Many of these psychoactive substances are little-known compounds culled from obscure research journals like Arnold’s Swiss periodical. While some published steroids have a research trail, most psychoactive drugs have never been tested on humans—until, that is, they show up at clubs or parties. When these recipes hit the mainstream, they often go viral through websites where chemists and entrepreneurs of all stripes trade recipes.

These drugs can end up being mass-produced by chemists for hire in China, who advertise “custom organic synthesis” on the web and take their orders from the emerging breed of transnational rogue chemists. “There are a lot of very, very smart people out there who know how to read chemistry papers,” says Nathan Messer, president of the nonprofit organization DanceSafe, which provides drug testing at festivals and parties. “It usually starts off as some people making it themselves, and if it works out, they will contract it out to China, set up a distribution chain, buy in bulk, and sell it.”

What effect these new, unregulated psychoactive drugs might have on the human body is typically not clear. Often they are chosen because their chemical structures resemble those of known illegal drugs, like MDMA (ecstasy), speed, or cocaine, but are just different enough that they can arguably be considered legal, or can be marketed in the United States as “not for human consumption” with a hint of credibility. Some vendors hope this distinction will allow them to evade a 1970 law that allows authorities to prosecute for drugs that are “substantially similar” to banned substances if they are intended for human consumption.

For underground chemists gearing their efforts to the parallel market for performance-enhancing drugs, tweaking a couple atoms—or brewing up an obscure compound most people aren’t aware exists—can render a banned substance undetectable to professional sporting bodies, since they need a reference sample to spot it.

This kind of kitchen chemistry can have devastating results. Throughout the 1970s and 1980s, dozens of drug users consumed homemade batches of a synthetic opiate called MPPP that gave them symptoms of Parkinson’s. The cause was a mundane chemistry error. The pH during one of the reactions was a bit too low, causing the drug to extrude a single small molecule of propionic acid, which transformed it from a powerful narcotic into a poison that laid waste to the brain’s dopamine receptors.

David Nichols, a professor in Purdue University’s pharmacology department, knows firsthand what can happen when research chemicals find their way into underground labs. He has spent decades feeding LSD, mescaline, and MDMA derivatives to rats in an effort to map the brain receptors they act upon. He works by tweaking the chemical structures of the drugs, sometimes changing just a few molecules to see what impact this might have on the interaction between the drug and the brain receptors their parent compounds normally act upon.

Nichols first became aware that rogue chemists were following his research more than 10 years ago, when one of his ecstasy derivatives called 4-methylthioamphetamine (MTA) appeared in Europe as a club drug. In a published paper, Nichols had reported that rats that had been trained to press a lever when administered MDMA also hit the button when given MTA. That apparently was enough to catch the attention of a rogue chemist who synthesized the drug, rechristened it Flatliners, and sold it in the Netherlands. The choice of name was a morbid harbinger. By 2002 Flatliners had killed at least six people. Nichols believes they died from an overdose of the neurotransmitter serotonin, which can lead to hyperthermia, muscle breakdown, and seizures.

Flatliners, it turns out, does not release the dopamine and norepinephrine that account for much of ecstasy’s euphoric effects, but, like ecstasy, it does release massive doses of serotonin and interferes with the body’s efforts to break it down. That apparently accounted for the reaction Nichols recorded in rats, which recognized the serotonin rush caused by MDMA. Nichols believes that when the initial dose of Flatliners failed to produce the ecstasy-like euphoria the human drug users were expecting, they upped their dosage—and kept upping it until it killed them.

Tragic as the deaths were, Nichols is more worried about what might happen if underground compounds cause side effects that are less obvious and take longer to manifest. “That is my biggest fear,” he says. “Suppose somebody makes something like ecstasy? That’s a big success for them. But nothing is known about how the drug reacts with the rest of the body. Suppose it kills cells in the pancreas or in another organ? And suppose people take it every weekend? If a couple of people die, that is not nearly the tragedy if a hundred thousand people suddenly needed heart transplants.”

Mike Cole, a forensic scientist at Anglia Ruskin University in Cambridge, England, has done research that indicates Nichols is right to be concerned. Cole has been studying a drug developed to combat parasitic worms in livestock. Now mass-produced in East Asia, it is peddled in the party scenes of San Francisco and elsewhere as a “legal” and “safe” alternative to ecstasy. The drug, benzylpiperazine, isn’t difficult to make; it requires a chemist to trigger a reaction between two chemicals in a flask, then cool them down until the compounds combine into crystals and the drug precipitates out.

But the drug, Cole demonstrated in his lab, can be highly toxic to the kidneys. “If you worked for a chemical company, you would clean up your final product,” he says. “But the guys on the street aren’t interested in it. They’re trying to make maximum profit, and you can get the effects without the cleanup process.”

