10 Performance-enhancing Drugs That Aren't Steroids

Red blood cells carry oxygen throughout the body, so it makes sense that if an athlete can increase their red blood cell count, they'll deliver more oxygen to their muscles and perform at a higher level. Blood doping — removing and preserving a supply of blood so it can be returned, via transfusion, to the body right before competition — is one way to do this. But it's messy and time-consuming. Taking erythropoietin, or EPO, increases red blood cell production without the need for transfusions.

The kidneys make the hormone naturally, although people with severe kidney disease don't have enough. That's what the biotechnology firm Amgen was looking to address when it introduced synthetic EPO in 1985. By the 1990s though, cyclists and other endurance athletes discovered that they could train longer and harder if they took the drug regularly.

Not surprisingly, taking EPO comes with significant risk. Yep, significant risk. Studies have shown that it increases the risk of events such as stroke, heart attack and pulmonary edema. One theory suggests that the drug thickens the blood to the point where it produces fatal clots. Such complications may have contributed to the deaths of at least 20 cyclists by 2000, increasing the urgency to develop a reliable test to detect EPO [source: Zorpette].

In 2007, anti-doping agencies introduced the concept of a "biological passport," a record of the substances found normally in an athlete's blood and urine, created by repeated sampling over time. By comparing the results of a blood test administered right before a competition to the passport, officials can determine if an athlete has been using EPO or other performance-enhancing drugs.

Like EPO, human growth hormone (hGH) occurs naturally in the body. In fact, the pituitary gland, the pea-sized organ located at the base of the brain, produces hGH to stimulate growth in children and adolescents and to increase muscle mass in adults.

As soon as synthetic hGH became available as a prescription medication in 1985, when the U.S. Food and Drug Administration approved its use for a number of diseases that retard growth or cause muscle deterioration, athletes began eyeing it as a doping agent. They figured it could mimic the muscle-building effects of anabolic steroids. At first, the high cost of the medication discouraged widespread use as a PED, but, as the saying goes, where there's a will to win, there's a way.

The 1996 Summer Olympic Games have been called the "hGH Games" because of the rampant use of the drug among competitors. And it continues to be a problem among athletes. In summer 2021, Nigerian sprinter Blessing Okagbare was kicked out of the Tokyo Olympics after testing positive for hGH.

Today, athletes get hGH from a variety of sources: doctors willing to write prescriptions for off-label use, online pharmacies, illicit websites for performance-enhancing drugs and clinics that use the hormone to reverse the effects of aging. A few athletes even turn to black-market dealers that collect hGH from human cadavers.

It's a risky gamble, especially considering the lack of scientific evidence to suggest that hGH actually increases athletic performance. Oh, and don't forget the side effects. Using hGH has been linked to a variety of medical conditions, including joint pain, muscle weakness, fluid retention, carpal tunnel syndrome, cardiomyopathy and hyperlipidemia [source: Mayo Clinic].

Another performance-enhancing drug that made the 1996 Summer Olympic Games memorable for the wrong reason was bromantane, a sort of stimulant and masking agent combined. Several Russians tested positive for the drug, which at the time, was not included on the International Olympic Committee's (IOC's) list of banned substances. That didn't stop the IOC from disqualifying several Russian athletes, stripping medals from two and, ultimately, blacklisting bromantane based on its performance-enhancing effects.

The effects of bromantane are quite unlike any other PED. Russian army doctors developed bromantane as a stimulant, something they could give to soldiers and cosmonauts to help them feel more alert and fight fatigue. Soon after, Russian athletes got hold of the drug, reporting that it helped them perform at peak levels without feeling exhausted. But the story appears more complicated.

Some anti-doping officials believe bromantane can hide the abuse of more serious drugs, such as steroids. This is known as masking, and it's just one more way athletes can find a way to cheat. For example, the masking agent probenecid stops the excretion of steroids for a few hours, decreasing the concentration of steroids in the urine. The exact masking mechanism of bromantane, however, remains unclear. That doesn't diminish the drug's appeal among athletes, who believe its stimulant/masking effects give them a doping double whammy.

