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The spice of life: An analysis of nutmeg exposures in California
SHAUN D. CARSTAIRS1 and F. LEE CANTRELL2
1Department of Emergency Medicine, Naval Medical Center, San Diego, CA, USA2California Poison Control System- San Diego, San Diego, CA, USA
Background. Nutmeg is widely used as a household spice. Numerous citations in the medical literature report its abuse as a psychoactiveagent, primarily for its purported hallucinogenic effects that are thought to be due to the compound myristicin; these are primarily limitedto case reports. Methods. We performed a retrospective review of the California Poison Control System database for the years 1997–2008 for all cases of single-substance human exposure to nutmeg. Results. There were a total of 119 single-substance exposures tonutmeg. Eighty-six (72.3%) exposures were intentional. Patients intentionally abusing nutmeg were more likely to be between the ages of13 and 20 than those with unintentional exposure to the spice (80.2% vs. 9.1%, p5 0.05). Abusers were significantly more likely torequire medical evaluation than nonabusers (61.6% vs. 33.3%, p5 0.05). Patients who abused nutmeg were significantly more likely(p5 0.05) to experience tachycardia and agitation than those whose exposure was unintentional. No major effects and no deaths werereported to occur in either group. Conclusions. Although nutmeg exposure is uncommonly encountered, clinical effects from ingestioncan be significant and can require medical intervention. While clinically significant effects were common, life-threatening toxicity anddeath did not occur in this series.
Keywords Poisoning; Nutmeg; Abuse
Introduction
Nutmeg has been used for centuries as a household spice.Numerous citations in the medical literature have reportedits use as a psychoactive agent, primarily for purportedhallucinogenic effects that are thought to be due to thecompound myristicin. These are primarily limited to casereports.1–12 We sought to identify characteristics of patientswith reported exposure to nutmeg and to comparecharacteristics of patients intentionally abusing nutmeg withthose of patients whose exposure to the spice wasunintentional.
Methods
The University of California-San Diego Institutional ReviewBoard approved this observational case series. A retro-spective chart review of the California Poison ControlSystem (CPCS) electronic database (Visual Dotlab, Madera,CA) for cases between 1997 and 2008 was performed
(standardized data collection in California with this systembegan in 1997). Search codes included the terms ‘‘nutmeg’’and ‘‘Myristica fragrans’’; to ensure that all cases wereidentified, the database was searched both according tosubstance coding and within free-text descriptions of thecases. Cases were assessed by the principal investigator onlyafter removal of all patient identifiers. Inclusion criteriaincluded patients of any age with reported single-substanceexposure to nutmeg. Exclusion criteria were history of anycoingestants.Descriptive data collected included date of exposure, age,
gender, dosage form, symptoms, site of exposure, whetherexposure was intentional or unintentional, management site,treatment administered, and clinical outcome. Tachycardiawas defined as a heart rate of 4100 beats per minute orthe presence of the term ‘‘tachycardia’’ in the free-textdescription of the case. Hypertension was defined as asystolic blood pressure 4140 mmHg, diastolic bloodpressure 490 mmHg, or the presence of the term‘‘hypertension’’ in the free-text description of the case.Outcomes were coded as no effect, minor effect, moderateeffect, major effect, or death according to the criteria setforth by the American Association of Poison ControlCenters.13 All data abstracted were transcribed into astandardized Microsoft Excel 2008 for Mac (Microsoft,Redmond, WA) spreadsheet. In total, 95% confidenceintervals were calculated for all proportions. Z tests forproportions were used to compare characteristics of patients
Received 27 January 2011; accepted 4 February 2011.Address correspondence to Shaun D. Carstairs, M.D., Departmentof Emergency Medicine, Naval Medical Center San Diego,34800 Bob Wilson Drive, San Diego, CA 92134-5000, USA.E-mail: [email protected]
Clinical Toxicology (2011) 49, 177–180� 2011 Informa Healthcare USA, Inc.ISSN 1556-3650 print/ISSN 1556-9519 onlineDOI: 10.3109/15563650.2011.561210
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who abused nutmeg to those of patients with unintentionalexposure to nutmeg.
Results
A total of 119 cases of nutmeg exposure that met theinclusion criteria were reported to the CPCS between 1997and 2008 (Table 1). Eighty-five (71.4%) patients weremales. Patient ages ranged from 1 to 96 years with a mean of22 years and median of 18 years. The majority of exposures(111 patients, 93.3%) were via the oral route; four patientsinsufflated nutmeg, two patients smoked it, one sustained anunintentional dermal exposure, and one sustained anunintentional ocular exposure. Eighty-six (72.3%) exposureswere intentional for recreational purposes; of these, 69(80.2%, 95% CI: 71.8–88.7%) were between the ages of 13and 20. No intentional exposures were reported in patientsunder the age of 13. In contrast, of the 33 patientsunintentionally exposed, only 3 (9.1%, 95% CI: 0–8.9%)were between ages 13 and 20; 22 were greater than 20 yearsof age; and 8 were children less than 13 years of age.
