Abstract

Cannabis sativa L. is one of the most consumed drugs in the world and recent studies have associated its use with an increase in the number of traffic accidents in different countries. In many countries, like Brazil, simple and reliable methodologies are still needed for the detection of drugs on site, mainly cannabinoids, considering its prevalence of use and oral fluid (OF) has been proved as an appropriate biological matrix for this purpose. Considering that, this work aims to review previous studies on immunochromatographic devices for on-site detection of cannabinoids in OF, discussing their sensitivity, specificity, cut-offs values and confirmatory methods. This data shows the importance of choosing a screening device and it reinforces the need for its implementation in Brazil. The research was conducted on 5 databases and all original articles, published in the last 10 years, were selected. A total of 32 articles were found, providing data for 17 screening devices of distinct brands. Only 2 screening devices showed satisfactory sensitivity and specificity in the evaluated studies (≥80% and ≥90% respectively). However, it should be considered that the screening devices still have some limitations, such as a higher cut-off than those recommended by international guidelines (cut-off > 2 ng/mL), therefore demonstrating the need for more studies in the area and the importance of confirmatory analysis usually fulfilled by LC-MS/MS, GC-MS/MS or GC-MS. Thus, the screening analyzes should not be evaluated by itself, but in association with confirmatory results and observational traits (behavioral changes), for a better understanding of the traffic scenario.

Keywords:
Screening devices; Drug test; Traffic accidents; Oral fluid; Cannabinoids; THC

INTRODUCTION

Traffic accidents (TA) are considered a major public health problem, at the expenses of approximately 3% of the national Gross Domestic Product (GDP) in most countries (WHO, 2020WHO. World Health Organization. Road Traffic Injuries [Internet]. 2020 [cited 2020 Mar 17]. Available from: Available from: https://www.who.int/news-room/fact-sheets/detail/road-trafficinjuries
https://www.who.int/news-room/fact-sheet... ; WHO, 2018WHO. World Health Organization. Global Status Report on Road Safety. Geneva: Management of Noncommunicable Diseases, Disability, Violence and Injury Prevention (NVI); 2018.). Among the factors that contribute to the statistics are fatigue, speeding and the consumption of alcohol and/or drugs abuse, followed by negligence of safety devices (Leyton et al., 2012Leyton V, Sinagawa DM, Oliveira KCBG, Schmitz W, Andreuccetti G, De Martinis BS, et al. Amphetamine, cocaine and cannabinoids use among truck drivers on the roads in the State of Sao Paulo, Brazil. Forensic Sci Int . 2012;215(1-3):25-7.; WHO, 2018WHO. World Health Organization. Global Status Report on Road Safety. Geneva: Management of Noncommunicable Diseases, Disability, Violence and Injury Prevention (NVI); 2018.). The legal framework that regulates the use of psychoactive substances (PSs) varies according to the social, legal and economic characteristics of each country, so it is not clear what are the acceptable limits in biological samples from motor vehicle drivers (Herrera-Gómez et al., 2018Herrera-Gómez F, García-Mingo M, Colás M, González-Luque JC, Álvarez FJ. Opioids in oral fluid of Spanish drivers. Drug Alcohol Depend . 2018;187:35-9.). In Brazil, driving under the influence of alcohol and other PSs is not allowed (Brasil, 2006Brasil. Secretaria Geral da Presidência da República. Lei No 11.343, de 23 de agosto de 2006. Diário Oficial da União 24 ago; 2006.); however, the legislation does not clarify which are the PSs and does not recommend ways of monitoring them as well as it does not establish acceptable limits - or levels - of PSs in a biological sample (Pechansky et al., 2019Pechansky F, Scherer JN, Schuch JB, Roglio V, Telles YM, Silvestrin R, et al. User experience and operational feasibility of four point-of-collection oral fluid drug-testing devices according to Brazilian traffic agents. Traffic Inj Prev. 2019;20(1):30-6.; Saldanha et al., 2014Saldanha RF, Pechansky F, Benzano D, de Barros CASM, De Boni RB. Diferenças entre homens e mulheres vítimas de acidente de trânsito atendidos em emergências de Porto Alegre, RS, Brasil. Cienc Saude Coletiva. 2014;19(9):3925-30.).

Cannabis is the second most consumed drug in the world (Callaghan et al., 2013Callaghan RC, Gatley JM, Veldhuizen S, Lev-Ran S, Mann R, Asbridge M. AlcoholOr drug-use disorders and motor vehicle accident mortality: A retrospective cohort study. Accid Anal Prev. 2013;53:149-55.; Perna et al., 2016Perna EB de SF, Theunissen EL, Kuypers KPC, Toennes SW, Ramaekers JG. Subjective aggression during alcohol and cannabis intoxication before and after aggression exposure. Psychopharmacology (Berl). 2016;233(18):3331-40.). Cannabinoids are also among the most detected psychoactive substances (PSs) in drivers (Berning, Compton, Wochinger, 2015Berning A, Compton R, Wochinger K. Results of the 2013-2014 national roadside survey of alcohol and drug use by drivers. Drug-Impaired Driv Data Reduct Strateg. 2015;(February):63-74.; Fierro et al., 2014Fierro I, González-Luque JC, Álvarez FJ. The relationship between observed signs of impairment and THC concentration in oral fluid. Drug Alcohol Depend. 2014;144:231-8.; Hartman et al., 2015Hartman RL, Brown TL, Milavetz G, Spurgin A, Pierce RS, Gorelick DA, et al. Cannabis effects on driving lateral control with and without alcohol. Drug Alcohol Depend . 2015 Sep;154:25-37.). The cannabinoid Δ⁹-tetrahydrocannabinol (THC) is the mainly PS present in cannabis samples and is often detected in biological samples from drivers approached in police roadblocks and in drivers involved in TA with minor injuries and/or fatal victims (Lee, Huestis, 2014Lee D, Huestis MA. Current knowledge on cannabinoids in oral fluid. Drug Test Anal . 2014;6(0):88-111.; Volkow et al., 2014Volkow ND, Baler RD, Compton WM, Weiss SRB. Adverse health effects of marijuana use. N Engl J Med. 2014;370(23):2219-27.). Cannabis exposure affects the ability to drive by promoting changes in perception and in the reaction time, altering the state of attention and compromising the motor skills of individuals (Hartman, Huestis, 2013Hartman RL, Huestis MA. Cannabis effects on driving skills. Clin Chem . 2013;59(3):478-92.). Considering the Brazilian traffic scenario and the constant discussion about the legalization and/or decriminalization of cannabis(CEE FIOCRUZ, 2016CEE FIOCRUZ. Centro de Estudos Estratégicos da FIOCRUZ. Descriminalizar a maconha reduziria o tráfico de drogas? [Internet]. FIOCRUZ. 2016. Available from: https://cee.fiocruz.br/?q=node/377
https://cee.fiocruz.br/?q=node/377... ; FIOCRUZ, 2013FIOCRUZ. Agência Fiocruz de Notícias. Drogas e saúde pública [Internet]. FIOCRUZ. 2013 [cited 2020 Mar 20]. Available from: Available from: https://agencia.fiocruz.br/drogas-e-saudepublica
https://agencia.fiocruz.br/drogas-e-saud... ; Moreira et al., 2016Moreira MR, Carvalho AI de, Ribeiro JM, Fernandes FMB. Agendas democráticas para o século XXI: percepções dos(as) brasileiros(as) sobre descriminalização e legalização da maconha. Saúde em Debate. 2016;40(spe):163-75.), it becomes evident the need for simple and reliable methodologies that allow its detection in biological samples of vehicle drivers, as well as the implementation of more specific laws (Pelição et al., 2016Pelição FS, Peres MD, Pissinate JF, de Paula DML, de Faria M das GC, Nakamura-Palacios EM, et al. Predominance of alcohol and illicit drugs among traffic accidents fatalities in an urban area of Brazil. Traffic Inj Prev . 2016;17(7):663-7.; Saldanha et al., 2014Saldanha RF, Pechansky F, Benzano D, de Barros CASM, De Boni RB. Diferenças entre homens e mulheres vítimas de acidente de trânsito atendidos em emergências de Porto Alegre, RS, Brasil. Cienc Saude Coletiva. 2014;19(9):3925-30.).

