Anti-doping Research Articles

The evolution of European legislation on doping: new challenges in the age of NPS.

The fight against doping in sport, formally started in 1960 with the constitution of the International Olympic Committee (IOC) and culminated in 1999 with the birth of the World Anti-Doping Agency (WADA), commissioned to chair various activities, including the publication of the annual list of prohibited substances and methods for doping. In Europe, as early as 1967, the Committee of Ministers of the Council of Europe adopted a resolution to stigmatise the intake of substances foreign to the body for the sole purpose of artificially and unfairly influencing sports performance. In 2002, the Council of Europe adopted an Additional Protocol to the 1989 Strasbourg Convention against Doping to ensure mutual recognition of doping controls and to strengthen the enforcement of the Convention. In Italy, the Law of 14 December 2000 n. 376 "Discipline of the health protection of sports activities and the fight against doping", defines doping as "the administration or intake of drugs or biologically or pharmacologically active substances and the adoption or submission to medical practices not justified by pathological conditions and suitable to modify the psychophysical or biological conditions of the organism in order to alter the athletic performance of athletes". The same law regulates the use of drugs or biologically or pharmacologically active substances and update an annual list in agreement with WADA. The article aims to analyse the legislation from a national perspective, offering as complete a view as possible of the current situation.

Dope and Deny: A Comparative Study of News Frames in American and Russian Coverage of American and Russian Athletes

This content analysis builds on past studies done on media coverage, rhetorical analyses, and journalistic role enactment by examining American and Russian news publications’ (N = 422) coverage of American and Russian doping scandals between 2013 and 2016. This time frame was selected because it was the height of Lance Armstrong and Major League Baseball doping coverage in the United States and the height of Olympic track-and-field doping coverage in Russia. It also fell between the time the World Anti-Doping Agency ratified its third code, which gave the antidoping organization the authority to conduct independent investigations. The study investigates media framing from the midpoint of the scandal, after the sports persona or sports entity denied using performance-enhancing drugs. Whether American and Russian coverage differ in the use of episodic and thematic frames, where blame is placed, and whether episodic or thematic framing predicts blame placement were all examined. Furthermore, the study investigates both nations’ coverage of “their own” athletes and of athletes from the other nation and analyzes whether or how the rhetorical posture of denial leads to adversarial journalism as a role enactment in coverage of sport-related scandals.

When a Ban Is Not a Ban: Institutional Work and the Russian Doping Scandal

There are fewer cases of such blatant acts to defy and subsequent heroic efforts to rearrange institutional norms than the Russian doping scandal. In adopting a neo-institutional perspective, the authors theorize the scandal as a case of attempted but failed institutional disruption. More specifically, the authors draw upon the institutional change literature and the institutional work perspective to explain the key events surrounding actors’ response to the scandal. The analysis utilized Gioia’s methodological approach to examine secondary empirical data. Findings reveal how stakeholders circumvented traditional governance structures in an attempt to disrupt institutional arrangements, but despite this, much of the preexisting institutional infrastructure has remained intact. The authors explain this outcome, in part, as a consequence of the counter-institutional work of key governing agencies and other actors to maintain the status quo within international sport.

The effects of resistance training and spirulina on the performance of the antioxidant system with emphasis on mir125b, mir146a and cognitive function in stanazolol-induced neurotoxicity in rats