Bromantane gained popularity because it appealed on multiple fronts. But stimulants by themselves function reasonably well as performance-enhancing drugs. Athletes take stimulants to improve endurance, reduce fatigue and increase aggressiveness. And someone trying to qualify for a lower weight class may rely on stimulants for their ability to suppress appetite.

You may think first of amphetamines — prescription-only "speed" pills — when you hear of this class of drugs, but not all stimulants require a physician's signature. Ephedrine, for example, is available behind the counter in drug products, mostly as decongestants. (Dietary supplements containing ephedrine are illegal in the U.S.) Athletes, of course, aren't interested in these. They want ephedrine for an extra boost of energy despite the warnings that the drug can cause high blood pressure, dizziness, shortness of breath and cardiac arrhythmia.

Along with bromantane, diuretics have long served to mask steroid use. Diuretics are any drugs that affect kidney function, resulting in increased urine output. The "water pill" chlorthalidone, for example, prevents fluids and salts from being reabsorbed into the kidney tubules and returned to the blood. As a result, more water leaves the body.

In patients with certain conditions, such as heart disease, diuretics can also help control high blood pressure. But athletes who take anabolic steroids pop diuretics to dilute their urine, which decreases steroid concentration and makes it much more difficult to detect in drug tests. (Of course, athletes can be tested for diuretics though, too.) Weightlifters and boxers may also down water pills to expel large amounts of fluid, which qualifies them to compete in a lower weight category. Then, right before the match, they stop taking the pills to return to their heavier fighting weight, giving them an advantage against their opponent. Of course, an athlete taking diuretics may also get dizzy, become dehydrated or experience a severe drop in blood pressure — symptoms that make it hard to fight with the eye of the tiger.

Sometimes, a drug's effect on athletic performance depends on how it's administered. Take the beta2-agonist albuterol. This well known asthma drug works by relaxing the muscles lining the bronchial tubes, allowing more air to flow into the lungs. Athletes with asthma (believe it or not, elite athletes tend to have higher rates of asthma than people in the general population) commonly use inhaled albuterol to treat their symptoms, allowing them to compete without shortness of breath [source: Kindermann].

But what about athletes who don't have asthma? Could they suck in a few shots of albuterol and increase their lung capacity? According to research published in the journal Sports Medicine, this performance-enhancing effect simply doesn't exist. The authors found that, in 17 of 19 clinical trials involving non-asthmatic competitive athletes, the performance-enhancing effects of inhaled beta2-agonists could not be proved.

All bets are off, however, when an athlete takes albuterol orally or by injection. When administered in this fashion, albuterol has been found to have anabolic properties, which means it can help build muscle like steroids and, according to a 2020 study published in the British Journal of Sports Medicine, it can also boost sprint and strength performance.

Another orally ingested beta2-agonist known as clenbuterol — or clen— packs an even bigger punch than albuterol. Athletes in several sports — cycling, swimming, baseball and soccer — have tested positive for clenbuterol use, although many have claimed that the drug could be traced to contaminated food. While clenbuterol has historically been given to animals to produce leaner meat, it has been banned for use in meat since 1991 in the U.S. and since 1996 in the European Union.

If the acronym sounds familiar, it probably is. GHB is known as a "date rape" drug because it can quickly render a user so relaxed and euphoric — especially when combined with alcohol — that they are easily taken advantage of. Even scarier, it can cause amnesia, improving the chances that predators who slip the tasteless chemical into an unsuspecting imbiber's cocktail will get away with their misdeeds.

Because of the risks it posed, GHB was banned by the Drug Enforcement Administration (DEA) in 2000 but then brought back to the market two years later after it was found to be useful in treating narcolepsy. It's use has since been expanded to include another rare sleeping disorder, but GHB is only prescribed under strict safety controls.

Even before it gained fame as a date rape drug, GHB was thought to improve exercise performance and muscle mass. There's even some scientific evidence that GHB increases growth hormone concentration. The drug apparently became popular among bodybuilders looking for alternatives to steroids in the 1980s when the hormones were first being controlled. Mike Fox, who was a personal trainer and good friend to retired New York Mets' player Mike Piazza, shot himself while trying to give up GHB in 2000. Bodybuilder Mike Scarcella, who was Mr. America and Mr. USA, died in August 2003 during a GHB withdrawal while hospitalized after a bar fight in Texas.

