CHICAGO — After discovering that a promising new drug caused multiple types of cancer in lab animals, the pharmaceutical company GlaxoSmithKline stopped developing the compound.
But the failed experimental drug, called GW501516, is making a comeback in another arena. Though it’s not approved for human use — and likely never will be — it’s among dozens of unregulated research chemicals being used by competitive bodybuilders, cyclists and other elite athletes seeking an edge.
These unapproved chemical compounds are sold by companies that purport to offer the substances for use in scientific experiments, which is legal. The buyer must agree the drugs will be given only to laboratory animals or used for in vitro research and will never be ingested by humans.
Yet so many athletes are trying GW501516 that the World Anti-Doping Agency, an independent international body, last month took the rare step of warning “cheats” about side effects, citing “serious toxicities.” In the last two weeks alone, five cyclists — four from Costa Rica and one from Russia — were provisionally suspended when tests revealed they had the drug in their systems.
On bodybuilding websites, it’s easy to find joking, thinly veiled comments referring to users as “lab rats.”
“Should I wait until my rodents are between cycles to use these compounds?” one person asked on elitefitness.com, where visitors debate topics such as radical supplementation, performance-enhancing drugs and anabolic steroids.
“My rats feel great when they’re on it,” a forum user posted in March. “They can run on their little wheels for hours on end and not feel a thing. It also aids in the gym with muscular endurance. They also have told me they have a feeling of breathing easier when on GW. It’s amazing stuff.”
Some distributors of research chemicals openly advertise their products on bodybuilding sites and even sponsor chat boards and competitions.
“The ‘research only’ references are a ‘wink-wink’ kind of thing,” said Lawrence Payne of the U.S. Drug Enforcement Administration. “We’ve seen about 200 new drugs flood the market over the last five years; most are unregulated, coming out of labs from China. It’s the new frontier of drug enforcement.”
And though the problem has been detected first among hard-core athletes, some experts say whatever top competitors do to get ahead inevitably is copied by others, including youngsters and recreational athletes, as well as people looking to improve their physique.
“As a research scientist, you feel both shock and anger when you’re developing a medicine to help someone live longer or walk down the street without pain, and you find out people are abusing it and using it to cheat in sport,” said Mark Luttmann, of GlaxoSmithKline, who works with the anti-doping agency to share confidential information on emerging compounds. “That’s what really gets to you.”
Luttmann said he is particularly concerned about young athletes emulating those who take illegal performance-enhancing drugs.
“Elite athletes know what they are doing is wrong,” he said. “What we need to do is reach the kids. That’s a huge role we play.”
GlaxoSmithKline doesn’t manufacture GW501516 or authorize its sale. According to the DEA, such products are often produced overseas, mainly in Chinese labs, which often can find in scientific journals the information necessary to manufacture them.
Many journals “insist we publish the structure” of an experimental drug, said Pauline Williams, who leads GlaxoSmithKline’s anti-doping initiative.
The legality of unregulated chemicals depends on the circumstances, said Rick Collins, a New York criminal defense attorney whose practice centers on performance-enhancing drugs and dietary supplements.
A chemical sold to scientists for the purpose of animal research requires no federal approval. But if that same chemical is sold to consumers for use in the body, it is considered an “unapproved, misbranded or adulterated” drug because of the dangers it may pose to health, according to the Food and Drug Administration.
“The question isn’t whether a drug is legal or illegal; it’s whether the compound is regulated,” said the DEA’s Payne. “The danger is that people are putting something into their body that the government hasn’t gotten its hands around.”
As for the person taking the substance, “typically, American laws don’t make the personal use of an unapproved drug illegal,” Collins said.
Those who distribute these types of chemicals to be used as drugs, however, can face charges of mail fraud or misbranding of drugs.
In addition to GW501516, dubbed “exercise in a bottle” for its ability to mimic the effects of physical activity on the body, athletes also use compounds called selective androgen receptor modulators, or SARMS, intended to treat conditions such as muscle wasting and osteoporosis.
“These are also still in clinical trials or have been discontinued due to undesirable effects, but they are still detected in doping control samples,” said Mario Thevis, editor in chief of the journal Drug Testing & Analysis and a professor at the Center for Preventive Doping Research at the German Sport University at Cologne.
Aromatase inhibitors, a class of drugs under investigation for the drugs’ ability to reduce estrogen synthesis, are also sold as research chemicals. Some are approved for human use and used to treat breast cancer, but many are still in clinical trials. The drugs are popular among athletes who take steroids because they prevent elevated levels of testosterone from being converted to estrogen, thus reducing potential side effects of the steroids, including male breast enlargement, acne and water retention.