Abuse of anabolic-androgenic steroids (AAS) is associated with neurological and cognitive problems in athletes. The Purpose of this study was to investigate the simultaneous effect of resistance training (RT) and spirulina supplementation (Sp) on the function of the antioxidant system with emphasis on mir125b, mir146a and cognitive function in Stanazolol (S)-induced neurotoxicity in rats.This experimental animal model study was performed with a post-test design with a control group. 45 male Sprague-Dawley rats were divided into six groups of 9 animals including (Althobaiti et al., 2022) [1]: sham (Sh/normal saline intake) (Havnes et al., 2019) [2], 25 mg/kg/wk of stanazolol (S) (Albano et al., 2021) [3], S + 100 mg/kg of Sp + (S + Sp) (Bjørnebekk et al., 2021) [4], RT (six weeks with an intensity of 50–100% of body weight) + S (S + RT) (Kanayama et al., 2013) [5] S + Sp + RT. Levels of superoxide dismutase (SOD), glutathione peroxidase (GPx), total antioxidant capacity (TAC), malondialdehyde (MDA), percentage of healthy cells in the C1 and C3 regions of hippocampus, miR125b, miR146a, step-through latency (STL), time spent in dark compartment (TDC), repeated entry in dark compartment (RDC) and percentage of alternation (PA%) were measured in the post-test. Results showed that the Sp, RT and SP + RT increased levels of SOD, GPx and percentage of healthy cells in C1 region, decreased MDA, mir125b, mir146a in hippocampal tissue and decreased TDC levels in S-exposed rats (P ≤ 0.05). Sp + RT decreased RDC and increased SOD levels; on the other hand, RT decreased RDC levels in S-exposed rats (P ≤ 0.05). Levels of TAC in the Sp groups were significantly higher than the S group (P ≤ 0.05). Also, the effect of Sp + RT in reducing miR125b, miR146a, and STL levels was much higher than the effect of Sp and RT alone (P ≤ 0.05). It seems that applying resistance training and spirulina supplementation both separately and interactively is effective in improving the antioxidant system as well as memory and learning in cognitive impairment caused by stanazolol. However, more studies on microRNAs are needed.

Analysis of doctors’ appeals on the issues of countering doping in sports

Objective: the main topics of the doctors’ questions were the preparation of medical documents for a TUE application, the determination of the anti­doping status of various substances and methods, as well as the use of dietary supplements in sports.Materials and methods: an analysis was carried out of more than 400 appeals of doctors providing medical assistance to athletes of various levels on the issues of countering doping in sports. The aim of the work was to identify ways to improve educational and informational activities aimed at improving the quality of medical documents for TUE applications.Results: the need for continuous work to improve the level of doctors’ knowledge in countering doping in sports was confirmed, including clarification of the procedure for using documents from anti­doping organizations, the need to use TUE guidelines for physicians and the specifics of prescribing substances prohibited only during the competitive period.

Relationship between Doping Prevalence and Socioeconomic Parameters: An Analysis by Sport Categories and World Areas.

Socioeconomic differences between countries, including corruption and doping scandals, have increased in the last few decades. The aims of the current investigation were to examine doping prevalence according to world areas and sport groups and its association with socioeconomic factors worldwide. The Anti-Doping Rule Violations (ADRVs) of 160 countries competing at 2016 Olympics were analyzed between 2013 and 2018. In addition, the relationship between doping prevalence and socioeconomic characteristics, including Human Development Index (HDI), Per Capita Income (PCI) and Corruption Index (CI), was investigated. Africa, Asia, and America were revealed to have a significantly lower doping prevalence than Europe and Oceania when observing the sum and the mean ADRV/10,000 inhabitants (p < 0.01). Strong to moderate correlations were identified between Corruption Index and ADRVs and HDI and ADRVs (p < 0.01). However, the number of Olympic athletes was positively associated with the ADRVs and the HDI (r = 0.663 and 0.424, respectively). In the comparison by sport groups, the Independent Recognized Sports (AIMS) showed significantly higher Adverse Analytical Findings (AAF) and ADRVs (p < 0.01) than Olympic and Recognized International Sports (ARISF). In conclusion, the results of the current study reveal doping prevalence differences between world areas and sport categories, identifying associations with socioeconomic characteristics of each country.

Криминологические проблемы российского спорта

The modern Russian Criminal Code provides for criminal liability for unlawfully influencing the result of a sports competition (fixed match), as well as for inducing an athlete to use or for using substances and (or) methods and means prohibited in sports against an athlete. In December 2021, the State Duma passed the first reading of the draft law on combating fixed matches. Russia is a party to international acts aimed at combating manipulation of the results of sports competitions and doping. Serious work is underway in the country to restore the sports image after the doping scandals of 2014. At the same time, official judicial statistics do not allow us to fully assess the real size of crime committed in the field of sports. There are practically no criminal cases. A significant factor that makes it difficult to understand the true state of affairs in the field of sports is its closeness and autonomy. Although articles about fixed matches and doping are systematically published in the media. It was these problems that determined the need for a comprehensive criminological study on crime in the field of sports. In the course of the research, content analysis, documentary method and general scientific methods were used, such as comparison, analysis and synthesis, statistical and specifically sociological methods, as well as deductive method. The results of the study showed that the criminal policy and the current criminal legislation in the field of sports cause well-founded criticism of scientists, lawyers, and athletes, primarily for its inefficiency.

