Chemistry:Performance-enhancing substance

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Short description: Substance used to improve any form of activity performance in humans

Performance-enhancing substances, also known as performance-enhancing drugs (PEDs),[1] are substances that are used to improve any form of activity performance in humans. A well-known example of cheating in sports involves doping in sport, where banned physical performance-enhancing drugs are used by athletes and bodybuilders. Athletic performance-enhancing substances are sometimes referred as ergogenic aids.[2][3] Cognitive performance-enhancing drugs, commonly called nootropics,[4] are sometimes used by students to improve academic performance. Performance-enhancing substances are also used by military personnel to enhance combat performance.[5]

The use of performance-enhancing drugs spans the categories of legitimate use and substance abuse.

Definition

The classifications of substances as performance-enhancing substances are not entirely clear-cut and objective. As in other types of categorization, certain prototype performance enhancers are universally classified as such (like anabolic steroids), whereas other substances (like vitamins and protein supplements) are virtually never classified as performance enhancers despite their effects on performance. As is usual with categorization, there are borderline cases; caffeine, for example, is considered a performance enhancer by some but not others.[6]

Types

The phrase has been used to refer to several distinct classes of drugs:

Anabolic steroids

Main page: Chemistry:Anabolic steroid

Anabolic steroids are synthetically derived from testosterone and modified to have greater anabolic effects.[7] They work by increasing the concentration of nitrogen in the muscle which inhibits catabolic glucocorticoid binding to muscle.[8] This ultimately prohibits the breakdown of muscle and preserves muscle mass.[9] Examples of anabolic steroids include: oxandrolone, stanozolol and nandrolone.[7] Anabolic steroids can be taken through a transdermal method, orally, or through injection. Injectable forms of the steroid are the most potent and long-lasting.[10] In general, potential side effects include: muscle hypertrophy, acne, hypertension, elevated cholesterol, thrombosis, decreased high-density lipoproteins, altered libido, hepatic carcinoma, cholestasis, peliosis hepatitis, septic arthritis, Wilm's tumor, psychosis, aggression, addiction, and depression.[11] Potential side effects specifically in males include: male pattern baldness, oligospermia, prostate hypertrophy, testicular atrophy, and prostate cancer.[12] Potential side specifically in females include: hirsutism, uterine atrophy, amenorrhea, breast atrophy, and thickening of vocal cords (voice deepening).[12] Urine samples are tested to determine the ratio of testosterone glucuronide to epitestosterone glucuronide, which should be 3:1. Any ratio of 4:1 or greater is considered a positive test.[13] The 1988 Anti-Drug Abuse Act and 1990 Anabolic Steroid Act both deemed anabolic steroids as an illegal substance when not used for disease treatment.[10]

Stimulants

Main page: Chemistry:Stimulant

Stimulants improve focus and alertness. Low (therapeutic) doses of dopaminergic stimulants (e.g., reuptake inhibitors and releasing agents) also promote mental and athletic performance, as cognitive enhancers and ergogenic aids respectively, by improving muscle strength and endurance while decreasing reaction time and fatigue;.[3][14][15] Stimulants are commonly used in lengthy exercises that require short bursts (e.g., tennis, team sports, etc.).[16] Stimulants work by increasing catecholamine levels and agonistic activity at the adrenergic receptors.[17] Examples of stimulants include: Caffeine,[2] ephedrine, methylphenidate and amphetamine.[3][14][15][18][19] Potential side effects include: hypertension, insomnia, headaches, weight loss, arrhythmia, tremors, anxiety, addiction, and strokes.[20] Some stimulants are allowed in competitive sports and are widely accessible, though may also be monitored by the World Anti-Doping Agency (WADA), such as caffeine.[2] Others are banned as per the (WADA) (e.g., cocaine, amphetamines, ephedrine, etc.).[21][22]

Ergogenic aids

Ergogenic aids, or athletic performance-enhancing substances, include a number of drugs with various effects on physical performance. Drugs such as amphetamine and methylphenidate increase power output at constant levels of perceived exertion and delay the onset of fatigue,[18][19][23] among other athletic-performance-enhancing effects;[3][14][15] bupropion also increases power output at constant levels of perceived exertion, but only during short term use.[23]

