Addiction Treatment Blog

Man is a gaming animal. He must always be trying to get the better in something or other.

Charles Lamb (1775-1834), ‘Essays of Elia’.

Performance Enhancing Drugs

A huge range of drugs have been used to enhance athletic and gymnastic performance, to increase strength, assist in training, boost stamina or promote a muscular physique. Stimulant drugs such as amphetamines, cocaine, over-the-counter sympathomimetics and caffeine have been used widely to enhance performance in endurance sports and to increase stamina during training but these are the subject of other chapters in this blog. Similarly, cannabis has been used to promote calmness and relaxation for events where this is desirable. The remaining substances discussed below range from simple chemical elements to complex naturally occurring proteins. Many of the preparations used are nutritional supplements and a detailed discussion of these is beyond the scope of this blog. However, some individual nutrients are highlighted.

Anabolic Steroids

Anabolic steroids are the classic performance enhancing drugs; associated with Soviet Block athletes in the Cold War, cheating at the Olympics and a range of unpleasant side effects. So much so that the generic term ’steroid’, which incorporates a wide range of drugs used therapeutically from vitamin D to oral contraceptives, has become synonymous with anabolic steroid in the minds of many members of the public.

Abuse of anabolic steroids has become increasingly prevalent in the West during the past decade. In the USA, both the possession and supply of these drugs were declared illegal in 1990. In the UK, the situation is more complex. It is not illegal to import anabolic steroids from outside the UK as long as these are for personal use. Consequently, possession of anabolic steroids in the form of a medicinal product is also not illegal. However, possession of anabolic steroids in the form of raw materials (i.e. unformulated) was made a criminal act under new legislation in September 1996. An offence is also committed if anabolic steroids are supplied in any form to another private individual within the UK without prescription.

Effects Sought

Anabolic steroids are taken to increase skeletal muscle mass, and physical strength. They also increase stamina, decrease fatigue and may even cause a mild euphoria. Such effects are particularly important because they enable users to train longer and harder. They also increase the risk of muscle and other body damage which is detrimental to the desired effects. The effectiveness of anabolic steroids in increasing the physical strength of an individual is open to doubt. Intensively trained athletes who take them may benefit if a vigorous training schedule is maintained with a high protein, high calorie diet but otherwise an improvement in strength may not occur.

Although anabolic steroids were initially abused mainly by international athletes, there has been a dramatic increase in the variety of users in the past decade. Bodybuilders, aspiring athletes and ‘keep-fit’ fanatics are some of the more obvious groups involved. However, anabolic steroids are increasingly taken by those who desire a more muscular physique for cosmetic purposes or who require increased aggression. Most of these also engage in weight training. In one study of attenders at gymnasia in Swansea, nearly 40 per cent of those questioned had taken anabolic steroids. A survey of 633 students attending a Scottish technical college in 1993 revealed an incidence of anabolic steroid use of 2.8 per cent. A larger UK study of 1659 gym participants from across the country was also described in 1993; it revealed a 7.7 per cent incidence of anabolic steroid use amongst men alone. Use amongst schoolchildren is also increasing. An investigation into the drug-taking habits of 7722 UK pupils aged 15 and 16 years old in 1996 found that 1 per cent girls and 2.2 per cent boys had used steroids on at least one occasion. A summary of surveys of secondary schoolchildren in the USA showed that between 1.4 per cent and 10.9 per cent of them had used anabolic steroids. In all studies in the US and UK a significantly greater proportion of users are male.

Administration

The drugs used are basically analogues of testosterone and examples are listed in the table below. Administration is via the oral or intramuscular route; the latter is more popular but frequently both routes are used simultaneously. Testosterone cannot be given orally because the high rate of first-pass metabolism in the liver results in inadequate plasma concentrations; the intramuscular route is therefore mandatory. Anabolic steroid injections are formulated in oil which allows a sustained release of drug from the intramuscular site over a period of weeks or days. A certain amount of discomfort or pain after injection is common, especially if the volume of a single injection exceeds 4 ml.

The doses used are usually considerably in excess of those used therapeutically – typically 10 to 100 times greater – and it is common for more than one anabolic steroid to be used at the same time. This practice is referred to as ’stacking’. Mixing different anabolic steroids in the same syringe is called ‘blending‘. Steroids are often taken intensively for a duration of 6 to 12 weeks and the course is then repeated after a suitable interval. This is termed ‘cycling‘. Commonly the dose of each steroid is started at a low level, built up to a maximum halfway through the course and then tapered off towards the end, a technique known as ‘pyramiding‘. If a particular drug appears to become ineffective after a period of time (’plateauing‘) then users usually switch to another.