Among the biological matrices used for screening analysis of PSs, oral fluid (OF) stands out as a biological sample that has been achieving more space in routine analyzes in Toxicology, specially related to DUID (Driving Under the Influence of Drugs) scenarios. Due to its numerous advantages, OF has shown to be a promising matrix for on-site testing (Gentili et al., 2016Gentili S, Solimini R, Tittarelli R, Mannocchi G, Busardò FP. A Study on the Reliability of an On-Site Oral Fluid Drug Test in a Recreational Context. J Anal Methods Chem. 2016;2016:1-10.). OF collection is easy and non-invasive, it can be performed under police supervision, without embarrassment to the driver, and its analysis provides a good correlation with blood, considering the recent use of several classes of PSs (Fiorentin et al., 2017Fiorentin TR, D’Avila FB, Comiran E, Zamboni A, Scherer JN, Pechansky F, et al. Simultaneous determination of cocaine/crack and its metabolites in oral fluid, urine and plasma by liquid chromatography-mass spectrometry and its application in drug users. J Pharmacol Toxicol Methods. 2017;86:60-6.; Gentili et al., 2016Gentili S, Solimini R, Tittarelli R, Mannocchi G, Busardò FP. A Study on the Reliability of an On-Site Oral Fluid Drug Test in a Recreational Context. J Anal Methods Chem. 2016;2016:1-10.; Logan, Mohr, Talpins, 2014Logan BK, Mohr ALA, Talpins SK. Detection and prevalence of drug use in arrested drivers using the dräger drug test 5000 and affiniton DrugWipe oral fluid drug screening devices. J Anal Toxicol . 2014;38(7):444-50.). Furthermore, OF can also be used for subsequent confirmatory analyzes, thus samples for both screening and confirmation can be collected at the same time, increasing the chances of consistent results. However, OF collection can be affected by some factors such as decreased salivary flow and dry mouth, attributed to lack of hydration or drug use (Logan, Mohr, Talpins, 2014Logan BK, Mohr ALA, Talpins SK. Detection and prevalence of drug use in arrested drivers using the dräger drug test 5000 and affiniton DrugWipe oral fluid drug screening devices. J Anal Toxicol . 2014;38(7):444-50.).

The most common on-site screening devices chosen by several countries for the detection of cannabis, and other PSs, are usually immunochromatography tests. In general, these assays consist of collection pads attached to porous membrane strips, which are inserted into the donor’s mouth. From the swab (pad), the OF migrates by capillarity, mobilizing the reservoir of colored antibodies that flow with the OF along the strip until the lines with the immobilized PSs are reached. In the presence of a positive sample for any PS in the cut-off concentration of the multi-drug device or above it, the binding sites of the respective colored antibody saturate and do not bind to the drug immobilized on the band (Souza et al., 2012Souza DZ, Boehl PO, Comiran E, Prusch DS, Zancanaro I, Fuentefria AM, et al. Which amphetamine-type stimulants can be detected by oral fluid immunoassays? Ther Drug Monit. 2012;34(1):98-109.). However, it is important to note that even with efficient screening devices for on-site use, the need for confirmatory analysis of the suspected drivers OF sample is not ruled out, considering that some devices still demonstrate a lack of specificity (≥ 90%) and of sensitivity (≥ 80%) for Δ⁹-THC (Blencowe et al., 2011Blencowe T, Pehrsson A, Lillsunde P, Vimpari K, Houwing S, Smink B, et al. An analytical evaluation of eight on-site oral fluid drug screening devices using laboratory confirmation results from oral fluid. Forensic Sci Int. 2011;208(1-3):173-9.; Musshoff et al., 2014Musshoff F, Hokamp EG, Bott U, Madea B. Performance evaluation of on-site oral fluid drug screening devices in normal police procedure in Germany. Forensic Sci Int . 2014;238:120-4.; Strano-Rossi et al., 2012Strano-Rossi S, Castrignanò E, Anzillotti L, Serpelloni G, Mollica R, Tagliaro F, et al. Evaluation of four oral fluid devices (DDS®, Drugtest 5000®, Drugwipe 5+® and RapidSTAT®) for on-site monitoring drugged driving in comparison with UHPLC-MS/MS analysis. Forensic Sci Int . 2012;221(1-3):70-6.). International guidelines suggest a cut-off value of 2 ng/mL for confirmatory tests, while they recommend the value of 4 ng/mL for screening tests (Department of Health and Human Services, 2019Department of Health and Human Services. Mandatory Guidelines for Federal Workplace Drug Testing Programs - Oral/Fluid. Subst Abus Ment Heal Serv Adm. 2019 p. 57554-600.; Walsh et al., 2008Walsh JM, Verstraete AG, Huestis MA, Mørland J. Guidelines for research on drugged driving. Addiction. 2008;103(8):1258-68.).

Considering that cannabis is among the main PSs related to TA in Brazil (DeBoni et al., 2014DeBoni RB, Bastos FI, De Vasconcellos M, Oliveira F, Limberger RP, Pechansky F. Drug use among drivers who drank on alcohol outlets from Porto Alegre, Brazil. Accid Anal Prev . 2014;62:137-42.; Pelição et al., 2016Pelição FS, Peres MD, Pissinate JF, de Paula DML, de Faria M das GC, Nakamura-Palacios EM, et al. Predominance of alcohol and illicit drugs among traffic accidents fatalities in an urban area of Brazil. Traffic Inj Prev . 2016;17(7):663-7.; Saldanha et al., 2014Saldanha RF, Pechansky F, Benzano D, de Barros CASM, De Boni RB. Diferenças entre homens e mulheres vítimas de acidente de trânsito atendidos em emergências de Porto Alegre, RS, Brasil. Cienc Saude Coletiva. 2014;19(9):3925-30.), and that there is a need for a screening tool implementation in this country, this article aims to review previous studies regarding immunochromatographic devices for cannabinoids detection, focusing on its main advantages and disadvantages.

MATERIAL AND METHODS

Our research strategy involved a comprehensive systematic review in the following databases: PubMed, Google Scholar, Science Direct, Scopus and Science. gov. The descriptor used for databases was “cannabis or cannabinoids and oral fluid detection”. The search was conducted in February 2020. Four independent researchers conducted the review, using the following inclusion criteria: a) original studies for immunochromatographic in loco devices, for cannabis detection in oral fluid; b) articles published in the last ten years (2010-2020), in order to present a recent panel of studies. Studies that do not include oral fluid as a biological matrix were excluded, as well as different types of screening tests. These studies could either include drivers or not, as long as it evaluated immunochromatographic screening test for cannabinoids in oral fluid.

Figure 1 shows the results for the systematic review. The initial search retrieved 92 non-repeated articles from the total (Google Scholar - 18.000; PubMed - 134; Science Direct - 153; Scopus - 141; Science.gov - 280) and, after a detailed analysis, 32 papers met the inclusion criteria. Other studies that include guidelines and laws were only included in the discussion.

FIGURE 1
Strategy used in the research of articles for review.

