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Current practice

Ann Biol Clin 2017; 75 (4): 462-5

Drowsiness and uncommon fever


in a child after cannabis ingestion
Somnolence et fièvre inhabituelle chez
un enfant après ingestion de cannabis

Catherine Feliu1,2 Abstract. Trivialization of cannabis consumption goes hand in hand with a
Yoann Cazaubon1,2 growing exposure of children and the number of cannabis poisoning cases is
Aurélie Fouley1 steadily increasing. As clinical presentation can be different from what is cur-
rently seen in adults, added to the fact that it is not always suspected, diagnosis
Hélène Guillemin1
of cannabis intoxication in children is often delayed or missed. A 16-month-old
Hervé Millart1,2 girl was admitted to the pediatric emergency unit for an important drowsiness
Claire Gozalo1 combined to moderate fever. After elimination of infectious causes, a toxic
Zoubir Djerada1,2 origin was considered and biological analyses led to the diagnosis of involun-
1 Laboratoire de pharmacologie et tary acute cannabis intoxication. In conclusion, cannabis intoxication in child
toxicologie, Hôpital Maison Blanche, has uncommon presentations compared to that seen in adults. In this context,
CHU de Reims, Reims, France biological analyses have a great importance for a rapid diagnosis and also for
2 SFR Cap-Santé-EA3801-Université de
the understanding intoxication circumstance. This is of paramount importance
Reims, Laboratoire de pharmacologie
médicale, Faculté de médecine de
because it may lead to consider child protection measures.
Reims, Reims, France
<cfeliu@chu-reims.fr>
Key words: child, involuntary intoxication, drowsiness, cannabis, mass spec-
trometry

Résumé. La banalisation de la consommation de cannabis va de pair avec une


augmentation de l’exposition des enfants. Le nombre de cas d’intoxications chez
les enfants par le cannabis ne cesse d’augmenter. La symptomatologie pouvant
être différente de celles observées chez les adultes, le diagnostic de l’intoxication
au cannabis chez les enfants est souvent retardé ou manqué, d’autant plus qu’il
n’est pas toujours suspecté. Une fille de 16 mois a été admise à l’unité d’urgence
pédiatrique pour une somnolence importante associée à une fièvre modérée.
Après élimination des causes infectieuses, une origine toxique a été consi-
dérée et les analyses biologiques ont mené au diagnostic d’intoxication aiguë
involontaire au cannabis. En conclusion, l’intoxication au cannabis chez l’enfant
présente des manifestations peu communes par rapport à celles observées chez
l’adulte. Dans ce contexte, les analyses biologiques ont une grande importance
pour un diagnostic rapide, mais aussi pour la compréhension des circonstances
d’intoxication, ceci pouvant conduire à envisager des mesures de protection de
l’enfance.

Article received November 16, 2016, Mots clés : enfant, intoxication involontaire, somnolence, cannabis, spec-
accepted January 4, 2017 trométrie de masse
doi:10.1684/abc.2017.1261

With the trivialization of cannabis consumption, the num- toxicological tests (rapid tests in first intention and specific
ber of cannabis poisoning in child is steadily increasing. tests as mass spectrometry for confirmation) to make the
This case describes an involuntary cannabis intoxication in right diagnosis and improve patient care during and after
an infant and shows the importance of using the adequate the hospital stay.
To cite this article: Feliu C, Cazaubon Y, Fouley A, Guillemin H, Millart H, Gozalo C, Djerada Z. Drowsiness and uncommon fever in a child after cannabis ingestion.
462 Ann Biol Clin 2017; 75(4): 462-5 doi:10.1684/abc.2017.1261
Cannabis intoxication in child