Abusers were significantly more likely to require medicalevaluation than nonabusers [61.6% (95% CI: 51.4–71.9%)vs. 33.3% (95% CI: 17.3–49.4%)]. Treatments administeredincluded activated charcoal (n¼ 10), benzodiazepines(n¼ 7), antiemetics (n¼ 6), intravenous fluids (n¼ 5), andgastric lavage (n¼ 1). No major effects and no deaths werereported to occur in either group.Clinical effects are summarized in Table 2. The most
frequently reported effect was tachycardia, which occurredin 24 (20.2%) patients. Patients who abused nutmeg weresignificantly more likely (p5 0.05) to experience tachycar-dia and agitation than those whose exposure was uninten-tional. Abusers more commonly experienced nausea,vomiting, and hallucinations, but these results were notstatistically significant (p4 0.05).
Discussion
Nutmeg, in addition to its use as a spice, has also beenprescribed medicinally for more than a thousand years. Asearly as the ninth century, Middle Eastern physicians used itfor treatment of digestive ailments and dermatologicproblems. Hindu physicians were known to administernutmeg for treatment of ‘‘headache, nerve fevers, coldfevers, foul breath, and intestinal weakness’’.14 That nutmegcould result in toxicity in overdose was first detailed byLobelius in 1576, who described a pregnant woman whobecame ‘‘deliriously inebriated’’ after ingestion of 10 or 12nutmegs.15
For unclear reasons, in the late 19th century nutmeggained favor among women in Europe and North America asan emmenagogue and abortifacient. It was at this time thatincreasing reports of its potential for toxicity began to appearin Western medical literature, albeit with highly variableclinical presentations. Gillespie16 in 1887 reported a womanwho ingested five grated nutmegs in an attempt to induceabortion and experienced skin flushing, miosis, tachycardia,nausea, and headache, but no alteration in her mental status.Reekie17 in 1909 described a woman who had ingested onefreshly ground nutmeg and presented with bradycardia,tachypnea, cool skin, and hypothermia. Green18 reported a
Table 1. Patient characteristics.
Intentional(%), n¼ 86
Unintentional(%), n¼ 33
Total(%), n¼ 119
GenderMale 67 (77.9) 18 (54.5) 85 (71.4)Female 18 (20.9) 15 (45.5) 33 (27.7)Unknown 1 (1.2) 0 (0.0) 1 (0.8)
Age (years)513 0 (0.0) 8 (24.2) 8 (6.7)13–20 69 (80.2) 3 (9.1) 72 (60.5)420 14 (16.3) 22 (66.7) 36 (30.3)Unknown 3 (3.5) 0 (0.0) 3 (2.5)
Route of exposureOral 82 (95.3) 31 (93.9) 113 (95.0)Insufflation 4 (4.7) 0 (0.0) 4 (3.4)Dermal 0 (0.0) 1 (3.0) 1 (0.8)Ocular 0 (0.0) 1 (3.0) 1 (0.8)
Treatment siteHome 33 (38.4) 22 (66.7) 55 (46.2)Doctor’s office 0 (0.0) 1 (3.0) 1 (0.8)Refer to ED 9 (10.5) 5 (15.2) 14 (11.8)ED 39 (45.3) 3 (9.1) 42 (35.3)Inpatient (non-ICU) 1 (1.2) 2 (6.1) 3 (2.5)Inpatient (ICU) 4 (4.7) 0 (0.0) 4 (3.4)
OutcomeNone 10 (11.6) 8 (24.2) 18 (15.1)Minor 43 (50.0) 15 (45.5) 58 (48.7)Moderate 20 (23.3) 6 (18.2) 26 (21.8)Major 0 (0.0) 0 (0.0) 0 (0.0)Death 0 (0.0) 0 (0.0) 0 (0.0)Unable to follow(potentially toxicexposure)
13 (15.1) 4 (12.1) 17 (14.3)
Table 2. Frequency of symptoms in groups.
#Intentional
(%)
#Unintentional
(%) Total
Tachycardia* 23 (26.7) 1 (3.0) 24 (20.2)Vomiting 18 (20.9) 4 (12.1) 22 (18.5)Agitation* 15 (17.4) 1 (3.0) 16 (13.4)Hallucinations 12 (14.0) 3 (9.1) 15 (12.6)Dizziness 6 (7.0) 6 (18.2) 12 (10.1)Abdominal pain 4 (4.7) 5 (15.2) 9 (7.6)Nausea 5 (5.8) 1 (3.0) 6 (5.0)
*Clinically significant difference between groups (p5 0.05).