RESULTS AND DISCUSSION

Among the 32 selected articles, some studies used a device to collect the sample and other device to analyze it, while others use the same for both collection and analysis. The screening devices are multi-drug detection tests; however, only the detection of cannabinoids was approached in this review. All 32 studies evaluated the cannabinoid THC, the major psychoactive cannabis component, for drug detection, but Anzillotti et al.,(2014Anzillotti L, Castrignanò E, Rossi SS, Chiarotti M. Cannabinoids determination in oral fluid by SPME-GC/ MS and UHPLC-MS/MS and its application on suspected drivers. Sci Justice. 2014;54(6):421-6.) and Newmeyer et al.,(2017Newmeyer MN, Swortwood MJ, Andersson M, Abulseoud OA, Scheidweiler KB, Huestis MA. Cannabis edibles: Blood and oral fluid cannabinoid pharmacokinetics and evaluation of oral fluid screening devices for predicting Δ9-tetrahydrocannabinol in blood and oral fluid following cannabis brownie administration. Clin Chem . 2017;63(3):647-62.) also included more cannabinoids, like cannabidiol (CBD), cannabinol (CBN), 11-Nor-9-carboxy-Δ⁹-tetrahydrocannabinol (11-THCOOH), Tetrahydrocannabivarin (THCV) and cannabigerol (CBG). Table I compiles the review results, considering the detected cannabinoids, the analyzed devices, and the confirmatory methods. Also, the cut-offs and the tests parameters, such as specificity and sensibility, are shown.

Sixteen different devices, from distinct manufacturers, were evaluated in these studies. However, some of their brands have different presentations of drug tests. For example, Dräger^® brand has four test devices (Drug Test 5000, DCH 5000, DCD 5000, 5000 STK) and DrugWipe^® brand have six types of devices (5/5+, 5A, 5, 5+, II Twin, 6S). DrägerDrugTest^®5000 is the most used device in the studies - also presenting the lowest cut-off (5 ng/mL) -, followed by DrugWipe^®, with a cut-off at 30 ng/mL, and Alere DDS2, with a 25 ng/mL cut-off. For confirmatory methods in OF, Walsh et al. (2008Walsh JM, Verstraete AG, Huestis MA, Mørland J. Guidelines for research on drugged driving. Addiction. 2008;103(8):1258-68.) recommends a cut-off of 2 ng/mL for the analysis of cannabinoids, but they do not mention any screening devices(Walsh et al., 2008Walsh JM, Verstraete AG, Huestis MA, Mørland J. Guidelines for research on drugged driving. Addiction. 2008;103(8):1258-68.). Thus, from all studied brands, Dräger DrugTest^® 5000 presents the cut-off (5 ng/mL) which is closer to the limit recommended by the current guidelines (2 ng/mL).

Based on the review, the only two screening devices that showed good sensitivity and specificity were Dräger DrugTest^®5000 (DDT5000) and Alere^TM DDS^®2 (DDS2).

For Dräger DrugTest^®5000, sensitivity and specificity ranged from 76-95% and 71-99.3%, respectively, in the studies. As for Alere^TM DDS^®2 screening device, the sensitivity varied from 75-100% and the specificity ranged from 80-100%.However, these two devices present a higher cut-off than the recommended the aforementioned guides, and the DDT5000 has the closest value (5 ng/mL), followed by DDS2 (25 ng/mL).

Even after a decade of action for road safety, which it has started in 2011, the American region continues to record approximately 155.000 traffic deaths per year (ONU, 2019aONU. Organização das Nações Unidas. Brasil, México e Uruguai mostram como segurança no trânsito pode ser melhorada [Internet]. 2019a [cited 2020 Mar 17]. Available from: Available from: https://nacoesunidas.org/brasil-mexico-e-uruguaimostram-como-seguranca-no-transito-pode-ser-melhorada/
https://nacoesunidas.org/brasil-mexico-e... ). Brazil had an estimated traffic mortality rate of 19.7 per 100.000 inhabitants, which is higher than the rate in the entire South America continent (15.6) and the average rate in the Southern Cone (18.4) (ONU, 2019bONU. Organização das Nações Unidas. Região das Américas registra quase 155 mil mortes no trânsito por ano, diz agência da ONU [Internet]. 2019b [cited 2020 Mar 17]. Available from: Available from: https://nacoesunidas.org/regiao-dasamericas-registra-quase-155-mil-mortes-no-transito-porano-diz-agencia-da-onu/
https://nacoesunidas.org/regiao-dasameri... ). Although Brazil has managed to reduce the number of deaths in traffic, the country still registers a high number of victims with minor and serious injuries, and this is relative to different factors, including the use of alcohol and/or drugs.

Brazilian Law 11.343/2006 (Brasil, 2006Brasil. Secretaria Geral da Presidência da República. Lei No 11.343, de 23 de agosto de 2006. Diário Oficial da União 24 ago; 2006.) prohibits drug use, its cultivation and/or distribution, and also differentiates drug use and drug trafficking, with a social approach. Likewise, it defines the severity of the crime and its penalty, but it does not specify a law on driving under drug influence. Brazilian Traffic Code (Brasil, 1997Brasil. Ministério da Casa Civil. Lei No 9.503, de 23 de setembro de 1997. Diário Oficial da União 25 set; 1997.) considers forbidden the use of any PS while driving; however, it does not specify a drug concentration, as it does for alcohol use (≥6 dg/L of ethanol in blood or ≥0.3 mg/L of ethanol in alveolar air), and it does not define ways of monitoring. There is no specific regulation in Brazil for testing devices for drug detection in drivers or a regulated device registered in the national health surveillance agency.

While in other countries drug screening is already performed on roadsides (EMCDDA, 2012EMCDDA. European Monitoring Centre for Drugs and Drug Addiction. Driving Under the Influence of Drugs, Alcohol and Medicines in Europe findings from the DRUID project. Luxembourg: Publications Office of the European Union; 2012.), in Brazil there are still no screening tests available for routine monitoring in DUID scenarios, to help prevent TA. Since Cannabis sativa L. is the second most consumed drug in Brazil and in the world, along with its relation to TA (Callaghan et al., 2013Callaghan RC, Gatley JM, Veldhuizen S, Lev-Ran S, Mann R, Asbridge M. AlcoholOr drug-use disorders and motor vehicle accident mortality: A retrospective cohort study. Accid Anal Prev. 2013;53:149-55.; Perna et al., 2016Perna EB de SF, Theunissen EL, Kuypers KPC, Toennes SW, Ramaekers JG. Subjective aggression during alcohol and cannabis intoxication before and after aggression exposure. Psychopharmacology (Berl). 2016;233(18):3331-40.), it should be considered a priority for drug screening, besides alcohol. Thus, recently, the Cannabis product cannabidiol (CBD) has been authorized as a controlled substance for therapeutic purposes in Brazil, and any product of Cannabis must not exceed the maximum concentration of 30 mg/mL of Δ⁹-THC and 30 mg/mL of CBD, considering health recommendations (ANVISA, 2019ANVISA. Agência Nacional de Vigilância Sanitária. Resolução da Diretoria Colegiada RDC No 325, de 3 de dezembro de 2019. Diário Oficial da União 04 abr; 2019 p. 85.). Since driving under the influence of cannabis is an expressive risk factors that contribute to TA, the legalization of cannabis, even for medical and very punctual purposes, can be a risk on the road, demonstrating the importance of the understanding how sensitive, specific and accurate are the methods available in the market that make it possible to monitor the driver’s impairment.

