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Clinical Toxicology
ISSN: (Print) (Online) Journal homepage: https://www.tandfonline.com/loi/ictx20
Comparison of clinical characteristics between
meth/amphetamine and synthetic cathinone users
presented to the emergency department
Te-I Weng, Hsien-Yi Chen, Lengsu W. Chin, Hsin-Hui Chou, Meng-Huan Wu,
Guan-yuan Chen, Ju-Yu Chen, Chia-Pang Shih, Chih-Chuan Lin & Cheng-
Chung Fang
To cite this article: Te-I Weng, Hsien-Yi Chen, Lengsu W. Chin, Hsin-Hui Chou, Meng-
Huan Wu, Guan-yuan Chen, Ju-Yu Chen, Chia-Pang Shih, Chih-Chuan Lin & Cheng-
Chung Fang (2022): Comparison of clinical characteristics between meth/amphetamine and
synthetic cathinone users presented to the emergency department, Clinical Toxicology, DOI:
10.1080/15563650.2022.2062376
To link to this article: https://doi.org/10.1080/15563650.2022.2062376
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Published online: 19 Apr 2022.
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CLINICAL RESEARCH
Comparison of clinical characteristics between meth/amphetamine and
synthetic cathinone users presented to the emergency department
Te-I Weng
a,b,c
, Hsien-Yi Chen
d,e
, Lengsu W. Chin
f
, Hsin-Hui Chou
g
, Meng-Huan Wu
e,h
, Guan-yuan Chen
b,c
,
Ju-Yu Chen
b,c
, Chia-Pang Shih
i
, Chih-Chuan Lin
d,e
and Cheng-Chung Fang
a,b
a
Department of Emergency Medicine, National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei,
Taiwan;
b
Forensic and Clinical Toxicology Center, College of Medicine and National Taiwan University Hospital, National Taiwan University,
Taipei, Taiwan;
c
Department of Forensic Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan;
d
Department of
Emergency Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan;
e
College of Medicine, Chang Gung University, Taoyuan,
Taiwan;
f
Department of Emergency Medicine, Da Chien General Hospital, Miaoli, Taiwan;
g
Department of Emergency Medicine, Chang Gung
Memorial Hospital, Keelung, Taiwan;
h
Department of Emergency Medicine, Chang Gung Memorial Hospital, Kaohsiung, Taiwan;
i
Department
of Nursing, Yuanpei University of Medical Technology, Hsin-Chu, Taiwan
ABSTRACT
Background: Synthetic cathinones (SC) are popular new psychoactive substances that produce sym-
pathomimetic toxicity. Meth/amphetamine and SC have similar chemical structures and pharmaco-
logical effects. We aimed to compare the clinical characteristics between meth/amphetamine and SC
users presenting to the emergency department (ED).
Methods: This retrospective observational cohort study included patients who presented to six EDs
from May 2017 to April 2021 with symptoms that related to recreational drug use and whose urine
toxicology tests were positive only for meth/amphetamine or SC through liquid chromatography-tan-
dem mass spectrometry.
Results: There were 379 patients who tested positive only for meth/amphetamine (MA group), and 87
patients tested positive only for SC (SC groups). Patients in the MA group were older than those in
the SC group (median (IQR); MA: 37.0 (30–43.7), SC: 25.0 (21.0–32.7), p<0.001). There were no signifi-
cant between-group differences in the sex distribution and initial chief complaints. Compared with the
MA group, the SC group had more cases of tachycardia (135/min; MA: 29 (8.2%), SC:16 (19.0%),
p¼0.0031) and hyperthermia (38C; MA: 31 (8.2%), SC:18 (20.7%), p¼0.001). Besides, the SC group
had significantly higher levels of creatinine kinase (CK, IU/L; MA: 263 (115–601), SC: 497 (206–9216),
p¼0.008) as well as a higher risk of rhabdomyolysis (CK >1000; MA:32 (8.4%), SC: 16 (18.4%),
p¼0.006) and severe rhabdomyolysis (CK >10,000; MA:10 (2.6%), SC:10 (11.5%), p¼001).
Multivariable logistic regression analyses indicated SC group in comparison with the MA group
(adjusted odds ratio: 2.732, 95% confidence interval: 1. 250–5.972, p¼0.012) was an association with
the risk of rhabdomyolysis.
Conclusion: Our findings demonstrate that tachycardia, hyperthermia, and rhabdomyolysis were more
common among cathinone users than among meth/amphetamine users presented to EDs.
