The Drug Revolution That No One Can Stop

AT MIDDAY ON A THURSDAY this past April, a radio call crackled through from an ambulance team to the emergency department of Calvary Hospital in Canberra, Australia.

Dr. David Caldicott, who was leading the shift as admitting officer, immediately noticed a tense quality in the ambulance driver’s voice. His tone was higher-pitched than normal, and his words came fast and clipped. Two young men had been found unconscious in the grounds of the local university, the ambulance driver said. They would both require immediate tracheal intubation. That was it: the line closed. No further information. The ambulance raced through the city traffic towards the hospital, sirens wailing.

“Emergency medicine is like flying a plane,” says Caldicott. “Hours of mundanity punctuated by moments of sheer terror. If you’re worth your salt, you’re not scared, though. Just focused.”

The men arrived, deeply unconscious and in need of immediate intensive care. Neither patient could breathe properly without assistance, and the ER teams scrambled to stabilize them by splinting open their airways and ventilating their lungs with breathing tubes.

What had happened to the men? They were inert and unresponsive as if they had overdosed on heroin, but they had no injection marks and their pupils were not constricted. Still, they were injected with Naloxone, a safe and rapid heroin antidote. It didn’t do a thing.

Tests showed none of the standard drugs in the men’s systems. There was no evidence to suggest they had suffered heart attacks or strokes. They had no names, no ages. Nurses draped the men, who were cold, in a pair of warming blankets. All investigations were drawing a blank.

Through the confusion, Caldicott’s instincts told him that he had seen this before, three years previously, on the other side of the world. He had treated an overdose of something called methoxetamine or MXE—a designer drug based on the common tranquilizer ketamine—in the small market town of Abergavenny, South Wales, in 2010.

“The guy had faceplanted in a quantity of white powder,” he says. “It was everywhere, all over his face. Like Scarface. The patient was out of it, but very happy. But once again, it didn’t seem to be something typical, like cocaine. So we sorted him out and sent a sample to the labs to work out, and they found it was MXE.”

Caldicott couldn’t quite believe it might be the same rare drug he’d seen 10,000 miles away. Nor could his colleagues. “They looked at me as if to say, ‘Who is this crazy man? What are you talking about?’”

IN 2011, CALDICOTT HELPED FOUND WEDINOS, a Welsh-government-funded group that identifies and investigates new psychoactive substances. In the years before, there had been a sharp increase in the number of cases in which patients arrived at emergency departments requiring help for drug overdoses, but clinicians—and often even the patients themselves—were unsure what they had taken. After moving to Australia in 2012, Caldicott set up a similar project, called ACTINOS.

But when the tests came back, Caldicott’s hunch was right. The men were treated by putting them into a chemically induced coma, which gave them time to purge the drug from their system. It was a lucky escape: MXE overdoses have been linked to at least two deaths.

“We are tracking the arrival of new species as they arrive in a society,” he says. “It’s toxico-surveillance.”

Methoxetamine is just one of the novel drugs identified by these groups. It has existed for just over three years, and while it remains legal in much of Europe, and in many other countries in the world, it was made illegal in the UK in 2012. It is closely chemically related to ketamine, but several times more potent. Many of its effects are the same: extreme dissociation, hallucinations, and a semi-paralyzed overdose. And above all, in nearly every country on earth, it is entirely legal to buy.

MXE is part of a cultural shift that started a generation ago, but has taken on a new edge in the last few years. In 2008, the first in a wave of new, legal, synthetic drugs emerged into the mainstream. They had little to no history of human use. Instead, they were concocted in labs by tweaking a few atoms here and there—creating novel, and therefore legal, substances. Sold mainly online, these designer drugs cover every category of intoxication imaginable, and their effects resemble the full range of banned drugs, from the mellowness of marijuana to the extremes of cocaine and LSD. They are known as “legal highs,” and they have exploded in popularity: the 2012 Global Drugs Survey found that one in twelve people it surveyed worldwide takes them.

Legislators around the world have been put off-balance by the emergence of this massively distributed, technically complex and chemically sophisticated trade. And the trade is growing rapidly.

In 2009 The European Monitoring Centre for Drugs and Drug Addiction’s early warning system identified 24 new drugs. In 2010, it identified 41. In 2011, another 49, and in 2012, there were 73 more. By October 2013, a further 56 new compounds had already been identified—a total of 243 new compounds in just four years.

