Performance-enhancing substance

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 to 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 article: 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, increased blood pressure, 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 article: 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 (e.g., caffeine). Others are banned as per the World Anti-Doping Agency (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
Main articles: Human growth hormone, Creatine, and Beta-Hydroxy-Beta-methylbutyrate
  • 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 article: 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]

Nootropics
Main article: Nootropic

Nootropics, or "cognition enhancers", 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][35]

Painkillers
Main article: 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 articles: Sedative and Anxiolytic

Used in sports like archery which require steady hands and accurate aim, and also to overcome excessive nervousness or discomfort. Diazepam and propranolol are common examples; ethanol and cannabis are also used occasionally.

Blood boosters
Main article: Blood doping

Blood doping agents increase the oxygen-carrying capacity of blood beyond the individual's natural capacity. 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]

Erythropoietin
Main article: Erythropoietin

Erythropoietin, or EPO, is a hormone that helps increase the production of red blood cells which increases the delivery of oxygen to muscles.[36] It is commonly used among endurance athletes such as cyclists.[36] It functions by protecting red blood cells against destruction whilst simultaneously stimulating bone marrow cells to produce more red blood cells.[37] Potential side effects include: dehydration and an increase in blood viscosity which could result in a pulmonary embolism or stroke.[38] Per the World Anti-Doping Agency, it is a banned substance.[22] Urine samples can be tested via electrophoresis, and blood samples via indirect markers.[39]

Gene doping
Main article: 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 April 2015.[24]

Prohormones
Main article: Prohormone

Also known as anabolic steroid precursors, they promote lean body mass.[40] Once in the body, these precursors are converted to testosterone and because they increase endogenous testosterone.[41] The desired effects of steroid precursors however, are often not seen as they do not bind well to androgen receptors.[41] Examples of prohormones include norandrostendione, androstenediol, and dehydroepiandrosterone (DHEA).[40] These steroids have little desired effect compared to anabolic steroids, but have the same side effects.[42] 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.[43]

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.[44] 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.[45] Ancient Greek athletes at the time also incorporated stimulants such as wine and brandy into their training routines.[46] Stimulants derived from plants (e.g., Cola Nitida, Bufotein, etc.) were used by the Roman Gladiators to overcome injuries and fatigue.[47]

In the late 19th century as modern medicine and pharmacology were developing, PEDs saw an increase in use.[48] Supplements were now exclusively being used to enhance muscular work capacity.[48] 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).[49] Testosterone was also a commonly taken stimulant, however, it was more difficult to obtain.[49] 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.[50] By 1895, it had been assessed that testicular extracts did in fact improve athletic performance by increasing muscular strength.[51]

In the 20th century, testosterone was isolated and characterized by scientists.[52] In 1941, the first record of synthesized testosterone use occurred when a horse was given testosterone which successfully improved its race performance.[53] Sports trainers soon after began advocating for testosterone use.[52] Images of bodybuilders with massive muscles began circulating which further perpetuated a desire among athletes to use testosterone.[50][52]

In the 1980s, the main PEDs were cortisone and anabolic steroids.[54] In 1988, the United States Congress establishes the Anti-Drug Abuse Act to criminalize the distribution and possession of non-medical anabolic steroids.[55] In 1999, WADA was formed to address the escalating use of substances in sports, particularly after the 1998 doping scandal in cycling.[55]

Risk factors

Adolescents are the most vulnerable group when it comes to taking performance-enhancing substances.[56] 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.[56] 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.[57] Having a negative body image or a history of depression can also be a significant risk factor.[57] These are further exacerbated by parental pressures surrounding appearance, media influence, and peer pressure.[56][47] Studies show that adolescent males who engage with fitness magazines are twice as likely to use performance-enhancing substances.[47] Adolescents who partake in competitive sports are at a particularly high risk, with those involved in football, basketball, wrestling, baseball, and gymnastics at the top.[47]

Usage in sport
Main article: Doping in sport

In sports, the phrase 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.[58] There are agencies such as WADA and USADA that try to prevent athletes from using these drugs by performing drug tests. WADA was founded on 10 November 1999, by Dick Pound. WADA focuses on establishing and enforcing rules and codes for all sports around the world. Their goal is to make all sports played fairly between all athletes in a doping free organization with the power to prevent athletes from using any form of performance-enhancing drugs. When medical exemptions are granted they are called therapeutic use exemptions. USADA started 1 October 2000, as non-profit to combat doping in the United States and was composed of nine members. Five of which were former Olympic athletes with the other four elected from independent companies. This is the United States Anti-doping Agency and have the ability to test athletes across the nation.[59][60]

See also

References
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    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
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  35. Ilieva IP, Hook CJ, Farah MJ (June 2015). "Prescription Stimulants' Effects on Healthy Inhibitory Control, Working Memory, and Episodic Memory: A Meta-analysis". Journal of Cognitive Neuroscience. 27 (6): 1069–1089. doi:10.1162/jocn_a_00776. PMID 25591060. S2CID 15788121. 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.
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