Meanwhile, many bodybuilding steroids have been shown to cause liver and kidney disorders and male infertility. The likelihood these side effects will occur is dependent on the potency and dosage of the compounds consumed, and the less one knows about the steroid in question, the harder it is to get the dosage right. The impact of years of doping is even more difficult to determine. “We have yet to do an epidemiological study of long-term effects,” says Penn State professor emeritus Charles Yesalis, one of the foremost experts on steroids. “And if we don’t know the long-term health effects of the known drugs produced by pharmaceutical companies, we sure as heck aren’t going to know the effects of the unknown ones.”

A week after Arnold took his first dose of liquid mestanolone, his life began to change. At the gym, he was on fire. The amount he could bench-press spiked and kept rising, topping out at 30 extra pounds. Soon his clothes were tighter, and his muscles popped with new veins. The physical transformation was hard to ignore, and Arnold confessed his actions to his office friends. “It got around; everybody found out,” Arnold recalls. “But I didn’t give a damn.”

Arnold left his job, moved back to Connecticut, and started taking graduate-level chemistry classes at the state university. He also joined an Internet discussion group on fitness and weight lifting. Arnold’s knowledge of steroids quickly set him apart from other members of the discussion group. People began to seek his advice.

One of them was former bodybuilder Dan Duchaine, the author of The Underground Steroid Handbook, an indispensable reference manual for juicers. He had also served two prison stints for trafficking in steroids. Duchaine was well connected in the emerging field of gray-market nutritional supplements, products that often pushed the limits of laws regulating steroids. Through a friend, he put Arnold in touch with a Trinidadian entrepreneur, Ramlakhan Boodram, who owned a company that sold soy-processing and farm equipment in Champaign, Illinois, and had manufactured a nutritional supplement for Duchaine’s friend. Boodram was hoping to break into the booming field himself and needed a chemist to develop products for him.

Arnold moved to the Midwest. There, surrounded by cornfields, he set up a lab in an old brick warehouse that was crammed with tractors, metal presses, and oversize mixers used to process soy. He started out with just a few flasks and a hot plate, but eventually he filled his corner of the building with a mass spectrometer, vacuum pump, and all the lab equipment he would need to brew up new substances. Arnold focused his efforts on a patent he came across while flipping through chemical abstracts. It came from an East German pharmaceutical company called Jenapharm, which produced most of the steroidal compounds used in the former communist nation’s athletic doping program.

Jenapharm’s patent concerned a compound known as androstenedione, a naturally occurring testosterone precursor produced by the adrenal glands, testicles, and ovaries. Synthesized andro was widely used in labs as a steroid precursor. But the patent noted that if you administered the hormone orally, the body’s own enzymes would catalyze reactions that would convert it to testosterone, theoretically providing performance-enhancing benefits similar to those of steroids derived from the substance in the lab.

Andro would be potent, easy to make, and possibly legal; after all, Arnold reasoned, how can you regulate something that occurs naturally in the body? Still, he knew it would push legal boundaries to sell something that would turn into a banned substance once ingested. He worried he might get arrested. As an entrepreneur trying to break into nutritional supplements, he decided to take the risk anyway. “Nobody was going to buy vitamins from me,” Arnold says. “When you’re trying to start a business from nothing, you have to have something unique to sell.”

Once andro hit the market, word of its potency spread quickly through the athletic community. Then a reporter spotted a vial of the supplement in the locker of baseball slugger Mark McGwire during the season when he shattered the 37-year-old single season home run record. Suddenly Arnold was famous. In 1998 Sporting News named him number 84 on its list of the 100 most powerful people in sports, sandwiched between sportscaster Bob Costas and superagent Arn Tellem.

Arnold moved to cash in on his renown. He went back to the journals, scanning abstracts for other naturally occurring metabolites that looked likely to be converted into testosterone once ingested. He came out with several more so-called prohormones. In 2003 he and his partners moved to a shiny new 38,000-square-foot warehouse with 30-foot ceilings, 2,000-gallon reactors, and a state-of-the-art research lab with a gas chromatograph and other analytic instrumentation. By 2004 their revenues hit $12 million a year.

Secretly Arnold continued to experiment with illegal steroids. Back in New Jersey, he had come across an anabolic steroid he’d never seen anywhere else, a compound that had been developed by Wyeth Pharmaceuticals (now owned by Pfizer) in the early 1960s. Called norbolethone, it had a unique chemical structure that would be impossible to detect, but it also seemed to have many characteristics of the more potent steroids Arnold had tried. Back then, as a lowly lab tech at a chemical company, Arnold could never get hold of the precursor, a prohibitively expensive synthetic progestogen known as levonorgestrel, the active ingredient in the morning-after pill.