Examples

  • Human biomolecules – creatine and β-hydroxy β-methylbutyrate are naturally occurring compounds in humans that have well-established ergogenic effects and effects on body composition when supplemented.[24]
  • Creatine: one of the most popular nutritional supplements, it contributes to 400 million dollars in sales globally every year.[25] It is a nonessential amino acid that helps to improve an athlete's performance during short-term, high intensity exercises such as weightlifting.[26] Supplementation of creatine increases skeletal muscle creatine levels, this boosts performance by increasing the rate at which adenosine triphosphate can be replenished from adenosine diphosphate, thereby increasing maximal power output.[25] Potential side effects include gastrointestinal cramps, weight gain, fatigue, and diarrhea.[27] Creatine is currently not recognized as a prohibited substance and can be purchased as a legal dietary supplement.[28]
  • Human Growth Hormone (hGH): endogenous hormone that can help decrease fat mass while increasing lean body mass.[29] hGH is one of the most commonly used substances among professional athletes because it has a small window for detection.[29] It works by promoting the release of IGF-1, insulin-like growth factor, the release of which has anabolic effects on the body.[30] Potential side effects include: cardiomyopathy, diabetes, renal failure, and hepatitis.[31] If not prescribed by a professional, it is a banned substance in competition per WADA.[22] Despite its small window for detection, two primary methods of testing have been developed for hGH, one being an isoform test which detects changes in growth hormone structure in the blood,[32] and the markers test, which detects changes in serum protein ratios.[32]

Adaptogens

Main page: Unsolved:Adaptogen

Adaptogens are plants that support health through nonspecific effects, neutralize various environmental and physical stressors while being relatively safe and free of side effects.[33] As of 2008, the position of the European Medicines Agency was that "The principle of an adaptogenic action needs further clarification and studies in the pre-clinical and clinical area. As such, the term is not accepted in pharmacological and clinical terminology that is commonly used in the EU."[34]

Actoprotectors

Main page: Unsolved:Actoprotector

Actoprotectors or synthetic adaptogens are compounds that enhance an organism's resilience to physical stress without increasing heat output. Actoprotectors are distinct from other doping compounds in that they increase physical and psychological resilience via non-exhaustive action. Actoprotectors such as bemethyl and bromantane have been used to prepare athletes and enhance performance in Olympic competition.[35][36] However, only bromantane has been placed on the World Anti-Doping Agency's banned list.[36]

Nootropics

Main page: Chemistry:Nootropic

Nootropics, or "cognition enhancers", are substances that are claimed to benefit overall cognition by improving memory (e.g., increasing working memory capacity or updating) or other aspects of cognitive control (e.g., inhibitory control, attentional control, attention span, etc.).[4][37]

CNS agents

Painkillers

Main page: Biology:Analgesic

Allows performance beyond the usual pain threshold. Some painkillers raise blood pressure, increasing oxygen supply to muscle cells. Painkillers used by athletes range from common over-the-counter medicines such as NSAIDs (such as ibuprofen) to powerful prescription narcotics.

Sedatives and anxiolytics

Main pages: Chemistry:Sedative and Chemistry:Anxiolytic

Sedatives and anxiolytics are used in sports like archery which require steady hands and accurate aim, and also to overcome excessive nervousness or discomfort for more dangerous sports. Diazepam, nicotine, and propranolol are common examples. Ethanol, the most commonly used substance by athletes, can be used for cardiovascular improvements though has significant detrimental effects. Ethanol was formerly banned by WADA during performance for athletes performing in aeronautics, archery, automobile, karate, motorcycling and powerboating, but was taken off the ban list in 2017. It is detected by breath or blood testing. Cannabis is banned at all times for an athlete by WADA, though performance-enhancing effects have yet to be studied. Cannabis and nicotine are detected through urine analysis.[2][38]

Blood boosters

Blood doping agents increase the oxygen-carrying capacity of blood beyond the individual's natural capacity.[39] They are used in endurance sports like long-distance running, cycling, and Nordic skiing. Recombinant human erythropoietin (rhEPO) is one of the most widely known drugs in this class.[24][39] The Athlete Biological Passport is the only indirect testing method for detection of blood doping.