Adverse Effects

Testosterone, the hormone on which other anabolic steroids are based, has both androgenic and anabolic actions. None of the synthetic derivatives is devoid of androgenic effects, and these are responsible for a high proportion of the side effects seen in the abuser. It has not proved possible to synthesise an anabolic steroid which is devoid of these masculinising qualities. Almost all of the side effects of anabolic steroids are dose-dependent and are more likely when prolonged administration occurs.

In men, the large doses of anabolic steroids used commonly depress the pituitary-testicular axis giving rise to testicular atrophy and oligospermia or azoospermia. Any sperm which are produced are more likely to be abnormal. The amount of semen produced is also less. Increased or decreased libido may occur. Impotence is quite common but priapism is rare and tends to be associated with very high doses. Usually all these effects are reversible.

Anabolic steroids can be metabolised to female sex hormones by the liver which can produce feminising effects in men in the presence of suppressed testosterone production. For example, gynaecomastia is a recognised effect and often the breasts are painful or tender. ‘Hot flushing’ is another well-known problem.

The prostate gland tends to enlarge and existing prostate problems are made worse. This may result in impaired micturition.

In women, anabolic steroids tend to cause irregular, smaller, infrequent mestruations or amenorrhoea, and reduced fertility. Virilisation may occur with increased growth of hair on the body and face, deepening of the voice, enlargement of the clitoris, increased libido and reduced breast size. Anabolic steroids may make it impossible to breast feed. Unfortunately, most of these effects are permanent and do not improve when anabolic steroids are stopped.

Anabolic steroids cause sodium (fluid) retention. This can worsen hypertension and could theoretically exacerbate heart/kidney disorders, epilepsy, migraine or diabetes. Long-term use seems to increase the risk of thrombosis, myocardial infarction, pulmonary embolus, stroke, ischaemic heart disease and hypertension. Anabolic steroids can increase the blood concentrations of low-density lipoprotein cholesterol and decrease beneficial high-density lipoprotein levels.

Cancer caused by anabolic steroids is rare. However, abuse has been recognised as a rare cause of cancer of the liver and other cancers have been reported including those of the prostate and kidney. Brygden et al. suggest that these may arise due to the relatively higher levels of tumorigenic circulating oestrogen and the hypertrophic effects of synthetic androgens.

Relatives and friends of an anabolic steroid user commonly confide that an individual’s personality has changed since commencing abuse. As a result of these observations, the effects of anabolic steroids on the mind have been investigated in some detail. Initially use of anabolic steroids may produce stimulatory effects such as an increased confidence, decreased fatigue, heightened motivation, agitation, irritability and insomnia. This may progress so that users become argumentative, impetuous, moody, suspicious and aggressive. Eventually dangerous, violent and antisocial behaviour may occur. Not uncommonly, violent periodic outbursts of temper are reported (’roid rages‘) particularly when large doses are taken for a long time.

Anabolic steroid use may also cause frank psychiatric illness such as depression, severe paranoia and psychosis. A recent review highlighted that weight-training itself may cause some personality and mood changes, and increased assertiveness. This possibility is not always taken into consideration in studies of the effects of anabolic steroids on personality.

It is not clear whether anabolic steroids can cause physical dependence; some case reports suggest that this might occur in certain individuals. However, these drugs do not cause addisonian-like withdrawal reactions akin to those produced by glucocorticosteroids so abrupt cessation is acceptable.

Injecting any drug carries the risk of injection site infection as well as systemic infection such as septicaemia. In one study, 13 per cent of users acknowledged that they had shared injecting equipment or loaned it to someone else, thus increasing the risk of infections such as AIDS and hepatitis. Another study showed an incidence of 16 per cent. AIDS cases in injecting steroid abusers have been reported. Concern has been expressed that this population is not as well-informed as other parenteral drug abusers concerning the risks of HIV transmission via shared needles. the chance of sharing may be raised because the larger bore needles needed for intramuscular injection of these viscous solutions may not be as easily available as the narrower gauge intravenous varieties.

A link between regular anabolic steroid use and immunosuppression has not been proven but has been suggested by some others. For example, two cases of infections characteristic of immunosuppression in otherwise healthy anabolic steroid users led to speculation that the link might go unnoticed because of failure to identify anabolic steroid use. One case involved sight-threatening Candida albicans endophthalmitis and the other severe chickenpox pneumonitis. A survey of 70 anabolic steroid users in North Wales discovered that 54 per cent of those questioned reported ‘frequent colds’ as a side effect.

Cholestatic jaundice with concomitant abnormal liver function tests can be caused by anabolic steroids because they have a dose-dependent ability to inhibit bile production. The condition appears to be reversible in almost all cases.

