Journal of Forensic and Legal Medicine 79 (2021) 102151

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Journal of Forensic and Legal Medicine

journal homepage: http://www.elsevier.com/locate/yjflm

Review

Drug-facilitated sexual assault and other crimes: A systematic review

by countries
M.G. García 1, M.D. Pérez-Cárceles 1, E. Osuna, I. Legaz *
Department of Legal and Forensic Medicine, Biomedical Research Institute (IMIB), Regional Campus of International Excellence “Campus Mare Nostrum”, Faculty of
Medicine, University of Murcia, Murcia, Spain

A R T I C L E I N F O A B S T R A C T

Keywords: Drug-facilitated sexual assault (DFSA) and drug-facilitated crime (DFC) constitute a mode of violence that is
Chemical submission generally unknown to the population and may go unnoticed by health professionals. The aim of this systematic
Crime victim review was to analyze the victims of DFC, compiling their sociodemographic characteristics, the toxic substances
Date rape
used and their biological matrices and modes of action, in order to identify the substances that are commonly put
Drug-facilitated crime
to criminal use. The aim would be to establish political and health strategies that inform and warn people about
Drug-facilitated sexual assault
Forensic toxicology possible criminal social behaviors consequent danger to health. This systematic review was conducted following
Forensic medicine the PRISMA guidelines. Alcohol, benzodiazepines and cocaine were among the most commonly detected sub­
stances. In most of the hospitals, immunoassays, liquid chromatography (LC-MS), or gas chromatography-mass
spectrometry (GC-MS) analyses were used to identify the substances, while the most frequently used biological
matrices were blood and urine. From a judicial point of view, the instrumental protocols and techniques followed
for the detection of toxics in different biological matrices must guarantee the reliability and validity of the results
for use in a court of law. The recommendations of international organizations should be followed and must be
called upon to strengthen their respective national laws against this chemical submission (CS) phenomenon.

make clinical diagnosis even more difficult.

1. Introduction
Chemical submission (CS) is a form of violence associated with
criminal practices, especially sexual aggression, robberies and property
crime, which is gaining increasing media coverage.1–4 While the term CS
is used to cover a wide variety of crimes, drug-related sexual crimes is
called Drug-facilitated sexual assault (DFSA),5,6 while Drug-facilitated
crime (DFC) is used to define robberies and crimes against property
that are unrelated with sexual crimes.5 Most authors and international
organizations classify DFSA as a subset of DFC.7–9 In recent years, this
phenomenon has acquired greater relevance throughout the world due
to the increase in cases and the important social and health impact.
Alcohol and other drugs used in sexual assault are, for the most part,
easily accessible and effective in low doses, which makes them difficult
to detect. In terms of administration, it must be discreet (preferably
oral), and the victim should not be able to detect its color or taste. The
drug in question will produce disinhibition on the victim’s part and thus
facilitate assault,1,10,11 while the confusing symptoms that it causes will
A victim under the influence of a drug will show modified behavior,
and their perception or their ability to make decisions will be affected,
encouraging theft, assault, sexual assault, extortion of money or
mistreatment.12,13 While an inhibitory substance can be administered
covertly or by force by the aggressor with the purpose of carrying out an
assault, sometimes a victim may have become severely intoxicated
voluntarily, to the point of having reduced, or even no,
consciousness.14,15
DFSA constitutes a mode of violence that may go unnoticed by health
personnel, despite it having been the subject of media coverage on many
occasions in recent years.4,16–18 Studies on DFSA generally reveal a high
presence of illicit substances that the victim has involuntarily consumed,
causing intoxication and increasing their vulnerability.19–23 Further­
more, the non-medical use of prescription and over-the-counter drugs,
such as benzodiazepines, Z drugs, antihistamines, non-benzodiazepine
sedatives, and neuroleptics, has become an expanding phenomenon in
western countries, with serious forensic implications.24,25
In the case of Drug-Facilitated Crimes (DFCs), the substances used

* Corresponding author. Department of Legal and Forensic Medicine, Biomedical Research Institute (IMIB), Regional Campus of International Excellence "Campus
Mare Nostrum", Faculty of Medicine, University of Murcia, E-30110 (Murcia), Spain.
E-mail address: isalegaz@um.es (I. Legaz).
1
The contribution of these authors is equal and the order is arbitrary.

https://doi.org/10.1016/j.jflm.2021.102151
Received 14 October 2020; Received in revised form 16 December 2020; Accepted 7 March 2021
Available online 12 March 2021
1752-928X/© 2021 Elsevier Ltd and Faculty of Forensic and Legal Medicine. All rights reserved.
M.G. García et al.
Abbreviations
BAC blood alcohol concentration
BZE benzoylecgonine
CS Chemical submission
DFC Drug-Facilitated Crimes
DFSA Drug-Facilitated Sexual Assault
GC-ECD Gas Chromatography – Electron Capture Detector
GC-FID Gas Chromatography - Flame Ionization Detection
GC-MS Gas chromatography - mass spectrometry
GC-MS/MS Gas chromatography - tandem mass spectrometry
GC-NPD Gas Chromatography - Nitrogen Phosphorus Detector
GHB-GLUC Glucuronated GHB metabolite
GHB Gamma-hydroxybutyric acid
HPLC-DAD High performance liquid chromatography - diode-array
detector
(HS)GC-FID Headspace Gas Chromatography - Flame Ionization
Detection
(HS)GC Headspace Gas Chromatograph
LC-DAD Liquid chromatography - diode-array detector
are not limited to medical drugs, and various studies have their diversity
with respect to the psychotropic effects that can be expected through
many neuropharmacological mechanisms or combinations of
mechanisms.18,26
Indeed, this type of crime is a challenge for forensic laboratories due
to the multitude of substances that cause similar effects in the body, their
rapid action and elimination, but, mainly because the available analyt­
ical technology in many cases is unable to detect low levels of the sub­
stances used.27 It should be noted that only a single dose of the substance
may be administered and, in some situations, the victim cannot recall
the event that occurred while under the influence of the drug due to
amnesia or sedation.28 The consequence is that, in most cases, victims
report the suspected crime more than 24, or even 72 h, after ingestion,
and so blood and urine samples can often lead to inaccurate conclusions
and the premature destruction of samples.4,29 The number of scientific
publications on this phenomenon has increased in recent years,
reflecting the number of cases of aggression that now occur through the
use of submission.
The aim of this systematic review was to analyze the victims of DFSA
and DFC, collating the sociodemographic characteristics, the chemicals
used and the keys to the toxicological diagnosis, in order to identify the
substances and establish future, political and health strategies that
inform people of the danger concerning their health and the criminal
social behaviors associated with their use.
2. Methods
2.1. Search strategy and methods
For studies published between January 2005 and May 2020, a
literature search compliant with Preferred Reporting Items for System­
atic Reviews and Meta-Analyses (PRISMA)30 was conducted using the
methodology detailed in the Cochrane Collaboration Handbook on
Systematic Reviews of Health Promotion and Public Health Programs.31
The protocol for this systematic review was registered with the Inter­
national Prospective Register of Systematic Reviews (PROSPERO).
2.2. Inclusion criteria
Studies in human forensic sciences that explore CS in all age ranges
were included. The articles were selected based on three main criteria
for inclusion: i) cases of CS in forensic sciences; ii) CS in humans iii)
2
Journal of Forensic and Legal Medicine 79 (2021) 102151
LC-ES-MS Liquid chromatography - electrospray - mass
spectrometry
LC-MS Liquid chromatography - mass spectrometry
LC-MS/MS Liquid chromatography - tandem mass spectrometry
LC-PDS Liquid chromatography in parallel dynamic spectroscopy
LC-TOF-MS Liquid chromatography-time-of-flight- mass
spectrometry
LC/QTOF-MS liquid chromatography - quadrupole time-of- flight -
mass spectrometry
MDA Methylene dexamphetamine
MDMA 3,4-methylene-dioxymethyl-methamphetamine
MS/MS Tandem mass spectrometry
THZ tetrahydrozoline
UHPLC–MS/MS Ultra-high performance liquid chromatography -
tandem mass spectrometry
UHPLC–TOF-MS Ultra-high performance liquid chromatography-
time-of- flight - mass spectrometry
UPLC-MS/MS Ultra performance liquid chromatography - tandem
mass spectrometry
English language. Of the 33 articles analyzed, a total of 23 were original
articles and ten were case reports.
2.3. Exclusion criteria
A total of 198 studies were excluded from this systematic review,
based on the following exclusion criteria; a) bibliographic reviews (n =
50), b) studies based solely on analytical techniques (n = 62) and c)
unspecific (n = 86).
2.4. Search strategy
Based on the most frequently consulted online scientific electronic
database, MEDLINE®/PubMed® and a Google Scholar, a freely acces­
sible web search engine, and keywords, a literature search strategy was
developed in collaboration with a health sciences librarian.32
The main characteristics of the studies included in the review are:
topic being discussed, first author and year. We conducted primary
systematic literature searches using a combination of keywords,
including “chemical submission”, “drug-facilitated crimes” “drug-facil­
itated sexual assault” and “forensic”. Three independent reviewers (MG,
MDPC and IL) reviewed titles and abstracts, and then the full-text studies
satisfying the inclusion criteria. An inter-rater research agreement be­
tween the three reviewers was determined as the ratio of positive
agreement (PA).33
2.5. Data extraction
The same three independent testers (MG, MDPC and IL) used
Microsoft Excel to gather duplicate data. Multiple reports from the same
study were checked and compared, and specific data were extracted if
available. The following data were extracted for all studies which met
the inclusion criteria: authors, year of publication, geographical area,
population research, research nature, sample size, age range, gender,
population analyzed, chemical submission motive, substance detected,
method of analysis and biological matrix. Both original articles and case
reports were analyzed. Although case reports are articles that have the
lowest scientific evidence within the scale of the different research
studies, and are obviously not representative, they do include the dis­
covery of new situations, and may lead to new research hypotheses to be
confirmed in future investigations based on a greater number of cases. In
addition, in the matter that concerns us here, these cases reports allow us
M.G. García et al.
to identify new substances that may be used to commit crimes, any
special characteristics of the victims and to understand the diagnostic
and analytical strategy used by the investigators.
2.6. Risk of bias assessment
Comparing the Cohort Research Checklist Critical Assessment Skills
Program (CASP),34 the probability of bias was evaluated for each study.
In the CASP checklist, the following confounding variables were
assessed: sample size, age, gender, population analyzed, motive for
chemical submission, substance identified, method of analysis and bio­
logical matrix analyzed. The study performance was rated as “poor,”
“moderate” or “good” based on the CASP checklist. The overall proof
standard was rated as strong, moderate, poor or extremely low.35
3. Results
3.1. Characteristics of articles included in the systematic review
A total of 673 studies were identified in two scientific electronic
databases, PubMed (505) and Google Scholar (168) (Fig. 1), and 441
duplicates or non-relevant studies were eliminated.
The titles and abstracts of the remaining 232 studies were reviewed
to assess their relevance against exclusion criteria. Where the title pro­
vided insufficient information, the abstract was reviewed or, if required,
Fig. 1. Flow diagram of the systematic review.
3
Journal of Forensic and Legal Medicine 79 (2021) 102151
the complete article was screened. In accordance with the exclusion
criteria, a total of 198 studies were excluded for being: (i) narrative
reviews (n = 50); (ii) based on analytical techniques (n = 62); (iii) un­
specific, or treating other perspectives of crime, compound pharmaco­
kinetics, or focusing on instrumentation and/or toxicology from a
theoretical point of view (n = 86).
Finally, this search strategy identified 33 descriptive studies for in­
clusion in this systematic review: 23 related with DFSA 10 related with
DFC.
3.1.1. Risk of bias assessment
According to the CASP probability of bias evaluation, most studies
(88.2%) were considered either “good” or “moderate” due to the
considered variables, while 11.8% was considered “poor” primarily due
to confounding variables which were not considered (Table 1). Partici­
pants were recruited from the geographic regions associated with the
study. Overall, the literature was of “good” quality.
3.2. Laboratory methods
The different types of biological matrices used by the different
studies to carry out the toxicological determinations were assessed
(Table 2). The methods used to evaluate chemical submission varied
although most studies used chromatography (31/34), spectrometry (29/
34) and immunoassay (5/34) to amplify the range of substances. Two
M.G. García et al. Journal of Forensic and Legal Medicine 79 (2021) 102151