Ten years of collecting hematological athlete biological passport samples-perspectives from a National Anti-doping Organization.

The hematological module of the Athlete Biological Passport (ABP) aims to reveal blood doping indirectly by looking at selected biomarkers of doping over time. For Anti-Doping Organizations (ADOs), the ABP is a vital tool in the fight against doping in sports through improved target testing and analysis, investigations, deterrence, and as indirect evidence for use of prohibited methods or substances. The physiological characteristics of sport disciplines is an important risk factor in the overall risk assessment and when implementing the hematological module. Sharing of experiences with implementing the hematological ABP between ADOs is key to further strengthen and extend its use. In this study, we present 10 years of experience with the hematological ABP program from the perspectives of a National ADO with special attention to sport disciplines' physiological characteristics as a potential risk factor for blood doping. Not surprisingly, most samples were collected in sport disciplines where the aerobic capacity is vital for performance. The study highlights strengths in Anti-Doping Norway's testing program but also areas that could be improved. For example, it was shown that samples were collected both in and out of season in a subset of the data material that included three popular sports in Norway (Cross-Country Skiing, Nordic Combined, and Biathlon), however, from the total data material it was clear that athletes were more likely to be tested out of competition and on certain days of the week and times of the day. The use of doping control officers with a flexible time schedule and testing outside an athlete's 60 min time-slot could help with a more even distribution during the week and day, and thus reduce the predictability of testing. In addition to promoting a discussion on testing strategies, the study can be used as a starting point for other ADOs on how to examine their own testing program.

Abuse of Anabolic-Androgenic Steroids and Adverse Effects on Human Organ Health: A Review

Anabolic-androgenic steroids (AAS) are large groups of molecules structurally and functionally similar to the male hormone testosterone. The use of AAS is well known and widespread worldwide due to its androgenic and anabolic properties that can increase muscle mass and strength to support athlete performance. The prevalence of AAS worldwide reaches an incidence of 5% and is generally used by men aged 18-35. AAS has many side effects on the body's organs and is a serious problem for public health and athletics. This review aims to highlight the abuse of AAS and its detrimental effects on the health of human organs. Oxidative stress and apoptosis are common mechanisms that cause organ damage due to AAS use. Chronic administration of high doses of AAS results in cardiac dysfunction and increases the risks of life-threatening arrhythmias and sudden death. In addition, several organs that have the potential to be damaged by the use of AAS include the liver, kidneys, brain, musculoskeletal system, and reproductive organs. In this regard, education intervention and knowledge sharing are the important factors that should be used to raise awareness about preventing AAS abuse.

Anabolic Androgenic Steroids Persistently Modify the User's Lipid Profile: a Case Report

The aim of the study was to show a lasting modification of the lipid profile and atherogenic indices by the abuse of anabolic androgenic steroids (AAS) by a amateur bodybuilder. This study reports a case of a 27-year-old non-competitive bodybuilder with severe abnormalities in lipid profile and atherogenic indices. He used anabolic androgenic steroids and had no other risk factors for heart disease or associated risk factors. After some educational lectures, he decided to continue his training without using anabolic androgenic steroids or any illegal ergogenic drugs. Lipid profile and atherogenic indices returned to normal values ​​in the third laboratory test performed five years after her last cycle of AAS. Abusing anabolic androgenic steroids can promote increased risk of cardiovascular disease, a trait that can persist for many years after even after discontinuing anabolic androgenic steroid use.

Comparative evaluation of host immune response and cytokine signature pertaining to Th1 and Th2 immune arms in serum and tissue among patients of acute localised vs. chronic disseminated dermatophytosis.

