Accepted Manuscript

Title: The Cutting of Cocaine and Heroin: A critical review

Author: Julian Broseus Natacha Gentile Pierre Esseiva

PII: S0379-0738(16)30055-X
DOI: http://dx.doi.org/doi:10.1016/j.forsciint.2016.02.033
Reference: FSI 8340

To appear in: FSI

Received date: 14-8-2015

Revised date: 6-2-2016
Accepted date: 18-2-2016

Please cite this article as: J. BROSEUS, N. GENTILE, P. ESSEIVA, The Cutting
of Cocaine and Heroin: A critical review, Forensic Science International (2016),
http://dx.doi.org/10.1016/j.forsciint.2016.02.033

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1 Highlights
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3 - A review of relevant publications of criminology and criminalistics

4 - A single article covering the main aspects of illicit drug cutting: who, when, why?
5 - Empirical information on cocaine and heroin adulteration/dilution

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- Summary of past trends and current cutting approaches

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7 - Propositions to improve knowledge of cutting phenomenon

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10 The Cutting of Cocaine and Heroin : A critical review
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13 Julian BROSEUSa*, Natacha GENTILEa, Pierre ESSEIVAa
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15 : Ecole des sciences criminelles, Faculté de droit, des sciences criminelles et

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16 d’administration publique, Université de Lausanne
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18 * : Corresponding author.
19 Tel.: +41 21 692 46 46.

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20 E-mail address: julian.broseus@unil.ch (J. Broséus).
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22 Abstract
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24 The illicit drug cutting represents a complex problem that requires the sharing of knowledge
25 from addiction studies, toxicology, criminology and criminalistics. Therefore, cutting is not
26 well known by the forensic community.

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27 Thus, this review aims at deciphering the different aspects of cutting, by gathering

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28 information mainly from criminology and criminalistics. It tackles essentially specificities of
29 cocaine and heroin cutting. The article presents the detected cutting agents (adulterants and

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30 diluents), their evolution in time and space and the analytical methodology implemented by
31 forensic laboratories. Furthermore, it discusses when, in the history of the illicit drug, cutting

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32 may take place. Moreover, researches studying how much cutting occurs in the country of
33 destination are analysed. Lastly, the reasons for cutting are addressed.

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34 According to the literature, adulterants are added during production of the illicit drug or at a
35 relatively high level of its distribution chain (e.g. before the product arrives in the country of
36 destination or just after its importation in the latter). Their addition seems hardly justified by
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37 the only desire to increase profits or to harm consumers’ health. Instead, adulteration would
38 be performed to enhance or to mimic the illicit drug effects or to facilitate administration of
39 the drug. Nowadays, caffeine, diltiazem, hydroxyzine, levamisole, lidocaïne and phenacetin
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40 are frequently detected in cocaine specimens, while paracetamol and caffeine are almost
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41 exclusively identified in heroin specimens. This may reveal differences in the respective
42 structures of production and/or distribution of cocaine and heroin.
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43 As the relevant information about cutting is spread across different scientific fields, a close
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44 collaboration should be set up to collect essential and unified data to improve knowledge and
45 provide information for monitoring, control and harm reduction purposes. More research, on
46 several areas of investigation, should be carried out to gather relevant information.
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48 Keywords: illicit drug; adulterant; diluent; drug market; interdisciplinary; drug policy
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49 Context
50
51 The wider public has the perception that drugs are deliberately and frequently cut using
52 substances potentially harmful for health, such as household cleaning products, brick dust,
53 strychnine or ground glass [1-3]. It is worth noting that such perception is spread both among

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54 consumers (who are largely ignorant of the actual content of their samples) and even street

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55 dealers [4-8]. This perception may arise because of the main argument put forward to justify
56 cutting. Indeed, cutting is usually explained by the seller’s desire to increase its profits. This

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57 would be performed by adding to the illicit drug any substance that looks like it and/or would
58 have the same effect, with no possibilities for the buyer to notice the addition, and that may be

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59 harmful [9]. However, the dealer sells commodity and relies on repeat custom, sometimes
60 interacting with the same people. Thus, he should be seen as a businessman: poisoning

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61 customers does not make good business sense regarding income supply or reputation [3].
62 Furthermore, some dealers even say being concerned by their customers’ health [5, 10, 11].
63 This is why presence of harmful substances in illicit drugs may only occur if dealers or
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64 suppliers were ignorant or inexperienced (i.e. that they would try cutting drugs by themselves,
65 with available substances, therefore taking the risk to create toxic mixtures), if they wanted to
66 kill the maximum number of people or had a desire for revenge. But these scenarios are not
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67 considered as “normal” cutting approaches [1, 12].

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68 Usually, substances detected by forensic laboratories in cocaine and heroin specimens either
69 are natural compounds, by-products, cutting agents or artefacts. Typically, cutting agents refer
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70 to diluents (pharmacologically inactive and readily available substances) and adulterants

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71 (pharmacologically active substances, usually more expensive or less available than diluents)
72 [13]. Cutting agents may be added at different steps in the history of the illicit drug.
73 Therefore, cutting may be studied at the production stage, in the country of origin, as well as
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74 at different levels of the distribution chain, until the final one, in the country of consumption
75 [12].
76 Information (type, appearance frequency, concentration, etc.) related to cutting agents
77 detected in illicit drugs is limited in forensic literature. This is probably due to the fact that
78 these substances are not listed and therefore the record and transmission of their presence are
79 not compulsory. Furthermore, their identification is not straightforward due to their various
80 types (pharmaceuticals and sugars). Thus, forensic laboratories mainly focus on the

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 81 qualification and the quantitation of the illicit drug under analysis, especially when both
82 aspects are used for judiciary purposes [14].
83 Therefore, this article aims at improving the knowledge of this key aspect of illicit drug
84 markets. It provides the forensic science community with an in-depth analysis of cutting,
85 based on data convergence mainly from criminology and criminalistics. The article

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86 summarizes the evolution in time and space of adulterants and diluents detected in cocaine

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87 and heroin specimens as well as the analytical methodology used by laboratories to identify
88 cutting agents. Furthermore, it discusses when, from the country of production to that of

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89 destination, cutting takes place. Moreover, researches studying how much cutting occurs in
90 the country of destination are compared. Lastly, the reasons for cutting are analysed.