Compared to other biological matrices, OF is an advantageous matrix for on-site analysis. Due to the practicality of collection, donor acceptability and the noninvasive collection method (Anizan et al., 2015Anizan S, Bergamaschi MM, Barnes AJ, Milman G, Desrosiers N, Lee D, et al. Impact of oral fluid collection device on cannabinoid stability following smoked cannabis. Drug Test Anal. 2015;7(2):114-20.), OF has become increasingly popular in drug testing programs, mainly in the investigation of DUID (Newmeyer et al., 2014Newmeyer MN, Desrosiers NA, Lee D, Mendu DR, Barnes AJ, Gorelick DA, et al. Cannabinoid disposition in oral fluid after controlled cannabis smoking in frequent and occasional smokers. Drug Test Anal . 2014;6(10):1002-10.). Since the collection can be assisted by law enforcement officers without causing embarrassment to the donor, the possibility of adulteration of the matrix is reduced (Lund et al., 2011Lund HME, Øiestad EL, Gjerde H, Christophersen AS. Drugs of abuse in oral fluid collected by two different sample kits Stability testing and validation using ultra performance tandem mass spectrometry analysis. J. Chromatogr B Anal Technol Biomed Life Sci. 2011;879(30):3367-77.).

The Society of Forensic Toxicologists (SOFT/AAFS), through the guide “Oral Fluid as a Test Specimen for Roadside Studies: Guidelines for Implementing a Data Collection Program” addresses OF as a biological matrix for monitoring DUID cases, as well as the importance of the commitment of all parties in the implementation and the management of a roadside testing program. This guide also reinforces the advantages of using OF over blood, considering it the “gold standard” for alcohol and drugs detection in traffic - for instance, the possibility of sample collection and analysis onsite, without the need of a health professional,like with blood collection, and with the least possible embarrassment to the driver. Furthermore, the guide provides a brief protocol for the Oral Fluid Program, with recommended steps for the suspected drunk and/or drugged driver approach, as well as for on-site analysis, for sample collection and for sample storage, also pointing when to submit the sample for confirmatory analysis (SOFT, 2014SOFT. Society of Forensic Toxicology. Oral Fluid as a Test Specimen for Roadside Studies: Guidelines for Implementing a Data Collection Program. Driving Under the Influence of Drugs (DUID); 2014.).

It is important to point out here that the screening devices (multi-drug devices) for OF analysis are a tool that would help the police to investigate and control DUID cases in loco on the roads, allowing the monitoring of the use of psychoactive substances in different traffic scenarios (Gjerde et al., 2018Gjerde H, Clausen GB, Andreassen E, Furuhaugen H. Evaluation of dräger drugtest 5000 in a naturalistic setting. J Anal Toxicol. 2018;42(4):248-54.). In forensic analyzes focused on the traffic scenario, the use of prohibited substances is considered a crime (HealthNewsReview.org, 2020HealthNewsReview.org. Understanding medical tests: sensitivity, specificity and positive predictive value [Internet]. [cited 2020 Jun 18]. Available from: Available from: https://www.healthnewsreview.org/toolkit/tips-for-understandingstudies/understanding-medical-tests-sensitivity-specificityandpositive-predictive-value/
https://www.healthnewsreview.org/toolkit... ). In order to fit in this scenario, the chosen screening device must have high sensitivity and specificity, since the main objective is to identify drivers under the effect of PS, contributing in the future to compliance with the traffic safety law (Strano-Rossi et al., 2012Strano-Rossi S, Castrignanò E, Anzillotti L, Serpelloni G, Mollica R, Tagliaro F, et al. Evaluation of four oral fluid devices (DDS®, Drugtest 5000®, Drugwipe 5+® and RapidSTAT®) for on-site monitoring drugged driving in comparison with UHPLC-MS/MS analysis. Forensic Sci Int . 2012;221(1-3):70-6.). The screening device sensitivity is the proportion of true positive OF samples that have been correctly identified (Beirness, Smith, 2017Beirness DJ, Smith DR. An assessment of oral fluid drug screening devices. J Can Soc Forensic Sci. 2017;50(2):55-63.). On the other hand, the screening device specificity is the proportion of true PS negative samples that have been correctly identified (Beirness, Smith, 2017Beirness DJ, Smith DR. An assessment of oral fluid drug screening devices. J Can Soc Forensic Sci. 2017;50(2):55-63.). Both are calculated using the cut-off points adopted by a DRUID study, a fact that reflects the variations observed between studies, and they are calculated according to the equations presented in Table I. In addition, in order to determine the usefulness of a screening device, the true predictive value and the negative predictive value are calculated (Table I) and both are directly dependent on the PS prevalence in the studied population (Blencowe et al., 2010Blencowe T, Pehrsson A, Lillsunde P, Bernhoft IM, Engblom C, Langel K, et al. Analytical evaluation of oral fluid screening devices and preceding selection procedures. Alcohol Drug Anal. Unit Natl Inst Heal Welf Helsinki, FIN. 2010.).Thus, the use of a screening device with low sensitivity and/or selectivity can result in an increase of false negative and/or false positive results. In both cases, it leads to wrong tests results and it can have serious legal consequences, considering that the legally controlled substances consumption has a close relationship with crime. False negative results lead to impunity for drivers who pose as a risk in traffic, demonstrating the failure of the evaluation system. As for false positives results, there are risks of condemnation and embarrassment provoked on an innocent driver. Thus, besides sensitivity and specificity, screening devices must be reliable and easy to handle (Strano-Rossi et al., 2012Strano-Rossi S, Castrignanò E, Anzillotti L, Serpelloni G, Mollica R, Tagliaro F, et al. Evaluation of four oral fluid devices (DDS®, Drugtest 5000®, Drugwipe 5+® and RapidSTAT®) for on-site monitoring drugged driving in comparison with UHPLC-MS/MS analysis. Forensic Sci Int . 2012;221(1-3):70-6.), with an easy and fast interpretation of the results, in order to allow that trained police officers can identify the use of psychoactive substances by motor vehicle drivers (Newmeyer et al., 2017Newmeyer MN, Swortwood MJ, Andersson M, Abulseoud OA, Scheidweiler KB, Huestis MA. Cannabis edibles: Blood and oral fluid cannabinoid pharmacokinetics and evaluation of oral fluid screening devices for predicting Δ9-tetrahydrocannabinol in blood and oral fluid following cannabis brownie administration. Clin Chem . 2017;63(3):647-62.).