ARTICLE HISTORY
Received 22 January 2022
Revised 29 March 2022
Accepted 31 March 2022
KEYWORDS
Meth/amphetamine;
synthetic cathinone;
emergency department;
rhabdomyolysis;
drug poisoning
Background
Over the past decade, new psychoactive substances (NPS)
have become very popular in recreational drug markets [1].
Worldwide, there has been rapid growth in the NPS market
given their easy availability through the internet [2]. The sub-
stituted molecules of synthetic cathinones (SC) developed
rapidly change to evade legal sanctions. By 2020, there were
more than 1000 NPS drugs listed in the United Nations
Office on Drugs and Crime system. Further, more than 350
synthetic stimulants (accounting for >36% of all NPS drugs),
including SC, have been reported [3]. Compared with other
traditional psychostimulants, SC is cheaper and have similar
stimulant and hallucinogenic properties; therefore, they are
considered alternatives for 3,4-methylenedioxymeth/amphet-
amine (MDMA) or amphetamine [4]. Since most studies on
the acute toxicity of NPS lack analytical confirmation, there is
limited information available for physicians treating patients
with SC toxicity [2,5]. The exponential increase in NPS, com-
bined with the lack of information regarding acute toxicity,
has prompted significant concern regarding the worldwide
health, social, and economic burden resulting from NPS [6].
The use of SC may cause severe adverse health effects
[7,8]. Meth/amphetamine or amphetamine and SC have simi-
lar chemical structures and mechanisms [9]; however, few
CONTACT Cheng-Chung Fang conrad@ntu.edu.tw Department of Emergency Medicine, National Taiwan University Hospital, 7 Chung Shan S. Rd,
Taipei,100,Taiwan;Chih-ChuanLin bearuncle@yahoo.com Department of Emergency Medicine, Linkou Chang Gung Memorial Hospital and College
of Medicine, Chang Gung University, 1 Fu Shih Rd, Taoyuan, 131, Taiwan
These authors contributed equally to this study.
Supplemental data for this article can be accessed here.
ß2022 Informa UK Limited, trading as Taylor & Francis Group
CLINICAL TOXICOLOGY
https://doi.org/10.1080/15563650.2022.2062376
studies have compared their toxicological effects [10]. The
acute toxicity of SC belongs to sympathomimetic toxidromes
such as agitation, delirium, hypertension, tachycardia, and
hyperthermia [11]. Complications related to SC include seiz-
ures, rhabdomyolysis, multiple organ failure, and death,
which are similar to those of amphetamine toxicity [12,13].
However, users are unaware of the risk of adverse health
effects due to inconsistent ingredients and unknown doses
in the package used. There is a need for studies using data
regarding ED visits with analytical confirmation. This could
help elucidate the acute harm caused by SC.
Meth/amphetamine remains the most popular illicit drug
in Taiwan. There has been an increase in the use of NPS.
Since 2017, SC has become the most predominant NPS in
Taiwan [14]. In Taiwan, there have been previous case series
of patients presenting to the ED after using different cathi-
nones [8,15–17]. Given the popularity of meth/amphetamine
and SC use in Taiwan, we aimed to compare the clinical
characteristics of patients in the ED who had meth/amphet-
amine or SC detected in their urine samples through liquid
chromatography-tandem mass spectrometry. Further, we
aimed to compare the acute complications of these drugs.
Methods
Study design and selection of participants
This retrospective observational cohort study was conducted
at six EDs in Taiwan: National Taiwan University Hospital
(NTUH), a metropolitan academic medical center in Taipei;
NTUH Yunlin branch in Douliu, a rural tertiary care hospital;
Chang Gung Memorial Hospital (CGMH) Linkou branch in
Taoyuan and CGMH Kaohsiung branch in Kaohsiung, two
academic medical centers; CGMH Keelung branch, a regional
hospital in Keelung; and Da-Chien Hospital, a rural tertiary
care hospital in Miaoli. This study was approved by the
accredited Medical Research Ethics Committee of NTUH
(201711102RIND) and CGMH (202001418B0). The authors
underwent data collection training before data collection.