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91
92 1. Evolution in time and space

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94 As aforementioned there is a lack of standardised analyses and reporting of cutting agents.
95 This makes the comparison of cutting approaches over time and space uncertain.
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96 Furthermore, the knowledge of various factors such as changes in production of illicit drugs,
97 supply routes of drugs and cutting agents (in particular, adulterants) and the history, structure
98 and organisation of drug markets in each country are often unknown. It is also worth to note
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99 that according to the chemical form of cocaine and heroin (i.e. base or salt forms), different
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100 cutting agents may be found. Nevertheless, a review of the literature enables to discuss public
101 perceptions with objective results and highlights trends in the cutting approaches of cocaine
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102 and heroin.

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103 The review of literature reveals that the perceptions spread among the wider public were not
104 really supported by the analysis of cocaine and heroin specimens (see Appendix 1 – Table 1:
105 cocaine and Table 2: heroin). Indeed, forensic results indicate that cutting consists more in
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106 diluents such as sugars or substances that will enhance/mimic the effects of the illicit drug
107 than with substances chosen to cause serious health problems or death (see section 5).
108 The review of literature reveals temporal differences in the type of cutting agents and/or their
109 appearance frequency and the evolution in the cutting of cocaine and heroin may be
110 summarised as follows. In cocaine, lidocaïne and sugars were the two main cutting agents in
111 the 1980s [15]. At the beginning of the 1990s, lidocaïne was not anymore detected in Spain
112 [16], while at the end of this period this was one of the main adulterants in Italy – along with
113 caffeine and phenacetin [17]. Diltiazem, hydroxyzine and levamisole were first reported from

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114 2004 to 2006, in the Netherlands [18], the United-States [19, 20], Switzerland [21, 22], Italy
115 [23] and France [7, 24]. Nowadays, phenacetin, levamisole, caffeine, diltiazem, hydroxyzine
116 and lidocaine are considered as the main adulterants of cocaine in Europe [7, 18, 22, 24-29].
117 Several studies performed in Brazil, the country with important trafficking routes to North
118 America, Africa and Europe, showed that adulterants similar to the ones mentioned above

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119 were detected [30-38] (see Appendix 1 – Table 1). Recently, presence of new psychoactive

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120 substances (NPS) has been reported in cocaine specimens, but at very low appearance
121 frequency [39]. Concerning heroin, substances such as caffeine, quinine, lactose and mannitol

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122 were reported between the 1960s and the 1970s in Europe [15]. In the 1980s, caffeine,
123 procaine, paracetamol and phenobarbital were common adulterants and quinine was less

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124 detected [15]. At the beginning of the 1990s, procaine, phenobarbital and methaqualone
125 progressively disappeared, for instance in France [40], Denmark [41] and Spain [42]. Since

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126 then, caffeine and paracetamol were reported as the main adulterants for heroin in many
127 European countries and the most recent studies reported their detection at similar and high
128 appearance frequency (more than 90% of specimens contain caffeine and paracetamol) [21,
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129 22, 25, 28, 29, 40, 42-50] (see Appendix 1 – Table 2). Griseofulvin, an antifungal drug, was
130 first mentioned as an adulterant of heroin in 2000 [28]. Lastly, nowadays, the most detected
131 diluents both for cocaine and heroin are glucose, sucrose (saccharose), lactose, mannitol and
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132 even inositol [15, 22]. Starch and carbonates are also reported as diluents for cocaine [33].
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133 These results provide us with important information to better understand the cutting of illicit
134 drugs. Indeed, the presence of similar adulterants detected in different countries tends to
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135 highlight a consensus or knowledge from the people involved in production or distribution
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136 about which cutting substances to use. Their choice does not seem to be meaningless. This
137 makes us also infer that these substances may be added during the production of the illicit
138 drug or at a high level of the distribution chain of the product (see section 3). Moreover,
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139 forensic results inform on the structure/organisation of illicit drug markets. Thus, from 1980
140 to date, we have observed an increase (resp. a decrease) in the number of cutting agents
141 detected in cocaine specimens (resp. heroin specimens) [18, 25, 28, 41, 48]. In particular,
142 since the beginning of the 1990s, the adulteration of heroin market was particularly stable
143 with the predominance of caffeine and paracetamol, even at similar concentrations (see
144 section 2). Since, in the same time, we have observed more changes in the adulteration of
145 cocaine (increase in the number of adulterants, variation in frequencies of appearance and
146 concentrations), we may say that cocaine market is more dynamic than heroin market. Thus,

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147 these observations may reflect differences in the organisation of the production and
148 distribution chains of both drugs. We may infer that these differences could be due to the
149 cocaine market being managed by more independent actors using their own cutting approach.
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151 2. Analytical methodology and recorded or transmitted information

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153 In order to promote the systematic analysis of cutting agents, this article reviews the analytical
154 methodologies implemented by forensic laboratories for their identification. This parameter is

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155 of utmost importance when discussing the type and appearance frequency of cutting agents
156 that were detected. In particular, regarding chromatographic methods, a proper solvent should

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157 be chosen to enable the extraction of a wide range of adulterants and diluents. According to
158 literature, methanol and chloroform are the two main used solvents; acetonitrile, acetic acid or

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159 toluene are rarely mentioned. Separation and detection of compounds is performed through
160 the combination of GC to FID, MS or NPD and HPLC to DAD, MS, RI or UV (see Appendix
161 1 – Table 1 and Table 2). Results that are published concern almost only the presence of
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162 adulterants. Unfortunately, the frequency of adulterated/diluted specimens is rarely reported,
163 and yet this is crucial to get a sound knowledge on the cutting phenomenon (e.g. its spread) as
164 well as on the structure of drug markets. This will inevitably influence the quality of public
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165 health or control responses.