But the alleged performance-enhancing benefits of GHB live on. In 2015, "Full House" actor John Stamos was arrested for driving erratically through Beverly Hills under the influence of GHB. Stamos claimed he was taking the drug to "lean out" body mass before his new TV show, "Grandfathered."

It's easy to see why baseball players, cyclists, boxers, swimmers and runners sometimes turn to pharmaceuticals for a competitive advantage. These sports require deep reservoirs of muscle strength and endurance — the very targets of the most popular performance-enhancing drugs.

But what about sports like pistol shooting or archery? They certainly demand a keen eye, a steady hand and rock-solid concentration but not Herculean strength. Even so, athletes in these sports may also take PEDs. In fact, two North Korean pistol shooters competing in the 1998 Olympic Games in Seoul, South Korea, tested positive for propranolol.

As it turns out, propranolol belongs to a class of drugs known as beta blockers, which nonathletes use to control high blood pressure. Beta blockers work by blocking the effects of epinephrine, a hormone secreted by the adrenal glands that increases blood circulation. People who take beta blockers have a slower heart rate and more relaxed blood vessels, conditions that help reduce blood pressure.

But the drugs have an interesting secondary effect: They also mask anxiety by diminishing nervous sweat and trembling and are sometimes prescribed off-label to treat performance anxiety. And that's exactly why marksmen are drawn to the drugs. If they have a steadier hand, they can perform better in competition. In addition to propranolol, beta blockers include atenolol, acebutolol, alprenolol, bisoprolol and metoprolol, all of which are banned in pistol shooting and archery.

In June 2012, outfielder Marlon Byrd faced a 50-game suspension after testing positive for tamoxifen, a substance banned from Major League Baseball and many other sports. Why would an athlete want to take a drug normally used by breast cancer patients? The answer lies in some interesting biochemistry.

Many breast cancers have receptors for estrogen, a hormone that promotes the development and maintenance of female characteristics of the body. When estrogen molecules fit into these receptors like a key fitting into a lock, the malignant cells become activated. Tamoxifen blocks these estrogen receptors, interfering with the cancer's ability to grow and develop. This is why scientists refer to tamoxifen as an anti-estrogenic agent.

Now let's turn our attention to a homerun slugger taking steroid injections — usually synthetic testosterone — to grow his muscles. Large doses of the male hormone cause the body to produce additional estrogen. This in turn can result in enlarged breasts, a feature that most power hitters find unappealing. To counteract the effects of estrogen and mask their steroid use, these players may opt to take tamoxifen. That means anti-estrogens don't really enhance performance, but, because they alleviate symptoms of PEDs, they appear on the World Anti-Doping Agency's list of more than 200 banned substances and methods.

There's one popular performance-enhancing drug that won't land an athlete in hot water with anti-doping agencies. It's creatine, and it's not a drug at all, at least according to the U.S. Food and Drug Administration (FDA). Because it's an over-the-counter supplement, creatine is regulated like a food by the FDA, which means creatine manufacturers don't conform to the same standards as pharmaceutical companies.

That doesn't diminish its appeal. Creatine remains one of the most widely used substances among athletes, especially football players, sprinters and weightlifters. Why? Because a growing body of evidence suggests that the chemical does indeed deliver athletic benefit by boosting levels of adenosine triphosphate (ATP) in muscle tissue. ATP powers muscle contractions, so increasing ATP levels is clearly a desirable thing. But the benefit seems to be limited to short, high-energy bursts of muscle activity, not long, slow burns common in endurance athletes.

Interestingly, the liver produces creatine every day, so taking supplemental creatine is a little bit like adding extra frosting to an already-frosted cake. Not only that, but excess amounts of the chemical also exit the body through the kidneys, making it unnecessary to power-gulp creatine tablets with the idea that doing so will deliver extra benefit.

And one final cautionary note: In some cases, supplements have been known to pick up contaminants from other substances, including performance-enhancing drugs. Try explaining that one to the team doctor.

Originally Published: Nov 6, 2012