Doping agents and their effects

WADA’s classification of prohibited substances and methods into principal categories is based on whether the doping agent or method is prohibited at all times or in-competitions or in particular sports. The substances are divided into subcategories according to their mechanisms of action and effects.

WADA’s list of doping agents includes approximately 300 different compounds. In addition to the substances used as examples, the categories typically specify that compounds with the same mechanisms of action, i.e. compounds that belong in the same category of pharmacological substances, are also prohibited. Fewer than 100 substances specified in the list are used as medicine.

The following information about substances and methods is presented below:

  • the most common official indications for using medicine with a marketing authorisation
  • the effects of methods and substances on performance and
  • the most common adverse effects.

Important information about applying for a Therapeutic Use Exemption is also provided.

Table of contents

I Substances and methods prohibited at all times 

S0. Non-approved substances

S1. Anabolic agents

S2. Peptide hormones, growth factors, related substances and mimetics

S3. β2-agonists

S4. Hormone and metabolic modulators

S5. Diuretics and masking agents

M1. Manipulation of blood and blood components

M2. Chemical and physical manipulation

M3. Gene and cell doping

II Substances and methods prohibited in-competition

S6. Stimulants

S7. Narcotics

S8. Cannabinoids

S9. Glucocorticoids

III Substances prohibited in particular sports

P1. Beta-blockers

I Substances and methods prohibited at all times 

Samples taken in-competitions and out of competitions are tested for substances and methods prohibited at all times. Tests for substances prohibited in-competitions are only performed on samples taken during in-competition periods.

S0. Non-approved substances

The category of non-approved substances includes products that are not included in any other category of the list and that have not been approved for medical use on humans by any national health authority. This definition includes pharmacological substances in early phase or clinical trials and substances that are no longer under development.

S1. Anabolic agents

Anabolic agents are divided into two categories: anabolic androgenic steroids such as testosterone and nandrolone, also known simply as anabolic steroids, and other anabolic agents.

Anabolic androgenic steroids

In Finland, testosterone is used most commonly as a mode of replacement therapy to treat the symptoms of low testosterone levels in elderly men (functional hypogonadism) and as a short-term treatment for delayed puberty in young boys.

Approximately 40–50% of all doping agents listed in WADA’s annual statistics of positive tests are anabolic steroids. This indicates that anabolic steroids are the most commonly used prohibited substance, which is due to the significant additional advantage provided by them in many different sports. Anabolic steroids increase muscle mass and strength and affect the body’s metabolism by making the body more tolerant to hard training while boosting recovery. Anabolic steroids increase and improve the user’s red blood cell count and oxygen uptake.

Compared with the doses of normal testosterone replacement therapy, the doses administered for doping purposes are unphysiological, up to 5–10 times larger doses or even larger doses. Anabolic androgenic steroids can cause the following adverse effects, which may be very severe depending on the dosage, duration of use and individual factors:

  • more frequent heart and circulatory system problems due to adverse effects on lipid metabolism, the coagulation system, blood pressure and, possibly, harmful structural changes in the heart
  • psychological effects such as aggression, violent behaviour, affective disorders (up to the level of mania) and, in rare cases, psychotic symptoms such as delusions
  • elevated liver blood test value and, as a result of long-term use, liver damage
  • skin symptoms such as acne, stretch marks, parietal scalp hair loss and infections if the agent is administered to muscle and
  • early puberty resulting in premature closure of a growth plate.

Women

  • hirsutism in the face and other parts of the body
  • permanent deepening of the voice
  • mammary hypoplasia and clitoral hyperplasia and
  • disturbances in the menstrual cycle.

Men

  • disturbances in semen production, infertility and testicular hypoplasia
  • gynaecomastia and
  • the onset of typical symptoms of the lack of testosterone (hypogonadism) after quitting the use of the agent, such as tiredness, depression, impotence and continued infertility.

A therapeutic use exemption for testosterone can only be granted to an athlete if the lack of testosterone is unambiguously due to an organic reason. As an exception, a therapeutic use exemption may be granted for short-term use of testosterone to start puberty.

Other anabolic agents

Other anabolic agents on the list of doping agents include selective androgen receptor modulators (SARMs) and certain other components, such as tibolone, zeranol and clenbuterol.