Erythropoietin

Main page: Biology:Erythropoietin

Erythropoietin, or EPO, is a hormone that helps increase the production of red blood cells which increases the delivery of oxygen to muscles.[40] It is commonly used among endurance athletes such as cyclists.[40] It functions by protecting red blood cells against destruction whilst simultaneously stimulating bone marrow cells to produce more red blood cells.[41] Potential side effects include: dehydration and an increase in blood viscosity which could result in a pulmonary embolism or stroke.[42] Per the WADA, it is a banned substance.[22] Urine samples can be tested via electrophoresis, and blood samples via indirect markers.[example needed][43]

Gene doping

Main page: Biology:Gene doping

Gene doping agents are a relatively recently described class of athletic performance-enhancing substances.[24] These drug therapies, which involve viral vector-mediated gene transfer, are not known to currently be in use (As of 2020).[24][44]

Prohormones

Main page: Biology:Prohormone

Also known as anabolic steroid precursors, they promote lean body mass.[45] Once in the body, these precursors are converted to testosterone and because they increase endogenous testosterone.[46] The desired effects of steroid precursors however, are often not seen as they do not bind well to androgen receptors.[46] Examples of prohormones include norandrostendione, androstenediol, and dehydroepiandrosterone (DHEA).[45] These steroids have little desired effect compared to anabolic steroids, but have the same side effects.[47] Androstenedione in 2005 became classified as a controlled substance by WADA, however DHEA can still be obtained legally as an over-the-counter nutritional supplement.[48]

History

While the use of PEDs has expanded in recent times, the practice of using substances to improve performance has been around since the Ancient Olympic Games.[49] In the Olympic Games of 668 BC, Charmis had consumed a diet consisting of dried figs which was a significant factor in winning the 200-yard stade race.[50][39] Ancient Greek athletes at the time also incorporated stimulants such as wine and brandy into their training routines.[51] Stimulants derived from plants (e.g., Cola Nitida, Bufotein, etc.) were used by the Roman Gladiators to overcome injuries and fatigue.[52]

In the late 19th century as modern medicine and pharmacology were developing, PEDs saw an increase in use.[53] Supplements were now exclusively being used to enhance muscular work capacity.[53] The main stimulants being used included alcoholic drinks, caffeine, and mixtures created by the athletic trainers (e.g., strychnine tablets made of cocaine and brandy).[54] Testosterone was also a commonly taken stimulant, however, it was more difficult to obtain.[54] In 1889, a three-week program began where an athlete injected themselves with blood from the testicular veins, semen, and fluids from the testicles of a dog or guinea pig.[55] By 1895, it had been assessed that testicular extracts did in fact improve athletic performance by increasing muscular strength.[56]

In the 20th century, testosterone was isolated and characterized by scientists.[57] In 1941, the first record of synthesized testosterone use occurred when a horse was given testosterone which successfully improved its race performance.[58] Sports trainers soon after began advocating for testosterone use.[57] Images of bodybuilders with massive muscles began circulating which further perpetuated a desire among athletes to use testosterone.[55][57] In 1967, the first prohibited substance list and anti-doping measures were implemented at the 1968 Olympics.[39]

In the 1980s, the main PEDs were cortisone and anabolic steroids.[59] In 1988, the United States Congress established the Anti-Drug Abuse Act to criminalize the distribution and possession of non-medical anabolic steroids.[60] In 1999, WADA was formed to address the escalating use of substances in sports, particularly after the 1998 doping scandal in cycling.[60]