We included patients who presented to the ED between May
2017 and April 2021 with symptoms potentially related to
recreational drug use and whose urine toxicology tests
(liquid chromatography-tandem mass spectrometry) were
positive for meth/amphetamine or SC. According to regula-
tions in Taiwan, paramedics are not allowed to give any pre-
hospital medications except for treating patients with out-of-
hospital cardiac arrest. The analytical methods are described
in our previous work [18]. One hundred and sixty illicit drugs
(the drugs are listed in the Supplementary Table 1)
were screened.
Data collection
We used a standardized record form and independently
abstracted each case to collect detailed data from charts
regarding age, sex, past medical history chief complaints, ini-
tial vital signs at triage, initial Glasgow coma scale score,
laboratory tests, toxicology test results, treatment, and dis-
position after ED were recorded for data analysis.
Data analysis
Statistical analyses were performed using IBM SPSS Statistics
(version 24; IBM, Armonk, NY). Continuous data are
expressed as the median and interquartile range (IQR), with
between-group comparisons using Mann–Whitney U-test.
Categorical data are expressed as counts and percentages,
with between-group comparisons using the Chi-Square test
or Fisher’s exact test. Statistical significance was set at a two-
tailed p-value <0.05.
We conducted univariable and multivariable logistic
regression analyses to investigate the associations between
independent variables and the outcome. We considered the
available independent variables in the initial model-building
process, regardless of their significance in univariate analyses.
We applied the backward selection procedure to obtain the
final regression model. The significance thresholds for entry
and stay in the model were set at 0.1 to avoid excluding
candidate variables during the variable selection process.
Next, we sequentially removed individual variables with a p-
value >0.05 from the interim statistical models until all
regression coefficients were significant in the final model.
Results
Between May 2017 and April 2021, there were 909 cases that
tested positive for at least one illicit drug at the 6 EDs. The
flow diagram of the selection process of the study popula-
tion is presented in the Supplementary Figure. We excluded
ten patients aged <10 years old since five patients were vic-
tims of child abuse and the other five were cases of neonatal
drug abstinence syndrome. Among the remaining patients,
556 and 232 patients had meth/amphetamine or SC
detected, respectively. For further analysis, patients who only
meth/amphetamine detected were designated as the MA
group (n¼379 cases), and those who SC without other illicit
drugs detected were designated as the SC group (n¼87
cases). The MA group comprised 77 cases that were positive
for only methamphetamine, 21 cases were positive for only
amphetamine, and 281 cases were positive for both amphet-
amine and methamphetamine. The SC group comprised
patients whose urine samples were tested positive for at
least one of the cathinones presented in Figure 1. The top 5
detected SC were mephedrone (37 cases), eutylone (35
cases), ephylone (18 cases), ethylone (16 cases), and 4-
methyl-a-ethylaminopentiophenone (15 cases). Further, the
median number of cathinones detected in each case was 2
(IQR: 1–3; minimum: 1, maximum: 5). Only 37 cases showed
only one type of cathinone, including only mephedrone (11
cases), ephylone (8 cases), and eutylone (7 cases) (Figure 1).
Socio-demographic profiles
Table 1 shows the sociodemographics as well as the neuro-
psychiatric and physical comorbidities in both groups.
2 T.-I. WENG ET AL.
Patients in the MA group were significantly older than those
in the SC group (MA group: median: 37.0, IQR: 30.0–43.7; SC
group: median: 25.0, IQR: 21.0–32.7, p<0.001). There were
no significant between-group sex differences. Compared
with the SC group, the MA group showed a higher frequency
of physical comorbidities (p<0.001). There were no signifi-
cant between-group differences in the prevalence of psychi-
atric comorbidities and the self-reported concurrent use
of alcohol.
Clinical manifestations, laboratory data, treatments,
and post-ED disposition
There were no significant between-group differences in the
initial chief complaints (Table 2). Regarding the initial vital
signs, compared with the MA group, the SC group had more
cases of tachycardia (135/min) and hyperthermia (38 C)
(p<0.003 and p¼0.001, respectively) (Table 3). There were
no significant between-group differences in the other vital
signs and physical examinations, including systolic blood
pressure, respiratory rate, and Glasgow coma scale scores.
