About Us


We set out to study the phenomena of Appearance and Performance Enhancing Drug Use (APED), its benefits and consequences, short-term and long-term in the most intellectually honest and scientifically responsible way.  There exists a large gap between what is known in scientific, academic, clinical, and medical communities and those who use these substances and we believe this to be unacceptable.  We will continue to do our best to fill this gap, looking for opportunities to answer scientific and clinical questions that are relevant to those who use APEDs and may even help those outside the APED using community.  This involves characterizing the physical, psychological, and behavioral effects of these drugs in individuals over time and identifying what type of clinical needs the population may encounter.

What are APEDs?

The term APED refers to a large and diverse set of substances, some legal and some illegal, that are used for the primary purpose of changing one's outward appearance or improving their performance in some context (e.g., sports, academics, mixed martial arts, stock trading, etc.). The term APED is not widely used but we think best captures the range of substances used.

We further break down these substances in the following categories.  We recognize that these are not perfect, but serve as a manageable system for understanding the types and range of substances used.

Anabolic-androgenic Steroids (AAS): AASs constitute a majority of APEDs used with the most popular forms being testosterone ("Test"), trenbolone acetate ("Tren"), stanozolol ("Winny" or "Win-V"), nandrolone decanoate (Deca-Durabolin, "Deca," "Nan"), methandrostenolone (Dianabol, "Dbol"), methyltestosterone, oxandrolone, and oxymetholone ("Anavar"). This popularity will vary as new substances are available, as supply and demand networks change, and as legal definitions evolve. All synthetic and endogenous androgens are four-ringed structures with 19 carbon atoms, but AAS generally consist of modified testosterone molecules. The chemical structure of these synthetic androgens differs in several important ways. For example, many AASs represent testosterone molecules modified by 17α-alkylation, where a methyl group (CH3) is added at the C17α position. This process slows hepatic inactivation and allows for these AAS to become active through oral administration. Such modifications are seen in a range of AASs including methyltestosterone, oxandrolone, oxymetholone, and stanozolol. A second, equally important modification to the chemical structure of testosterone, is the 17β-estrification of the 17-hydroxy group with a chain of hydrocarbon molecules. This process allows esters of different lengths to be added to the testosterone molecule, which slow the metabolism of the molecule to biologically inactive keto steroids. Finally, a third modification includes both esterification and substituting hydrogen for the methyl group at C19, which further extends the half-life of the molecule. Although these methods are the most common alterations to the testosterone molecule, more than 100 synthetic steroids have been developed.

Biological Activity. The body naturally produces C19 steroid hormones (known as the androgens) through a series of biotransformations primarily in the gonads, where pregnenolone is eventually converted into testosterone and androstenedione through cleavage of the ethyl group from a progestin precursor at C17. These androgens are produced in the Leydig cells of testes and Sertoli cells produce the androgen-binding proteins that carry androgens through the blood and able to cross the blood-brain barrier.  Endogenous as well as synthetic androgens exert a majority of their biological activity through androgen receptors, which are spread widely throughout the mammalian body with the highest concentrations being in the reproductive tissue (e.g., gonads) and nonreproductive tissues such as the kidneys, liver, muscles, brain, and bone.

In addition to direct activation of androgen receptors by AASs, these hormones are also subject to different metabolic processes. Testosterone breaks down into several metabolites including dihydrotestosterone (DHT) and estradiol (E2). The biotransformation of testosterone into these molecules is a result of enzymatic activity of 5α-reductase and aromatase respectively. These enzymes have different concentrations across different areas of the body. Of most relevance, these enzymes have differential concentrations in relevant brain regions. These metabolites are also responsible for the effects of AAS. For instance, DHT is responsible for much of the androgenic or virulizing effects of AAS and is associated with particularly high concentrations in the prostate.  Conversely, E2 is an estrogen with higher activity found in bone and breast tissues and there is some evidence that this metabolite is associated with aggression in male mice, although this may be related to amount of E2 receptors in the brain.

Non-Steroidal Anabolics: There are at least three primary non-steroidal anabolics that are used by APED users, although non-steroidal anabolics are used only by a small percentage of users.  These substances include insulin ("slin"), insulin-like growth hormone (IGF), and human growth hormone (HGH). All three substances are produced by the human body and have legitimate medical uses. This area is rapidly evolving but presumably less widespread than AAS or legal APED use.

Ergo/thermogenics: Ergogenic, thermogenic, and anorexigent compounds are typically used to increase energy, boost metabolism, raise body temperature, reduce appetite, and "burn fat." These substance fall into three basic categories (a) xanthines - caffeine, theophylline, and theobromine; (b) sympathomimetics - such as ephedrine and ephedra; and (c) thyroid hormones - mainly Cytomel or T3. All three categories work as central nervous stimulants (CNS) with the latter category requiring a prescription for legal use. Other substance that may be used by some APED users include dinitrophenol (DNP) which is a protein uncoupler and will increase internal body temperatures and eyrthropotein (EPO) which stimulates red blood cell production and is used for increased endurance.