Acne and alopecia are common side effects in both sexes. Abusers may take antibiotics or topical retinoids to counteract drug-induced acne. Reduced growth and short stature is likely in children and young teenagers due to premature closure of the epiphyses. At all ages, anabolic steroids may increase the risk of tendon damage on exercise. Over-exercise can trigger rhabdomyolysis and its sequelae.

Some of the more common anabolic steroid preparations

Accessory Drugs Associated With Anabolic Steroid Use

A whole range of other drugs may be abused by athletes to counteract the side effects of anabolic steroids or to augment their side effects. Some common examples are highlighted below.

Diuretics

Diuretics counteract the fluid retention caused by anabolic steroids and may sharpen the definition of skeletal muscle contours.

Tamoxifen

This drug helps to reduce the gynaecomastia which may develop as a side effect of anabolic steroid use. Gynaecomastia is not only unsightly but can also be painful.

Human chronic gonadotrophin

Human chronic gonadotrophin (HCG) stimulates the Leydig cells of the testis to increase secretion of testosterone thus theoretically minimising the adverse effects of a depressed pituitary-testicular axis. It is given intramuscularly, usually in association with anabolic steroids, but at least two cases are known in which HCG was taken alone with purportedly the desired anabolic effects.

Growth hormone (somatropin)

There is little evidence that growth hormone has any beneficial effects on muscle mass or athletic performance. Supplies from illicit sources may be of poor quality and very expensive; this also applies to HCG. Concern has been expressed in the past that illicit growth hormone with a cadaveric source has increased the risk of users developing Creutzfeldt-Jakob disease. Prolonged excessive use of growth hormone can cause adverse reactions reminiscent of acromegaly.

Thyroxine

Thyroxine increases the rate of metabolism, which might theoretically increase the ability of anabolic steroids to boost physical strength. Thyroxine also encourages rapid utilisation of a high calorie diet.

Clenbuterol

This drug is a long-acting beta-2 adrenoceptor agonist which is used medicinally in some European countries as an oral bronchodilator. Clenbuterol is not licensed as a medicine for human use in the UK or USA. It is abused by bodybuilders and athletes because it supposedly has anabolic-like effects, although some scientists refer to clenbuterol as a ‘repartitioning’ agent because the mode of action is not the same as that of anabolic steroids.

In several species of animal, clenbuterol increases the bulk of certain groups of skeletal muscles and reduces the amount of subcutaneous fat. The doses required for this effect are greater than those needed for bronchodilation. These experiments in animals have been extrapolated to humans by proponents of the use of clenbuterol. However, it is often the case that drugs which produce one effect in animals do not produce the same effect in humans and the actions of clenbuterol have not been studied in humans or any closely related species such as primates. Another limitation of the laboratory work available is that, unlike the human athletes who take it, the animal species involved were not engaged in regular heavy exercise and were studied under controlled conditions. Animal work also shows that skeletal muscles are affected unequally and the importance of this observation to the hopeful athlete or bodybuilder is not clear.

The typical dose taken for an anabolic effect in man is 60 to 120 micrograms daily, usually in the form of 20 microgram tablets. Interestingly, clenbuterol has been reported as an adulterant of anabolic steroid injections in sufficient quantities (2 mg) to cause toxicity after injection.

The mechanism of action is not clearly understood but the drug may produce but the drug may produce an initial increase in the rate of skeletal muscle protein synthesis which is then subsequently accompanied by a drug-induced decrease in the rate of protein breakdown. This has led to interest in the therapeutic potential of clenbuterol for treating conditions where muscle wastage can occur due to sepsis, immobility or cachexia.

Gamma Hydroxybutyrate

This drug is also known as 4-hydroxybutyrate, hydroxybutric acid, sodium oxybate, GHB, GBH or liquid X. It is usually supplied as a white powder, sometimes as capsules or occasionally tablets. It is not subject to the Misuse of Drugs Act in the UK but it is a prescription- only drug so unauthorised synthesis or supply without a prescription is illegal. As is the case with anabolic steroids, GHB can be lawfully imported into the country for personal use.

GHB is actually a product of normal human metabolism that is known to increase dopamine concentrations in the brain and to interact with endogenous central nervous system opioids. It is a catabolite of the inhibitory neurotransmitter GABA and is found at 1000-fold lower concentrations that GABA itself. It may be a neurotransmitter in its own right as transport mechanisms and binding sites have been identified in the brain. GHB has been used medicinally as an adjunct to anaesthesia, to alleviate the symptoms of narcolepsy, to treat alcoholism and heroin addiction, and to ameliorate the effects of cerebral ischaemia in patients with head injuries.