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166 Concentrations of adulterants/diluents in specimens are rarely assessed. Concerning heroin,

167 similar mean concentrations for caffeine and/or paracetamol have been observed in different
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168 countries (see Appendix 2 – Table 2). Furthermore, as mentioned above similar frequencies of
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169 appearance for these compounds have been observed. Therefore, this highlights a relative
170 similarity in the cutting of heroin sold in Europe. To the contrary, the composition of cocaine
171 seems to be more heterogeneous according to the respective frequencies of appearance (see
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172 Appendix 1 – Table 1) and concentrations of cutting agents (see Appendix 2 – Table 1).
173 Little information is available about diluents, maybe because forensic laboratories do not
174 carry out their systematic detection and identification. This may lead to an underestimation of
175 dilution. According to recent data, heroin is less diluted than cocaine regarding the number,
176 frequencies of appearance and/or concentrations of diluents [22, 28].
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177
178 3. When does cutting take place?
179
180 A spatiotemporal analysis of adulterants detected in cocaine and heroin specimens indicate
181 that these substances may be added during the production of the illicit drug or at a high level
182 in the distribution chain of the product, since they are respectively detected in cocaine and

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183 heroin specimens while confiscated in different countries in the world. An explanation of this
184 widespread detection may be related to the availability and price of adulterants. Indeed,

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185 adulterants are certainly not readily available in the amounts that are required for cutting large
186 batches of cocaine or heroin. Furthermore, they are relatively pricy – over 400 euros per gram

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187 for diltiazem for instance [51]. Thus, this would badly explain their addition by street dealers
188 just before selling illicit drugs and may instead support the hypothesis of an addition of
189 adulterants at the production or at a relatively high level of the distribution chain [49].

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190 In particular, several studies assessed that heroin adulteration would take place before
191 exportation or just after importation in the country of destination, where it would be realized
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192 by the minority of those involved in its distribution [1, 11, 41, 49, 52]. Since years, it was
193 estimated that paracetamol added to heroin was illicit paracetamol, which was made brown
194 (like base heroin), and not originating from pharmaceutical suppliers [41, 49]. In many
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195 European countries, significant seizures of the mixture paracetamol – caffeine, linked to
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196 heroin trafficking and up to several tens of kilograms and physically resembling to heroin
197 base, indicated the use of this mixture for heroin adulteration [22, 25, 48]. This is consistent
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198 with the composition of heroin specimens, in which this combination is frequently present.
199 The mixture caffeine – paracetamol may be added during the manufacture of heroin base
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200 and/or during its distribution [48].

201 Concerning cocaine, it has been estimated in the United States that for example diltiazem was
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202 added at the end of the production process [19]. In France, according to the adulterants
203 detected in specimens confiscated at airports, it has been deduced that diltiazem, hydroxyzine
204 and levamisole were added in the country of production. Phenacetin, procaine and lidocaine
205 would instead be added after importation in Europe and caffeine could be added before as
206 well as after importation [24]. In the country of destination, seizures of substances frequently
207 used to adulterate cocaine specimens are also reported in the literature (in particular,
208 phenacetin and lidocaine) [22].
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209
210 Theoretically, since adulteration may occur at the production stage or high in the distribution
211 chain, the origin of illicit drugs could be a very good indicator of the presence, the type and
212 proportions of cutting agents [49]. Conversely, the presence of certain adulterants could
213 indicate a geographical origin or a particular distribution network [12, 41, 53, 54]. For
214 instance, at the end of the 1980s caffeine was absent from all heroin specimens analysed in

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215 Turkey and procaine present in half of them [53]. In United States, theophylline was detected
216 in heroin specimens coming from South America and diphenhydramine in the ones from

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217 South West Asia [12]. More recently, it was hypothesised that levamisole was used as a
218 chemical marker to track distribution of the illicit drug [23]. Lastly, phenacetin is commonly

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219 found in Brazilian seizures confiscated close to borders with Peru and Bolivia, while
220 levamisole is frequently detected in seizures close to the Colombian border [34]. In order to
221 evaluate the potential of cutting agents – in particular, adulterants – to indicate a geographical

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222 origin the authors have undertaken a survey intended for member laboratories of the European
223 Network of Forensic Science Institutes (ENFSI) and regarding the analysis of cutting agents
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224 (e.g. the most frequent detected adulterants in different illicit drugs). The results of the survey
225 were shared at the ENFSI Drug Working Group in 2015 held in Espoo (Finland) and
226 highlighted similar trends in the type of adulterants that were detected in different countries.
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227 Nevertheless, some countries showed specificities in the most frequent adulterants that were
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228 reported, which may reveal that the type and appearance frequency of adulterants may
229 indicate a geographical origin. The possibility to highlight a particular distribution network
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230 through the analysis of cutting agents would especially be interesting in the case of cocaine
231 trafficking, since cocaine specimens showed high diversity in their adulteration. This should
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232 be investigated through a study combining the analysis of cutting agents with the chemical
233 profiling of alkaloids. Indeed, thanks to the chemical profiling of alkaloids, it would be
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234 possible to link cocaine specimens coming from different seizures and thus to reveal the
235 history of a physical unit after it was broken up for further distribution [27]. Therefore, the
236 cutting approaches of specific distribution networks may be evaluated. The authors currently
237 undertake this research.
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239
240 4. How much cutting does take place in the country of destination?
241
242 Are illicit drugs systematically and highly cut prior to their sale to consumers? This was the
243 question addressed by some studies to evaluate the hypothesis that cutting would take place at
244 each step of the distribution chain and would especially be decided by street dealers. Illicit

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245 drugs such as cocaine and heroin would therefore see a decrease in their purity and be sold
246 intensively cut [2, 12, 50].

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247 Based on interviews with heroin dealers in the United Kingdom or Australia [5, 10, 11], it has
248 been assessed that after the illicit drug has entered the destination country but before it has

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249 reached consumers, cutting was not systematic at each level of the distribution chain. Indeed,
250 cutting was not the only way for dealers to make profits, argument that was usually put
251 forward to justify cutting. The only fact of selling the product in small quantities allowed a