Current programs that monitor the use of PS in traffic, such as the European Union’s (Driving under the Influence of Drugs, Alcohol and Medicines - DRUID), suggest that OF screening devices should be evaluated for their analytical sensitivity, specificity and efficiency and that these values should be higher than 80% (Newmeyer et al., 2017Newmeyer MN, Swortwood MJ, Andersson M, Abulseoud OA, Scheidweiler KB, Huestis MA. Cannabis edibles: Blood and oral fluid cannabinoid pharmacokinetics and evaluation of oral fluid screening devices for predicting Δ9-tetrahydrocannabinol in blood and oral fluid following cannabis brownie administration. Clin Chem . 2017;63(3):647-62.). Other studies established that screening devices must present higher standards (sensitivity ≥ 80%, specificity ≥ 90% and accuracy ≥ 95%), so that it can be considered a satisfactory test (Strano-Rossi et al., 2012Strano-Rossi S, Castrignanò E, Anzillotti L, Serpelloni G, Mollica R, Tagliaro F, et al. Evaluation of four oral fluid devices (DDS®, Drugtest 5000®, Drugwipe 5+® and RapidSTAT®) for on-site monitoring drugged driving in comparison with UHPLC-MS/MS analysis. Forensic Sci Int . 2012;221(1-3):70-6.). Based on this information, and the data collected in our review, it is possible to verify that only Dräger DrugTest 5000^® (DDT5000) and Alere^TM DDS^®2 (DDS2) devices fits the recommendation for the investigation of cannabis metabolites in OF, presenting sensitivity and specificity greater than 80% in a considerable number of studies (Beirness, Smith, 2017Beirness DJ, Smith DR. An assessment of oral fluid drug screening devices. J Can Soc Forensic Sci. 2017;50(2):55-63.; Gjerde et al., 2018Gjerde H, Clausen GB, Andreassen E, Furuhaugen H. Evaluation of dräger drugtest 5000 in a naturalistic setting. J Anal Toxicol. 2018;42(4):248-54.; Newmeyer et al., 2017Newmeyer MN, Swortwood MJ, Andersson M, Abulseoud OA, Scheidweiler KB, Huestis MA. Cannabis edibles: Blood and oral fluid cannabinoid pharmacokinetics and evaluation of oral fluid screening devices for predicting Δ9-tetrahydrocannabinol in blood and oral fluid following cannabis brownie administration. Clin Chem . 2017;63(3):647-62.; Rohrig et al., 2018Rohrig TP, Moore CM, Stephens K, Cooper K, Coulter C, Baird T, et al. Roadside drug testing: An evaluation of the Alere DDS ® 2 mobile test system. Drug Test Anal . 2018;10(4):663-70.; Strano-Rossi et al., 2012Strano-Rossi S, Castrignanò E, Anzillotti L, Serpelloni G, Mollica R, Tagliaro F, et al. Evaluation of four oral fluid devices (DDS®, Drugtest 5000®, Drugwipe 5+® and RapidSTAT®) for on-site monitoring drugged driving in comparison with UHPLC-MS/MS analysis. Forensic Sci Int . 2012;221(1-3):70-6.; Swortwood et al., 2017Swortwood MJ, Newmeyer MN, Andersson M, Abulseoud OA, Scheidweiler KB, Huestis MA. Cannabinoid disposition in oral fluid after controlled smoked, vaporized, and oral cannabis administration. Drug Test Anal . 2017;9(6):905-15.). However, it is important to note that some studies have found low specificity for the DDT5000 device, even though they have found satisfactory sensitivity(Domingo-Salvany et al., 2017Domingo-Salvany A, Herrero MJ, Fernandez B, Perez J, del Real P, González-Luque JC, et al. Prevalence of psychoactive substances, alcohol and illicit drugs, in Spanish drivers: A roadside study in 2015. Forensic Sci Int . 2017;278:253-9.; Lema-Atán et al., 2019Lema-Atán JÁ, de Castro A, Lendoiro E, López-Rivadulla M, Cruz A. Toxicological oral fluid results among Spanish drivers testing positive on on-site drug controls from 2013 to 2015. Drug Alcohol Depend . 2019;195:106-13.; Logan, Mohr, Talpins, 2014Logan BK, Mohr ALA, Talpins SK. Detection and prevalence of drug use in arrested drivers using the dräger drug test 5000 and affiniton DrugWipe oral fluid drug screening devices. J Anal Toxicol . 2014;38(7):444-50.). As for DDS2 device, Veitenheimer and Wagner (2017Veitenheimer AM, Wagner JR. Evaluation of oral fluid as a specimen for DUID. J Anal Toxicol . 2017;41(6):517-22.) have found a 100% of specificity, while the sensitivity was below the recommended values (75%). The Rapid STAT^® device showed 71-91% of sensitivity and specificity values ranging from 09-97, thought the studies in this review (Blencowe et al., 2011Blencowe T, Pehrsson A, Lillsunde P, Vimpari K, Houwing S, Smink B, et al. An analytical evaluation of eight on-site oral fluid drug screening devices using laboratory confirmation results from oral fluid. Forensic Sci Int. 2011;208(1-3):173-9.; Musshoff et al., 2014Musshoff F, Hokamp EG, Bott U, Madea B. Performance evaluation of on-site oral fluid drug screening devices in normal police procedure in Germany. Forensic Sci Int . 2014;238:120-4.; Strano-Rossi et al., 2012Strano-Rossi S, Castrignanò E, Anzillotti L, Serpelloni G, Mollica R, Tagliaro F, et al. Evaluation of four oral fluid devices (DDS®, Drugtest 5000®, Drugwipe 5+® and RapidSTAT®) for on-site monitoring drugged driving in comparison with UHPLC-MS/MS analysis. Forensic Sci Int . 2012;221(1-3):70-6.; Wille et al., 2010Wille SMR, Samyn N, Ramírez-Fernández M del M, De Boeck G. Evaluation of on-site oral fluid screening using Drugwipe-5+®, RapidSTAT® and Drug Test 5000® for the detection of drugs of abuse in drivers. Forensic Sci Int 2010;198(1-3):2-6.). However Röhrich et al.(2010Röhrich J, Zörntlein S, Becker J, Urban R. Detection of Δ9tetrahydrocannabinol and amphetamine-type stimulants in oral fluid using the rapid statTM point-of-collection drugtesting device. J Anal Toxicol . 2010;34(3):155-61.) have found > 80% values for both sensitivity and specificity for this device.