GHB is taken orally, usually dissolved in water, although occasional reports of injection are described. Doses range from 2 g to over 30 g. It is claimed to be an alternative to anabolic steroids which purportedly increases muscle bulk and reduces body fat by stimulating the secretion of growth hormone. In addition GHB has been abused because it has sedative properties and it can produce a prolonged euphoria which may last in excess of 24 hours. The sedative effects, if undesirable, can be counteracted by administration with a stimulant such as amphetamine. Psychoactive effects are generally potentiated when taken with other psychotropic substances but begin about 15 to 60 minutes after ingestion.

GHB is metabolised to carbon dioxide and water alone; there are no active metabolities. The human elimination half-life has been measured as about 20 to 30 minutes for small doses, but it has been suggested that the elimination pathway is saturable and that at high doses the half-life would effectively be increased as a result.

Side effects are summarised in the table below. GHB was reported to cause a withdrawal reaction in one patient. A 30 year old woman who had taken 25g daily in five divided doses for two years decreased the dose to 10 g per day before stopping completely. Twelve hours after the last dose she experienced tremor, anxiety and insomnia which this persister for 12 days after cessation, but then resolved. Subsequent to this report several other cases of a withdrawal reaction have been described.

Adverse Effects of GHB

• Drowsiness, hypnagogic states, confusion, agitation, amnesia, unconsciousness, respiratory depression, coma
• Nausea, vomiting, diarrhoea
• Ataxia, hypotonia, myoclonic seizure-like episodes, tremors, headache, possibly extrapyramidal symptoms
• Vertigo, dizziness
• Bradycardia, hypotension
• Hypothermia
• Metabolic acidosis, hypernatraemia, hyperglycaemia

Natural Products and Nutritional Supplements

A survey of advertisements for nutritional supplements in UK bodybuilding magazines in 1994 identified 145 different products. Of these, 53 per cent contained vitamins and/or metal cations and 19 per cent disclosed no ingredients at all. The most popular claim, made by one-third of advertisements, was that of enhanced performance. Other common claims were: assisting muscle gain, promoting weight reduction and a ‘general supplement’. The author of the report highlighted that, in the UK, as long as no medicinal claims are made, the manufacturers of nutritional products can make any claims they wish about the benefits of using their preparations. No scientific evidence is necessary to back up such claims.

Many preparations are simply mixtures of protein, amino acids, carbohydrate, fats, minerals and/or vitamins in varying proportion. Others contain more specific, unusual, or exotic ingredients. Whatever the formulation, any claims of efficacy that are made are often unreasonable extrapolations from animal studies or from unrepresentative or limited human exposer. The table below lists some of the ingredients which have been identified in such products. Vitamins are not included in this table although most of them can be found in various guises in such products. Vitamin C, B12 and E are probably the most popular. Although certain ingredients have been studied in some detail, none of them has been tested adequately enough in humans to fully support the claims made for them.

In summary, these products are marked with no, or very little, evidence of efficacy or safety. Often details of dosage or contraindications are lacking. Without detailed  study in humans such products should be viewed at best as a waste of money and no substitute for a professionally organised and supervised training programme.

Ingredients found in natural or nutritional products used by athletes and body builders

Prescription Medicines

Anabolic steroids and the accessory drugs discussed above, together with clenbuterol and gamma hydroxybutyrate, are all prescription medicines in the UK. Consequently, supply by any person in the UK to another individual in the UK is illegal without prescription. This also applies to the drugs listed below.

Beta blockers

These can decrease tremor and pulse in sports where intense concentration and a steady hand are a necessity, e.g. archery, shooting, darts, snooker.

Diltiazem

Diltiazem is not a drug that would be expected to enhance performance in a healthy adult. However, a report in 1993 described a man who took 480 mg of diltiazem per day and developed severe abdominal cramps as a result. He revealed that the drug was widely abused amongst bodybuilders and rugby players locally to augment training but the exact benefits that he anticipated from the drug were no made clear.

Diuretics

These may be taken to promote a rapid short-lasting weight loss prior to ‘weighing in’ before competitions where exceeding a maximum weight may result in disqualification.

Erythropoietin

There is a belief among certain elements of sporting community that increasing plasma haemoglobin, and thence the oxygen carrying the capacity of the blood, is beneficial to muscular function during sustained physical exercise. Blood transfusions are given to achieve this but erythropoietin is also used because it increases the rate of production of red blood cells. However, there are dangers involved in this practice. Strenuous exercise is known to promote haemoconcentration due to loss of fluid and this in turn results in increased blood viscosity. Elevating the red blood cell concentration has a similar effect on viscosity so erythropoietin administration may increase the risk of thrombosis during exercise.

Drugs that stimulate release of growth hormone

Clonidine, levodapa and vasopressin can all stimulate growth hormone production and each one has been abused for this effect.