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252 dealer to make significant profits [1].
253 The analyses of heroin seizures may indicate that once cut at source or high up in the chain of
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254 distribution (for example, before arrival in the country of destination or just after importation
255 in the latter), heroin would not be adulterated or diluted further down. Indeed, on the one
256 hand, little difference was observed between the purity of heroin seized by customs (thus,
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257 prior to its distribution in the country of consumption) and that of heroin seized at street level
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258 (end of the distribution chain) [41, 42, 49, 50, 52]. On the other hand, the concentration of
259 caffeine and paracetamol – the two main cutting agents of heroin – varies very little between
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260 specimens yet to be packaged before sale and those intended for direct sale to consumers [45].
261 Concerning cocaine, according to the diversity of adulterants detected in the specimens and
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262 their concentrations (see sections 2 and 3) as well as cocaine purity [16, 50], adulteration
263 seems relatively higher as the illicit drug progresses in the distribution chain.
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264 However, there is no extensive empirical data available in the literature about the composition
265 – purity and cutting agents – of specimens seized at different levels of the distribution chain in
266 the country of destination. Therefore, assessing precisely when cutting occurs as well as its
267 degree is quite a difficult task, both for cocaine and heroin. Thus, we would slightly modify
268 the following statement of Cole et al. (2010) “[…] the evidence suggests that the majority of
269 adulteration of heroin takes place at or close to the time of synthesis and significantly less
270 ‘cutting’ than would be generally perceived takes place after heroin leaves the country of
271 origin“. Indeed, this “evidence” is essentially based on a study of differences in purity
272 between specimens seized at importation and street specimens, in the country of destination.
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273 As aforementioned, this type of analysis should be combined to a study of the evolution in the
274 number, appearance frequency and concentrations of adulterants/diluents at each stage of
275 distribution in which illicit drugs pass. Moreover, as mentioned above, literature reports
276 significant seizures of substances used to adulterate cocaine or heroin in countries of
277 destination, for instance the caffeine/paracetamol mixture in the case of heroin. This indicates

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278 the existence of an adulteration of illicit drugs, which may take place at wholesale level (i.e.

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279 just after importation in the country of consumption). Moreover, adulterants may be added
280 during the transit from the country of origin to the country of destination. Thus, for all these

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281 reasons, assessing the magnitude of adulteration of cocaine or heroin specimens in the country
282 of destination vs. the country of origin is currently difficult.

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283
284 5. Why are cocaine and heroin cut?

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286 Dilution, using pharmacologically inactive, cheap, readily available and licit substances
287 (sugars, starch, carbonates), could be explained by the seller’s desire to increase its profits at
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288 each level of the distribution chain [25]. Concerning adulterants, they are used [14, 25] :
289 - To enhance or mimic the effects of illicit drugs; the aim is either to give the impression
290 of a better quality drug or mask a poor quality product using substances with similar
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291 properties to the illicit drug. Concerning cocaine, that would be the case of levamisole
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292 (boost cocaine effects) [55], diltiazem (decrease cocaine effect on skin temperature),
293 caffeine (similar though milder stimulant properties), procaine and lidocaïne (similar
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294 anaesthetic properties) and phenacetin (similar analgesic and physical properties).
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295 Concerning heroin, we could mention paracetamol (similar analgesic properties) and
296 griseofulvin (similar bitter taste) [28], for instance.
297 - To ease or make the administration of the illicit drug more efficient; for example,
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298 caffeine, procaine and even strychnine [56, 57] have been found to vaporize heroin at
299 a lower temperature and therefore facilitate smoking.
300 These two hypotheses reveal that cutting – in particular adulteration – would be more
301 strategic rather than random or unpredictable [12, 58].
302 Even if adulterants have health effects [15, 18, 25, 59], adulteration does not seem to be
303 performed to harm consumers, according to the substances that are detected and their
304 concentrations in specimens. At low dosages, consumption of adulterants is assessed to be
305 less harmful than consumption of the illicit drug itself [15].

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306 Furthermore, cutting would not be justified by the only desire of maximising the profits, using
307 any available substances. If so, diluents – like starch, talc or sugars – would be more
308 frequently detected than adulterants – like levamisole or phenacetin –, since they are readily
309 available and cheaper substances. Moreover, adulteration may take place already at the
310 production or at a relatively high level in the distribution chain, as discussed above.

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311 From a marketing point of view, using adulterants that enhance the effects of illicit drugs or

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312 make their administration more efficient does make sense. The aim of producers or sellers is
313 making their product attractive, keeping their consumers, attracting new ones and they are

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314 therefore sensitive to new trends in administration routes of illicit drugs [12]. Thus,
315 adulteration may result from a market-sensitive activity on the part of people involved in

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316 production and/or distribution of illicit drugs [12, 58]. An interesting illustration is the
317 evolution of heroin adulteration in the United States from 1970-1980 to 1990 according to

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318 new trends in its consumption [12]. Lastly, the use of some substances could be related to
319 their higher availability at a given time.
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320
321 Conclusion
322
323 A review of the relevant literature showed that the provided information concerning
324 adulterants and diluents enable to devise efficient drug policies, especially for prevention,
325 harm reduction and control purposes. They also contribute to a better understanding of the

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326 structure and organisation of cocaine and heroin markets.
327 Thus, while the cutting of heroin sold in Europe tends to be homogeneous, that of cocaine

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328 could be defined as relatively heterogeneous, in terms of number, frequencies of appearance
329 and concentrations of cutting agents. Caffeine, diltiazem, hydroxyzine, levamisole, lidocaïne

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330 and phenacetin are currently the main adulterants for cocaine. Paracetamol and caffeine are
331 detected in more than 90% of heroin specimens seized in different European countries, in
332 general at similar concentrations. The temporal evolution in the frequencies of adulterants

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333 also illustrates the dynamism of illicit drug market, in particular for cocaine. This could reveal
334 differences between the respective structures of production and/or distribution of cocaine and
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335 heroin. These differences could be due to the cocaine market being managed by more
336 independent actors using their own cutting approach.
337 According to the detected adulterants and their concentrations, addition of such substances
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338 seems hardly justified by the only desire to increase profits or to harm consumers’ health.
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339 Their presence would be more strategic, to enhance or mimic the effects of illicit drugs or
340 make their administration more efficient. The aim of producers or sellers is to make their
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341 product attractive, keep their consumers and attract new ones. Adulteration may also result
342 from a market-sensitive activity on the part of people involved in production and/or
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343 distribution of illicit drugs (i.e. they will change the composition according to consumer
344 preferences). Thus, adulteration would be decided at the production stage of the illicit drug or
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345 at a high level of the distribution chain (e.g., before arrival in the country of destination or just
346 after importation in the latter). Therefore, identifying adulterants may provide information on
347 the geographical origin of illicit drugs, specific distribution networks and the entry pathways
348 in the country of destination. Nevertheless, as discussed in this publication, more studies
349 should be undertaken to better evaluate this potential of information.
350 Adulteration may also take place just after the importation of the illicit drug into the country
351 of destination, in particular at the wholesale level, according to the huge seizures of
352 adulterants. Thus, traffic of adulterants does exist. Studies about the composition – purity and
353 cutting agents – of specimens seized at different levels of the distribution chain should be
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354 encouraged to help assessing which substances are especially used, when cutting occurs as
355 well as its magnitude. Moreover, for control purposes, law enforcement and customs should
356 be informed on the type and use of these substances (i.e. that some substances are specifically
357 and significantly used to adulterate cocaine/heroin). Indeed, people possessing such
358 substances may have information on their supply routes. This would improve our knowledge