178 S.D. Carstairs and F.L. Cantrell
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woman who ingested 18.3 g of ground nutmeg to induce hermenses and experienced burning abdominal pain, disorienta-tion, and a feeling of impending death. It is notable thatamong all of the early reports of inadvertent toxicity fromnutmeg ingestion, there is no distinct toxidrome that can beattributed to its use.It is unclear when nutmeg first began to be abused for its
purported hallucinogenic effects. One of the first reports ofits use for such purposes was by Payne in 1963, whodescribed two young adult males who had each ingestedabout 14 g powdered nutmeg. Both patients experiencedhypertension, tachycardia, dry mouth, flushed skin, andagitation; of note, neither experienced any apparenthallucinations.1 Since that time, numerous reports in themedical literature have described patients who intentionallyingested nutmeg in order to experience psychotropiceffects.2–12 Clinical effects described in these case reportshave been variable; although most patients were describedas having tachycardia and agitation, not all patients werereported to experience hallucinations. Additionally, somepatients had profound nausea and vomiting, whereas othershad minimal gastrointestinal upset.The method by which nutmeg is purported to cause
psychoactive and sympathomimetic effects is not wellcharacterized, although myristicin is generally thought tobe the primary psychoactive constituent. Shulgin19 postu-lated that myristicin may be transaminated to 3-methoxy-4,5-methylenedioxyamphetamine (MMDA), a known psy-choactive compound. Indeed, formation of MMDA has beenshown to occur in isolated rat liver perfused with amyristicin-containing medium;20 however, such transforma-tion has never been demonstrated to occur in humans in vivo.Truitt et al.21 demonstrated that nutmeg and myristicin caninhibit monoamine oxidase (MAO) in a rat model, whichcould also provide an explanation for nutmeg’s sympatho-mimetic effects. Elemicin, another compound found innutmeg, has been shown in rodent studies to impaircoordination and decrease motor activity and may also bepartially responsible for some of the clinical effects seen inhumans.22
Aside from isolated case reports, only two small caseseries of nutmeg poisoning have been reported to this date.Stein et al. reported seven patients, six of whom hadintentionally abused nutmeg. Four patients experiencedtachycardia and three had gastrointestinal symptoms; othersymptoms reported included drowsiness, restlessness, drymouth, and a ‘‘bad feeling’’ in a minority of patients.10
Forrester23 described 17 patients, 11 of whom had ingestednutmeg with the intent of achieving psychotropic effects.Clinical effects described in these case series wereinconsistent, with only a minority of patients experiencinghallucinations or altered sensorium.Only two nutmeg-associated fatalities have been de-
scribed to date. The first, reported in 1887, describes an 8-year-old boy who reportedly ingested two nutmegs and wasfound semi-comatose; he was administered an emetic and‘‘diffusible stimulants’’, followed by ‘‘hypodermic injec-
tions of brandy, ammonia, and small doses of sulphate ofatropia’’ but died the following morning (one may questionwhether the treatment was more toxic than the ingestion).24
The second case was that of a 55-year-old woman founddead with a postmortem blood flunitrazepam level of 0.072mcg/ml (considered within the ‘‘toxic’’ range) but who wasfound to have stomach contents that smelled strongly ofnutmeg; myristicin was subsequently identified in post-mortem blood samples and was quantitated at 4.0 mcg/ml.10
However, the significance of this finding is unclear in lightof the fact that there is no accepted ‘‘toxic’’ myristicin leveland that the elevated flunitrazepam level suggests anotherpotential cause of death.In this case series, most cases of nutmeg exposure were
associated with minor or moderate clinical effects, withtachycardia, CNS effects, and gastrointestinal upset mostcommonly seen. Intentional abusers of nutmeg were morelikely to be male, younger in age, and to require evaluationat a health care facility.Our study has several limitations. This was a retrospective
study, which significantly limited the amount of data wewere able to retrieve for each case. Some symptoms mayhave been present but were not reported to CPCS, and ourfrequency of clinical effects might not represent the actualfrequency of effects. Our study is likely to be subject toreporting bias, given that reporting of cases of nutmegexposure by health care practitioners (and patients and/orcaregivers) to CPCS is voluntary. In addition, confirmationof exposure in all cases was not possible, since assays formeasurement of plasma myristicin levels are not routinelyavailable. We also could not exclude the possibility ofcoingestants that might have contributed to the patients’symptoms.
Conclusion
Although nutmeg exposure is uncommonly encountered,clinical effects can be significant and can require medicalintervention. Of those who developed symptoms, neurolo-gic, cardiovascular, and gastrointestinal symptoms predo-minated. Most abusers of nutmeg were adolescent or youngadult males, which is in keeping with other drugs of abuse.Additionally, abusers were more likely to demonstrateclinically significant effects compared to those patients whowere unintentionally exposed. While clinically significanteffects were common in this series, most nutmeg intoxica-tions appear to be mild in nature and are unlikely to producelife-threatening symptoms. However, when consideringnutmeg’s toxic potential, one must take into account dosage,susceptibility of the individual, and possible dangers tothe patient when under the psychological influence of thespice.
Declaration of interest
The authors report no conflicts of interest. The authors aloneare responsible for the content and writing of the paper.
Nutmeg exposures in California 179
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