Table 1
Risk of bias assessment.
Study [Ref.] Did the Cohort Exposure Outcome Important Important Are the Are the Do the Overall
DFSA study recruitment accurately accurately confounding confounding results results results fit quality
address a acceptable? measured? measured? factors factors precise? believable? with other score
clearly identified? accounted for? available
focused data?
issue?

SPAIN
Xifró-Collsamata + + - - - - - - + Poor
et al., 2015
Quintana et al., + + - - - - - - + Poor
2020
Escayola and + + - - - - - - + Poor
Vega, 2013
FRANCE
Eiden et al., 2013 + + - - - - + + + Mod
Djezzar et al., + + + + + + + + + Good
2009
Gaillard et al., + + + + + + + + + Good
2006
ITALY
Bertol et al., 2018 + + + + + + + + + Good
NORWAY
Hagemann et al., + + - - - - + + + Mod
2013
NETHERLANDS
Bosman et al., + + - - - - + + + Mod
2011
BELGIUM
Wille et al., 2013 + + - - - - + + + Mod
ENGLAND
Scott-Ham and + + - - - - + + + Mod
Burton., 2005
DENMARK
Johansen et al., + + + + + + + + + Good
2017
GERMANY
Andresen- + + - - - - + + + Mod
Streichert
et al., 2017
Mehling et al., + + + + + + + + + Good
2016
UNITED STATES
Fiorentin and + - - - - - + + + Mod
Logan., 2019
Hagan and + + + + + + + + + Good
Reidy., 2015
Stillwell and + + + + + + + + + Good
Saady., 2012
Krebs et al., 2009 + + - - - - + + + Mod
CANADA
Du Mont et al., + + - - - - + + + Mod
2010
COSTA RICA
Cerdas et al., + + + + + + + + + Good
2014
CHINA
Pan et al., 2019 + + + + + + + + + Good
SOUTH AFRICA
Tiemensma et al., + + + + + + + + + Good
2018
NEW ZEALAND
Poulsen et al., + + + + + + + + + Good
2020
DFC
FRANCE
Richeval et al., + + - - - - + + + Mod
2017
Questel et al., + + - - - - - - + Poor
2009
Chèze et al., 2005 + + + + + + + + + Good
ITALY
Pelletti and + + - - - - + + + Mod
Rossi., 2018
NETHERLANDS
+ + + + + + + + + Good
(continued on next page)

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M.G. García et al. Journal of Forensic and Legal Medicine 79 (2021) 102151

Table 1 (continued )
Study [Ref.] Did the Cohort Exposure Outcome Important Important Are the Are the Do the Overall
DFSA study recruitment accurately accurately confounding confounding results results results fit quality
address a acceptable? measured? measured? factors factors precise? believable? with other score
clearly identified? accounted for? available
focused data?
issue?

Lusthof et al.,
2017
BELGIUM
Ramadan et al., + + - - - - + + + Mod
2013
HUNGARY
Kapitány-Fövény + + + + + + + + + Good
M. et al., 2018
PORTUGAL
Castro et al., + + + + + + + + + Good
2019
DENMARK
Wang et al., 2018 + + + + + + + + + Good
THAILAND
Krongvorakul + + - - - - + + + Mod
et al., 2018

Data based on CASP-based risk of bias assessment. (-); this variable was unable to be assessed. Mod; Moderate.