Regarding the laboratory results, compared with the MA
group, the SC group showed higher levels of creatinine kin-
ase (CK) (263 [115–601] U/L vs. 497 [206–9216] U/L,
p¼0.008) (Table 4). The SC group had more patients with
CK >1000 U/L(rhabdomyolysis) or >10,000 U/L (severe
rhabdomyolysis) than the MA group (p¼0.006, 0.001
respectively). The treatments given in the MA and SC groups
are presented in Table 5, which shows no statistically signifi-
cant differences between the two groups. Five patients pre-
sented to the ED due to out-of-hospital cardiac arrest and all
of them had a return of spontaneous circulation at the ED
(MA: 2 [0.5%], SC: 3 [3.4%]; p¼0.047). There were no signifi-
cant between-group differences in patients who required
intensive care (MA: 44 [11.6%], SC: 10 [11.5%], p¼1.000) or
died finally (MA: 7 [1.8%], SC: 3 [3.4%], p¼0.405). Patients
who were older, male, with high body temperature, or with
rhabdomyolysis were more likely to die or require ICU care
(Supplementary Table 3).
Risk factors for rhabdomyolysis
We performed univariable logistic regression analyses to
determine the risk factors for rhabdomyolysis (CK level
1000 U/ml). The variables used in the model-building pro-
cess included age, sex, hyperthermia (temperature 38 C),
tachycardia (heart rate 135/min), seizure, hallucinations,
delirium, and agitation/violent behaviors (details are pre-
sented in the Supplementary Table 2). The final multivariable
0
5
10
15
20
25
30
35
40
case numbers
single cathinone detetected mulple cathinones detected
Figure 1. A number of cases with cathinone were detected in the synthetic cathinone (SC) group.
1
4-MEAPP: 4-Methyl-a-ethylaminopentiophenone,
2
4-CEC: 4-
Chloroethcathinone,
3
4-CMC: 4-Chloromethcathinone,
4
4-methyl-N,N-DMC: 4-methyl-N,N-dimethylcathinone,
5
4-Chloro-N,N-DMC : 4-Chloro-N,N-dimethylcathinone,
6
MDPBP :
3,4-Methylenedioxy-a-pyrrolidinobutiophenone,
7
4-MEC : 4-Methylethcathinone,
8
4-MPD : 4-Methylpentedrone,
9
4-Cl-a-PVP :4-Chloro-a-Pyrrolidinovalerophenone,
10
a-PHP
:a-pyrrolidinohexiophenon
Table 1. Sociodemographic and clinical profiles of individuals with meth/
amphetamine (MA group) or synthetic cathinones (SC group) related emer-
gency department visits.
MA group
(n¼379)
SC group
(n¼87) P
#
Age (median and IQR) 37.0 (30–43.7) 25.0 (21.0–32.7) <0.001
11–20 10 (2.6%) 20 (23.0%)
21–30 90 (23.7%) 42 (48.3%)
31–40 149 (39.3%) 18 (20.7%)
41–50 92 (24.3%) 6 (6.9%)
50 38 (10.1%) 1 (1.1%)
Sex 0.334
Male 297 (78.4%) 64 (73.6%)
Female 82 (21.6%) 23 (26.4%)
Psychiatric comorbidity
a
59 (15.6%) 8 (9.2%) 0.127
Physical comorbidity
b
58 (15.3%) 0 <0.001
Combination with alcohol 39 (10.3%) 8 (9.2%) 0.760
a
Psychiatric comorbidities includes schizophrenia, bipolar disorders, major
depression, and other psychiatric diseases.
b
Physical comorbidities include diabetes mellitus, hypertension, liver cirrhosis,
cancer, chronic obstructive pulmonary diseases, and human immunodeficiency
virus infection.
#
Bold values indicate statistical significance with p<0.05.
CLINICAL TOXICOLOGY 3
logistic regression analyses revealed the following significant
risk factors: SC group (adjusted odds ratio (aOR): 2.732, 95%
confidence interval (CI): 1. 250–5.972, p¼0.012), tachycardia
(aOR: 2.737, 95% CI: 1.086–6.899, p¼0.033), and hyperther-
mia (aOR: 5.153, 95% CI: 2.145–12.379, p<0.001).
Discussion
Meth/amphetamine and SC are both highly prevalent in
Taiwan [19]. Clinical presentations and complications
following SC exposure are quite similar to those of meth/
amphetamine poisoning [20]. By application of LC-MS/MS in
toxicology assay for ED recreational drug users, we found
that patients who used SC were more likely to develop
rhabdomyolysis, hyperthermia, and tachycardia as compared
with patients who used meth/amphetamine.
Meth/amphetamine and SC are chemically similar except
for differences in the ketone functional group [21].