Jeff Johnson, a bodybuilding promoter who owns Flex Gym and Fitness Center in Ottawa, Ill., said the products’ safety is a concern because when drugs are bought over the Internet, it’s impossible to know what’s really in the bottle. But he has no doubt that some are effective.
“It’s a tight-knit community; if something works, they pass it on,” said Johnson, a former competitor who stressed that he doesn’t advocate drug use. “Part of the bodybuilding mentality is ‘more is better.’ They’ll try anything that enhances performance and adjust the dosage. Bodybuilders are guinea pigs.”
The websites that sell the compounds often cite fragments of scientific studies and toxicology reports; many also often contain misleading or incorrect information.
The Chicago Tribune bought a vial labeled GW501516 from Osta-Gain for $69.98. The label included a disclaimer: “For Research Purposes Only. Not For Human Consumption.” The Osta-Gain site states that the drug is “being investigated for drug use by GlaxoSmithKline” and adds that the “increase in endurance, muscle fiber performance, fat loss and metabolism suggests it has the potential for ergogenic use and abuse.”
Kentucky attorney J. Clark Baird, who represents Osta-Gain and several other companies that sell research chemicals on the Internet, noted that customers who buy research chemicals through Osta-Gain must, prior to ordering, sign an electronic disclaimer that specifically states human consumption is illegal.
Baird acknowledged that some experimental products might be diverted for human use despite the warnings. But a consumer’s misuse of the product “doesn’t mean it’s the fault of the manufacturer,” he said.
Baird said he counsels his clients not to advertise on bodybuilding boards. “At the end of the day, all they can do is sell products that aren’t illegal, sell them in a responsible way and make sure purchasers are aware of the limitations on the product,” he said.
Collins, however, said warnings aren’t necessarily enough to protect a distributor.
“The government can view it as a trick or a cover,” he said.
Adam Higdon of Palatine faces federal charges, including mail fraud and misbranding of drugs, after he falsely represented on his websites that he was selling substances “for research use only … not for human consumption,” according to a indictment announced this month. In emails to customers, Higdon is accused of describing the benefits of his products for burning fat and tanning in preparation for bodybuilding shows.
Attempts to reach Higdon for comment were unsuccessful.
In January, Nevada’s Chandan Manansingh pleaded guilty to “introducing a misbranded drug into interstate commerce.” He was accused of repackaging, relabeling and reselling unapproved experimental drugs to consumers who injected themselves with the products. Though the website had numerous disclaimers stating the drugs were for research only, “Manansingh knowingly used these disclaimers as a ruse to avoid FDA scrutiny,” according to court documents.
Manansingh advertised his website and products extensively in bodybuilding magazines and sold his products to bodybuilders for their personal use, according to the plea agreement. He also advised his customers — including an undercover federal agent — via email and telephone “on how to self-administer the drugs, including recommended dosages and placement of the injections to best produce the desired bodily enhancements,” documents state.
Manansingh’s attorney, Andrew Ira Alperstein, declined to comment as the sentencing is pending.
GlaxoSmithKline originally began developing GW501516 in 2005 as a way to treat high cholesterol associated with metabolic syndrome. When safety studies found it caused multiple types of cancer in mice and rats, the company pulled the plug in 2006 and reported its findings to regulatory authorities and at a scientific meeting.
“We don’t have a patent for GW501516 and can’t control what is sold on the Internet,” said Williams, leader of the drugmaker’s anti-doping initiative. “We just have to be vigilant in working with (the World Anti-Doping Agency) and getting the message out that there are dangers in taking these chemicals that have not been approved for use.”
The drug’s long-term effects are unknown because the initial human trials were limited and involved small numbers of patients, according to information the company gives to physicians who ask about it.
“It’s not a great compound,” said Ronald Evans, a professor and director of the Gene Expression Laboratory at the Salk Institute for Biological Studies in La Jolla, Calif. His research showed GW501516 may boost endurance and had the potential to be abused by athletes.
“It has a certain toxicity; it tends to accumulate and doesn’t metabolize well,” Evans said. “It can crystallize when it gets to be concentrated in such high levels.”
But in some circles, the long-term effects are secondary issues. On a recent thread on elitefiness.com, users discussed how to improve the taste of GW501516 for their lab rats. A user weighed in with the final word: “Who gives a (expletive) if it doesn’t taste like candy? My rats and I agree. Results (are greater than) taste.”