studies were based on guided surveys36–38 and one on a guided Aged between 14 and 37 years old, 95% were women. In addition, 68%
interview.39 of victims admitted having voluntarily consumed alcohol before the
assault. Once the pertinent analyses had been carried out, the presence
of psychoactive substances was detected in 47% of the subjects. The
3.3. Analysis of criminal practices associated with chemical submission
three most common substances were cocaine, cannabinoids, and ben­
zodiazepines, in that order.41
Two overall motives were seen to be behind the use of CS, so-called
DFSA and DFC.
3.3.1.2. France. One study analyzed a case of a 22-year-old woman in
France who had been sexually assaulted. The victim described a state of
3.3.1. Drug facilitated sexual assault
stupefaction, which led to an inability to physically or verbally resist her
A total of 23 studies looked at DFSA, which was clearly the most
attacker, recall anything that had happened. The first clinical suspicion
widespread crime of this type worldwide (Table 3). This crime is not
was alcohol poisoning, but toxicological analysis revealed the presence
new, and many classic texts refer to potions that help in sexual practice,
of 3,4-methylene-dioxymethyl-methamphetamine (MDMA) in the urine
or the use of certain mushrooms or opiates in the rituals of certain sects.5
and a blood concentration of 0.09 mg/l, while Methylenedioxy
However, the prevalence of using submission drugs for criminal pur­
amphetamine (MDA), the metabolite of MDMA, was also detected at a
poses has been increasing for more than two decades.
concentration of 0.013 mg/l. The researchers emphasize the fact that the
The substance most used in cases of DFSA was ethanol, the most
results were negative for alcohol or other substances.42
commonly detected drug according to the European Monitoring Center
In France, 309 cases were analyzed nationwide, of which 158 met the
for Drugs and Drug Addiction in 200810 and which played a part in
requirements described by the authors to be classified as chemical
almost half of the cases analyzed by the Dublin Rape Crisis Center in
submission.
2007.23
The victims were mostly women (89.5%) and the type of assault was
Different studies related to DFSA in different parts of the world were
mainly DFSA (50%). Benzodiazepines (Clonazepam, Zolpidem, and
analyzed in this systematic review and are shown in Fig. 2.
Bromazepam) were detected in 129 victims (82%), while Flunitrazepam
and gamma hydroxybutyrate, well known for their use in chemical
3.3.1.1. Spain. A study carried out in Barcelona (Spain), analyzed a
submission cases, were identified in 11 (7%) and five (3%), respectively,
total of 114 victims, of whom 30.7% (35) were confirmed cases of DFSA.
of the 158 victims.43
Through toxicological analysis, it was possible to say that 33 of the
Worthy of note is another event that occurred in France, in which
victims had in all probability suffered DFSA. As regards the gender of the
chloroform was used, and which resulted in the death of the victim, a 13-
victims, 91.4% were women and only 8.6% were men. The victim’s
year-old girl. The rapist had used a very high dose of chloroform (833.9
average age was 27 years and most were foreign visitors, (23 of the 35
mg/l) as a disabling agent, which was detected by GC-MS.44
DFSAs). The toxicological analyses carried out showed that 48.4% of the
victims had ethanol in their blood. Twenty patients had ethanol in
3.3.1.3. Italy. In Italy, Bertol et al.45 carried out a retrospective study of
combination with other substances, the most common being cocaine,
256 women over 18 years of age who had been subjected to sexual as­
codeine, and amphetamines.40
sault, and who requested medical attention in the Sexual Assault Centre
A study carried out in the National Institute of Toxicology and
at Careggi University Hospital, Florence (Italy). Of the patients, 37.1%
Forensic Sciences in Madrid between 2010 and 2012, analyzed a total of
were positive for at least one substance, mostly alcohol, followed by
306 people, of whom 107 (35%) presented the symptoms to suggest they
cannabis, cocaine and opiates/methadone (heroin, morphine, metha­
had been victims of DFSA. All the victims were women of Spanish or
done). The authors also found benzodiazepines and amphetamines.
Latin American nationality with a mean age of 25.9 ± 9.4 (mean ± SD).
They observed only one case of gamma-hydroxybutyrate (GHB) con­
Many victims admitted alcohol consumption, whose presence was
sumption and no psychoactive substances were detected.
confirmed in the analyses carried out, together with benzodiazepines
and other stimulant drugs such as cocaine.27
In another study of 179 cases related to sexual assault between 2009 3.3.1.4. Norway. Of note is a retrospective study carried out in Nor­
and 2012 in Alicante (Spain), 19 of them (10.6%) could have been DFSA. way36 describing the toxicological findings among women seeking

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M.G. García et al. Journal of Forensic and Legal Medicine 79 (2021) 102151

Table 2
Description of the different biological matrices and analytical techniques used to detect the chemical substances.
Study [Ref] Detection Matrix Time between Analysis techniques Other
ingestion and techniques
determination

DFSA Chromatography Spectrometry Immunoassay Survey Guided

study interview

SPAIN
Xifró-Collsamata Blood and urine <24 horas GC-FID; GC-MS; LC-MS
et al., 2015
Quintana et al., 2020 Blood and urine - LC-MS-MS; GC-MS ✓
Escayola and Vega, Blood, urine and hair 2–51 h (mean 18,26 (HS) GC; GC-MS ✓ ✓
2013 h)
FRANCE
Eiden et al., 2013 Blood and urine 12 h (HS)GC; LC-MS-MS ✓ ✓
Djezzar et al., 2009 Blood, urine, hair, capsule, <72 h LC-DAD; LC-MS; LC-MS-MS; ✓
drink and food LC-ES-MS; GC-MS
Gaillard et al., 2006 Urine Bile Gastric liquid Liver <24 h GC-MS; LC-PDS; (HS)GC- ✓
Kidney Lung Subcutaneous fat MS; LC-MS-MS
and Intestinal fat
ITALY
Bertol et al., 2018 Blood, urine and hair <24 h GC-MS; LC-MS-MS ✓
NORWAY
Hagemann et al., Blood and urine 1 hour-16 days (mean LC-MS; GC-MS ✓ ✓
2013 29,6 h)
NETHERLANDS
Bosman et al., 2011 Blood and urine <24 hous GC-MS; GC-MS-MS; HPLC- ✓ ✓
DAD
BELGIUM
Wille et al., 2013 Blood and urine 30 h GC-MS; HPLC-DAD ✓
ENGLAND
Scott-Ham and Blood and urine 12–36 h GC-FID; GC-MS; GC-MS ✓ ✓
Burton., 2005
DENMARK
Johansen et al., 2017 Blood, urine and hair 43 h UHPLC–TOF-MS; ✓
UHPLC–MS/MS
GERMANY
Andresen-Streichert Blood and urine <24 h GC-MS ✓ ✓
et al., 2017
Mehling et al., 2016 Blood, bile, vitreous humor, - LC-MS-MS; GC-MS ✓
liver, kidney, brain tissues and
hair
UNITED STATES
Fiorentin and Logan, Blood and urine - LC/QTOF-MS ✓ ✓
2019
Hagan and Reidy, Urine - GC-MS ✓
2015
Stillwell and Saady., Urine 7–23 h GC-MS ✓
2012
Krebs et al., 2009 - - ✓
CANADA
Du Mont et al., 2010 Urine <24 hous GC-MS; GC-FID
COSTA RICA
Cerdas et al., 2014 - - ✓
CHINA
Pan et al., 2019 Blood, urine, stomach contents - GC-FID; LC-MS-MS; GC-MS; ✓
and hair GC-FPD; GC-NPD; GCECD
SOUTH AFRICA
Tiemensma et al., Blood, urine and hair - LC-MS-MS ✓
2018
NEW ZEALAND
Poulsen et al., 2020 Blood and urine 2–93 h (mean 16 h) (HS)GC-FID; LC-TOF-MS; ✓ ✓
GC-MS; LC-MS-MS
DFC
FRANCE
Richeval et al., 2017 Blood 10 h (HS)GC-MS ✓
Questel et al., 2009 Blood and urine 91 h GC-MS; HPLC ✓ ✓
Chèze et al., 2005 Blood urine and hair <24 h (Blood and HPLC-DAD; GC-MS ✓
urine). 4–8 weeks
(Hair)
ITALY
Pelletti and Rossi., Blood <24 h (HS)GC-FID; LC-MS; GC-MS ✓
2018
NETHERLANDS
Lusthof et al., 2017 Blood, urine, stomach contents Case 1: 5 days
and hair

(continued on next page)

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M.G. García et al. Journal of Forensic and Legal Medicine 79 (2021) 102151

Table 2 (continued )
Study [Ref] Detection Matrix Time between Analysis techniques Other
ingestion and techniques
determination