Compared with amphetamine, cathinones are less potent in
the central nervous system (CNS) effect because the b-ketone
moiety of cathinones has hydrophilic properties which make
most cathinones less lipophilic than amphetamine [22].
Additionally, most cathinones, especially the N-alkyl deriva-
tives, have an extensive first-pass effect [23]. A rat study
found that meth/amphetamine induces 2- to 3-fold the
dopamine and 5-HT potency of methcathinone [24]. A
human study found that oral administration of 200 mg
mephedrone and 100 mg MDMA had similar psychiatric and
physiological effects [25]. Since SC has weaker CNS potency,
users may take repeated or increased doses to achieve the
desired effects, further resulting in more severe sympatho-
mimetic toxicity and adverse muscular effects.
Hyperthermia was more common in the SC group than in
the MA group. Hyperthermia is an important factor that
exacerbates the deleterious effects (including rhabdomyoly-
sis) of psychostimulants and should be aggressively treated
[26]. Based on prior literature, norepinephrine, dopamine,
and serotonin have all been suggested to play major roles in
Table 2. Clinical characteristics of individuals with meth/amphetamine (MA
group) or synthetic cathinone (SC group) related emergency depart-
ment visits.
MA group
(n¼379)
SC group
(n¼87) P
Initial clinical presentations
Hallucination 82 (21.6%) 23 (26.4%) 0.334
Suicide attempts/ideas 109 (28.8%) 17 (19.5%) 0.081
Agitation/violent behaviors 104 (27.4%) 22 (25.3%) 0.683
Insomnia/anxiety 10 (2.6%) 4 (4.6%) 0.334
Seizure 15 (4.0%) 5 (5.7%) 0.555
Delirium 35 (9.2%) 13 (14.9%) 0.114
Palpitation 9 (2.4%) 5 (5.7%) 0.153
Chest pain 14 (3.7%) 2 (2.3%) 0.747
Dyspnea 20 (5.3%) 8 (9.2%) 0.165
Dizziness 18 (4.7%) 3 (3.4%) 0.778
Headache 7 (1.8%) 3 (3.4%) 0.405
General weakness 6 (1.6%) 1 (1.1%) 0.764
Focal neurological deficits 7 (1.8%) 0 0.357
Trauma 60 (15.8%) 17 (19.5%) 0.401
Out of hospital cardiac arrest 2 (0.5%) 3 (3.4%) 0.047
Table 3. Initial vital signs of individuals with meth/amphetamine (MA group) or synthetic cathinone (SC group) related emergency
department visits.
MA group
(n¼379)
SC group
(n¼87) P
#
Glasgow coma scale (GCS) 8 33 (8.7%) 11 (12.6%) 0.257
Heart rate
Median (IQR) 102 (90–118) 106 (91–127.75) 0.584
Heart rate 135/min 29 (8.2%) 16 (19.0%) 0.003
Systolic blood pressure
Median (IQR) 129 (113–145) 131 (116–143) 0.265
Systolic blood pressure 140 mmHg 112(31.2%) 25 (30.9%) 0.953
Body temperature
Median (IQR) 36.7 (36.2–37.3) 37.0 (36.3–37.8) 0.001
Body temperature 38 C 31 (8.2%) 18 (20.7%) 0.001
Respiratory rate
Median (IQR) 18.5 (16–22.5) 19.5 (16–23) 0.960
Respiratory rate >20/min 117 (30.9%) 27 (31.0%) 0.976
#
Bold values indicate statistical significance with p<0.05.
Table 4. Laboratory results of individuals with meth/amphetamine (MA group) or synthetic cathinone (SC group) related
emergency department visits.
MA group
(n¼379)
SC group
(n¼87) P
#
Peak troponin T>14 ng/L 24 (6.3%) 7 (8.0%) 0.563
Peak creatinine kinase (U/L) 263 (115–601)
Median (IQR) 497 (206–9216) 0.008
Peak creatinine kinase >1000 U/L 32 (8.4%) 16 (18.4%) 0.006
Peak creatinine kinase >10000 U/L 10 (2.6%) 10 (11.5%) 0.001
Peak creatinine >1.4 mg/dL 41 (10.8%) 13 (14.9%) 0.278
Lowest glucose <70 mg/dl 19 (5.0%) 5 (5.7%) 0.788
Peak alanine transaminase >41 U/L 64 (16.9%) 9 (10.3%) 0.130
Peak potassium >5.3 mmol/L 7 (1.8%) 3 (3.4%) 0.864
Lowest sodium <130 mEq/L 88 (23.2%) 24 (27.6%) 0.390
Peak lactate >4.0 mmol/L 17 (4.5%) 8 (9.2%) 0.108
#
Bold values indicate statistical significance with p<0.05.