Risk factors

Adolescents are the most vulnerable group when it comes to taking performance-enhancing substances.[61] This is in part due to the significance placed on physical appearance by this age group as well as feelings of invincibility combined with a lack of knowledge surrounding long-term consequences.[61] Studies have shown that the most common gendered risk factors include being an adolescent female dissatisfied with their body weight or an adolescent male who perceives larger body sizes as the ideal.[62] Having a negative body image or a history of depression can also be a significant risk factor.[62] These are further exacerbated by parental pressures surrounding appearance, media influence, and peer pressure.[61][52] Studies show that adolescent males who engage with fitness magazines are twice as likely to use performance-enhancing substances.[52] Adolescents who partake in competitive sports are at a particularly high risk, with those involved in gridiron football, basketball, wrestling, baseball, and gymnastics at the top.[52]

Usage in sport

Main page: Biology:Doping in sport

In sports, the term performance-enhancing drugs is popularly used in reference to anabolic steroids or their precursors (hence the colloquial term "steroids"); anti-doping organizations apply the term broadly.[63] Agencies such as the WADA and United States Anti-Doping Agency try to prevent athletes from using these drugs by performing drug tests. When medical exemptions are granted they are called therapeutic use exemptions.[64][65]

See also

References

  1. ↑ "Effects of Performance-Enhancing Drugs | USADA". May 2019. http://www.usada.org/substances/effects-of-performance-enhancing-drugs/. 
  2. ↑ 2.0 2.1 2.2 2.3 "The effects of caffeine, nicotine, ethanol, and tetrahydrocannabinol on exercise performance". Nutrition & Metabolism 10 (1): 71. December 2013. doi:10.1186/1743-7075-10-71. PMID 24330705. 
  3. ↑ 3.0 3.1 3.2 3.3 "Nutritional supplements and ergogenic AIDS". Primary Care 40 (2): 487–505. June 2013. doi:10.1016/j.pop.2013.02.009. PMID 23668655. "Amphetamines and caffeine are stimulants that increase alertness, improve focus, decrease reaction time, and delay fatigue, allowing for an increased intensity and duration of training ...
    Physiologic and performance effects [of amphetamines]
     • Amphetamines increase dopamine/norepinephrine release and inhibit their reuptake, leading to central nervous system (CNS) stimulation
     • Amphetamines seem to enhance athletic performance in anaerobic conditions 39 40
     • Improved reaction time
     • Increased muscle strength and delayed muscle fatigue
     • Increased acceleration
     • Increased alertness and attention to task".     
  4. ↑ 4.0 4.1 "Smart drugs and synthetic androgens for cognitive and physical enhancement: revolving doors of cosmetic neurology". Current Neuropharmacology 13 (1): 5–11. January 2015. doi:10.2174/1570159X13666141210221750. PMID 26074739. "Cognitive enhancement can be defined as the use of drugs and/or other means with the aim to improve the cognitive functions of healthy subjects in particular memory, attention, creativity and intelligence in the absence of any medical indication. ... The first aim of this paper was to review current trends in the misuse of smart drugs (also known as Nootropics) presently available on the market focusing in detail on methylphenidate, trying to evaluate the potential risk in healthy individuals, especially teenagers and young adults.". 
  5. ↑ Anon. Better Fighting Through Chemistry? The Role of FDA Regulation in Crafting the Warrior of the Future. Food and Drug Law: Final Paper. 8 March 2004.
  6. ↑ "Caffeine and Sports Performance". Vanderbilt.edu. http://www.vanderbilt.edu/AnS/psychology/health_psychology/caffeine_sports.htm. 
  7. ↑ 7.0 7.1 Kicman, A T (June 2008). "Pharmacology of anabolic steroids". British Journal of Pharmacology 154 (3): 502–521. doi:10.1038/bjp.2008.165. ISSN 0007-1188. PMID 18500378. 