DFSA Chromatography Spectrometry Immunoassay Survey Guided

study interview

Case 2: Urine 12 h
and hair 79 days
Case 3: 22 h GC-FID; GC-MS; LC-MS-MS; ✓
HPLC-DAD; GC-MS
BELGIUM
Ramadan et al., 2013 Blood <24 h GC-MS ✓
HUNGARY
Kapitány-Fövény M. Blood and urine - GC-MS ✓
et al., 2018
PORTUGAL
Castro et al., 2019 Blood - GC-MS-MS ✓
DENMARK
Wang et al., 2018 Blood, urine and Hair 19–180 days (main 38 UHPLC–TOF–MS; ✓ ✓
days) UHPLC–MS/MS
THAILAND
Krongvorakul et al., Blood, aurine and gastric fluid Case 1: 4 hoursCase 2: LC-MS-MS; GC-MS ✓
2018 8 hoursCase 3: 6 h

n.i. not indicated; (HS)GC-FID: Headspace Gas Chromatography - Flame Ionization Detection; (HS)GC: Headspace Gas Chromatography; GC-ECD: Gas Chromatog­
raphy – Electron Capture Detector; GC-FID: Gas Chromatography - Flame Ionization Detection; GC-FPD: Gas Chromatography – Flame Photometric Detector; GC-MS:
Gas chromatography - mass spectrometry; GC-MS/MS: Gas chromatography - tandem mass spectrometry; GC-NPD: Gas Chromatography – Nitrogen Phosphorous
Detector; HPLC-DAD: High performance liquid chromatography - diode-array detector; LC-DAD: Liquid chromatography - diode-array detector; LC-ES-MS: Liquid
chromatography – electrospray - mass spectrometry; LC-MS: Liquid chromatography - mass spectrometry; LC-MS/MS: Liquid chromatography – tandem mass spec­
trometry; LC-PDS: Liquid chromatography in parallel dynamic spectroscopy; LC-TOF-MS: Liquid chromatography-time-of-flight- mass spectrometry; LC/QTOF-MS:
liquid chromatography - quadrupole time-of- flight - mass spectrometry; UHPLC–MS/MS: Ultra-high performance liquid chromatography - tandem mass spectrom­
etry; UHPLC–TOF-MS: Ultra-high performance liquid chromatography-time-of- flight - mass spectrometry; UPLC-MS/MS: Ultra performance liquid chromatography -
tandem mass spectrometer.

medical attention after sexual assault, and evaluating the relationship
with so-called “Proactive DFSA”. Urine and blood samples were
analyzed for ethanol and medicinal or recreational drugs. Among the
264 patients included in the study, ethanol and/or drugs were detected
in 59%, while 19% showed positive results for benzodiazepines or
similar drugs, central stimulants, cannabinoids, or opioids. No subject
tested positive for GHB. Proactive DFSA was suspected in 57 patients
(22%), but only in five cases were sedative drugs found that were not
accounted for by self-reported voluntary intake. No case could be un­
equivocally attributed to proactive DFSA. Among the 120 patients
evaluated for ethanol within 12 h of the assault, 102 were positive. The
median estimated blood alcohol concentration (BAC) at the time of the
assault was 1.87 g/l. Patients who tested positive for ethanol reported a
public assault and, more frequently, an unknown assailant more
frequently. A high BAC estimated for the time of the assault was asso­
ciated with a greater suspicion of proactive DFSA. High concentrations
of ethanol, the most prevalent toxicological finding, were found in the
urine/blood of victims of sexual assault. Among the patients who sus­
pected proactive DFSA, very few showed the presence of sedatives that
could not be explained by voluntary intake, suggesting a predominance
of opportunistic assault over proactive assault.
3.3.1.5. Netherlands. Bosman et al.46 identified the scope and types of
drugs in 135 cases of alleged DFSA in the Netherlands, analysing blood
and urine samples for the presence of alcohol, drugs (drugs abuse and
prescription drugs), or both. In 27% of cases they did not find alcohol or
drugs, although the authors affirm that in some of these cases, the
absence of either may represent false negatives due to the time elapsing
between the alleged sexual assault and sampling. In 47% of cases the
authors detected the presence of alcohol and in 54% other drugs were
detected. The most common group of drugs identified was the
non-opioid analgesic group, with acetaminophen and ibuprofen as the
most frequent. Cocaine, MDMA and THC, along with their metabolites,
were the most commonly found illicit drugs. In addition, they detected
benzodiazepines and other drugs like amphetamines, GHB or Ketamine.
3.3.1.6. Belgium. Another study in Belgium describes the administra­
tion of Ketamine and Diazepam to a young woman of 29 by her gyne­
cologist. The authors describe how they detected Nordiazepam,
Temazepam, Ketamine and Norketamine in the urine, while the blood
concentrations 30 h after the alleged events were: 28 ng/ml of Diaz­
epam, 8 ng/ml of Nordiazepam, 2 ng/ml of Temazepam, 2 ng/ml Ke­
tamine and 6 ng/ml Norketamine. They further point out that
determination of dose and associated effects at the time of the suspected
assault by retrospective calculations was not possible in the case of
Ketamine due to its nonlinear pharmacokinetics and the delay between
the suspected assault and sampling. However, the plasma concentration
of Diazepam was estimated between 79.5 and 138.5 ng/ml. The
administered dose of Diazepam was estimated at 2.4–20.8 mg. The au­
thors concluded that in this case, the toxicological data contributed
relevant data to the investigation, supporting the victim’s statements.47
3.3.1.7. United Kingdom. In the UK, Scott-Ham et al.48 analyzed the
toxicological results of 1014 DFSA cases from the London Forensic Sci­
ence Service, using blood and urine samples. They describe how alcohol
was detected (alone or in combination with illicit drugs or medications)
in 470 cases (46% of the total). Illicit drugs were detected in 344 cases
(34%), with cannabis being the most commonly detected (26% of cases),
followed by cocaine (11%). In 21 cases (2%), a sedative or disinhibitory
drug was detected, which the victims did not describe as having been
voluntarily consumed, suggesting these may represent cases of proactive
FDSA. In the same study, the authors also describe three cases in which
the victims were proactively intoxicated with MDMA. In addition, other
drugs that were detected included GHB, Diazepam and Temazepam.
3.3.1.8. Denmark. In Denmark, Johansen et al. describe the case of a
DFSA that occurred in Copenhagen using Quetiapine, a sedative anti­
psychotic medication, to subdue the victim.10 Spectrometry
(UPLC-MS/MS) revealed a concentration of 0.007 mg/l of Quetiapine in
blood and 0.19 mg/l in urine. Six months after DFSA, a hair sample was
collected and a segmental hair analysis was performed on four washed

7
M.G. García et al. Journal of Forensic and Legal Medicine 79 (2021) 102151

Table 3
Criminal practices analysis associated with chemical submission.
Type of substance

Study [Ref] Country Study Period N Gender W/ Age* Nationality victim Stimulating Depressor
M, (%)

DFSA
SPAIN
Xifró-Collsamata Spain 2011 35 W (91.4%) 27.0 ± 7.37 Spanish (34,8%) Cocaine Benzodiazepines
et al., 2015 M (8.6%) Western Europe
(56,5%) Latin
American (8,7%)
Codeine
Quintana et al., Spain 2010–2012 306 (107 W (100%) 25.9 ± 9.4 Spanish (63.6%) Cocaine Ethanol
2020 DFSA) Latin American
(26.4%)
Benzodiazepines
Escayola and Vega, Spain 2009–2012 179 W (97%)M 14–37 - Cocaine Ethanol
2013 (3%) Amphetamines
Cannabinoids
Benzodiazepines
FRANCE
Eiden et al., 2013 France 2013 1 W (100%) 22 French MDMA
Djezzar et al., 2009 France 2003–2007 309 (79DFC- W (89.5%) - - Benzodiazepines
79 DFSA) M (10.4%)
Flunitrazepam
GHB
Gaillard et al., France 2005 1 W (100%) 13 - Chloroform
2006
ITALY
Bertol et al., 2018 Italy 2010–2018 256 W (100%) 22 Italian (27%) Foreign Cocaine Cannabis
(73%)
NORWAY
Hagemann et al., Norway 2003–2017 264 W (100%) - Norwegian/ Benzodiazepines
2013 European (96%)
Cannabinoids
Opioids
NETHERLANDS
Bosman et al., Holland 2004–2006 135 W (94%) M 25.4 - Cocaine MDMA THC
2011 (6%)
Benzodiazepines
Analgesics
BELGIUM
Wille et al., 2013 Belgium 2013 1 W (100%) 29 Belgian Ketamine
Diazepan
ENGLAND
Scott-Ham and England 2000–2002 1014 (DFSA W (56%)M - - Cocaine
Burton., 2005 2%) (44%)
MDMA Ethanol
Cannabis
GHB
Benzodiazepines
DENMARK
Johansen et al., Denmark 2016 1 W (100%) - - Quetiapine
2017
GERMANY
Andresen- Germany 2015 1 M (100%) 4 German Xilazima
Streichert et al.,
2017
Mehling et al., Germany 2013 1 W (100%) 6 German GHB
2016
UNITED STATES
Fiorentin and U.S. 2015–2016 1000 W (91.6%) 26.8 Amphetamine
Logan., 2019 M (24%)
Methamphetamine
Cocaine
Clonazepam Ethanol
Cannabinoids
Hagan and Reidy., U.S. 2013 6 W (100%) - - Synthetic
2015 cathinones
Stillwell and U.S. 2012 2 W (100%) 17.5 Native American
Saady., 2012 (50%)
Hispanic (50%) Tetrahydrozoline
Krebs et al., 2009 U.S. - 5446 W (100%) 18–25 U.S.
CANADA
Du Mont et al., Canada 2005–2007 882
2010
(184 DFSA) 25.8 ± 8.5 n.i. Amphetamines
(continued on next page)