Studies using Cozart^® DDS805, Dräger DCH^® 5000, Dräger DCD 5000, Envite CSmartClip^®THC/Amph, Oral twist, Reader DDS^®202S, Drug Wipe^® and DrugWipe^® II Twin sorting devices do not provide data sensitivities and specificity (Davey et al., 2014Davey J, Armstrong K, Martin P. Results of the Queensland 2007-2012 roadside drug testing program: The prevalence of three illicit drugs. Accid Anal Prev . 2014;65:11-7.; Griffiths et al., 2017Griffiths A, Leonars R, Hadley L, Stephenson M, Teale R. Smoke on the water - Oral fluid analysis at sea. Forensic Sci Int . 2017;278:361-6.; Matzopoulos et al., 2013Matzopoulos R, Lasarow A, Bowman B. A field test of substance use screening devices as part of routine drunkdriving spot detection operating procedures in South Africa. Accid Anal Prev . 2013;59:118-24.). The Cozart^® DDS 806, OrAlert^TM, OraLab^®6, BIOSENS^® Dynamic, OraLab^®6, Oratect1 III devices, presented average sensitivity and specificity of 38% and 95% respectively (Blencowe et al., 2011Blencowe T, Pehrsson A, Lillsunde P, Vimpari K, Houwing S, Smink B, et al. An analytical evaluation of eight on-site oral fluid drug screening devices using laboratory confirmation results from oral fluid. Forensic Sci Int. 2011;208(1-3):173-9.). The Saliva Screen^® and Ora-Check^® screening devices showed 100% specificity (Tang et al., 2018Tang MHY, Ching CK, Poon S, Chan SSS, Ng WY, Lam M, et al. Evaluation of three rapid oral fluid test devices on the screening of multiple drugs of abuse including ketamine. Forensic Sci Int . 2018;286:113-20.). Devices of DrugWipe^® brand have (5/5+, 5A, 5, 5+, II Twin, 6S) showed variations between sensitivity and specificity results, when comparing studies (Beirness, Smith 2017Beirness DJ, Smith DR. An assessment of oral fluid drug screening devices. J Can Soc Forensic Sci. 2017;50(2):55-63.; Blencowe et al., 2011Blencowe T, Pehrsson A, Lillsunde P, Vimpari K, Houwing S, Smink B, et al. An analytical evaluation of eight on-site oral fluid drug screening devices using laboratory confirmation results from oral fluid. Forensic Sci Int. 2011;208(1-3):173-9.; Gentili et al., 2016Gentili S, Solimini R, Tittarelli R, Mannocchi G, Busardò FP. A Study on the Reliability of an On-Site Oral Fluid Drug Test in a Recreational Context. J Anal Methods Chem. 2016;2016:1-10.; Logan, Mohr, Talpins, 2014Logan BK, Mohr ALA, Talpins SK. Detection and prevalence of drug use in arrested drivers using the dräger drug test 5000 and affiniton DrugWipe oral fluid drug screening devices. J Anal Toxicol . 2014;38(7):444-50.; Musshoff et al., 2014Musshoff F, Hokamp EG, Bott U, Madea B. Performance evaluation of on-site oral fluid drug screening devices in normal police procedure in Germany. Forensic Sci Int . 2014;238:120-4.; Pehrsson et al., 2011aPehrsson A, Blencowe T, Vimpari K, Impinen A, Gunnar T, Lillsunde P. Performance evaluation of the DrugWipe® 5/5+ on-site oral fluid screening device. Int J Legal Med. 2011a;125(5):675-83.; Pehrsson et al., 2011bPehrsson A, Blencowe T, Vimpari K, Langel K, Engblom C, Lillsunde P. An evaluation of on-site oral fluid drug screening devices drugwipe® 5+ and rapid STAT® using oral fluid for confirmation analysis. J Anal Toxicol . 2011b;35(4):211-8.; Strano-Rossi et al., 2012Strano-Rossi S, Castrignanò E, Anzillotti L, Serpelloni G, Mollica R, Tagliaro F, et al. Evaluation of four oral fluid devices (DDS®, Drugtest 5000®, Drugwipe 5+® and RapidSTAT®) for on-site monitoring drugged driving in comparison with UHPLC-MS/MS analysis. Forensic Sci Int . 2012;221(1-3):70-6.; Tang et al., 2018Tang MHY, Ching CK, Poon S, Chan SSS, Ng WY, Lam M, et al. Evaluation of three rapid oral fluid test devices on the screening of multiple drugs of abuse including ketamine. Forensic Sci Int . 2018;286:113-20.; VanderLinden et al., 2015VanderLinden T, Wille SMR, Ramírez-Fernandez M, Verstraete AG, Samyn N. Roadside drug testing: Comparison of two legal approaches in Belgium. Forensic Sci Int . 2015;249:148-55.; Wille et al., 2010Wille SMR, Samyn N, Ramírez-Fernández M del M, De Boeck G. Evaluation of on-site oral fluid screening using Drugwipe-5+®, RapidSTAT® and Drug Test 5000® for the detection of drugs of abuse in drivers. Forensic Sci Int 2010;198(1-3):2-6.). Dräger DrugTest^® and Cozart^® DDS 801 devices showed a sensitivity of 87%, however the Cozart^® DDS 801 showed improved specificity (Arroyo et al., 2014Arroyo A, Sanchez M, Barberia E, Barbal M, Marrón MT, Mora A. Comparison of the Cozart DDS 801 on-site drug test device and gas chromatography/mass spectrometry (GC/ MS) confirmation results of cannabis and cocaine in oral fluid specimens. Aust J Forensic Sci. 2014;46(3):272-81.; Musshoff et al., 2014Musshoff F, Hokamp EG, Bott U, Madea B. Performance evaluation of on-site oral fluid drug screening devices in normal police procedure in Germany. Forensic Sci Int . 2014;238:120-4.). Among the studies that used the DDS^® concatene screening device, only the study of Strano-Rossi et al., (2012Strano-Rossi S, Castrignanò E, Anzillotti L, Serpelloni G, Mollica R, Tagliaro F, et al. Evaluation of four oral fluid devices (DDS®, Drugtest 5000®, Drugwipe 5+® and RapidSTAT®) for on-site monitoring drugged driving in comparison with UHPLC-MS/MS analysis. Forensic Sci Int . 2012;221(1-3):70-6.) provided sensitivity and specificity values (38% and 100%, respectively) (Anzillotti et al., 2014Anzillotti L, Castrignanò E, Rossi SS, Chiarotti M. Cannabinoids determination in oral fluid by SPME-GC/ MS and UHPLC-MS/MS and its application on suspected drivers. Sci Justice. 2014;54(6):421-6.; Strano-Rossi et al., 2012Strano-Rossi S, Castrignanò E, Anzillotti L, Serpelloni G, Mollica R, Tagliaro F, et al. Evaluation of four oral fluid devices (DDS®, Drugtest 5000®, Drugwipe 5+® and RapidSTAT®) for on-site monitoring drugged driving in comparison with UHPLC-MS/MS analysis. Forensic Sci Int . 2012;221(1-3):70-6.). For the Varian Oralab^®6 device, sensitivity was low (41%), but specificity is adequate (99%) (Goessaert et al., 2010Goessaert AS, Pil K, Veramme J, Verstraete A. Analytical evaluation of a rapid on-site oral fluid drug test. Anal Bioanal Chem. 2010;396(7):2461-8.). It is desirable that the screening device present a high degree of tracking, in order to present adequate sensitivity and specificity. (Beirness, Smith 2017Beirness DJ, Smith DR. An assessment of oral fluid drug screening devices. J Can Soc Forensic Sci. 2017;50(2):55-63.). Although these values are independent of prevalence, it must be considered that the study population can reflect it, so that the concentrations can be compared between different populations (Blencowe et al., 2010Blencowe T, Pehrsson A, Lillsunde P, Bernhoft IM, Engblom C, Langel K, et al. Analytical evaluation of oral fluid screening devices and preceding selection procedures. Alcohol Drug Anal. Unit Natl Inst Heal Welf Helsinki, FIN. 2010.). Other important parameters include the positive predictive values (PPV) and the negative predictive value (NPV). These are dependent on the PS prevalence the investigated population (Blencowe et al., 2010Blencowe T, Pehrsson A, Lillsunde P, Bernhoft IM, Engblom C, Langel K, et al. Analytical evaluation of oral fluid screening devices and preceding selection procedures. Alcohol Drug Anal. Unit Natl Inst Heal Welf Helsinki, FIN. 2010.). Thus, the prevalence of a certain PS within the study population is derived from the cases proportion in which the PS is detected in the confirmatory samples of all study participants (Blencowe et al., 2010Blencowe T, Pehrsson A, Lillsunde P, Bernhoft IM, Engblom C, Langel K, et al. Analytical evaluation of oral fluid screening devices and preceding selection procedures. Alcohol Drug Anal. Unit Natl Inst Heal Welf Helsinki, FIN. 2010.). Thus, it is possible to calculate PPV and NPV values through the combination of sensitivity, specificity, and prevalence values (Bayes’ theorem) (Blencowe et al., 2010Blencowe T, Pehrsson A, Lillsunde P, Bernhoft IM, Engblom C, Langel K, et al. Analytical evaluation of oral fluid screening devices and preceding selection procedures. Alcohol Drug Anal. Unit Natl Inst Heal Welf Helsinki, FIN. 2010.).

THC is traditionally known to be a problematic analyte for on-site screening devices (Fierro, GonzálezLuque, Álvarez, 2014Fierro I, González-Luque JC, Álvarez FJ. The relationship between observed signs of impairment and THC concentration in oral fluid. Drug Alcohol Depend. 2014;144:231-8.). DUID studies have shown low sensitivity of THC screening tests, and it may be associated with their higher cut-offs (Domingo-Salvany et al., 2017Domingo-Salvany A, Herrero MJ, Fernandez B, Perez J, del Real P, González-Luque JC, et al. Prevalence of psychoactive substances, alcohol and illicit drugs, in Spanish drivers: A roadside study in 2015. Forensic Sci Int . 2017;278:253-9.). Other factors that can contribute for the device’s low sensitivity and its inadequate performance are the possibility of cross-reactivity and poor analyte recovery from the device (Mazina et al., 2015Mazina J, Spiljova A, Vaher M, Kaljurand M, Kulp M. A rapid capillary electrophoresis method with LED-induced native fluorescence detection for the analysis of cannabinoids in oral fluid. Anal Methods. 2015;7(18):7741-7.). These factors are particularly difficult to elucidate for cannabinoids (Domingo-Salvany et al., 2017Domingo-Salvany A, Herrero MJ, Fernandez B, Perez J, del Real P, González-Luque JC, et al. Prevalence of psychoactive substances, alcohol and illicit drugs, in Spanish drivers: A roadside study in 2015. Forensic Sci Int . 2017;278:253-9.) and it raises concerns about the use of these devices in police routine.