  8. ↑ Ganesan, Kavitha; Rahman, Sajedur; Zito, Patrick M. (2022), "Anabolic Steroids", StatPearls (Treasure Island (FL): StatPearls Publishing), PMID 29494025, http://www.ncbi.nlm.nih.gov/books/NBK482418/, retrieved 2022-04-12 
  9. ↑ "Performance Enhancing Anabolic Steroid Abuse in Women" (in en). https://www.acog.org/en/clinical/clinical-guidance/committee-opinion/articles/2011/04/performance-enhancing-anabolic-steroid-abuse-in-women. 
  10. ↑ 10.0 10.1 Reardon, Claudia L; Creado, Shane (2014-08-14). "Drug abuse in athletes". Substance Abuse and Rehabilitation 5: 95–105. doi:10.2147/SAR.S53784. ISSN 1179-8467. PMID 25187752. 
  11. ↑ van Amsterdam, Jan; Opperhuizen, Antoon; Hartgens, Fred (June 2010). "Adverse health effects of anabolic-androgenic steroids". Regulatory Toxicology and Pharmacology 57 (1): 117–123. doi:10.1016/j.yrtph.2010.02.001. ISSN 1096-0295. PMID 20153798. https://pubmed.ncbi.nlm.nih.gov/20153798/. 
  12. ↑ 12.0 12.1 Albano, Giuseppe Davide; Amico, Francesco; Cocimano, Giuseppe; Liberto, Aldo; Maglietta, Francesca; Esposito, Massimiliano; Rosi, Giuseppe Li; Di Nunno, Nunzio et al. (2021-01-19). "Adverse Effects of Anabolic-Androgenic Steroids: A Literature Review". Healthcare 9 (1): 97. doi:10.3390/healthcare9010097. ISSN 2227-9032. PMID 33477800. 
  13. ↑ "Epitestosterone - an overview | ScienceDirect Topics". https://www.sciencedirect.com/topics/neuroscience/epitestosterone. 
  14. ↑ 14.0 14.1 14.2 "Attention-deficit hyperactivity disorder and the athlete: new advances and understanding". Clinics in Sports Medicine 30 (3): 591–610. July 2011. doi:10.1016/j.csm.2011.03.007. PMID 21658550. "In 1980, Chandler and Blair47 showed significant increases in knee extension strength, acceleration, anaerobic capacity, time to exhaustion during exercise, pre-exercise and maximum heart rates, and time to exhaustion during maximal oxygen consumption (VO2 max) testing after administration of 15 mg of dextroamphetamine versus placebo. Most of the information to answer this question has been obtained in the past decade through studies of fatigue rather than an attempt to systematically investigate the effect of ADHD drugs on exercise. ... In 2008, Roelands and colleagues53 studied the effect of reboxetine, a pure NE reuptake inhibitor, similar to atomoxetine, in 9 healthy, well-trained cyclists. They too exercised in both temperate and warm environments. They showed decreased power output and exercise performance at both 18 and 30 degrees centigrade. Their conclusion was that DA reuptake inhibition was the cause of the increased exercise performance seen with drugs that affect both DA and NE (MPH, amphetamine, and bupropion).". 
  15. ↑ 15.0 15.1 15.2 "Executive dysfunction in Parkinson's disease and timing deficits". Frontiers in Integrative Neuroscience 7: 75. October 2013. doi:10.3389/fnint.2013.00075. PMID 24198770. "Manipulations of dopaminergic signaling profoundly influence interval timing, leading to the hypothesis that dopamine influences internal pacemaker, or "clock," activity. For instance, amphetamine, which increases concentrations of dopamine at the synaptic cleft advances the start of responding during interval timing, whereas antagonists of D2 type dopamine receptors typically slow timing;... Depletion of dopamine in healthy volunteers impairs timing, while amphetamine releases synaptic dopamine and speeds up timing.". 
  16. ↑ "Office of Dietary Supplements - Dietary Supplements for Exercise and Athletic Performance" (in en). https://ods.od.nih.gov/factsheets/ExerciseAndAthleticPerformance-HealthProfessional/. 
  17. ↑ Farzam, Khashayar; Faizy, Rubina M.; Saadabadi, Abdolreza (2022), "Stimulants", StatPearls (Treasure Island (FL): StatPearls Publishing), PMID 30969718, http://www.ncbi.nlm.nih.gov/books/NBK539896/, retrieved 2022-04-12 
  18. ↑ 18.0 18.1 "Neurophysiological determinants of theoretical concepts and mechanisms involved in pacing". Sports Medicine 43 (5): 301–311. May 2013. doi:10.1007/s40279-013-0030-4. PMID 23456493. 