In its latest World Drug Report, the United Nations acknowledged this extraordinary expansion: “While new harmful substances have been emerging with unfailing regularity on the drug scene,” it said, “the international drug control system is floundering, for the first time, under the speed and creativity of the phenomenon.”

Technology and drugs have always existed in an easy symbiosis: the first thing ever bought and sold across the Internet was a bag of marijuana. In 1971 or 1972, students at Stanford University’s Artificial Intelligence Laboratory used ARPANET—the earliest iteration of the Internet—to arrange a marijuana deal with their counterparts at the Massachusetts Institute of Technology.

That groundbreaking deal connected two teams of people who were separated by a 45-hour drive east-west across the entire continent. Today, buying drugs online is far easier and faster—and in many cases, you don’t even have to break the law.

Caldicott, speaking from his office in Canberra, says we are living through tumultuous times.

“I compare the phenomenon of illicit drug use to influenza. During the course of a year influenza changes slightly, which is why you get a new jab every year. But every 10 to 15 years we see a major shift. The year-to-year swaying and back-and-forth of influenza is called antigenic drift: the world and the bug interacting. When avian or pig flu or something like that appears, that’s called an antigenic shift. When these big changes occur, our immune response is negligible. We can’t fight it. And then we need completely new vaccines.”

He continued: “I would argue that we have seen an antigenic shift in the drugs market with the emergence of legal highs since 2008. But the truly extraordinary thing about this is that it’s not just the products that are new. We have all this supplementary stuff: the change in delivery and payment and information and communication systems. All of them have exponentially increased the hazard. It is one of the biggest shifts we have ever seen in the drugs world, to my mind.”

THERE’S A PHOTOGRAPH OF THE BEATLES that most people, even some of the band’s most dedicated fans, have not seen. Shot in Hamburg in 1962, it shows each of the band looking slightly manic—but not in the irreverent, comic style that endeared them to the world when they first burst out of the backstreets of Liverpool and on to the global stage.

In the photograph, which their manager Brian Epstein kept buried for years, the Beatles appear to be very, very high. John Lennon’s eyes are popping out of their sockets, eyebrows almost reaching his hairline, his teeth locked into a fierce grin. Paul McCartney looks a little better, though his gurning face is matched in desperation only by his clutching hands, which are reaching for the small metal tubes held by Lennon.

The tubes contained Preludin tablets, also known as Prellies: diet pills bought to keep the band awake during grueling, multiple sets at the Star-Club on the Reeperbahn in Hamburg’s tough dock district. The active ingredient in Prellies is phenmetrazine, a stimulant drug that is now illegal all over the world. It was patented in 1952 by German pharmaceutical firm Boehringer Ingelheim and came to market in 1956, but was banned internationally fifteen years later.

Phenmetrazine was incredibly popular in its day, taken, biographers claim, by John F. Kennedy, Elvis Presley, Frank Sinatra, Tennessee Williams, Truman Capote, and Marilyn Monroe, among others. It was sold all over the U.S. and Europe in the 1960s, as an anorectic—a diet aid, since it controls appetite. It also produces a euphoric rush by hitting the brain’s dopamine pleasure and reward centers, just as good food with friends, a gambling win, and sex do. But phenmetrazine—like cocaine, amphetamines and other stimulants—hits those pleasure centers harder and longer.

Phenmetrazine was no different from most of the synthetics used in the 1960s: legitimate prescription drugs that were diverted into the hands of users looking for a kick. But with the consumption of drugs so prevalent following the 1960s psychedelic and countercultural explosion, the authorities felt the need to act. The UN conventions of 1961 and 1971 were designed to prevent addiction and long-term health problems. The new laws laid out which substances were banned, but did not prohibit substances that were chemically similar, but not precisely the same. The conventions have hundreds of signatories, and many of these countries have their own additional laws, producing a legal patchwork whereby certain chemicals and modifications are banned in one country, but remain legal in another.

Designer drugs are officially known as “controlled substance analogs”. (An analog of a drug, in this definition, is a version of a banned compound that has been created with the aim of making it legal.)

The UK and U.S. are the market leaders in consumption and marketing of these new substances, which means the two key pieces of legislation that govern—or fail to govern—contemporary drug culture are Britain’s Misuse of Drugs Act of 1971, and America’s Controlled Substance Analog Enforcement Act of 1986.