4 T.-I. WENG ET AL.
regulating hypothalamic control of body temperature [27].
Drugs altering the levels of these neurotransmitters in the
hypothalamus are therefore capable of altering body tem-
perature regulation. Previous studies have also shown that
hyperthermia is a major symptom in overdose cases of 3,4-
methylenedioxypyrovalerone (MDPV), mephedrone, and
other cathinones [8,12,28]. Users may increase their intake
since most cathinones do not have a high potency on the
CNS effects, and the exaggerated peripheral effects may
cause severe vasoconstriction and limited heat dissipation,
which causes hyperthermia [29]. Cathinone users who simul-
taneously use different SC may have aggravated hyperther-
mic toxicity [30]. A previous mouse study reported enhanced
locomotor-stimulant effects of MDPV, but not MDMA, at a
warm ambient temperature. The locomotor-stimulant effects
may further aggravate hyperthermia [31].
In our series, patients in the SC group were more likely to
develop rhabdomyolysis than those in the MA group. The
mechanism underlying the increased risk of rhabdomyolysis
with exposure to SC remains unclear. The pathophysiology
of rhabdomyolysis caused by cathinones and meth/amphet-
amine could be similar and multifactorial [10]. Stimulant-
induced rhabdomyolysis may be due to skeletal muscle
overuse occurs when patients experience agitation, delirium,
extreme vasoconstriction, hyperthermia, and/or decreased
adenosine triphosphate production from impaired cellular
respiration [10]. Stimulants can also delay the onset of
fatigue and exhaustion allowing longer exercise, which fur-
ther aggravates hyperthermia and muscular injury [32]. In
addition, psychostimulant-induced seizures can exaggerate
muscular injury. In our study, SC use was significantly associ-
ated with rhabdomyolysis even after adjustment for age, sex,
tachycardia, hyperthermia, hallucination, delirium, agitation/
violent behaviors, and seizure. The higher risk of rhabdo-
myolysis with SC use may be attributed to between-drug dif-
ferences in the pharmacokinetics or pharmacodynamics.
O’Connor et al. compared 19 users of SC with users of
other stimulants, including 55 meth/amphetamine users and
9 cocaine users. They observed an increased risk of rhabdo-
myolysis and severe rhabdomyolysis in cathinone users [10].
In this cohort, there were 12 and 7 users of MDPV and a-
pyrrolidinovalerophenone (a-PVP). MDPV and a-PVP are both
N-pyrrolidine derivatives of cathinones, which are considered
more potent than other cathinone derivatives [24]. N-pyrroli-
dine derivatives of cathinones are thought to more easily
penetrate the blood-brain barrier as they have reduced
hydrophilic properties conferred by the b-ketone moiety [33]
and show similar pharmacodynamics to cocaine [34]. Severe
and even fatal intoxications after MDPV abuse are not
uncommon due to their high potency [35]. In our study, the
patients used a wide range of cathinones of which mephe-
drone and eutylone were most frequently detected. Despite
the less common of our patients used cathinones belonging
to N-pyrrolidine derivatives, cathinone users showed a higher
frequency of muscular injury and rhabdomyolysis as com-
pared with meth/amphetamine users. The adverse muscular
effects seem a general clinical feature of SC, not limited only
to N-pyrrolidine derivatives.
There were no significant between-group differences in
the chief complaints, including neuropsychiatric symptoms
(hallucinations, delirium, and agitation/aggressive behaviors).
However, tachycardia was more common in the SC group
than in the MA group. It has been reported that despite a
weaker neuropsychiatric effect, mephedrone administration
caused similar cardiovascular effects (including tachycardia)
compared with meth/amphetamine in rats [36]. Users may
take a higher cathinone dose to achieve the desired psychos-
timulant response, which leads to a higher frequency of
tachycardia as compared with meth/amphetamine users.
Although the SC group had a higher risk of hyperthermia
and rhabdomyolysis, the outcome and the requirement of
intensive treatments were not different between SC and MA
groups. One of the potential explanations is that in our
study, the SC users were much younger and had fewer med-
ical comorbidities, which means that they are less likely to
develop cerebrovascular or cardiovascular complications. It
has been reported that NPS users who presented to the ED
are younger than the users of traditional illicit drugs [37]. A
Sweden study also reported that NPS was highly prevalent
among adolescents and young adults, and the median age
of NPS users who had presented to the ED was 20 years [38].