SARMs are experimental anabolic compounds that are developed to retain the beneficial anabolic effects on the musculoskeletal system without the typical adverse effects of anabolic steroids. The compounds have similar effects on performance as anabolic steroids, but the adverse effects have not yet been eliminated. SARMs are typically sold illegally online as “nutritional supplements”.

The following adverse effects may occur:

  • there is only limited scientific data available, but similar effects as caused by anabolic steroids may occur depending on the compound and dosage and
  • severe heart problems and liver damage, which have stopped the development of certain compounds. 

Clenbuterol is a β2-agonist administered orally in some countries to treat asthma. Tests on animals indicate that clenbuterol has a significant effect on the growth of muscle mass, which is why it is included in this group in WADA’s list. β2-agonists also improves the body’s ability to burn fats.

Clenbuterol is associated with several adverse effects of β2-agonists due to the oral mode of administration:

  • increased heart rate, arrhythmia and, in some cases, even myocardial infarctions
  • tremor
  • electrolyte imbalance and muscle cramps.

This category includes, for example, erythropoietins (EPO, CERA, darbepoetin), human chorionic gonadotrophin (hCG), luteinising hormone (LH), human growth hormone (hGH) and several experimental substances stimulating the secretion of growth hormone.

Erythropoietins increase red blood cell production in the body and they are used to treat anaemia caused by chronic kidney disease, for example. With them, athletes can enhance their oxygen uptake.

The adverse effects include, for example:

  • coagulation disorders resulting in myocardial and cerebral infarctions, thrombosis and
  • elevated blood pressure.

Human chorionic gonadotrophin and luteinising hormone increase the secretion of testosterone in men.

In adolescents, growth hormone is one of the factors that controls growth in height. It increases muscle growth, but if it is the only product used to increase strength, the effect is marginal compared with anabolic steroids. 

The use of growth hormone is associated with the following adverse effects:

  • increased blood pressure and heart disease
  • growth of cartilage and bone in the facial area
  • issues with joints
  • thyroid disorders and
  • blood cancer.

S3. β2-agonists

β2-sympathomimetics, also known as β2-agonists, cause bronchodilation, which is why they are used to treat asthma, typically in inhaled form. β2-agonists are prohibited at all times as, according to tests on animals, they have an anabolic effect on muscles when doses larger than normal therapeutic doses are administered orally. They may also improve maximum performance temporarily when doses larger than normal therapeutic doses are inhaled.

According to current estimates, none of the additional advantages specified are gained when normal therapeutic doses of β2-agonists are inhaled. Because of this, formoterol, salbutamol, salmeterol and vilanterol are permitted when used in limited inhaled doses and therapeutic use exemption is not needed then.

The following adverse effects may occur (in milder form when inhaled than when administered orally, for instance):

  • increased heart rate and arrhythmia
  • tremor
  • electrolyte imbalance and muscle cramps.

Grounds for not using a permissible alternative must be presented when applying for a therapeutic use exemption. An additional criterion for granting a therapeutic use exemption is an asthma diagnosis backed up by a spirometry test.

S4. Hormone and metabolic modulators

This category includes compounds that affect metabolism and hormonal balance through various mechanisms of action. Anti-estrogenic substances are used in treating breast cancer in order to prevent the estrogen-dependent tumour from growing. These substances slightly increase the secretion of testosterone and affect hormonal balance, which is why they are prohibited. Substances preventing the activation of the activin type IIB receptor that have an anabolic effect on muscles are still only being in clinical development.

“Metabolic modulators” produce similar beneficial metabolic changes as physical exercise but without the need for physical stress. Insulins, which are used in the treatment of diabetes, are considered to belong to this category as well. Due to their various effects on metabolism, insulins have a weak anabolic effect on muscles. In excessively large doses, they lead to low blood sugar (hypoglycaemia) and, in some cases, death.

A therapeutic use exemption for insulins can always be granted to patients diagnosed with type 1 diabetes.

S5. Diuretics and masking agents

Diuretics such as hydrochlorothiazide and furosemide are substances used as antihypertensive drugs and in the treatment of cardiac insufficiency. Diuretics remove salt and fluids from the body. They increase urine secretion and, consequently, can dilute the content of doping agents in urine. Because of this, diuretics are called masking agents, and the list contains other masking agents besides diuretics. Diuretics can also be used to lose weight in order to compete in lower weight classes.