One day, talking to a business associate at another nutritional supplements company, Arnold mentioned norbolethone and his problems getting the precursor. Soon afterward, a gift arrived in the mail from China: a package of levonorgestrel. Arnold brewed up a batch of norbolethone, cross-checked the molecular structure with his instruments, and gave himself a mild dose.

Arnold rationalized that the compound was probably safe. “One dose of a steroid will never kill you, even if it is massive,” he later explained. Whereas psychoactive drugs can have immediate unpredictable and dramatic effects, steroids work primarily by activating genes, a slow process that only gradually yields detectable physiological effects. “Only with chronic intake will you see adverse effects from a steroid,” Arnold says. He did notice the compound turned his urine a dark shade of yellow, which led him to believe it might be placing a strain on his liver. On the other hand, he was on fire again at the gym. It was potent stuff.

As a side job, Arnold gave phone consultations for people aiming to bulk up, which he advertised on a bodybuilding website. If a client inquired about untraceable steroids, Arnold would send him samples of his compound. “I must emphasize,” he would later say, “that I made everyone aware these drugs had potential long-term adverse effects.”

That such a potent steroid could be so easily distributed alarms Gordon Hughes, who invented norbolethone in 1961 as part of his Ph.D. thesis at the University of Manchester in England. While employed by Wyeth, he developed the compound to help elderly surgery patients who needed to build more protein; he never imagined it might someday be used by athletes. “It bothers me that people are getting these drugs,” Hughes says. “You don’t know how pure they are. They haven’t passed FDA requirements. You don’t know anything about them.”

That is a sentiment shared by plenty of other research chemists. Clemson University professor emeritus John W. Huffman devoted 27 years of his career to developing biological analogues to THC, the principal active component of marijuana. Huffman hoped to understand how THC and related compounds interact with brain receptors and perhaps find treatments for nausea and glaucoma.

In 2008 he learned his chemicals were being marketed as “legal” highs in Germany. “There have been some rather severe cases of psychosis,” he sighs. “I figure people are responsible for their own actions. If they use this stuff, which they shouldn’t, they are going to suffer the consequences.”

Just as Arnold suspected, norbolethone was so obscure that professional doping programs had no reference sample and thus could not detect it. It was a brash entrepreneur named Victor Conte who pushed the limits of that obscurity. He ran a sports-nutrition center in Burlingame, California, called the Bay Area Laboratory Co-operative (BALCO). Through BALCO, Conte sold legal zinc-magnesium supplements of questionable efficacy and enlisted topflight athletes to promote them. Among them were true superstars: Marion Jones, who would become the fastest woman in the world, and Barry Bonds, who would go on to break the record for most home runs in a single season. In addition to providing these athletes with supplements, Conte offered up secret supplies of illegal steroids on the side.

Arnold, who met Conte in an Internet chat group, sent him the new compound. Conte rechristened it “the clear” and began distributing it to top athletes. Arnold himself gave the clear to Olympic cyclist Tammy Thomas, whose heavy use would eventually alert authorities to the drug. Thomas ignored Arnold’s dosing advice, he claims, and by 2002 was using so much norbolethone that she had grown facial hair. When her natural testosterone dropped to levels far below normal, testers began to scrutinize her urine. It was only a matter of time before they identified metabolites that led them to norbolethone.

Conte got wind that the authorities were closing in and told Arnold to find a replacement compound. In response, Arnold gambled with a move both rare and bold in underground chemistry: He created an entirely new steroid. To do so, he sat down with The Merck Index, a standard reference manual for chemicals, drugs, and other compounds, and turned to the section on the class of hormones to which norbolethone’s precursor belonged. He hoped to find a different precursor that could be transformed into a steroid using the same molecular processes used to render norbolethone.

Arnold dismissed some because he knew they were associated with steroids on watch lists. Others he knew from experience had molecular properties that would make them weak. Then he spotted tetrahydrogestrinone, a compound never before used to create a steroid. It had three alternating carbon double bonds, called conjugations, that he had seen in some potent steroids, as well as an additional carbon atom that he recognized would give it extra strength.

“I knew I was looking at an exciting structure,” Arnold recalls. “It’s very complex compared with other ones. It was more potent. People would not have to take as much. The stuff would have been invisible forever. It was perfect, perfect stuff.” He put clients on 10 milligrams a day, then reduced it to 5 milligrams when he was sure it worked.