  19. ↑ 19.0 19.1 "Is it time to turn our attention toward central mechanisms for post-exertional recovery strategies and performance?". Frontiers in Physiology 6: 79. March 2015. doi:10.3389/fphys.2015.00079. PMID 25852568. "Aside from accounting for the reduced performance of mentally fatigued participants, this model rationalizes the reduced RPE and hence improved cycling time trial performance of athletes using a glucose mouthwash (Chambers et al., 2009) and the greater power output during a RPE matched cycling time trial following amphetamine ingestion (Swart, 2009). ... Dopamine stimulating drugs are known to enhance aspects of exercise performance (Roelands et al., 2008)". 
  20. ↑ Reardon, Claudia L.; Factor, Robert M. (May 2016). "Considerations in the Use of Stimulants in Sport". Sports Medicine (Auckland, N.Z.) 46 (5): 611–617. doi:10.1007/s40279-015-0456-y. ISSN 1179-2035. PMID 26712509. https://pubmed.ncbi.nlm.nih.gov/26712509/. 
  21. ↑ Cappelletti, Simone; Daria, Piacentino; Sani, Gabriele; Aromatario, Mariarosaria (January 2015). "Caffeine: Cognitive and Physical Performance Enhancer or Psychoactive Drug?". Current Neuropharmacology 13 (1): 71–88. doi:10.2174/1570159X13666141210215655. ISSN 1570-159X. PMID 26074744. 
  22. ↑ 22.0 22.1 22.2 "The Prohibited List" (in en). https://www.wada-ama.org/en/prohibited-list. 
  23. ↑ 23.0 23.1 "Neurophysiological effects of exercise in the heat". Scandinavian Journal of Medicine & Science in Sports 25 (Suppl 1): 65–78. June 2015. doi:10.1111/sms.12350. PMID 25943657. "Physical fatigue has classically been attributed to peripheral factors within the muscle (Fitts, 1996), the depletion of muscle glycogen (Bergstrom & Hultman, 1967) or increased cardiovascular, metabolic, and thermoregulatory strain (Abbiss & Laursen, 2005; Meeusen et al., 2006b). In recent decennia however, it became clear that the central nervous system plays an important role in the onset of fatigue during prolonged exercise (Klass et al., 2008), certainly when ambient temperature is increased ... 5-HT, DA, and NA have all been implicated in the control of thermoregulation and are thought to mediate thermoregulatory responses, certainly since their neurons innervate the hypothalamus (Roelands & Meeusen, 2010). ... This indicates that subjects did not feel they were producing more power and consequently more heat. The authors concluded that the "safety switch" or the mechanisms existing in the body to prevent harmful effects are overridden by the drug administration (Roelands et al., 2008b). Taken together, these data indicate strong ergogenic effects of an increased DA concentration in the brain, without any change in the perception of effort. ... The combined effects of DA and NA on performance in the heat were studied by our research group on a number of occasions. ... the administration of bupropion (DA/NA reuptake inhibitor) significantly improved performance. Coinciding with this ergogenic effect, the authors observed core temperatures that were much higher compared with the placebo situation. Interestingly, this occurred without any change in the subjective feelings of thermal sensation or perceived exertion. Similar to the methylphenidate study (Roelands et al., 2008b), bupropion may dampen or override inhibitory signals arising from the central nervous system to cease exercise because of hyperthermia, and enable an individual to continue maintaining a high power output". 
  24. ↑ 24.0 24.1 24.2 24.3 "Performance-enhancing substances in sports: a review of the literature". Sports Medicine 45 (4): 517–531. April 2015. doi:10.1007/s40279-015-0308-9. PMID 25663250. 
  25. ↑ 25.0 25.1 Butts, Jessica; Jacobs, Bret; Silvis, Matthew (2017-10-23). "Creatine Use in Sports". Sports Health 10 (1): 31–34. doi:10.1177/1941738117737248. ISSN 1941-7381. PMID 29059531. 
  26. ↑ Kreider, Richard B. (February 2003). "Effects of creatine supplementation on performance and training adaptations". Molecular and Cellular Biochemistry 244 (1–2): 89–94. doi:10.1023/A:1022465203458. ISSN 0300-8177. PMID 12701815. https://pubmed.ncbi.nlm.nih.gov/12701815/. 