8
M.G. García et al. Journal of Forensic and Legal Medicine 79 (2021) 102151

Table 3 (continued )
Type of substance

Study [Ref] Country Study Period N Gender W/ Age* Nationality victim Stimulating Depressor
M, (%)

W (96.2%)M
(3.8%)
Cocaine
MDMA Cannabinoids
Ethanol
GHB
COSTA RICA
Cerdas et al., 2014 Costa Rica 2012–2013 272 (39% W (100%) 22 Costa Rica Ethanol and other
DFSA) drugs
CHINA
Pan et al., 2019 China 2017 9083 (35 - - China Benzodiazepines
DFSA)
Ethanol
Dexmedetomidine
SOUTH AFRICA
Tiemensma et al., South Africa 2013–2016 107 W (98.1%) - -. Methamphetamine
2018 M (1.9%)
Cocaine Ethanol
Sedative hypnotic
Benzodiazepines
NEW ZEALAND
Poulsen et al., New Zealand 2015–2018 161 W (98.1%) 22 - Methamphetamine
2020 M (1.9%)
Ethanol
Opioid
Cannabinoids
Analgesics
Benzodiazepines
DFC
FRANCE
Richeval et al., France 2016 1 W (100%) 26 - Chloroform
2017
Questel et al., 2009 France 2005–2006 52 W (55.7%) 33 (W)34 (M) - Benzodiazepines
M (44.5%)
Chèze et al., 2005 France 2003–2004 128 (23 DFC) W (85%)M - - Benzodiazepines
(15%)
ITALY
Pelletti and Rossi., Italy 2013–2017 9 W (89%)M - - Cocaine Benzodiazepines
2018 (12%)
NETHERLANDS
Lusthof et al., 2017 Holland 2017 3 M (100%) 25.4 - Cocaine
MDMA THC
Benzodiazepines
Analgesics
BELGIUM
Ramadán et al., Belgium 2003 16 - 28.5 Asian Flunitrazepam
2013
HUNGARY
Kapitány-Fövény Hungary 2009–2013 352 W (46%) M 26.9 ± 10 - GHB
M. et al., 2018 (54%)
PORTUGAL
Castro et al., 2019 Portugal 2019 M M (100%) 25 - GHB
DENMARK
Wang et al., 2018 Denmark 2009–2016 130 (25 W (76%) M 30 - MDMA
confirmed (24%)
DFC/DFSA)
Cocaine Benzodiazepines
Antihistamines
Barbiturate
Antipsychotic
Opioids
THAILAND
Krongvorakul Thailand 2017 3 W (33.3%) 76 (M)72 (W) - Xilazine
et al., 2018 M (66.6%)

N, Number of individuals analyzed; n.i. not indicated; M, Men; W, Women; DFC, Drug-facilitated crime; DFSA, Drug-facilitated sexual assault; US, Criminal practices
analysis associated with chemical submission; MDMA, 3,4-methylenedioxy-methamphetamine; GHB, gamma-hydroxybutyrate; SD, Standard deviation. THC, tetra­
hydrocannabinol, *Age, is expressed as mean, mean ± SD or age range.

segments (0–3 cm, 3–5 cm, 5–7 cm, and 7–9 cm). The last segment
contained 0.011 ng/mg Quetiapine, while the other segments were
negative. According to the authors, the low level of Quetiapine in this
hair segment and its absence in the other segments indicate that the
victim had only consumed one or very few doses of Quetiapine within
that period and was not a regular consumer. The authors emphasize that
this case highlights the importance of having highly sensitive analytical
methods for measuring a single dose in blood and urine and how the
extended detection window for hair analysis can reveal more informa­
tion in such cases.