Besides, young people are usually physically active and have
higher muscle mass. They usually have higher baseline CK
levels [39] and theoretically have higher risks to develop
rhabdomyolysis during over-exercise, as compared with
older adults.
Table 5. The treatments in patients with meth/amphetamine (MA group) or synthetic cathinone (SC group) related to emergency department visits.
MA group
(n¼379)
SC group
(n¼87) P
Lorazepam injection 139 (36.7%) 35 (40.2%) 0.536
Haloperidol injection 108 (28.5%) 16 (18.4%) 0.054
Both lorazepam and haloperidol injection 93 (24.5%) 14 (16.1%) 0.091
ICU admission 44 (11.6%) 10 (11.5%) 1.000
Intubation 27 (7.1%) 9 (10.3%) 0.310
The duration (day) of mechanical ventilation (medium, IQR) 4 (2–8) 2 (1–4) 0.689
Defibrillation 3 (0.8%) 0 1.000
Chest compression 5 (1.3%) 4 (4.6%) 0.067
Extracorporeal membrane oxygenation 1 (0.3%) 1 (1.1%) 0.254
Active cooling 00
Amount (ml) of intravenous fluid in patients with peak creatinine kinase >1000 U/L N¼32 (8.4%) N¼16 (18.4%)
Amount (ml) at the first 24 h (medium, IQR) 2000
(1000–2500)
2000
(860–4300)
0.691
Total amount (ml)
(medium, IQR)
4679
(1185–8150)
7000
(1200–12110)
0.769
CLINICAL TOXICOLOGY 5
Multiple substance exposure observed in SC users pos-
sesses health threats. A previous study reported that cathi-
none users in Taiwan frequently co-exposed to different
cathinones [37]. Polysubstance use was also a common phe-
nomenon among “bath salt”users in western countries [40].
Co-ingestions of different cathinones and the uncertainty of
the cathinone contents, including concentrations and purity,
can cause unwanted effects or even overdose. Some reports
showed that concurrent exposure to other stimulants with
SC may enhance toxicity [41]. Patients who ingested an illicit
product containing SC are usually unaware of what they had
actually ingested, which may potentially result in cata-
strophic outcomes [16].
Limitations
We attempted to compare the toxicological effects between
meth/amphetamine and cathinones. Our data were retrieved
from the medical chart and the drug screening reports did
not provide the concentrations of the drug detected. Maybe
the clinical differences observed were due to higher sub-
stance concentrations (doses) in the SC group. The baseline
characteristics of the patients were different in the two
groups and could account for the differences in the clinical
presentations. Meth/amphetamine users were older than SC
users. Meth/amphetamine users may know more about how
to avoid the acute complications of drugs or have drug-toler-
ant because they are experienced drug users. The individual
differences in the sensitivity to the drugs, as well as geno-
typic and phenotypic variability in their metabolic clearance,
might limit between-drug comparisons of the toxicological
effects. Although our laboratory could detect 160 illicit
abused substances including 50 SC, some other NPS could
not be identified in our study. The cases with single-drug
group use in our study may involve other NPS contributing
to their clinical manifestations. The conclusions cannot be
generated for all drug users because the cases were col-
lected from patients who visited ED due to moderate to
severe complications. Patients with minor symptoms may
not visit ED. Drug users who did not visit ED may have dif-
ferent profiles from our findings.
Conclusion
Compared with meth/amphetamine users, cathinone users
more commonly present with tachycardia, hyperthermia,
muscular injury, and even severe rhabdomyolysis. Although
the treatments for meth/amphetamine and cathinone intoxi-
cation are similar, there is a need to further research the clin-
ical complications of these substances as well as to establish
a more delicate treatment protocol to reduce the morbidity
and mortality from meth/amphetamine or cathinone use.
Disclosure statement
No potential conflict of interest was reported by the author(s).
Funding
This study was supported by research grants from National Taiwan
University Hospital, Taiwan (NTUH:109-P08, and 110-S5144).
ORCID
Chih-Chuan Lin http://orcid.org/0000-0001-9613-115X
Cheng-Chung Fang http://orcid.org/0000-0001-5386-6674
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