But Conte had a lot of enemies, among them Marion Jones’s former coach Trevor Graham. In June 2003 Graham sent a syringe that contained the new substance to the U.S. Anti-Doping Agency. Once the group had a sample, it was only a matter of time. The authorities closed in and exposed one of the biggest scandals in the history of sports.

In 2005 the Feds raided Arnold’s home and lab. He was convicted and sentenced to three months in prison in 2006. The investigation touched off litigation that lasted through last year, when Barry Bonds was finally sentenced to 30 days of house arrest for obstructing justice during the inquiry.

Today, Arnold insists he is out of the steroid game. Andro and many other prohormones like it have been outlawed by Congress, and Arnold says he is focused solely on legal supplements. To pay fines, he and his partner were forced to auction off their new warehouse with all its top-of-the-line equipment. Today they are back in the old warehouse in the cornfields outside of Champaign, looking for compounds that are distinct from any banned substances to keep them out of trouble.

Don Catlin, the founder of the UCLA Olympic Analytical Laboratory in Los Angeles and the man who finally identified Arnold’s “clear,” says there are several hundred known steroids, and one could “spend a lifetime finding them, manipulating them, and getting them into a form where you could give them to a human being.”

Arnold says that in manufacturing their own supplements, he and Boodram are now an exception in the industry. Almost nobody makes steroids or supplements themselves nowadays; most outsource the job to China. As a respected underground chemist, Arnold is sometimes called upon by others in the industry to test products they have had made in Chinese factories. He says these factories “often substitute cheaper steroids for more expensive ones, or sometimes they just sell crap, which I can’t even characterize on my instruments.”

The same problem shows up in the new wave of psychoactive chemicals mass-produced overseas. At least five deaths and dozens of hospitalizations, for instance, are believed to have been caused by a compound called Bromo-Dragonfly that was first developed in Nichols’s Purdue lab and is now produced for Westerners in China.

In one fatal 2009 batch, a San Jose man died after consuming Chinese-made Bromo that contained “unspecified synthesis impurities,” which may have contributed to the product’s toxicity, according to the underground drug user website Erowid. His distributor sent more of that batch to other users in Denmark and Spain, leading to at least one other death and numerous hospitalizations. And just last May, a Chinese manufacturer sent a college student in Oklahoma a mislabeled batch of Bromo when he had ordered a far less potent product. As a result, two more people died and six others were hospitalized after overdosing.

The shifting realities of a world where legitimate chemical research can be hijacked by anyone with a hot plate and an Internet connection has forced Nichols to reconsider his craft. He works more closely with the Drug Enforcement Agency to monitor new compounds and is more aware of the consequences of making his research public. “Now when we publish, I think, ‘Is this going to be a problem?’ If we published an LSD analogue with 10 times the potency of LSD, I guarantee that six months later it would be all over the Internet.”

Nichols believes his work could help explain memory, depression, even the nature of consciousness. Science must continue, he says, and he can’t stop publishing. But now he knows who might be reading.

Adam Piore is a DISCOVER contributing editor. He last wrote for the magazine on regenerative medicine in the July/August 2011 Issue.

Russia’s Home-Brewed Drug Crisis
Crystal meth, synthesized in small-scale labs across the United States, exacts a harsh physical toll, rotting users’ gums and eating away at their teeth. But meth’s ill effects pale in comparison to those of an intravenous home-brewed opiate now sweeping through Russia. The drug’s nickname, krokodil, comes from a grisly sign of use: Tissue around the injection site dies and results in patches of skin that turn greenish gray and scaly, like the hide of a crocodile.

Desomorphine, as krokodil is formally known, can be cooked up at home according to online recipes that require only readily available ingredients. Codeine, the active component, is sold over the counter in Russia in cough medicines and painkillers. Other components are household items, including paint thinner, iodine, and red phosphorus shaved from matchbooks.

“Krokodil is a last resort for people who can’t get heroin or other injected drugs,” says Russian public-health researcher Kirill Danishevskiy. It costs only a tenth as much as heroin, though its high is shorter; addicts often have to inject the drug 7 to 10 times a day to stave off withdrawal.

Although statistics are scarce, Russia—a nation of about 140 million people—may have nearly a million krokodil users, estimates Anya Sarang, a public-health advocate who works with drug users in Moscow.

The drug’s toxicity has effects much grimmer than crocodile-like skin. Large areas of tissue can rot away, often down to the bone; in severe cases, the bone rots away, too. Addicts are often forced to have their limbs amputated and are prone to secondary infections such as tuberculosis. But many users are so caught up in the cycle of making and taking the drug, Sarang says, that they cannot be bothered to go to a doctor—and for the few who do, Russian hospitals are ill equipped to help them. Life expectancy for krokodil addicts after they begin using is about two years.
—Valerie Ross