U.S. law states that anything that is “substantially” similar in its chemical composition to a banned drug “shall, to the extent intended for human consumption, be treated… as a controlled substance.” However, this blunt phrasing, in an area as complex as organic chemistry, turned out to be legally and socially myopic. Many online designer drug dealers in America simply say the products are not for human consumption: a convenient lie that usually allows them to evade the authorities, but is easily, and willingly, ignored.

It could be absolutely anything, one of several million compounds of different potencies and effects and toxicities. Or it could be sugar. There’s only one way to find out for sure.

Most of the innovation around legal highs in recent years has come out of the UK. With the law now over 40 years old, it has hundreds of amendments employed to try and catch an ever-growing list of narcotics. There are currently more than 150 in its most heavily controlled category alone. The law is now caught in a race with runners half its age, who understand chemistry and technology as well or better than the people who wrote the statutes and implement them, and whose aim is specifically to outrun and outsmart the law in order to enrich themselves.

Many of those who design drugs do so merely to push the boundaries: these “psychonauts” as they are sometimes known, are early adopters of new drugs. Some share their knowledge freely and collaboratively; some are intensely geeky; some are pretentious and elitist chemical grandstanders, eager to be the first to try and document any new drug. Many psychonauts are extremely cautious, and fastidious in dosing and documenting a drug’s effects. Others still are reckless risk-takers—people who will try anything for a kick. One user I spoke to enjoyed his experiences with mushrooms so much that he began to seek out all the new hallucinogens he could find. He is a passionate advocate for psychedelics: “In life, you’re battling through the undergrowth and every so often it’s good to climb a tall tree to get your bearings. This is what psychedelics do for me.”

One of the most influential underground chemists is a British man known to me as Karl. In 2010, Karl conceived the recipe for methoxetamine, the drug that David Caldicott spotted in Wales and Australia. I met him first on a bulletin board five years ago, then in person recently. His design for MXE was more potent than its parent, ketamine, which is generally used as an anesthetic but is prized by users for its ability to deliver an out-of-body experience. A legal highs firm took Karl’s design, and had it synthesized by a legitimate Hong Kong lab. It went on sale first in Britain in 2010, before spreading across the world. The drug is now illegal in the UK.

Karl is far from alone. David Caldicott has met many of the web underworld’s chemical designers in an attempt to understand what it is that he is seeing.

“I was led to meet one once and I had to wear a blindfold,” he says. “These are hugely secretive people.”

“There’s a misguided assumption that the guys running clandestine chemistry labs have bad complexions and wear plaid shirts and that they are slightly dim and just follow cookbook recipes. That’s a mistake. These guys are incredibly bright. They are head-and-shoulders—intellectually, certainly—above some of the politicians who are attempting to legislate against them.”

IN THE WINTER OF 1944, the USS Pope, a 1,200-ton destroyer escort, was about 1,000 miles from the coast of England. It had recently finished a running battle with German U-boats off the Azores, one of the critical naval conflicts of the Second World War. On board, a young U.S. marine named Alexander Shulgin tried to relax by playing poker, but as he shuffled the cards, his left thumb ached intensely. It was badly infected and needed surgery, but there was no way to operate while at sea.

Shulgin’s ship docked at Liverpool, and he was transferred to a nearby army hospital for the operation. There, a nurse handed him a glass of orange juice, and as he drank he noticed a few undissolved grains of powder at the bottom of the glass. He assumed they were the remains of a sedative, and despite his best efforts to stay awake, he fell deeply unconscious.

When he awoke, Shulgin discovered he was wrong: the glass had contained only juice and sugar, and his collapse was caused entirely by the placebo effect. It was only after he’d already passed out that the doctors had administered an anesthetic and conducted the operation. The idea that his brain had fooled him was a revelation to the young marine: if a placebo could have such a dramatic effect, the possibilities for active drugs seemed boundless. Suddenly fascinated by the interface between the mind and molecular matter, Shulgin returned to the U.S. and embarked on a career in psychopharmacology. It was an odyssey that would change the lives of millions.