9
M.G. García et al.
Fig. 2. Representative diagrams illustrating the types of toxic substances used and their worldwide distribution, based on the articles included in this review.
There are only a few cases of drug-facilitated sexual assault in chil­
dren reported in the literature. Here, the case of a four-year-old boy is
presented.49 He was unconscious and the adults accompanying him re­
ported that the boy had been alone in a playground. Upon returning
home, he complained that he had been stung by bee and had immedi­
ately collapsed. The child’s urine and serum samples were investigated.
In toxicological analysis, Xylazine, a sedative and muscle relaxant used
in animals, was detected. Subsequent GC/MS quantification after solid
phase extraction revealed 0.053 mg/l Xylazine in serum and approxi­
mately 0.63 mg/l in urine. In addition, the boy was examined by a
forensic medical specialist. Police investigations revealed that it the
perpetrator was the boy’s godfather, who had previously been accused
of child sexual abuse.
Another study50 describes the case of a six-year-old girl who died
after sedation with γ-hydroxybutyric acid (GHB). The girl had been
sexually abused by a relative. Samples of cardiac blood, bile, vitreous
humor, liver, kidney, brain tissues and hair were analyzed using an
LC-MS/MS method. The following GHB concentrations were deter­
mined: cardiac blood: 150 mg/l; bile: 292 mg/l; vitreous humor: 58
mg/l; liver: 100 mg kg; kidney: 124.5 mg/kg, brain: 110 mg/kg. Very
high levels of GHB were found in the proximal part of the hair sample
(approximately 40.9 ng/mg). In distal hair segments, up to 12 cm away
from the scalp, GHB concentrations were higher than the total endoge­
nous range found of 2–3 ng/mg. Police investigations revealed that the
relative had also administered GHB to the older sister, and a sample of
her hair was analyzed accordingly, but no conclusive results were ob­
tained. Comparing the toxicological results with the police in­
vestigations and the offender’s statements, it can be assumed that the
6-year-old girl had ingested GHB. By excluding other causes of death,
lethal GHB poisoning was confirmed.
3.3.1.9. United States of America. A study conducted in the United
States attempted to identify the types of drugs associated with DFSA in
37 states and one U.S territory. Of a total of 1000 cases, only 21.6% were
negative for toxic substances, although the authors highlight that the
absence of alcohol and drugs in some cases may have been due to a delay
in sample collection. A total of 101 different substances were detected.
10
Journal of Forensic and Legal Medicine 79 (2021) 102151
In general, ethanol was the most prevalent substance, and was detected
in 309 cases (30.9%), followed by cannabinoids (THC; THC-COOH; 11-
OH-THC; 28.8% of cases), amphetamine and methamphetamine
(16.5%), cocaine and its metabolites (10.4%), and Clonazepam and its
metabolites (7.6% of cases). Ethanol and cannabinoids was the most
frequent combination found.51
In another study, urine samples from six sexual assault victims that
were sent to the Toxicology Laboratory at the University of Miami in
2013 were analyzed. The study used a qualitative method to detect ten
designer drugs. The authors highlighted that no commonly used drugs,
such as ethanol, GHB or Ketamine, were found in any DFSA although
13% of the samples were positive for synthetic cathinones. The study
reveals the correlation between DFSA and the use of synthetic
cathinones.52
Also in the United States,53 reported on two cases of drug-facilitated
sexual assault that involved Central Nervous System (CNS) depression,
making victims vulnerable to sexual assault and unable to recall events
that surrounded the crimes. In both cases, Tetrahydrozoline (THZ) was
used to poison victims. The first case had a urine ethanol concentration
of 0.15 g% w/v and a urine THZ concentration of 1.481 ng/ml,
approximately 7 h after ingestion. The second case was negative for
ethanol, but had a THZ concentration in urine of 108 ng/ml 23 h after
ingestion.
To evaluate the methods used in sexual assaults,37 a study carried out
in two American universities (The University of Cincinnati, and The
University of North Carolina, Chapel Hill), used a web survey and the
results on substance use were based on the victims’ statements. The
results indicated that almost 20% of undergraduate women had expe­
rienced some form of sexual assault since entering college. Most sexual
assaults occurred after the women had voluntarily consumed alcohol,
while only a few occurred after they had been given a drug without their
knowledge or consent.
3.3.1.10. Canada. A study was conducted at the Ontario Hospital,
Canada, to determine whether 882 patients reporting sexual assault had
been covertly drugged. The authors found that 20.9% of the patients met
the criteria for suspecting DFSA. Urine samples were positive for drugs
M.G. García et al.
in 44.9% of cases, for alcohol (12.9%) and for both in 18.0% of cases.
The drugs found in the toxicological screening were unexpected in
64.4% of cases and included cannabinoids (40.2%), cocaine (32.2%),
amphetamines (13.8%), 3,4-metilendioxi-metanfetamina (MDMA)
(9.2%), Ketamine (2.3%) and gamma-hydroxybutyrate (GHB) (1.1%).
The authors concluded that most of the unexpected drugs found were
not those typically described as “date rape drugs".16
3.3.1.11. Costa Rica. In Costa Rica, a retrospective study of 272 rapes
that occurred in one year was carried out. The authors describe how
96% of the victims were women, of whom 50% were between 10 and 19
years old. In addition, they observed how 99.5% of the aggressors were
men. The authors highlight how 14% of the rapes could be classified as
“proactive drug-facilitated violations” and 25% as “opportunistic drug-
facilitated violations".39 Study data came from reports received by the
Forensic Science Department (Biochemistry Section) of the Judicial
Investigation Agency. The authors explain that the toxicological findings
were analytically confirmed but do not indicate the methodology used.
3.3.1.12. China. A study carried out in Shanghai54 to assess specific
patterns in forensic toxicology analyzed a total of 9083 cases. Their
results show that 35 cases were deaths as a consequence of DFSA. Of
these, 23 were positive for some sort of drug. Benzodiazepines were the
most commonly detected drugs (77.8%), followed by alcohol (11.1% of
cases) and Dexmedetomidine (11.1%). The authors do not specify the
causes of death in these cases.
3.3.1.13. South Africa. In the African continent, Tiemensma et al.55
carried out a study with the aim of characterizing DFSA in a metropol­
itan environment in South Africa, identifying the drugs associated with
these attacks. A total of 107 cases involving suspected DFSA in Cape
Town were analyzed. The authors observed that 72 cases were positive
for drugs and/or ethanol, with multiple drugs detected in 35 cases and a
single drug in 37 cases. Other drugs combined with ethanol were
detected in blood and/or urine in 56% of the samples.
The most common substances detected, from highest to lowest fre­
quency, were stimulants in the form of methamphetamine, cocaine and
its metabolites, and sedative hypnotics, and Doxylamine or Diphenhy­
dramine. Combinations of Methaqualone, Diphenhydramine, and
Methamphetamine were detected in 15 cases. Benzodiazepines were
detected in 4 patients, none of whom reported the use of these drugs.
The authors concluded that DFSAs in this context are mostly opportu­
nistic, with ethanol suggested as the most commonly involved drug.
3.3.1.14. New Zealand. Finally, a study carried out in New Zealand
detailed the toxicological profile of 161 DFSA victims. The authors
analyzed blood and urine samples to detect legal and illegal drugs, in
addition to analyzing alcohol and correlating alcohol concentration with
delays in sample analysis.56 The authors describe how some victims
declared they had consumed alcohol prior to the attacks, although this
substance was not detected, probably because the average sampling
delay was 14 h for blood and 17 h for urine. The most frequently
detected alcohol concentration was in the range of 51–80mg/100 ml for
blood and 121–200mg/100 ml for urine, with an average sampling time
of 8.5 and 6.5 h, respectively. Cannabis was the most frequently detected
drug, in 31 blood samples and 15 urine samples. Methamphetamine was
the second most commonly found drug in DFSA cases (12 blood samples
and 18 urine samples). There were also 3 cases in which MDMA was
detected and 2 cases in which other illicit drugs related to glue inhala­
tion were detected. As regards medications, the most commonly detec­
ted were antidepressants, anticonvulsants, and antipsychotics. The three
drugs found most frequently were Citalopram, Fluoxetine, and Quetia­
pine. Opioids and pain relievers were also commonly found with Co­
deine. In addition, Tramadol and Morphine were found. Finally, among
benzodiazepines, the most frequently detected was Diazepam.
11
Journal of Forensic and Legal Medicine 79 (2021) 102151
Lorazepam and Clonazepam were detected but its use was only found in
one case. Other benzodiazepines and sedatives that were present in the
study include Zopiclone and Alprazolam.
3.3.2. Drug-facilitated crimes
A total of ten studies of DFC were found in this systematic review
(Table 3).
3.3.2.1. France. A study describes a case of chloroform poisoning from
an impregnated scarf worn by a 26-year-old woman in Clermont-
Ferrand. The victim’s clinical symptoms were of those of assault, but
with signs of sexual assault. Extensive drug and toxic substance deter­
mination was performed in whole blood samples using gas
chromatography-mass spectrometry (GC-MS) and tandem mass spec­
trometry methods coupled to a liquid chromatography electrospray.
However, only the presence of Chloroform was detected, and at a much
lower concentration than that associated with a fatal chloroform
poisoning of DFSA (834 mg/l).57
In a study of 52 cases unequivocally related with CS, in Paris,58 half
of which involved DFSA and the other half theft, it was observed that
77% were due to poisoning by benzodiazepines and other substances
such as antihistamines, neuroleptics and γ-hydroxybutyric acid. Gener­
ally, alcohol had been consumed before taking these substances.
In another study in Paris, 128 cases with suspected CS were analyzed
and drugs were detected in 18% of cases.12 The most frequent sub­
stances detected were benzodiazepines, Zolpidem and Clonazepam, and,
to a lesser extent, other benzodiazepines and analogues. In half of the
cases analyzed, the victim admitted having previously consumed other
types of narcotic substances.
3.3.2.2. Italy. In Italy,59 toxicological examinations from retrospec­
tively collected autopsies at the Forensic Toxicology Unit of the Uni­
versity of Bologna (Italy) included cases of DFC (other than DFSA) and
acute poisoning in which psychoactive drugs, prescription drugs, or
illicit drugs were found in victims’ blood samples. Of the nine cases of
DFC other than DFSA, one of the victims was repeatedly poisoned by her