Case presentation environment despite the mother’s story. The child recov-
ered after two days of hospitalization and returned home
A 16-month-old girl was admitted to the pediatric emer- with oversight by social services.
gency unit for an important drowsiness. She was unable
to remain seated and to open eyes. Physical examina-
tion revealed the following parameters: body temperature, Discussion
38.3◦ C; heart rate, 136 beats/minute; blood pressure 110/20
mmHg; respiratory rate regular at 30/minute; oxygen sat- Marijuana is a dry mixture of crushed leaves and flowers
uration, 98%; non-reactive mydriasis. Venous blood gas, of Cannabis sativa. 9-THC, tetrahydrocannabinol, is
complete blood count and blood ionogram showed no the major psychoactive drug which activates two specific
abnormality. The antipyretic treatment initiated during the cannabinoid-binding receptors (CB1 and CB2). CB1
transfer to the hospital brought the fever down. receptors are distributed in the central nervous system
Due to the onset of fever and sedation, infection was sus- (substantia nigra, basal ganglia, hippocampus and cerebral
pected. cortex), whereas CB2 receptors are mainly localized
Chest radiology did not reveal any sign of infection. Lum- peripherally in the immune system. CB1 receptors inhibit
bar puncture and urine were collected for biochemical and the release of neurotransmitters such as acetylcholine,
bacteriological examination. No bacteria or virus could be noradrenalin, dopamine and serotonin. Even if the mech-
detected neither in lumbar puncture nor in urine. Biochem- anisms of psychoactive effects are not fully understood,
ical parameters were also normal for both matrices. Serum CB1 receptors seem to be responsible for the mediation of
C-reactive protein and procalcitonin were normal. clinical effects [2].
Diagnosis of infection was therefore excluded and a Due to its high lipid-solubility, 9-THC is rapidly dis-
toxic cause was evoked. Urinary toxicology analysis by tributed into the adipose tissues, liver, lungs and central
immunochromatography was carried out, turning out posi- nervous system where it exerts its psychoactive effects
tive for paracetamol and cannabis. [1]. 9-THC undergoes oxidative metabolism in the
After questioning, the mother explained the child had liver (figure 1). The main metabolites are 11-hydroxy-
picked up in the street a small pebble that she had ingested. tetrahydrocannabinol (11-OH-THC) and 11-nor-9-
The mother had tried to extract the pellet from the child’s carboxytetrahydrocannabinol (THC-COOH).
mouth without success. Six hours after ingestion, fever and Only 11-OH-THC has a psychoactive effect (figure 1) [1].
behavioral disorders such as grumpiness had appeared. Six When cannabis is ingested, only 5-20% of 9-THC reaches
hours after the first symptoms an important drowsiness systemic circulation, because of its chemical instability
occurred. and of an important first-pass effect in the liver. Moreover,
Mass spectrometry confirmed the presence of cannabis in 9-THC is hydroxylated in 11-OH-THC in the intestinal
urine. Concentrations of tetrahydrocannabinol (9-THC) mucosa. Consequently, after an oral ingestion, 11-OH-
and its metabolites in blood were quantified by liquid THC concentration is higher than 9-THC concentration
chromatography coupled with tandem mass spectrometry: in blood [1]. The peak plasmatic concentration is achieved
4.1 ␮g/L, 7.4 ␮g/L and 174.3 ␮g/L for 9-THC, 2 to 6 hours after ingestion, and psychoactive effects appear
11-hydroxy-tetrahydrocannabinol (11-OH-THC) and up to 1 to 3 hours after.
11-nor-9-carboxytetrahydrocannabinol (THC-COOH), The majority of the 9-THC is excreted in metabolized
respectively. Toxicological screening did not reveal any form within 72 hours in the feces (40%, 11-OH-THC
other drug or poison. Oral cannabis consumption was and THC-COOH) and urine (30%, THC-COOH). The
suspected since 11-OH-THC concentration was higher elimination half-life is highly variable, depending on the
than 9-THC [1]. quantity taken and the frequency of use. THC-COOH can
Additionally, to confirm the information provided by the be excreted in urine up to 1 month after the last consumption
mother about a single and accidental exposure in the street, in regular smokers [1].
analysis of a hair strand was also performed. An unequiv- The effects of marijuana are largely described in the litera-
ocal proof of cannabis active chronic consumption is the ture [1]. It provides a “well-being” state. Generally, people
detection of the THC-COOH in the hair. If only 9-THC take cannabis to feel calm, euphoric or slightly disinhib-
is detected, external contamination by smoking cannabis ited. Cannabis can also induce tachycardia, hypertension
is suspected. In our case, only 9-THC was quantified and nausea. Cognitive disorders, perceptual alterations, hal-
(0.46 ng/mg) in the child’s hair. lucinations, excessive sedation or anxiety may occur [1].
Finally, these results confirmed an acute accidental inges- In children, drowsiness is the most frequently described
tion. Nevertheless, external contamination of the hair symptom but hypotonia, mydriasis, agitation, tachycardia
suggested a passive exposure of the child in the family are also reported [3-5]. Some isolated cases also described