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359 on the accessibility and supply routes of adulterants. Furthermore, they may inform on the

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360 trafficking of illicit drug as well as may be involved in illicit drug trafficking.
361 Information concerning adulterants and diluents should be disseminated to all relevant health

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362 agencies in contact with consumers and law enforcement authorities. Information may be
363 disseminated through a system collating the information from different sources (police and

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364 customs seizures, drug checking services, toxicology, etc.). Such system would be useful
365 internationally as well as nationally since it will improve the knowledge of drug markets, will

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366 help to monitor their evolution and will act as an early warning system. This may contribute
367 to improve public health responses. A concrete example is The Trans European Drug
368 Information, which is a European database system that collects, monitors and analyses the
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369 evolution of the various European drug scenes through results of drug checking services and
370 reports on them on a regular basis. From a surveillance point of view, an updated list of
371 adulterants, with their appearance frequency and their concentrations in illicit drug specimens
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372 may be created to help control them and be aware of new cutting approaches. Moreover,
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373 information on the true composition of illicit drug specimens may be useful to inform health
374 care specialists and consumers, who have limited knowledge about the composition of
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375 specimens sold on the market [6, 7]. Improving the knowledge of consumers about the
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376 composition of the illicit drug they consume, and in particular on the presence of adulterants
377 that could have health and side effects, may be part of a prevention strategy.
378 Lastly, analytical results alone are not sufficient to understand the cutting phenomenon.
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379 Knowledge of consumers on illicit drug cutting should be studied through interviews/surveys
380 or researches on Internet forums and social networks. In particular, it would be interested to
381 investigate how consumers relate effects they have during consumption to the presence of
382 adulterants in illicit drug (i.e. positive/negative feeling, side effects). Moreover, it would be
383 interesting to study how their consumption may be modified if they had precise information
384 on the composition of the drug they consume. In terms of prevention, consumers should be
385 questioned to evaluate the impact of the dissemination of information related to cutting
386 agents. Lastly, vendors of illicit drugs involved at different levels of the distribution chain in

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387 the country of destination could be interviewed to get information on the substances used to
388 adulterate illicit drugs, why they are used as well as the extent of cutting.
389

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15

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414 10. Coomber, R., Dangerous drug adulteration: An international survey of drug dealers
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421 York City. Addiction Research and Theory, 2000. 8(4): p. 357-379.
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424 14. Cole, C., L. Jones, J. McVeigh, A. Kicman, Q. Syed, and M. Bellis, Adulterants in
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470 30. Floriani, G., J.C. Gasparetto, R. Pontarolo, and A.G. Gonçalves, Development and
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499 approach and new adulterant routinely quantified (Aminopyrine). Journal of the
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509 J. Servera, C. Cordoba, C. Dominguez, J.L. Esquerra, H. Gutierrez, L. Dominguez, M.
510 Repetto, J. Santacreu, L. Senra, A. Vicente, C. Yeregui, and D. Garrido, Temporal and
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512 relation with the route of administration. Drug and Alcohol Dependence, 1996. 40(3):
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513 p. 185-194.
514 43. Risser, D., U. Alfred, M. Stichenwirth, S. Hönigschnabl, W. Hirz, B. Schneider, C.
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516 heroin-related deaths from 1987 to 1995 in Vienna, Austria. Addiction, 2000. 95(3):
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518 44. Risser, D., A. Uhl, F. Oberndorfer, S. Hönigschnabl, M. Stichenwirth, R. Hirz, and D.
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520 emergencies and/or drug-related deaths? An analysis from Vienna, Austria. Journal of
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524 46. Simonsen, K.W., E. Kaa, E. Nielsen, and D. Rollmann, Narcotics at street level in
525 Denmark: A prospective investigation from 1995 to 2000. Forensic Science
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527 47. Gomez, J. and A. Rodriguez, An evaluation of the results of a drug sample analysis.
528 Bulletin on Narcotics, 1989. 41(1): p. 121-126.
529 48. Dujourdy, L. and F. Besacier, L'héroïne saisie en France. Données statistiques issues
530 de la base nationale des laboratoires de police scientifique. Annales Pharmaceutiques
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532 49. Coomber, R., How often does the adulteration/dilution of heroin actually occur? An
533 analysis of 228 "street" heroin samples across the UK (1995-96) and discussion of
534 monitoring policy. International Journal of Drug Policy, 1997d. 8(4): p. 178-186.
535 50. King, L.A., Drug content of powders and other illicit preparations in the UK. Forensic
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537 51. Maietti, S., F. Castagna, L. Molin, S.D. Ferrara, and P. Traldi, Cocaine adulterants
538 used as marker compounds. Journal of Mass Spectrometry, 2009. 44(7): p. 1124-1126.
539 52. Coomber, R., The cutting of Heroin in the United States in the 1990s. Journal of Drug
540 Issues, 1999a. 29(1): p. 17-36.
541 53. Atasoy, S., F. Bicer, M. Acikkol, and Z. Bilgic, Illicit drug abuse in the Marmara
542 Region of Turkey. Forensic Science International, 1988. 38(1-2): p. 75-81.
543 54. Terrettaz-Zufferey, A.L., F. Ratle, O. Ribaux, P. Esseiva, and M. Kanevski, Pattern
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545 agents. Forensic Science International, 2007. 167(2-3): p. 242-246.

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546 55. Raymon, L.P. and D.S. Isenschmid, The possible role of levamisole in illicit cocaine
547 preparations. Journal of Analytical Toxicology, 2009. 33(9): p. 620-622.
548 56. Eskes, D. and J.K. Brown, Heroin-caffeine-strychnine mixtures : Where and why?

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549 Bulletin on Narcotics, 1975. 27(1): p. 67-69.
550 57. Huizer, H., Analytical studies on illicit heroin. V. Efficacy of volatilization during
551 heroin smoking. Pharmaceutisch Weekblad - Scientific Edition, 1987. 9(4): p. 203-

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552 211.
553 58. Coomber, R., Adulteration of Illicit Drugs with Dangerous Substances - The
554 Discovery of a Myth. Contemporary Drug Problems, 1997e. 24(2).