Over-the-Counter Ergo/Thermogenics: These substances are typically sold in the form of fat burning or performance enhancing nutritional supplements. Popular forms of these supplements will often stack xanthenes with a sympathomimetic (e.g., caffeine + ephedra) in order to maximize CNS effects. Almost all APED users will include these substances as part of an APED cycle, although the duration of use may be constant rather than cycled with some users. The side effects of these drugs are more clearly linked to aggression, irritability, and anger than AASs and are likely to play some significant role in the reported psychological effects often attributed to AAS.

The most common ingredient in OTC ergo/thermogenics (caffeine) acts as a stimulant by disabling the inhibitory effects of adenosine in the central nervous system. The blockade of adenosine receptors by caffeine results in increased concentrations of several cerebral neurotransmitters including serotonin, dopamine, acetylcholine, norepinephrine, and glutamate, which in turn cause increased spontaneous neuronal firing and also activate the peripheral nervous system. Thus, an individual taking high amounts of this substance will achieve a higher overall level of arousal which may lead to increased ability to attend to different stimuli in the environment and improve cognitive performance. Similarly, the stimulant properties will allow someone who is otherwise fatigued to continue to train and ultimately increase the productivity of their physical output. Finally, caffeine and other xanthenes will also decrease appetite and increase the likelihood of sticking to a restrictive caloric diet.

Sympathomimetic drugs are similar in structure and action (hence being called mimics) to epinephrine and norepinephrine in the sympathetic nervous system. Ephedrine, norephedrine, ephedra, Ma Huang, phenylpropanolamine (PPA), and pseudoephedrine are all substances in this category. Ephedrine, pseudoephedrine, PPA, and herbal preparations containing ephedra and Ma Huang have until recently been easily available over the counter and present in a number of herbal supplements. However, in November 2000, after a study found that the use of PPA caused an increased risk of stroke, the United States Food and Drug Administration released a health advisory and requested that all manufacturers discontinue marketing products containing PPA (FDA/Center for Drug Evaluation and Research, 2000). Although it is still available for some uses, it is no longer easily available over-the-counter. Ephedra has received similar legislative restriction, being placed on the FDA banned list as an herbal supplement with all legal sales ending in 2004. Similar substances have been developed to get around these restrictions as this market evolves very rapidly. Ephedrine's primary mechanism of action is through activation of the beta-andronergic receptors of muscle tissue which increase metabolic output and ultimately increases the likelihood of burning fat.

Illicit Ergo/Thermogenics: The thyroide hormones (T3 and T4) require a prescription for legal use. The most common hormone used is triiodothyronine (T3 or liothyronine). It is available in a synthetic preparation as Cytomel or combined with thyroxine (T4) as Thyrolar. T3 is only available by prescription in the United States. Synthetic thyroxine (T4) by itself is also available and is more frequently prescribed for thyroid disease. Thyroxine (T4) must be converted to T3 in order to be metabolically active and so it is often prescribed by itself for hypothyroidism since it is somewhat safer due to the brain's ability to autoregulate the conversion from T4 to T3. The most well known action of thyroid hormones is thermogenesis, which is believed to result from effects of these hormones either on mitochondrial metabolism or on transport of sodium and potassium across cellular membranes.

As described earlier, other substances potentially used by APED users include EPO and DNP which have their own unique mechanisms of action. EPO is primary and endurance booster believed to improve performance by increasing the available oxygen available in the blood for muscles. DNP on the other hand is an ingredient found in non-nutritive products such as TNT and pesticides. Taking this substance usually results in increased body temperature and is thought to reduce body fat through over-production of heat.

Prohormones and Nutritional Supplements. This category contains other legal substances that are added to APED cycles which can be purchased over the internet or through nutritional supplement stores. The most common of these substances include protein supplements and creatine, but these substances can target a wide range of potential biological mechanisms associated with muscle gain, performance enhancement, or fat reduction (see ergo/thermogenics above). Prohormones are a particularly relevant supplement as they are typically pre-cursor hormones that break down into testosterone through natural processes once injected. In some instances, individuals will inject these substances to maximize their effects as the prohormones often lose their potency when digested naturally through the stomach.

Ancillary Drugs. A number of substances are used to treat the side effects or to enhance the anabolic effects of other APED use. These can range from simple anti-inflammatory drugs to prescription anti-estrogenic drugs often used in the treatment of breast cancer. The management of side effects is an evolving area of APED use and will likely continue to evolve as APED use becomes more sophisticated.

Contact Us

Eleanna Varangis
Tel: 212-659-9298
Fax: 212-849-2561
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Icahn School of Medicine
Department of Psychiatry
Appearance and Performance Enhancing Drug Program
One Gustave L. Levy Place
Box 1230
New York, NY 10029