Ann Biol Clin, vol. 75, n◦ 4, juillet-août 2017 463


Current practice

Detection in blood : 2 to 10 hours THC Oral consumption


after consumption psychoactive
Undetected in urine
Intestinal mucosa

Hepatic microsomes

11-OH-THC 11-OH-THC
psychoactive

Hepatic microsomes

Detection in blood : 6 to 48 hours


Detection in urine : 1 day to more THC-COOH
than 1 month Non psychoactive
depending on frequency and dose
comsuption

Figure 1. Pharmacokinetics of cannabis: metabolism and detection window depending on mode of consumption.

breathing problems, hypoventilation, apnea and coma nosis and management of this intoxication. Clinicians
[3, 4]. should be aware of the magnitude of the phenomenon
In this clinical case, important drowsiness and mydriasis are and should not hesitate to question the children’s family
similar to those described in the literature. Hyperthermia about it. In front of a possible intoxication in a child, a
on the contrary is not described in the literature in acute first-intention urinary screening has to be done to get a
intoxication. quick result. If positive, quantitation of the incriminated
Accidental cannabis poisoning in young children has been drug(s) can be done on a blood sample to confirm the
increasing for many years [6]. The majority of cases involve drug taking and to estimate the gravity of the intoxication.
children under 2 years old. Intoxications occur most of the Comparing the ratios of the drug and its metabolites in dif-
time in the family environment, which has to be compared ferent biological matrices (blood, urine, and hair) will then
with the trivialization of cannabis consumption in the gen- allow distinguishing between acute and chronic poisoning
eral population. Seriousness of the intoxication is variable: when necessary. This last point cannot be neglected when
from mild to severe [3-6], and even life-threatening. How- dealing with children, as child protection measures may
ever, the evolution of these cases is favorable and so far no therefore have to be considered. This whole process will
death has been reported. Increase in 9-THC concentration result in an improvement in the diagnosis of the type of
in the consumed products seems to be partly responsible intoxication and therefore will improve patient care and
for this situation. Indeed, the mean concentration of 9- monitoring.
THC has been multiplied by approximately 3 in 15 years to
reach, in 2013, 17.4% in the resin and 12.6% in grass. The Conflicts of interest: All authors report no financial inter-
most common overdose incidents in children occur when ests or potential conflicts of interest.
the drug has been combined with food in an “edible” form
of marijuana [6].
References
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(CA) : Biomedical Publications, 2011.
Conclusion
2. Goldfrank LR, Flomenbaum N. Goldfrank’s toxicologic emergencies.
This cannabis poisoning is a typical example of an increas- New York : McGraw Hill Professional, 2006.
ing domestic accident, still too often forgotten. In children, 3. Appelboam A, Oades PJ. Coma due to cannabis toxicity in an infant.
the nonspecific clinical signs result in a delay on diag- Eur J Emerg Med 2006 ; 13 : 177-9.

464 Ann Biol Clin, vol. 75, n◦ 4, juillet-août 2017


Cannabis intoxication in child

4. Carstairs SD, Fujinaka MK, Keeney GE, Ly BT. Prolonged detecting neglectful situations and at-risk families. Pediatr Emerg Care
coma in a child due to hashish ingestion with quantita- 2014 ; 30 : 862-6.
tion of THC metabolites in urine. J Emerg Med 2011 ; 41 :
69-71. 6. Mowry JB, Spyker DA, Brooks DE, McMillan N, Schauben JL. 2014
Annual report of the american association of poison control centers’
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Ann Biol Clin, vol. 75, n◦ 4, juillet-août 2017 465