However, although the screening devices have some disadvantages that must be considered, they still are an important tool, and they are currently the method of choice for DUID cases in some countries. As an example, in 2015, the Norwegian Mobile Police Service (NMPS) have started DUID cases monitoring of PS, including cannabis metabolites, using the Dräger DrugTest5000^® (DDT5000) screening device for OF (Gjerde et al., 2018Gjerde H, Clausen GB, Andreassen E, Furuhaugen H. Evaluation of dräger drugtest 5000 in a naturalistic setting. J Anal Toxicol. 2018;42(4):248-54.). NMPS reported that DDT5000 did not correctly identified DUID offenders, but the screening device was helpful to assist in the identification of possible DUID suspects (Gjerde et al., 2018Gjerde H, Clausen GB, Andreassen E, Furuhaugen H. Evaluation of dräger drugtest 5000 in a naturalistic setting. J Anal Toxicol. 2018;42(4):248-54.).

In a study conducted in Italy, trained police officers randomly approached drivers during road patrols, collecting their OFs for screening analysis using two different devices. At the end of the study, they found that only DDT5000 presented acceptable sensitivity for on-site investigation (Strano-Rossi et al., 2012Strano-Rossi S, Castrignanò E, Anzillotti L, Serpelloni G, Mollica R, Tagliaro F, et al. Evaluation of four oral fluid devices (DDS®, Drugtest 5000®, Drugwipe 5+® and RapidSTAT®) for on-site monitoring drugged driving in comparison with UHPLC-MS/MS analysis. Forensic Sci Int . 2012;221(1-3):70-6.).

In Spain, the Traffic Police is responsible for conducting on-site OF screening tests for alcohol and drugs (Herrera-Gómez et al., 2018Herrera-Gómez F, García-Mingo M, Colás M, González-Luque JC, Álvarez FJ. Opioids in oral fluid of Spanish drivers. Drug Alcohol Depend . 2018;187:35-9.). DDS2 and DDT5000 are among the screening devices chosen by the Spanish law(Herrera-Gómez et al., 2018Herrera-Gómez F, García-Mingo M, Colás M, González-Luque JC, Álvarez FJ. Opioids in oral fluid of Spanish drivers. Drug Alcohol Depend . 2018;187:35-9.). The device’s performance was investigated in a study conducted by Lema-Atán et al. (2019Lema-Atán JÁ, de Castro A, Lendoiro E, López-Rivadulla M, Cruz A. Toxicological oral fluid results among Spanish drivers testing positive on on-site drug controls from 2013 to 2015. Drug Alcohol Depend . 2019;195:106-13.) and they have found an appropriated sensitivity considering the devices’ cutoffs for cannabis (Lema-Atán et al., 2019Lema-Atán JÁ, de Castro A, Lendoiro E, López-Rivadulla M, Cruz A. Toxicological oral fluid results among Spanish drivers testing positive on on-site drug controls from 2013 to 2015. Drug Alcohol Depend . 2019;195:106-13.). In this study, samples were collected by police officers, investigating the use of psychoactive substances in Spanish drivers, between 2013 and 2015.

In Canada, the government have approved a legislation that would allow the use of screening devices for cannabis on-site investigation in suspected drivers (Canadian Centre on Substance Use and Addiction, 2018Canadian Centre on Substance Use and Addiction. Oral Fluid Drug Screening [Internet]. 2018. Available from: https://ccsa.ca/sites/default/files/2019-04/CCSA-Oral-FluidDrug-Screening-Policy-Brief-2018-en.pdf
https://ccsa.ca/sites/default/files/2019... ). According to this document, the screening device can help the police to decide which actions will be taken for suspected drivers at a risk of causing an accident (Canadian Centre on Substance Use and Addiction, 2018Canadian Centre on Substance Use and Addiction. Oral Fluid Drug Screening [Internet]. 2018. Available from: https://ccsa.ca/sites/default/files/2019-04/CCSA-Oral-FluidDrug-Screening-Policy-Brief-2018-en.pdf
https://ccsa.ca/sites/default/files/2019... ) and allows the traffic officer to decree flagrant and remove drugged drivers from the roads. The Dräger DrugTest^® 5000 is one of the devices approved for monitoring DUID cases by the Canadian government, as long as it is used in conjunction with the Dräger DrugTest 5000^® STK-CA device. Other approved device includes SoToxa™, as long as used in conjunction with Abbott SoToxa™ test cartridge, and Abbott SoToxa™ OF collection device (Canada, 2019Canada. Criminal Code. Approved Drug Screening Equipment Order. Attorney General’s Office; 2019 p. R.S.C., 1985, c. C-46.).

In the United States, some studies have been developed in partnership with specialist drug recognition officers (DRE) from the Tulsa Police Department (Oklahoma, US) such as the one developed by Veitenheimer and Wagner (2017Veitenheimer AM, Wagner JR. Evaluation of oral fluid as a specimen for DUID. J Anal Toxicol . 2017;41(6):517-22.).The DDS2 device was used in routine approaches of suspected DUID drivers in 2013. At the end of the study, it was found that the DDS2 screening device is a tool that can provide police a greater confidence in detecting drivers who are under the influence of PS such as cannabis (Veitenheimer, Wagner, 2017Veitenheimer AM, Wagner JR. Evaluation of oral fluid as a specimen for DUID. J Anal Toxicol . 2017;41(6):517-22.).

After on-site analysis, any positive result from a screening test must be confirmed by a validated analytical method (Fiorentin et al., 2017Fiorentin TR, D’Avila FB, Comiran E, Zamboni A, Scherer JN, Pechansky F, et al. Simultaneous determination of cocaine/crack and its metabolites in oral fluid, urine and plasma by liquid chromatography-mass spectrometry and its application in drug users. J Pharmacol Toxicol Methods. 2017;86:60-6.). For confirmatory analysis, it is necessary to collect an additional volume of OF, which is usually performed with a specific collection device. There are also many different manufacturers for those devices, such as Quantisal™, Oral-Eze^®, StatSure Saliva Sampler™, and this also require studies to define the better one for cannabinoids recovery, case by case, country by country, scenario by scenario.