India is witnessing an epidemic of dermatophytosis. The role of host immune response against fungi in chronicity and dissemination is topic of ongoing research. We conducted cross-sectional comparative study to determine the difference in Th1 (IFN-γ) and Th2 (IL4) response in serum and tissue between acute and localised vs. chronic and disseminated cases. Patients (18-60 years) were divided in two groups-group A (n=114, BSA <5%, single anatomic site, duration <6 months, n=118) and group B (n=107 BSA >10%, > one anatomic site, duration >12months, n=118). Clinical parameters along with serum levels of IgE, IL-4 and IFN-γ and expression of IL4 and IFN-γ in dermal infiltrate were compared between group. Trichophyton mentagrophytes complex was commonest causative fungi. Serum levels of IgE were significantly higher (median A-539.2, B-2901.0, p < .001) whereas levels IL-4(median A-21.3, B-20.4, p < .001) and IFN-γ(median A-9.6, B-5.1, p < .001) were significantly lower in chronic cases. Expression of IL-4 was observed in most biopsy specimens in both groups without any difference in intensity of staining. Expression of IFN-γ was not detected in all but one specimen across both the groups. Severe itching (OR:0.050, CI:0.018, 0.139, p < .001), sign of topical steroid abuse (OR:0.203,CI:0.077, 0.537; p=.001), ↓IFN-γ (OR:4.683, CI:1.634, 13.418; p=.004) correlated significantly and independently with chronic dermatophytosis. Our study shows chronic and disseminated cases of dermatophytosis differ immunologically in terms of higher IgE, and lower IL4 and IFN-γ. Expression of IL4 is present in tissue of both acute, localised and chronic disseminated cases. Expression of IFN-γ cannot be established in our study.

Synthesis of 3α,6β‐Dihydroxyandrostan‐17‐one 3‐Glucuronides for the Detection of Testosterone Misuse

AbstractThe convenient synthesis of two 3‐glucuronide conjugates of 6β‐hydroxyandrosterone (6OH‐And‐3G 2) and 6β‐hydroxyetiocholanolone (6OH‐Etio‐3G 3) is reported. The conjugates are identified as long‐term markers of endogenous androgenic anabolic steroid abuse in doping control studies. Their resistance to enzymatic hydrolysis by E. coli β‐glucuronidase means they may be missed by conventional GC‐MS analysis protocols. One promising strategy to quantify these markers is by direct methods, which requires sufficient quantities of high purity reference materials. Our convergent synthesis features concurrent stereoselective introduction of 5α/5β hydrogen and 6β‐hydroxy groups on the steroid skeleton, and a mild Schmidt trichloroacetimidate glycosylation strategy.

Enhancing the Performance of Analytical Methods to Combat Doping in Sport

Ion mobility–mass spectrometry (IM–MS) has become a cornerstone bioanalytical technique over the last two decades. Major advances have included new technology and software that enabled higher resolving power measurements; however, chemistry-based approaches, such as derivatization reactions, have also shown tremendous promise. This article demonstrates our work using IM–MS to detect anabolic steroids and describes how this technology could one day find its way into the anti-doping world.

A quantitative approach for mathematical model of doping in high performance sport

Doping or administration of substances for purpose of improving the performances in various sport has a long history, even in the modern era to most common association of doping is connected to professional cycling. The usage of doping substances has become a major public health issue. Also, some abuse of doping substance was a major cause of death in some cases. As results of effort in fighting against doping, World Anti-Doping Agency (WADA) coordinated the implementation of the athlete hematological passport, or more commonly athlete biological passport (ABP). The decision of doped or not doped based on biological markers is made using Bayesian inference. But the code of implementation and the code of software used in decisions is not available to the public, and as sequels there are also some approaches in research, as methods based on psychological questionaries. In this case, the statistical analysis using structural equation models offer a valuable tool for management of antidoping policies in order to reduce this phenomenon. Material and method. In this paper, a novel method is novel model for quantitative analysis of doping is proposed. The model doesn’t use the biological markers but the effect of this as declared doping persons in a quantitative analysis over a lot of high performance athletes. The model is based on nonlinear equations as result of compartmental model with quantitative time dependent evolution of them. Results and discussions. The model was implemented in MATLAB and numerical solutions were obtained using ODE (Ordinary Differential Equations) tool. The stability of model was analyzed using analogies with an epidemic SIRS compartmental model. The implementation uses a GUI (Graphical User Interface) that make the application user friendly. The fitting tools model is in stage of implementation and the parameter are finding out using a data collected and optimization tools (an objective function and genetic algorithms in order to prevent the phenomenon in a trapping minima). Conclusions. The result is very encouraging, the model fit 99.7% in preliminary set of data. The future development will include the fitting module and a set of results structured on various high-performance sports. Keywords: doping in sport, compartmental models, anti-doping policy, modeling and simulation, data fit-ting