  27. ↑ Francaux, Marc; Poortmans, Jacques R. (December 2006). "Side effects of creatine supplementation in athletes". International Journal of Sports Physiology and Performance 1 (4): 311–323. doi:10.1123/ijspp.1.4.311. ISSN 1555-0265. PMID 19124889. https://pubmed.ncbi.nlm.nih.gov/19124889/. 
  28. ↑ Perishable (2021-03-10). "What Do Athletes Need to Know About Creatine? | USADA" (in en-US). https://www.usada.org/spirit-of-sport/education/athletes-need-know-creatine/. 
  29. ↑ 29.0 29.1 Saugy, M; Robinson, N; Saudan, C; Baume, N; Avois, L; Mangin, P (July 2006). "Human growth hormone doping in sport". British Journal of Sports Medicine 40 (Suppl 1): i35–i39. doi:10.1136/bjsm.2006.027573. ISSN 0306-3674. PMID 16799101. 
  30. ↑ Laron, Z (October 2001). "Insulin-like growth factor 1 (IGF-1): a growth hormone". Molecular Pathology 54 (5): 311–316. doi:10.1136/mp.54.5.311. ISSN 1366-8714. PMID 11577173. 
  31. ↑ Siebert, David M.; Rao, Ashwin L. (October 2018). "The Use and Abuse of Human Growth Hormone in Sports". Sports Health 10 (5): 419–426. doi:10.1177/1941738118782688. ISSN 1941-0921. PMID 29932857. 
  32. ↑ 32.0 32.1 Baumann, Gerhard P. (April 2012). "Growth hormone doping in sports: a critical review of use and detection strategies". Endocrine Reviews 33 (2): 155–186. doi:10.1210/er.2011-1035. ISSN 1945-7189. PMID 22368183. 
  33. ↑ "New insights into dietary supplements used in sport: active substances, pharmacological and side effects". Current Drug Targets 14 (9): 1079–1092. August 2013. doi:10.2174/1389450111314090016. PMID 23574283. 
  34. ↑ "Reflection Paper on the Adaptogenic Concept". European Medicines Agency Committee on Herbal Medicinal Products. 8 May 2008. http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2009/09/WC500003646.pdf. 
  35. ↑ Oliynyk, Sergiy; Oh, Seikwan (September 2012). "The pharmacology of actoprotectors: practical application for improvement of mental and physical performance". Biomolecules & Therapeutics 20 (5): 446–456. doi:10.4062/biomolther.2012.20.5.446. ISSN 1976-9148. PMID 24009833. 
  36. ↑ 36.0 36.1 Burnat, P.; Payen, A.; Le Brumant-Payen, C.; Hugon, M.; Ceppa, F. (1997-09-27). "Bromontan, a new doping agent". Lancet 350 (9082): 963–964. doi:10.1016/s0140-6736(05)63310-7. ISSN 0140-6736. PMID 9314900. 
  37. ↑ "Prescription Stimulants' Effects on Healthy Inhibitory Control, Working Memory, and Episodic Memory: A Meta-analysis". Journal of Cognitive Neuroscience 27 (6): 1069–1089. June 2015. doi:10.1162/jocn_a_00776. PMID 25591060. https://repository.upenn.edu/cgi/viewcontent.cgi?article=1141&context=neuroethics_pubs. "The present meta-analysis was conducted to estimate the magnitude of the effects of methylphenidate and amphetamine on cognitive functions central to academic and occupational functioning, including inhibitory control, working memory, short-term episodic memory, and delayed episodic memory. In addition, we examined the evidence for publication bias. Forty-eight studies (total of 1,409 participants) were included in the analyses. We found evidence for small but significant stimulant enhancement effects on inhibitory control and short-term episodic memory. Small effects on working memory reached significance, based on one of our two analytical approaches. Effects on delayed episodic memory were medium in size. However, because the effects on long-term and working memory were qualified by evidence for publication bias, we conclude that the effect of amphetamine and methylphenidate on the examined facets of healthy cognition is probably modest overall. In some situations, a small advantage may be valuable, although it is also possible that healthy users resort to stimulants to enhance their energy and motivation more than their cognition. ... Earlier research has failed to distinguish whether stimulants' effects are small or whether they are nonexistent (Ilieva et al., 2013; Smith & Farah, 2011). The present findings supported generally small effects of amphetamine and methylphenidate on executive function and memory. Specifically, in a set of experiments limited to high-quality designs, we found significant enhancement of several cognitive abilities. ...