For confirmation and quantification of cannabinoids in OF, the most commonly applied analytical tools are gas chromatography coupled to mass spectrometry (GC/ MS or GC-MS/MS) and liquid chromatography coupled to mass spectrometry (LC-MS/MS) (Table I). THC, as the major psychoactive cannabinoid, is also the chosen metabolite for confirmatory testing in OF, as it is for screening tests (Molnar et al., 2014Molnar A, Fu S, Lewis J, Allsop DJ, Copeland J. The detection of THC, CBD and CBN in the oral fluid of Sativex® patients using two on-site screening tests and LC-MS/MS. Forensic Sci Int . 2014;238:113-9.), along with CBD and CBN. When detecting these cannabinoids in OF, it can be generally assumed that there was the recent consumption of cannabis (Vindenes et al., 2011Vindenes V, Yttredal B, Øiestad EL, Waal H, Bernard JP, Mørland JG, et al. Oral fluid is aviable alternative for monitoring drug abuse: Detection of drugs in oral fluid by liquid chromatography-tandem mass spectrometry and comparison to the results from urine samples from patients treated with methadone or buprenorphine. J Anal Toxicol . 2011;35(1):32-9.). This information is also relevant, considering that the Brazilian Traffic Code (CTB) regulates the driving under drug influence, while an old drug consumption does not constitute a traffic crime (Baggio, 2017Baggio EV. Monitoramento do uso de canábis por condutores de veículo automotor: desenvolvimento de método bioanalítico compatível com a rotina laboratorial da perícia no Brasil. Universidade Federal do Rio Grande do Sul; 2017.). When develop a confirmatory method for THC in OF, one should consider THC capacity of adherence to plastic (Anzillotti et al., 2014Anzillotti L, Castrignanò E, Rossi SS, Chiarotti M. Cannabinoids determination in oral fluid by SPME-GC/ MS and UHPLC-MS/MS and its application on suspected drivers. Sci Justice. 2014;54(6):421-6.; Molnar, Lewis, Fu, 2013Molnar A, Lewis J, Fu S. Recovery of spiked Δ9tetrahydrocannabinol in oral fluid from polypropylene containers. Forensic Sci Int . 2013;227(1-3):69-73.), leading to its poor recovery from collection devices and affecting the recommended cut-off (2 ng/mL) (Walsh et al., 2008Walsh JM, Verstraete AG, Huestis MA, Mørland J. Guidelines for research on drugged driving. Addiction. 2008;103(8):1258-68.). Considering this, special devices with elution/stabilization buffers are generally used to collect OF (Anizan et al., 2015Anizan S, Bergamaschi MM, Barnes AJ, Milman G, Desrosiers N, Lee D, et al. Impact of oral fluid collection device on cannabinoid stability following smoked cannabis. Drug Test Anal. 2015;7(2):114-20.) which should favor the elution of THC with minimal dilution.

Another important factor for clinical and for forensic purposes is the investigation of the analyte stability in the OF, considering its importance in the interpretation of concentrations (Lee et al., 2012Lee D, Milman G, Schwope DM, Barnes AJ, Gorelick DA, Huestis MA. Cannabinoid stability in authentic oral fluid after controlled cannabis smoking. Clin Chem . 2012;58(7):1101-9.) and to guarantee accurate and reliable results (Scheidweiler et al., 2017Scheidweiler KB, Andersson M, Swortwood MJ, Sempio C, Huestis MA. Long-term stability of cannabinoids in oral fluid after controlled cannabis administration. Drug Test Anal . 2017;9(1):143-7.). Thus, the collection devices and the storage conditions of the sample are variables to be considered. Studies of the stability of cannabinoids in real OF collected by different collection devices are described in the literature. Lee et al.(2012Lee D, Milman G, Schwope DM, Barnes AJ, Gorelick DA, Huestis MA. Cannabinoid stability in authentic oral fluid after controlled cannabis smoking. Clin Chem . 2012;58(7):1101-9.) have found that THC and other cannabinoids (THCCOOH, CBD and CBN) are stable for 4 weeks when stored at 4°C, in the Quantisal™ device. StatSure Saliva Sampler™ and Oral-Eze^® devices also have presented stability for THC, THCCOOH, CBD and CBN in OF, under the same conditions of time and temperature. StatSure^TM device also have been able to maintain samples stability within 24 weeks, if stored at -20°C (Anizan et al., 2015Anizan S, Bergamaschi MM, Barnes AJ, Milman G, Desrosiers N, Lee D, et al. Impact of oral fluid collection device on cannabinoid stability following smoked cannabis. Drug Test Anal. 2015;7(2):114-20.). The stability of minority cannabinoids in real OF was investigated by Scheidweiler et al.(2017Scheidweiler KB, Andersson M, Swortwood MJ, Sempio C, Huestis MA. Long-term stability of cannabinoids in oral fluid after controlled cannabis administration. Drug Test Anal . 2017;9(1):143-7.). THC, THCV, 11-OH-THC, CBD and CBG had satisfactory stability when kept under refrigeration at 4°C during the period of 8 weeks, extracted from OF stored in Quantisal™ devices (Scheidweiler et al., 2017Scheidweiler KB, Andersson M, Swortwood MJ, Sempio C, Huestis MA. Long-term stability of cannabinoids in oral fluid after controlled cannabis administration. Drug Test Anal . 2017;9(1):143-7.). Therefore, the stability of cannabinoids depends on the collection device, as well as the time and conditions of the storage of the sample, and this aspect is also something to be considered.

In Brazil, the Ministry of Justice and Security organized a work team composed of members of the National Drug Policy Secretariat (SENAD), the Federal Highway Police (PRF) and the National Public Security Secretariat (SENASP), with the purpose of assisting in the implementation of the use of screening devices to monitor other PS in addition to alcohol (MJSP, 2020MJSP. Ministério da Justiça e Segurança Pública. MJSP cria Grupo de Trabalho para implantar aparelho que flagra uso de drogas por motoristas [Internet]. 2020 [cited 2020 Oct 15]. Available from: Available from: https://www.justica.gov.br/news/collectivenitf-content-1555076113.46
https://www.justica.gov.br/news/collecti... ). In order to be successful in the implementation of screening devices for PS monitoring in traffic, it is extremely important to have solid evidence-based information, considering local contexts (Scherer, 2017Scherer JN. Substâncias Psicoativas no Trânsito: Estudo sobre Fatores de Risco e Tecnologias de Detecção in loco. Universidade Federal do Rio Grande do Sul (UFRGS); 2017.). In addition, special attention should be paid to costs for both the implementation of screening devices and the processing of confirmatory analyzes. For example, non-volatile analytes that that require LC-MS/MS analysis present a higher cost when compared to GC/MS analysis (Huestis et al., 2011Huestis MA, Verstraete A, Kwong TC, Morland J, Vincent MJ, de la Torre R. Oral fluid testing: Promises and pitfalls. Clin Chem . 2011;57(6):805-10.; SENAD, 2014SENAD. Secretaria Nacional de Política sobre Drogas. Aperfeiçoamento em técnicas para fiscalização do uso de álcool e outras drogas no trânsito brasileiro. 2ed ed. SENAD. Brasília, DF: SENAD; 2014.). Particularly in Brazil, only a few forensic laboratories have a LC-MS/MS instrument available for sample processing (SENAD, 2014SENAD. Secretaria Nacional de Política sobre Drogas. Aperfeiçoamento em técnicas para fiscalização do uso de álcool e outras drogas no trânsito brasileiro. 2ed ed. SENAD. Brasília, DF: SENAD; 2014.).

In conclusion, this systematic review selected 32 articles for analysis of immunochromatographic devices and the analysis of cannabinoids in OF onsite. From all evaluated devices, only two have shown appropriated sensitivity and selectivity, as recommended by international guides. Some limitations that must be considered and improved, such as the devices cut-offs and the possibility of cross reactions, could lead to false positives results. Considering the legal and the emotional impact that false positive results can cause in the lives of drivers who are not under the influence of PS and the potential risk that false negative drivers represent for traffic, the improvement of screening devices by manufacturers is essential. Thus, confirmatory analyzes by GC/MS, GC-MS/MS and/or LC-MS/MS are also needed. However, drug screening tests results can assist the law enforcement in determining the offense of flagrante delicto, preventing possible traffic accidents. Besides the limitations, the implementation of screening tests for cannabinoids on the roadside still can be very helpful to reduce traffic accidents in Brazil, as it has been seen in some developed countries worldwide.

ACKNOWLEDGMENTS

The authors are thankful to the Graduate Program of Pharmaceutical Sciences, from the Federal University of Rio Grande do Sul (PPGCF-UFRGS), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) and Fundação de Amparo à Pesquisa do Estado do RS (FAPERGS).

REFERENCES

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