The attitudes and beliefs of paralympians and athletes with disabilities on doping in sport

Background: Modern sport is focused on success, generating high-level performance, and crossing physiological barriers. Breaking records and winning is associated with financial benefits but it also raises the social prestige of the athlete. Some competitors try every possible means in order to achieve better results and success in sport, including using doping. This study aims to analyze the opinions and attitudes of elite athletes with disabilities. Methods: Study participants included a group of elite Polish team members competing in international competitions (including Paralympics) in various sports. The research sample consisted of 100 individuals, including 67 men (67%) and 33 women (33%). The descriptive exploratory design used an instrument that combined a validated questionnaire (Performance Enhancement Attitude Scale; PEAS) with a special questionnaire adapted to athletes with disabilities. Results: The overall mean score from the PEAS scale (range, 11–66, with higher scores representing more permissive attitudes towards doping) was 20.61 11.35, with 21.20 10.96 in men, 19.39 12.20 in women, 20.46 10.92 in Paralympians and world championship participants (Masters), and 21.14 13.16 in other competitors. For more than half (58%) of respondents, doping is uncommon in sports, and sports success can be achieved without doping (88%). The vast majority of respondents (90%) do not know people who use doping. Conclusion: The lack of response and hesitation in answers suggest that the respondents did not use doping but also were unaware of doping. Therefore, it seems necessary to implement anti-doping education for athletes with disabilities from the early stages of their sports careers.

Martial Arts and Doping (the case of Sambo)

Background. Today, the problem of doping is the most well-known negative phenomenon in modern sport, which has become widespread in response to its active commercialization. The majority of people would agree that doping issue has moral and ethical basis, therefore the educational component of anti-doping policies is most promising in achieving the desired result – doping-free sport. &#x0D; Research purpose. The study was aimed to investigate the peculiarities of the ideas sambo athletes may have about the problem of doping in modern sport.&#x0D; Materials and methods. The study involved 97 highly professional sambo athletes from 21 countries, namely Russia, Ukraine, Mexico, Japan, the USA, Canada, Cuba, Guatemala, Republic of Korea, Colombia, Paraguay, Venezuela, Peru, Brazil, Nicaragua, El Salvador, Dominican Republic, Puerto Rico, Honduras, Uruguay, and Costa Rica.&#x0D; Results. A survey conducted among the professional sambo athletes, participants of the 2018 World Cup, made it possible to establish their knowledge about and their attitude to doping. It became known that 76.29% of the athletes were well familiar with the doping control procedure, while 23.71% were not. At the same time, 78.35% of the respondents believed that they knew their rights and responsibilities during the doping control procedure, and 21.65% of the athletes did not. 77.32% of the respondents knew the organizer of doping control and 22.68% did not.&#x0D; Conclusions. The analysis of the study results and WADA statistics give grounds to state that the problem of doping in modern athletes remains an urgent problem in professional sports, including sambo.

Multi-analyte screening of small peptides by alkaline pre-activated solid phase extraction coupled with liquid chromatography-high resolution mass spectrometry in doping controls

Peptidic drugs with wide spectrum of physiological activity are of interest for cheating athletes and can be misused as doping in sports. A growing number of small peptide drugs capable of enhancing performance are included in the prohibited list issued by World Anti-Doping Agency (WADA), therefore the improvement of the detection methods is constantly needed. In the present study, a screening assay was developed comprising 54 prohibited small peptides and the related substances in urine by means of the alkaline pre-activated weak cation exchange-solid phase extraction (WCX-SPE) with liquid chromatography-high resolution mass spectrometry (LCHRMS). This method performed good enrichment and purification effect of traditional WCX for basic peptides, and also improve the purification power of acidic peptides, which significantly expanded the coverage of detection substances. The method was validated in accordance with WADA relevant criteria and validated with a main focus on qualitative parameters including selectivity, limits of detection (0.02–0.2 ng/mL), linearity (0.1–20 ng/mL for 46 analytes and 0.2–20 ng/mL for 9 analytes), accuracy and precision (RE% and RSD% < 20% at 1, 5 and 10 ng/mL), recovery (39.2%–100.1% except for the TB500(1–2) free acid: 9.2%), matrix effects (ion suppression effect: 0 to 49.4% and ion enhancement effect: 100% and 264.6%), carryover, reliability and sample extract stability. As a proof-of-principle, urine samples from two patients received a single injection of leuprorelin acetate microspheres (3.75 mg) 30 days before were analyzed and the results proved the applicability of the method.