    The results of this meta-analysis cannot address the important issues of individual differences in stimulant effects or the role of motivational enhancement in helping perform academic or occupational tasks. However, they do confirm the reality of cognitive enhancing effects for normal healthy adults in general, while also indicating that these effects are modest in size.".     
  38. ↑ "“No need for laboratory to test for alcohol” - WADA". www.insidethegames.biz. 5 October 2017. https://www.insidethegames.biz/articles/1056196/no-need-for-laboratory-to-test-for-alcohol-wada. 
  39. ↑ 39.0 39.1 39.2 39.3 Breenfeldt Andersen, Andreas; Nordsborg, Nikolai Baastrup; Bonne, Thomas Christian; Bejder, Jacob (2022-12-26). "Contemporary blood doping—Performance, mechanism, and detection" (in en). Scandinavian Journal of Medicine & Science in Sports: sms.14243. doi:10.1111/sms.14243. ISSN 0905-7188. PMID 36229224. 
  40. ↑ 40.0 40.1 Mairbäurl, Heimo (2013-11-12). "Red blood cells in sports: effects of exercise and training on oxygen supply by red blood cells". Frontiers in Physiology 4: 332. doi:10.3389/fphys.2013.00332. ISSN 1664-042X. PMID 24273518. 
  41. ↑ Bhoopalan, Senthil Velan; Huang, Lily Jun-shen; Weiss, Mitchell J. (2020-09-18). "Erythropoietin regulation of red blood cell production: from bench to bedside and back". F1000Research 9: F1000 Faculty Rev–1153. doi:10.12688/f1000research.26648.1. ISSN 2046-1402. PMID 32983414. 
  42. ↑ Salamin, Olivier; Kuuranne, Tiia; Saugy, Martial; Leuenberger, Nicolas (2018-03-15). "Erythropoietin as a performance-enhancing drug: Its mechanistic basis, detection, and potential adverse effects". Molecular and Cellular Endocrinology 464: 75–87. doi:10.1016/j.mce.2017.01.033. ISSN 1872-8057. PMID 28119134. https://pubmed.ncbi.nlm.nih.gov/28119134/. 
  43. ↑ Schumacher, Yorck Olaf; Saugy, Martial; Pottgiesser, Torben; Robinson, Neil (November 2012). "Detection of EPO doping and blood doping: the haematological module of the Athlete Biological Passport". Drug Testing and Analysis 4 (11): 846–853. doi:10.1002/dta.406. ISSN 1942-7611. PMID 22374784. https://pubmed.ncbi.nlm.nih.gov/22374784/. 
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  47. ↑ Broeder, Craig E. (February 2003). "Oral andro-related prohormone supplementation: do the potential risks outweigh the benefits?". Canadian Journal of Applied Physiology 28 (1): 102–116. doi:10.1139/h03-009. ISSN 1066-7814. PMID 12671199. https://pubmed.ncbi.nlm.nih.gov/12671199/. 
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  61. ↑ 61.0 61.1 61.2 "Performance-Enhancing Drug Use in Adolescence". American Journal of Lifestyle Medicine 11 (2): 122–124. March 2017. doi:10.1177/1559827616680593. PMID 30202322. 
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  63. ↑ "Performance-Enhancing Drug Resources". Drug Free Sport. http://www.drugfreesport.com/drug-resources/performance-enhancing-drugs-steroids.asp. 
  64. ↑ "Who we are". 14 November 2013. https://www.wada-ama.org/en/who-we-are. 
  65. ↑ "U.S. Anti-Doping Agency – USADA". http://www.usada.org/. 

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