son by means of alcoholic beverages, causing fatal poisoning; in another
case, the victim was poisoned to facilitate her strangulation; in two
cases, the victims were poisoned to facilitate a planned homicide; in
another case, the victim was poisoned to facilitate a murder.
In another case, the perpetrator (the victim’s boyfriend and drug
supplier) gave the victim a drink containing benzodiazepines without
her knowledge, just prior to the use of cocaine (which the victim regu­
larly took), causing fatal poisoning. In three other cases, the victims
were poisoned by a caretaker or an acquaintance to enable the theft of
personal items. Regarding the toxicological findings of these cases, the
authors describe ten different drugs found in the victims’ blood. Ben­
zodiazepines were found in all cases, alone or in combination with other
drugs. In three cases, only one psychoactive drug was found, while in the
other cases, multiple psychoactive drugs were found in the blood of the
victims. Cocaine and its metabolites were found in two cases. Alcohol
was only found in one case, in which alcoholic beverages were used as a
means of administering other drugs.
3.3.2.3. Netherlands. In one study, the toxicological outcomes of three
cases (one fatal) of scopolamine-facilitated theft that had occurred in the
Netherlands were analyzed.60 In the fatal case, a heart blood scopol­
amine concentration of 0.30 mg/l was detected, while in femoral blood
the scopolamine concentration was 0.0048 mg/l, and was also very high
in the stomach (20 mg/kg). In one of the non-fatal cases, the serum
scopolamine concentration obtained 23 h after the incident was
0.00035 mg/l and the estimated scopolamine concentration at the time
of the incident was 0.0035 mg/l. In the other non-fatal case, scopol­
amine was detected in both urine and hair.
M.G. García et al.
3.3.2.4. Belgium. Of interest are several cases of robbery involving
tourists that were carried out in 2003 by means of CS in Brussels.61 The
data of the cases were collected by the Emergency Service of a Belgian
hospital center. The robberies occurred at the city’s main train station,
the victims being 16 Asian tourists aged between 28 and 50 years when
they were intoxicated. Flunitrazepam, a drug of the benzodiazepine
family, was detected, so it was concluded that the theft had been facil­
itated by CS. However, the case was closed.
3.3.2.5. Hungary. In Hungary, GHB poisoning was detected in 352
victims, each one with an assumed or proven GHB intake. In 113 cases
(27.7%), only GHB had been consumed, while the most frequently co-
ingested substance was ethanol, which was detected in 56 cases
(13.73%). Most of the victims were men in their twenties, and had
previously consumed alcohol. Among those who unintentionally took
the drug, 6.5% were sexually assaulted, while 21.7% were robbed.62 For
the full sample, the mean concentration of GHB was 1205.66 ng/ml (SD
= 2120.78) in serum samples, and 6910.76 ng/ml (SD = 10294.02) in
urine samples. For those cases where only GHB was detected, the mean
concentration was 9561 ng/ml (SD = 1224.74) in serum and 32881
ng/mL (SD = 7367.88) in urine samples.
3.3.2.6. Portugal. Castro et al., 2019 presented the first case of
poisoning with 1,4-butanediol reported in Portugal, and included the
quantification of GHB and GHB-GLUC in serum using GC-MS/MS-
TQD.63 The toxicological analysis revealed the presence of 1,4-butane­
diol and GHB (171 mg/l) and GHB-GLUC (13.7 mg/l) in serum. The
authors report how the victim recovered from the coma with no
neurological sequelae and emphasized the importance of analyzing all
samples in search of active compounds, precursors and metabolites that
could lead to the main source of the poisoning.
3.3.2.7. Denmark. In an analysis of the toxics found in hair segments
from 130 suspected cases (77% women) of drug-facilitated crime (DFC)
in Denmark,38 toxicological analysis confirmed CFD in 25 suspected
cases (76% women). The nineteen women were between 14 and 30
years old, while the six men were all over 40 years old. In the study, 24
drugs and metabolites related to DFC were detected: clonazepam and its
metabolite 7-aminoclonazepam, Diazepam, Nordazepam, Temazepam,
Oxazepam, Triazolam, Zolpidem, Zopiclone, Diphenhydramine, Prom­
ethazine, Morphodone, Codeine, Tramadolicine, Oxycodone, Tramado­
licine, the metabolite O-desmethyltramadol, Quetiapine,
Chlorprothixene and Desmethylchlorprothixene, Phenobarbital, 3,
4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenediox­
yamphetamine (MDA), cocaine and Benzoylecgonine (BZE).
3.3.2.8. Thailand. Lastly, a study carried out in Thailand described
xylazine being used for poisoning with criminal intent. Two incidents
were analyzed, the first involving one victim and the second involving
two victims. In the first case, the general screening of drugs by GC/MS
revealed Xylazine, but LC-MS/MS did not identify it in serum. In the
second incident, LC-MS/MS identified Xylazine in urine and serum
samples. After completing this report, the authors conclude that Xyla­
zine should be classified as a controlled drug.64
4. Discussion
This systematic review has analyzed victims of DFSA and DFC,
compiling sociodemographic data about the victims, the chemicals and
biological matrices used, and the keys to toxicological diagnosis, in
order to identify substances and their potential criminal use. In this way,
we hope to contribute to the future, political and health strategies that
will inform and warn society about the dangers to their health and the
criminal and social behavior associated with their use.
Many of the authors included in this review affirm that failure to
12
Journal of Forensic and Legal Medicine 79 (2021) 102151
report or delay in reporting drug-facilitated crimes to the police or
medical facilities contributed to an underestimation of the prevalence of
such crimes. The first part of the protocol to follow when a case of CS is
suspected is to ascertain whether there has been any alcohol intake. If
not, symptoms of drowsiness, confusion, difficulty in remembering, and
even nausea may be the key to uncovering a case of CS. It must be
decided whether the individual has a hangover and whether they are
still disoriented after drinking. If the individual feels that they have been
assaulted but have no memories of the events, their body and clothes are
examined for foreign substances or fluids. It is important that the sus­
pected victim reach a hospital as soon as possible after the alleged event,
without having bathed, cleaned or changed clothes, and even without
eating. The victims must try to reveal everything they remember and in
as much detail as possible, while the hospital will performs rape and
urinary tests to find any clues that may lead us to the discover of the use
of drugs or medication.5 It should be noted that in most hospitals to
which victims are admitted, only immunoassays, liquid chromatog­
raphy, or gas chromatography-mass spectrometry are used, and, since
most of the substances involved in DFC are not detectable at low levels
by these techniques, a false negative result may lead to inaccurate
conclusions and the premature destruction of samples.18,29
Furthermore, it should be borne in mind that the prevalence and
toxicology rates for DFC appear to differ between continents, depending
on the use of certain recreational drugs and social norms.54 Regarding
DFSA, it must be considered that victims of a sexual assault frequently
do not report the case, which makes it difficult to make an adequate
estimate of crimes of a sexual nature. The low reporting rates and the
prosecution that characterizes sexual assault are even more evident in
cases facilitated by drugs, when victims may feel powerless, a feeling
which is further aggravated by bureaucratic complexities and the
slowness of the judicial process.
In such crimes, victims are incapacitated and cannot mount any
resistance to the sexual abuse; moreover, they are unable to fight off the
abuser and unable to clearly recall the circumstances of the events due to
antegrade amnesia. The consequence may be a delay in carrying out
toxicological analyses, which is aggravated by the victim’s reluctance to
disclose the crime. Therefore, reporting is often late, so when laboratory
tests are carried out, the compounds that may have been used to facil­
itate DFSA may have already been metabolized and may not be
detectable in blood or urine.16,39,43,50,64
Authors such as51,59 further emphasize that as the delay between the
alleged sexual assault and sampling increases, especially if the delay
exceeds 24 h, laboratories are less likely to identify drugs in urine
samples. Therefore, a negative analytical result does not, in itself, rule
out the existence of chemical submission, since, as we have mentioned,
it may be due to the combined effect of a small dose and the passage of
time.40
There is a general perception in society that the perpetrators of these
crimes covertly administer drugs to their victims, aware of their effects
in order to achieve a state of vulnerability in the victim that will permit
them to commit a crime. However, despite the fact that some findings
such as those of Du Mont 201016 describe this, their study reinforces the
idea that it is a misperception. In very few of the patients who suspected
they had been victims of these crimes was there evidence that they had
involuntarily ingested the substances in question, and it was more
common to identify the voluntary consumption of drugs and/or alcohol.
Indeed, many authors suggest that crimes that are facilitated by drugs of
voluntary consumption cause a loss of consent and a state of vulnera­
bility in the victim are the most common.36,52,55,56
The approximate age of the victims mentioned in the reviewed
studies ranges from 14 to 30 years, an age that is frequently associated
with environments where alcohol and drugs are used for recreational
purposes. For this reason, in many cases it is difficult to separate
voluntary consumption from that induced by the perpetrator. However,
it seems that, in certain aspects, the prevalence of opportunistic crime
exceeds that of proactive crime. Several studies show that most of the
M.G. García et al.
drugs detected in these crimes are drugs that are in common use among
the population (alcohol and recreational drugs such as MDMA, cocaine
or cannabinoids) and not drugs normally used as precursor drugs (e.g.,
Flunitrazepam, Ketamine or GHB).52,55,56,62
As can be seen from most of the articles analyzed, ethanol poisoning
presents the greatest risk in terms of drug-facilitated crimes, especially
drug-facilitated sex crimes.16,51,53,55,65,66 In most cases the alcohol is
consumed voluntarily by the victim, and, since alcohol tends to be
present in any type of social event, and it does not seem unreasonable to
consider that a person could become intoxicated quite unforced, making
it very difficult to identify cases where this intake is induced, and not a
voluntary act.10 However, the reviewed literature suggests that alcohol,
by itself, is rarely a causal factor or the sole contributor in these crimes.
For example, what are known as “spiked drinks” produce effects with