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555 59. Laborde-Rouzaud, C., L. Rouch, F. Chautant, P. Calvet, B. Sallerin, J.J. Tiravy, and P.
556 Cestac, Les nouveaux cocaïnomanes : substances coupantes, prise en charge
557 médicamenteuse et aide aux réflexes médicaux pour la prise en charge. Le
558 Pharmacien Hospitalier et Clinicien, 2014. 49(4): p. 300-306.
M
559
560
d
p te
ce
Ac

19

Page 19 of 30
560
Years of data Solvent /
Country Source N° Frequency (%)
collection Analytical method
Not adulterated : 37
Base cocaine : Phenacetin : 41 ;
Aminopyrine : 14 ; Benzocaine : 6 ;
(Grobério et al., Lidocaine/Hydroxyzine/Caffeine/
2009-2013 1085 CH3Cl3 / GC-FID

t
2015) Paracetamol/Levamisole/Diltiazem : < 3

ip
Cocaine HCl : Levamisole : 8 ;
Aminopyrine/Lidocaine/Procaine/

cr
Phenacetin /Caffeine/Diltiazem : < 3
Not adulterated : 40
(Maldaner et al., CH3Cl3 / Phenacetin : 26 ; Levamisole : 19 ;
2010-2013 159

us
2015) GC-FID, GC-MS Caffeine : 14 ; Aminopyrin : 12 ;
Lidocaine : 11 ; Benzocaine/Diltiazem : 5
Adulterated : 70

an
(Lapachinske et MeOH/ Levamisole : 55 ; Lidocaine : 16
2011 54
al., 2015) GC-MS, GC-NPD Caffeine : 11 ; Phenacetin : 9 ;
4-dimethylaminoantipyrine : 2
Without cutting : 50
M
Brazil
(Botelho et al., CH3Cl3 / Phenacetin : 30 ; Levamisole : 19 ;
2009-2012 210
2014) GC-FID Caffeine : 6 ; Lidocaïne : 4 ;
Benzocaine/Hydroxyzine/Diltiazem : < 1
d
Without cutting : 55*
(Floriani et al., C2H3N-H2O / Caffeine : 37 ; Lidocaïne : 20 ;
2007-2012 115
te

2014) HPLC-DAD Benzocaine : 10 ; Phenacetin : 4 ;

Diltiazem : < 1
State 1 Without cutting : 100*
p

Without cutting : 24*

(Magalhães et CH3OH /
ce

2008-2010 31 Caffeine : 76 ;
al., 2013) GC-MS State 2
Lidocaïne : 67 ;
Benzocaine : 5
Lidocaïne : 65 ; Starch : 51 ;
Ac

CH3OH / Caffeine : 50 ; Carbonate : 41 ;

(Bernardo et al.,
2001 209 TLC, Sucrose : 15 ; Glucose : 12 ;
2003)
GC-FID Prilocaine : 11 ; Lactose : 6 ;
Fructose : 3
561
562 Table 1. Details about studies assessing the frequencies for cutting agents of cocaine
563 (N° : number of specimens analysed, NA : non available; a : number of specimens and frequency for the last year
564 of the time period ; * : that does not mean that no cutting agents at all were present as specific substances were
565 looked for)
566
567
20

Page 20 of 30
567
Years of data Solvent /
Country Source N° Frequency (%)
collection Analytical method
Without cutting : 60*
Mannitol : 13
Lidocaïne : 10
Belgium (Decorte, 2001) 1996-1997 30 Spectrometry IR
Glucose : 7

t
Caffeine : 3

ip
Starch : 3
Adulterated : 87
Diluted : 95

cr
Lidocaïne : 65
Phenacetin : 42

us
Mannitol : 41
Inositol : 41
GC-MS,
(Andreasen et al., Sucrose : 31
Denmark 2002-2003 147 HPLC-DAD,
2009) Lactose/Maltose : 24

an
HPLC-RI
Glucose : 22
Creatin : 22
Procaine : 5
M
Paracetamol/Benzocaine : 3
Phenazone/Ephedrin/Mirtazapine/
Ketamine : 1
No adulterant : 50
d

Levamisole : 33
te

Beta-Alanine/Ibuprofen/
Paracetamol : 2
(Broséus et al., CH3Cl3 /
Finland 2013 42 Caffeine : 19
p

2015) GC-MS
Glucose/Lidocaïne : 14
Lactose/Mannitol/Phenacetin : 12
ce

Creatin/Hydroxyzine : 7
Diltiazem : 5
At least one adulterant : 73
Ac

Phenacetin : 54
Caffeine : 17
Paracetamol : 14
(Evrard et al.,
France 2006 343 GC-MS Diltiazem/Lidocaïne : 11
2010)
Levamisole : 6
Hydroxyzine : 4
Acetylsalicylic acid/
Propoxyphen : 2
568
569 Table 1 (continued). Details about studies assessing the frequencies for cutting agents of cocaine
570

21

Page 21 of 30
571
Years of data Solvent /
Country Source N° Frequency (%)
collection Analytical method
Lidocaïne : 12
(Fucci and De Caffeine/Phenacetin : 6
Italy Giovanni, 1996-1997a 156 a CH3OH / GC-MS Salicylamide : 3
1998) Diphenidramine/Dipyrone/

t
Phenmetrazine/Procaine : < 2

ip
Levamisole : 85 ; Phenacetin : 55 ;
CH3COOH + CH3OH /
(Schneider Lidocaïne : 39 ; Caffeine : 25 ;
GC-MS,
2005-2010a 102 a

cr
Luxembourg and Meys, Hydroxyzine : 24 ; Diltiazem : 23 ;
HPLC-UV,
2011) Paracetamol : 7 ; Procaine : 2 ;
HPLC-DAD
Ephedrin : 1

us
Adulterated (substances below) : 54
Adulterated (other substances) : 4
Non adulterated : 40

an
TLC, Diluted : 3
(Brunt et al., a a
Netherlands 1999-2007 683 GC-NPD, Phenacetin : 41 ; Caffeine : 16 ;
2009)
GC-MS Levamisole/Diltiazem : 12 ;
Procaine : 8 ; Lidocaïne : 6 ;
M
Hydroxyzine : 4 ; Atropine : 1 ;
Benzocaine : ~ 0
(Barrio et al., GC, Caffeine : 12
1985-1993a NA a
d
1997) HPTLC Procaine : NA
Adulterated : 60
Spain (Gomez and TLC,
te

