are theoretically beneficial within the first few
             hours but be aware of any contraindications before their
             administration. Syrup of ipecac is not advisable because it
             may precipitate convulsions.  Milk or a demulcent may be
             given to alleviate gastric irritation.

        10.4 Enhanced elimination

             No data available.

        10.5 Antidote/antitoxin treatment

             10.5.1 Adults

                    No data available.

             10.5.2 Children

                    No data available.

        10.6 Management discussion

             No data available.

    11. ILLUSTRATIVE CASES

        11.1 Case reports from literature

             Two male college students, 19 and 20 years of age, each
             ingested 2 tablespoons (about 14 gm) of powdered nutmeg
             suspended in a glass of milk to produce a sense of
             exhilaration.  Five hours later, rapid heart rates and
             palpitations were noted and both complained of dry mouths and
             thirst.  Onlookers observed that one student became
             hyperactive, agitated and talked incoherently.  Their faces
             were "red as beets".  Nausea, vomiting and abdominal cramps
             were absent.  60 hours were needed for full recovery.
    
             A 37 year old woman drank a nutmeg tea at a party.  The tea
             consisted of two ground nutmegs in a glass of warm water. 
             She had flushed skin, rapid pulse, incoherent speech and felt
             giddy after 4 hours.  Her vision was disturbed and she had
             hallucinations of faces laughing at her and monsters in the
             bed trying to engulf her.  Symptoms gradually diminished and
             recovery made within 24 hours.

    12. ADDITIONAL INFORMATION

        12.1 Specific preventative measures

             No information available.

        12.2 Other

             No information available

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    14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
        ADDRESS(ES)

        Author: UKM
        Kuala Lumpur
        Malaysia
    
        Date: April 1991
    
        Peer Review: Singapore, November 1991
    
        General edit and botanical review:
    
        Christine Leon
        Medical Toxicology Unit
        Guy's & St Thomas Hospital Trust
        c/o Royal Botanic Gardens, Kew
        Richmond
        Surrey
        TW9 3AB
        United Kingdom
    
        Tel: +44 (0) 181 332 5702
        Fax: +44 (0) 181 332 5768
        e-mail: c.leon@rbgkew.org.uk
    
        July 1997
    


    See Also:
       Toxicological Abbreviations