similar toxicodynamics and so diagnosis can sometimes be erroneously
confused with classic ethanol poisoning. Therefore, as indicated by au­
thors,67 it is imperative to quickly consider a toxicological analysis in
cases of DFSA.
After alcohol, benzodiazepines were the most commonly detected
substances in DFCs and, as with ethanol, their presence is mentioned in
studies from many different parts of the world.12,36,38,40,54–56,59 This
may be due to the fact that access to them is relatively easy in many
countries since they are commonly prescribed drugs (sometimes not
even needing a prescription) and are also readily available through the
internet at low prices. When taken in conjunction with alcohol or other
drugs, they may increase a person’s vulnerability to criminal acts, which
highlights the need to establish stricter prescription and distribution
protocols for these substances. The same can be said about regulating
other sedative hypnotic drugs, whose use in DFC is mentioned in some of
the studies analyzed in this review.49,50,54,55,64 The non-medical use of
pharmaceuticals has sharply increased in recent years to become a sig­
nificant and rapidly growing problem. Nevertheless, the actual inci­
dence of these drugs in DFC is not known exactly, but the data seem to
indicate that they are increasingly used in this type of crime.59
The use of stimulant drugs to commit crimes is more frequent than
might be expected. It is true that in most cases they were commonly used
drugs of abuse, such as cocaine or methamphetamine, and when crimes
are committed against victims in a vulnerable state it seems more
probable that we are dealing with opportunistic crimes.38,42,45,51,59
However, stimulants can also be used in non-opportunistic crimes, as
seen in.52,53
In addition, criminals may experiment with other types of substances
that they consider to have advantages over those normally used, such as
chloroform.44,57 For example, chloroform shows its instability in in vitro
tests and there is a lack of pharmacokinetic information on this toxic,57
which may contribute to increasing cases of DFSA and other undetected
DFCs. As the popularity of these substances increases among the po­
tential perpetrators of these crimes, it is necessary to search for more
efficient detection methods for identifying volatile compounds in toxi­
cological investigations.
Regarding the analytical strategies followed to detect the substances
used in this type of crime, it must first be emphasized that many of the
substances associated with DFC induce similar clinical symptoms, so it is
not possible to conclude that the symptoms are due to exposure to a
given drug if there is no clear analytical evidence. Furthermore, as we
have found in this review, it is normal for several drugs to be present
simultaneously. All the above means that the toxicological methods used
must be solid and reliable enough to guarantee the validity of the results
obtained.
As this review has shown, many countries of the world are still far
from establishing a clear consensus on the action protocol for investi­
gating cases of DFC, even as regard the toxicological analysis of the
samples. Authors such as55 highlight the need for comprehensive and
systematic toxicological analyses to be established and followed by all
centers involved in the study of samples taken from DFC victims,
including adequate chain of custody procedures and the exact
13
Journal of Forensic and Legal Medicine 79 (2021) 102151
toxicological experiments to be carried out. On the same lines, point to
the need to offer toxicological screening routinely in order to achieve a
comprehensive evaluation of each individual case45. Such analyses
should be conducted by specialized personnel so that the correct choice
is made concerning the detection of compounds (drugs and their me­
tabolites) in different matrices (blood, urine, hair), adopting the most
sensitive and advanced technologies (UHPLC, GC-MS, LC-MS/MS).
The peculiarity of this type of crime, whereby the victim is given a
single dose at a specific time, makes it necessary for the limits of
quantification of the detection equipment to be very low. For this reason
toxicologists have started to use highly sensitive detection methods for
drugs and their metabolites in blood, urine or hair.12 Furthermore, a
chromatographic analysis must always complement an immunological
analysis, which, alone, is not specific or sensitive enough for these
cases.58
As for the various biological matrices, venous blood and urine are
recommended for determining drug exposure, and, while hair analysis
also seems to be a good complimentary action, it cannot replace other
biological samples.50 Regarding the analysis of urine and blood and in
order to improve detection, it is recommended that MS/MS techniques,
such as LC-MS/MS or GC-MS/MS, be because of their high sensitivity
and selectivity. In the case of hair, too, GC-MS/MS or LC-MS/MS is
recommended.68 The analysis of urine, blood and hair has proven
effective for the detection of most drugs used in DFC. However, such
analyses are ineffective if the disabling agent is a volatile substance,
because their metabolization is very fast and so they are not fixed in the
hair. In such cases, the analysis of adipose tissue takes on special
importance.44
Regarding the main limitations in studying cases of DFC, it should be
emphasized that the results of one study cannot be extrapolated to other
geographic regions because, as mentioned above, the prevalence of this
type of crime seems to differ between countries and even within
different regions in the same country, depending on the use of certain
recreational drugs and social norms 40,54. Furthermore, only searching
for relevant articles in English has perhaps prevented us from including
other interesting articles in this field of knowledge. Whatever the case,
to avoid linguistic misinterpretations, this study was limited to articles
in English throughout. Another important limitation is the judicial
sphere because in many countries prosecutors often demand to know the
effects of drugs at the time of the reported event and, while retrospective
calculations and dose estimates can be made, ambiguities will remain
due to uncontrolled parameters such as the metabolization rates of
certain drugs. In addition, it must be taken into account that many of the
victims discussed here self-administered recreational drugs prior to their
assault, so the figures could be inaccurate.
However, the main problem today is the widespread fear among DFC
victims and especially DFSA victims, that they will not be believed or
may even be blamed by judicial authorities, especially in cases where
victims take drugs voluntarily.69 This is a major problem and the cause
of DFC being underestimated, not only due to victims who never report
the crime but also to victims who delay doing so to such an extent that
the drugs are no longer detectable in blood or urine. Furthermore, not all
victims will undergo toxicological screens even if they attend hospital,
so that that many victims will not be seen as such.
It is clear that current public awareness campaigns aimed at publi­
cizing the risk of sexual victimization after alcohol and drug use are
markedly deficient. Appropriate strategies are necessary to educate at-
risk populations and, importantly, to demonstrate to potential perpe­
trators that the detection of drugs is constantly improving, lessening
their possibility of escaping legal justice system. Victims of sexual as­
sault should be encouraged to seek immediate help, but also need to
have available quick and easy access to emergency medical care offered
by trained personnel.
M.G. García et al.
5. Conclusions
CS crimes pose a growing global health and social problem, and to
reduce such crimes, it is necessary to have available instrumental
techniques for the detection of a variety of toxics in different matrices
that will guarantee the reliability and validity of the results obtained.
The substances used in CFDs are many and varied, and some may be
given to the victim simultaneously, making them difficult to detect in
analytical tests. On the other hand, there is also a need for worldwide
consensus on the protocols to be followed in the case of DFCs. It is
necessary to establish the most effective methods and to generalize their
use at a global level, thus allowing forensic scientists to draw up reliable
scientific standards that will provide results that are acceptable from a
judicial point of view. In addition, it would also be useful to unify the
description of what the symptoms of chemical submission are in order to
facilitate its diagnosis. For all these reasons, public awareness cam­
paigns aimed at highlighting the risk of becoming a victim of CFDs after
the consumption of alcohol and drugs should be set in motion. Although
programs that advise people to protect their drinks and exercise caution
when accepting drinks from others are important, educational materials
should also alert them to the risks of voluntarily mixing alcohol and
drugs. Furthermore, as point out, awareness campaigns should not be
directed only at women, as this would help perpetuate the attitude that
it is the victims themselves who are, at least partially, responsible for
sexual assaults.70
However, it is increasingly difficult to find a way to control the use of
these substances on a global scale, or even within one country, because
of the increasing variety of substances available to aggressors, such as
volatile substances, including chloroform. Thus, it is a very difficult
topic to address but one that must be investigated if these acts are to be
understood and properly recognized in the judicial sphere.
Regarding the analysis techniques used, immunoassays are the
standard method used in most laboratories to analyze drug samples,
possibly because they are less technically demanding and less expensive
than other methods.27 However, immunochemical methods can present
problems since they are often insensitive to low doses of drugs,61 and
they can also present cross-reactivity, so the potential for false positives
is always present when such methods are used.71 This is why gas chro­
matography coupled to mass spectrometry (GC-MS) and liquid chro­
matography coupled to tandem mass spectrometry (LC-MS/MS) or diode
matrix detector (LC-DAD) have become the most recommended tech­
niques for forensic tests because they allow a wide range of metabolites
to be detected, even at low concentrations.36,49
Regarding the substances used, some differences can be observed
between the different continents, possibly due to the differences be­
tween the patterns of drug abuse in each.55 In Europe, America, Africa
and Oceania, the most frequently used drugs are ethanol, cannabinoids
and benzodiazepines. By contrast, in Asia no stimulant drugs were found
and in the cases reviewed from this continent, only depressant drugs
were observed.
Declaration of competing interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
Acknowledgement
Not applicable.
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