Lidocaïne : 52
Rodriguez, 1985-1987 52 GC-MS,
Sugars (Mannitol et Glucose) : 45
1989) HPLC-MS
Caffeine/Procaine : NA
p

Lidocaïne/Procaine : 40
ce

Phenacetin : 35
(Musset et al., HPLC-UV,
1999-2003 48 Caffeine : 8
2005) GC-MS
Tolperisone (Mydocalm®)/
Paracetamol/Saccharose : NA
Ac

Adulterated : 97
Diluted : 88
Phenacetin : 80 ; Lactose : 73 ;
Switzerland
Glucose : 48 ; Mannitol : 46 ;
Levamisole : 65 ; Lidocaine : 47 ;
(Broséus et CH3Cl3 + Pyridine /
2006-2014 6586 Caffeine : 39 ;
al., 2015) GC-MS
Diltiazem/Hydroxyzine : 25
Inositol/Sucrose/Fructose : < 10
Procaine : 10 ; Tetracaine : 6 ;
Paracetamol/Creatin/
Benzocaine : < 5

22

Page 22 of 30
572
573 Table 1 (end). Details about studies assessing the frequencies for cutting agents of cocaine

t
ip
cr
us
an
M
d
p te
ce
Ac

23

Page 23 of 30
574
Years of data Solvent /
Country Source N° Frequency (%)
collection Analytical method
Sugars (ess. Saccharose) : 65
(Maher et al., GC-MS, Paracetamol : 41
Australia 1996-1997 88
2001) HPLC-RI Caffeine : 36
Glucose/Sorbitol/Mannitol : 8

t
Sugars (ess. Lactose) : 100

ip
(Risser et al., Caffeine : 92
1999 415 GC
2007) Paracetamol : 91
Austria Lidocaïne : < 1

cr
Sugars (ess. Lactose) : 100
(Risser et al.,
1987-1995 386 GC-MS Caffeine : 25
2000)

us
Paracetamol/Methaqualone : < 2
(Denooz et al., HPLC-DAD,
Belgium 2003-2005 50 Caffeine/Paracetamol : 98
2005) GC-MS

an
Diluted : 5
Caffeine : 99
GC-MS, Paracetamol : 97
(Andreasen et
2002-2003 132 HPLC-DAD, Griseofulvin : 26
M
al., 2009)
HPLC-RI Diazepam : 1
Mannitol : 2
Sucrose : 2
d
Caffeine : 39
Denmark
Lactose : 33
te

Glucose : 30
GC, Paracetamol : 22
(Kaa, 1994) 1981-1992a 383 TLC, Phenobarbital : 14
p

HPLC Mannitol : 13
Procaine : 10
ce

Sucrose : 9
Methaqualone : 5
Caffeine : 67
Ac

Paracetamol : 40
Mannitol : 35
(Chaudron-
GC-MS, Lactose : 15
France Thozet et al., 1991 980
HPLC Saccharose/Sucrose : 15
1992)
Glucose/Procaine/Phenobarbital/
Lidocaïne/Methaqualone/Piracetam/
Acetylsalicylate/Phenolphtaléine : NA
575
576 Table 2. Details about studies assessing the frequencies for cutting agents of heroin
577 (N° : number of specimens analysed, NA : non available; a : number of specimens and frequency for the last year
578 of the time period)

24

Page 24 of 30
579
Years of data Solvent /
Country Source N° Frequency (%)
collection Analytical method
Caffeine : 57
Paracetamol : 53
Procaine : 16
Germany (Neumann, 1994) 1986-1992a NA Toluene / GC-FID Phenobarbital : 6

t
Methaqualone/Nicotinamide/

ip
Phenolphthaleine/
Acide salycilique : < 2

cr
Caffeine : 70
Dextromethorphan : 42
Iran (Akhgari et al., 2012) 2008-2009 85 MeOH / GC-MS
Phenobarbital : 12

us
Diazepam / Chloroquine: 5
Adulterated : 50
Sugars

an
CH3OH / (saccharose, glucose, lactose) : 55
Italy (Chiarotti et al., 1991) NA 33 HS-GC, GC-MS, Phenobarbital : 24
TLC, HPLC, AA Caffeine : 21
Methaqualone : 15
M
Procaine : 6
CH3COOH + CH3OH/ Paracetamol : 98
(Schneider and Meys,
Luxembourg 2005-2010a 232 a GC-MS, HPLC-UV, Caffeine : 98
2011)
d

HPLC-DAD Phenacetin/Diltiazem : < 1

(Eskes and Brown,
te

Netherlands 1972-1973 NA NA Caffeine/Strychnine : NA

1975)
Caffeine : 40 – 60
p

Phenobarbital : 39 – 52
Madrid Piracetam/Paracetamol : > 30
ce

Procaine : 15 – 30
(De La Fuente et al., Lidocaïne : < 10
1985-1993 NA GC, HPTLC
1996) Caffeine : 85 – 90
Ac

Piracetam : 40 – 60
Sevilla Paracetamol : 30
Spain Procaine : 5
Lidocaïne : < 6
Adulterated : 80
Sugars (glucose, lactose, mannitol) : 73
TLC, Caffeine : 68
(Gomez and Rodriguez,
1985-1987 263 GC-MS, Phenobarbital : 20
1989)
HPLC-MS Methaqualone/Procaine : 13
Piracetam : 7
Lidocaïne : 5
580
25

Page 25 of 30
581 Table 2 (continued). Details about studies assessing the frequencies for cutting agents of heroin

t
ip
cr
us
an
M
d
p te
ce
Ac

26

Page 26 of 30
582
Years of data Solvent /
Country Source N° Frequency (%)
collection Analytical method
Adulterated : 99
Diluted : 15
Caffeine : 97 ; Paracetamol : 96 ;
CH3Cl3 + Pyridine / Griseofulvine : 12 ; Mannitol : 7 ;

t
(Broséus et al., 2015) 2006-2014 3054
GC-MS Glucose : 6 ; Lactose/Sucrose/

ip
Inositol : < 3 ; Phenacetin : 5 ;
Switzerland
Dextromethorphane/Lidocaine/

cr
Levamisole : < 5
Caffeine : 100
HPLC-UV, Paracetamol : 83

us
(Musset et al., 2005) 1999-2003 52
GC-MS Griseofulvin/Zolpidem/
Oxazepam : NA
Procaine : 47
Colour tests,

an
Turkey (Atasoy et al., 1988) 1986-1987 140 Salycilate/Antipyrine/
TLC, GC
Paracetamol : NA
Non adulterated : 44
Paracetamol : 33
M
Caffeine : 32
United-
(Coomber, 1997d) 1995-1996 228 GC-MS Procaine/Bupivacaine: 5
Kingdom
Phenobarbitone : 4
d