Substances and Methods Prohibited for Use in Sport: Object or Means of Committing Crimes?

Countering doping in modern sport plays an important role. In order to effectively apply various types of legal liability, it is necessary to determine what substances and methods are prohib­ited in sport. Since the advent of full-fledged anti-doping rules (1967), the list of such substances and methods, as well as the doping control system, have been dynamically changing. The anti-doping system received significant development after the formation of the World Anti-Doping Agency (1999). For the purposes of bringing to criminal responsibility, there is a list, initially somewhat reduced, sub­sequently substantially supplemented. The legislator's decision to create a special list raises questions. Therefore, the Author considers various approaches to such substances and methods and determines their place in the crime. In the first part of the work, prohibited substances and methods are analyzed and their characteristics are given. In the second part, the Author explores the need for a specific list of prohibited substances or methods for the purpose of criminalizing anti-doping rule violations. In ad­dition, it distinguishes between narcotic, psychotropic, potent substances, on the one hand, and prohib­ited substances, on the other. The Author comes to the conclusion that the existence of a special list for the purposes of implementing Art. 2301 and 2302 of the Criminal Code of the Russian Federation is inap­propriate due to the specifics of the acts themselves, as this limits the possibility of being held liable for the use of analogues of substances. In the third part of the work, the Author explores the understanding of prohibited substances or methods as the subject of a crime. It is concluded that to consider prohibited substances or methods as the subject of crimes under Art. 2301 and 2302 of the Criminal Code of the Rus­sian Federation is impossible, since the crime is not directly directed at them. Accordingly, in the fourth part of the work it is substantiated that such substances and methods constitute the means of committing a crime. As a result, the Author comes to the conclusion that it is necessary to change the legislative regulation of criminal liability for violation of anti-doping rules.

Self administration of topical steroids in face: A cross-sectional study from a tertiary care hospital in Northeast India

Topical steroid (TS) creams are easily available in pharmacies all over India, as OTC (over the counter) drugs. So are easily being misused even without the dermatologist’s prescription, which leads to side effects pertaining to the lack of awareness about the contraindications and adverse effects of the topical steroids. This was a cross-sectional, questionnaire-based study, conducted from July 2021 to December 2021, at the outpatient Department of Dermatology, Venereology and Leprosy, of a tertiary care hospital in North East India. Patients of both sexes (males and females), 15 years onwards were included in this study who presented with any kind of facial dermatoses resulting from use of topical steroid on face. Out of 300 patients who misused TS, majority were females (72%). The most common brand used was Betnovate C which contained betamethasone (0.1% w/w) &amp; clioquinol (3% w/w). The average duration of use was less than 6 months (51%), shortest being 15 days and longest being 4 years. The most common reason for misuse was acne (38%) followed by fairness (22%) and the most common effect observed after misuse was acne form eruptions (25%) followed by dyspigmentation (16%). Most of the users had attained education till primary school. Abuse was commonly from purchase of the drug OTC or from pharmacists. As steroid abuse is increasing alarmingly, awareness about its various adverse effects becomes necessary.

Sports Illustrated tackles drugs in sports: examining the influence of a seminal magazine series

ABSTRACT In 1969, author Bil Gilbert wrote a three-part series on performance-enhancing drugs (PEDs) for Sports Illustrated. Garry Valk, publisher of the magazine, characterised the series as ‘the first comprehensive and authoritative study of a vastly complicated problem.’ This study examined the influence of the Gilbert series on newspaper coverage of PEDs and the reactions of policymakers to both the magazine investigation and subsequent newspaper reporting. Coverage of amphetamines and anabolic steroids increased significantly in the three years following the series, while references to anti-inflammatory drugs and painkillers decreased. These patterns reflected an apparent shift from restorative aids to additive substances following the magazine investigation. Additionally, one in three sources cited in Sports Illustrated served as a news source in subsequent press coverage, and some of those sources then testified at government hearings held at the state and national levels. Government hearings on PEDs appeared to function more symbolically than substantively, as did anti-drug campaigns and resolutions in sporting organisations. The study considers implications for sport history and the regulation of performance-enhancing drugs.