The use of diuretics is associated with the following adverse effects, which may be severe in connection with dehydration caused by heavy sweating:

  • electrolyte imbalance
  • loss of strength and 
  • low blood pressure.

Plasma expanders, such as hydroxyethyl starch, pull water out of tissues and into blood vessels, enabling blood to enter small capillaries more easily and increasing the oxidation of tissues. As the amount of liquid in the circulatory system increases, its haemoglobin count decreases, which affects the interpretation of the Haematological Module of the Athlete Biological Passport.

Prohibited methods

M1. Manipulation of blood and blood components 

The following methods of improving blood’s capacity to oxidate tissues are prohibited:

  • Blood transfusion involving own blood collected earlier in the training season or blood donated by someone else. Blood donated by another person is detected directly in a blood test. The transfusion of own blood can be detected directly with the Athlete Biological Passport as, when timed correctly, blood tests indicate significant changes in the red blood cell values. Possible adverse effects of blood transfusions include infections caused by unsanitary equipment, kidney damage caused by red blood cells breaking down during storage or handling and heart disorders caused by excessively high haemoglobin levels.
  • Experimental compounds that release oxygen from red blood cells in tissues, synthetic haemoglobin products and other forms of manipulation designed to artificially improve the transport of oxygen.

M2. Chemical and physical manipulation 

The following methods designed to prevent or hinder the detection of doping agents in a sample are prohibited:

  • Urine substitution or adulteration, for example, by adding an enzyme that breaks down proteins to the sample.
  • Intravenous infusions or injections of more than a total of 100 mL per a 12-hour period are prohibited except for those legitimately received in the course of hospital treatment, surgical procedures or clinical diagnostic investigations. Outpatient infusions of liquids performed to administer medicine (iron, biological medicinal products) are prohibited if the specified limit values are exceeded, in which case a therapeutic use exemption must be applied for in advance.

M3. Gene and cell doping 

Gene editing and cell transplants that may improve performance are prohibited.

II Substances and methods prohibited in-competition

Tests for substances prohibited in-competitions are only performed on samples taken during in competition periods. 

An athlete may only use medicine prohibited in-competitions if the athlete does not participate in any competitions during the use of medicine. If an athlete participates in competitions during the use of medicine, the athlete must have a valid therapeutic use exemption for the prohibited medicine in question. If the medicine has been discontinued out-of-competition during the washout period, the concentration of the prohibited medicine may exceed the reporting limit of the doping sample during the in-competition period. However, the athlete can apply for a therapeutic use exemption retroactively after the positive doping test result in accordance with the International Standard for Therapeutic Use Exemptions (if the athlete has not applied for it in advance) when a prohibited glucocorticoid or strong opioid has only been used out-of-competitions within the washout period (but not in-competition period). In this case, it should be ensured in advance that the terms and conditions related to the granting of a therapeutic use exemption are fulfilled.  The athlete should have the medical file prepared and ready in case an application for retroactive therapeutic use exemption is necessary following doping test. The in-competition period starts on the day preceding the competition at 11:59 p.m., unless otherwise specified.

In addition to the substances and methods prohibited at all times specified above (S0.–S5. and M1.–M3.), the following substances are prohibited during competitions:

S6. Stimulants

Stimulants in medicinal uses include for example dexamfetamine, lisdexamfetamine, methylphenidate in the treatment of ADHD, pseudoephedrine and ephedrine in the treatment of common cold, cough and allergies and compounds used in the treatment of severe allergic reactions (adrenaline). In addition, several compounds are used as illegal drugs (amfetamine, metamfetamine, cocaine, ecstasy). Several stimulants (such as DMAA, DMBA) are also sold illegally online as nutritional supplements.

Stimulants increase vigour and reduce feelings of fatigue as central nervous system agents. Stimulants are the second-largest category of prohibited substances in WADA’s annual lists of positive doping samples after anabolic-androgenic steroids, totalling approximately 15% of all positive samples. Most of these anti-doping rule violations are probably associated with recreational use or the prohibited additives or impurities of nutritional supplements.