Griseofulvin/Diazepam/
Methaqualone : < 3
te

Procaine : 26
Quinine : 21
p

Caffeine : 11
(Furst, 2000) 1991-1996 406 Chemical assay
Paracetamol : 10
ce

Diphenydramine/Thiamine : 7
Lidocaïne : < 5
Mannitol : 39
United States
Lactose : 33
Ac

Starch : 25
Quinine : 23
(Coomber, 1999a) 1990-1995a 818a NA
Procaine : 14
Diphenhydramine/Caffeine : 12
Paracetamol : 10
Dextrose : 4
583
584 Table 2 (end). Details about studies assessing the frequencies for cutting agents of heroin
585
586

27

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587
Country Source Adulterant Concentration1 Min – Max (%)
Benzocaine 0.6
Phenacetin 24
Caffeine 37.2
(Maldaner et al., 2015) Lidocaine 9.7 NA
Aminopyrine 3.1

t
ip
Levamisole 6.3
Diltiazem 2.5
Benzocaine 0.5 – 14.2

cr
Paracetamol 0.1 – 3.0
Phenacetin 0.5 – 56.8

us
Caffeine 0.5 – 25.4
(Grobério et al., 2015) Lidocaine NA 0.4 – 29.2
Aminopyrine 0.1 – 41.2
Hydroxyzine 2.7 – 42.5

an
Levamisole 1.3 – 24.4
Diltiazem 0.7 – 1.0
Levamisole 7.5 0.7 - 23
M
Brazil Lidocaine 11.3 0.6 – 30.6
(Lapachinske et al., 2015) Caffeine 9.9 2.4 -16.1
Phenacetin 8.9 5.4 – 12.1
d
4-Dimethylaminoantipyrine 1.2 NA
Location (state)  AM/MS BFP AM/MS BFP
te

Benzocaine - 0 - NA – 8
Caffeine NA 1 2 – 12 NA – 46
(Zacca et al., 2014)
Diltiazem NA - 3 -
p

Lidocaïne - 1 - NA – 58
ce

Phenacetin NA 0 2 – 14 NA – 2
Benzocaine NA 0.3 – 41.4
Caffeine NA 0.2 – 87.8
(Floriani et al., 2014)
Ac

Diltiazem NA 1.4
Lidocaïne NA 1.8 – 93.4
Phenacetin NA 2.1 – 15.6
Caffeine 10.4 2.8 – 63.3
(Bernardo et al., 2003) Lidocaïne 25.5 0.5 – 92
Prilocaine 1.9 1.2 – 20.7
588 Table 3. Adulterants concentrations in cocaine specimens
1
589 ( : mean value in percentage; NA : non available; AM/MS : Brazilian states; BFP : Brazilian Federal Police
590 seizures)
591

28

Page 28 of 30
591
592
Country Source Adulterant Concentration1 Min – Max (%)
Caffeine 3 0.1 – 54
Creatin 24 5 – 40
Lidocaïne 11 0.3 – 36
Paracetamol 21 11 – 35

t
Phenacetin 9 0.7 – 37

ip
Denmark (Andreasen et al., 2009) Procaine 3 0.2 – 14
Glucose 23 < 8 – 44

cr
Inositol 38 < 8 – 87
Lactose/Maltose 24 < 9 – 50
Mannitol 16 < 6 – 37

us
Sucrose 31 < 6 – 60
Caffeine 5.1 0.1 – 62.6
Diltiazem 1.3 0 – 10.3

an
Hydroxyzine 1.2 0 – 8.8
Levamisole 3.3 0 – 21.3
Luxembourg (Schneider and Meys, 2011)
Lidocaïne 1.9 0 – 36.6
Paracetamol 16.5 0.1 – 67.6
M
Phenacetin 24.2 0.1 – 75.2
Procaine 3.1 0.1 – 11.5
593 Table 1 (end). Adulterants concentrations in cocaine specimens
d

1
594 ( : mean value in percentage; NA : non available; AM/MS : Brazilian states; BFP : Brazilian Federal Police
595
te

seizures)
596
597
p
ce
Ac

29

Page 29 of 30
597
Country Source Adulterant Concentration1 Min – Max (%)
Caffeine 29 0.7 – 65
Austria (Risser et al., 2007) Lidocaïne 35 1.5 – 87
Paracetamol 36 0.1 – 92
Specimens mass <5g 25 – 359 g <5g 25 – 359 g
Belgium (Denooz et al., 2005) Caffeine 27.3 21.8 15.8 – 58.7 0 – 32.1

t
Paracetamol 31.2 30.3 0.3 – 55 0 – 55.4

ip
Caffeine 22 0.2 – 41
Griseofulvin 2 0.1 – 16

cr
(Andreasen et al., 2009) Paracetamol 27 0.2 – 53
Mannitol <6 <6
Sucrose 12 < 6 – 15

us
Denmark
Caffeine > 10 NA – 92
Methaqualone NA NA – 30
(Kaa, 1994) Paracetamol > 10 NA – 43

an
Phenobarbital NA NA – 45
Procaine < 10 NA – 45

Caffeine 26 NA
M
France (Dujourdy and Besacier, 2010)
Paracetamol 49 NA

Caffeine 24.2 0 – 51.1

d

Diltiazem 0.8 0.1 – 1.6

Luxembourg (Schneider and Meys, 2011) Paracetamol 46.9 0 – 69.9
te

Phenacetin 9.4 0.5 – 18.3

Piracetam 7.9 4.5 – 18.1
p

Caffeine NA 0.5 – 2.8

Methaqualone NA 1.5
ce

Spain (Gomez and Rodriguez, 1989) Lidocaïne NA 1 – 8.9

Phenacetin NA 2.5
Procaine NA 20 – 23
Ac

598 Table 4. Adulterants concentrations in heroin specimens

599 (1 : mean value in percentage; NA : non available)
600
601
602
603
604
605

30

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