The following adverse effects may occur:

  • increased heart rate and blood pressure, arrhythmia and, if large doses are administered, myocardial infarction
  • tremor
  • anxiety, nervousness and insomnia
  • if large doses are administered, confusion and paranoia and
  • heat stroke in connection with long-term stress and large doses.

According to WADA’s guidelines, a therapeutic use exemption may be granted for medicine used in the treatment of ADHD, such as methylphenidate, if the diagnosis has been made by a physician specialised in the treatment of ADHD and the patient records and surveys related to the diagnosis are submitted to the Therapeutic Use Exemption Committee as appendices to the therapeutic use exemption application.

S7. Narcotics

Narcotics are morphine-like substances that are used in cases of severe pain, including post-operative settings and severe injuries. They are also used as narcotic agents due to their narcotic effect. Narcotics my improve performance in endurance sports by reducing the feeling of fatigue associated with long term physical stress.

Common adverse effects include the following:

  • inability to control movement, which may increase the risk of accidents in cycling and automobile sports
  • nausea and constipation
  • respiratory depression if large doses are used
  • sedative effect and
  • euphoria and the resulting addiction.

S8. Cannabinoids

Cannabinoids are the active ingredients (such as tetrahydrocannabinol, TCH) in plant-based cannabis (marihuana and hashish) and their synthetic derivatives. The use of TCH for medical purposes is very rare.

The possible performance-enhancing effect of cannabinoids is based on their sedative effect, although they primarily reduce performance due to their adverse effects. One of the reasons why cannabinoids are prohibited is that they violate the spirit of sport. Most anti-doping rule violations are probably associated with recreational use. Cannabidiol, which is used to treat severe epilepsy in children, is not prohibited as it does not produce the typical euphoric effects of cannabinoids.

Common adverse effects include the following:

  • decreased ability to perceive of time, place, speed and distance and
  • impaired memory, coordination and reactions.

S9. Glucocorticoids

Glucocorticoids are used to prevent the inflammatory reactions of the body in various diseases if the reactions cause the disease or its symptoms to become worse. Such diseases include rheumatic diseases, inflammatory bowel diseases, asthma, various types of skin diseases, allergies and tendon strain injuries. Depending on the type of disease, glucocorticoids can be administered through different routes. All glucocorticoids are prohibited when systemic routes of administration are applied, i.e. they are administered orally, rectally, intravenously or intramuscularly. When inhaled or applied locally on skin or mucous membranes, the use of glucocorticoids is permitted. According to a decision made by the WADA Board, all glucocorticoid injections will be prohibited from the beginning of 2022 regardless of the location of injection.

Glucocorticoids are prohibited as they may increase the body’s tolerance to stress and their euphoric effect may reduce the feeling of fatigue related to physical stress when larger doses are administered. However, there is only little clear evidence that glucocorticoids improve athletic performance.

The adverse effects of glucocorticoids are closely linked with the route of administration, dosage and the duration of treatment. When systemic routes of administration are applied, the following adverse effects may occur, for instance:

  • euphoria, which may reduce the feeling of fatigue under physical stress
  • loss of muscle and bone (catabolism) and, when administered locally, thinning of the skin and weaken tendons
  • susceptibility to stomach ulcers
  • increased blood pressure and swelling and
  • susceptibility to infections.

Therapeutic use exemptions for systemic routes of administration (oral, rectal, intravenous or intramuscular) of glucocorticoids can be granted for example for the purpose of short-term treatment of asthma or attacks of inflammatory bowel disease. Local administration of glucocorticoids on the skin and the inhalation of glucocorticoids to the mucous membranes of the nasal cavity or eyes is permitted.

III Substances prohibited in particular sports

P1. Beta-blockers

Beta-blockers are used for treating hypertension and coronary artery disease, for example. Their effect, which tranquillises the central nervous system and reduces heart rate and tremors, can improve performance in sports that require concentration, calm nerves and steady hands. Beta-blockers are prohibited only in certain sports that are listed on the List of Prohibited Substances and Methods. Beta-blockers impair performance significantly in sports that require endurance.

The following adverse effects may occur:

  • low pulse and slow nerve impulses in the heart and
  • attacks of asthma.
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