From the late 1960s into the 1990s, Shulgin, a tall, loping, grinning man given to gaudy shirts and untamed hair, invented an extraordinary range of drugs. Convinced of the positive benefits of cognitive enhancers, Shulgin worked as an expert chemist for drug manufacturers and the U.S. government, and used his work to subsidize an extraordinary investigation into new psychedelic drugs. Many of them had effects that had never been seen before and often remain little-understood, even now.

Shulgin’s discoveries included drugs like DiPT, an analog of a psychedelic chemical found in some plants and fungi, that was manipulated to produce one curious effect: it makes anyone listening to music hear the sounds an octave or so lower than before. Another drug, MMDA, gave users intricate “brain movies”—extraordinarily bizarre and incredibly detailed narratives that seemed to spring from untapped parts of users’ minds.

Shulgin’s breakthrough came with MDMA. Today, known as ecstasy, E, or X, it is now one of the world’s most popular recreational drugs—but it has a complex history. It was first synthesized by German pharmaceutical firm, Merck, in 1912, to get around a patent on a common clotting agent, and later used by the US military in experiments in mind control. But it wasn’t until Shulgin got a tip-off from a fellow researcher in 1965 that he started to investigate the drug. By the 1970s he was hailing it as a breakthrough and circulating it to his friends and family, and in 1978 published a research paper with his colleague David Nichols that explained the drug’s psychotropic nature.

Popular for its euphoric, intimate effects, MDMA found its way into the gay club scene in Texas, and from there, by the mid-1980s, to hangouts such as Dallas’s Starck Club, where celebrities like Stevie Nicks and Grace Jones gave it a glamorous sheen. By 1988 the drug had moved to Europe: Ibiza, Manchester, London and beyond, where it gained a soundtrack: acid house. The rave scene’s fascination with ecstasy and illegal warehouse parties echoed the LSD boom of the 1960s, and by the time the first wave of ecstasy use had subsided in the 1990s, Europe’s psychic shoreline had changed. And the liberation offered by this new generation of psychedelics and music was soon augmented by the birth of another lawless free zone: the Web.

THE DESIGNER DRUGS SCENE first hit the Internet around 1998, when clandestine chemists started creating small batches of chemicals for their friends and discussing them on sites such as Erowid and forums such as Bluelight. It was a tiny movement, with perhaps a few thousand people worldwide interested in these potent and unusual substances. But circumstances were coming together in a way that nobody could have predicted.

Shulgin had meticulously recorded the synthesis and impact of each of his drugs in a pair of strange manuals, PiHKAL and TiHKAL (the first exploring “Phenethylamines I Have Known And Loved”, the second dedicated to tryptamines). Published in the 1990s, each of them combines dry academic passages with flights of fanciful description documenting the drugs’ effects.

At the same time, Shulgin’s frequent collaborator, David Nichols, was becoming similarly renowned for his prolific research on mapping the brain’s serotonin and dopamine receptors. And although Nichols, who worked at Purdue University in Indiana for 38 years until his retirement in 2012, partly focused on discovering new treatments for schizophrenia, depression, and Parkinson’s disease, he also explored how these substances worked in the brain: precisely the same psychotropic territory as Shulgin.

Until the 1990s, their work had been known only to a small cadre of scientists and psychonauts, but the Internet allowed knowledge previously locked away in books and journals to be shared widely and easily. The studies and research papers of Shulgin, Nichols and others suddenly became instruction manuals, discussed and dissected online by Karl and other chemists. They turned the scientists’ work into mass-produced club drugs.

Within a couple of years, dozens of these substances had been cleverly rebranded as “research chemicals” and were being—entirely legally—sold over the Web by the underground pharmacists and their entrepreneurial associates. Users sampled the drugs, much as Shulgin had, and documented their experiences online; millions of pages of discussion about their use and effects were created.

Then, at the start of the 2000s, the scene hit its first major problem. In a series of separate but highly publicized incidents, three young American men overdosed on a compound named 2C-T-7 that had first been detailed in Shulgin’s books. The resulting backlash against legal highs was then compounded by high-profile busts by the Drug Enforcement Agency. Although few of the people arrested in these raids were actually involved in the manufacture and distribution of the drugs—most were simply customers of the websites that sold these strange new compounds—it did succeed in sending users and dealers into a kind of hibernation.

But what law enforcement and everybody else had failed to understand was that the drug market was not going away. It was atomizing and virtualizing. A new market—smaller, more agile—was forming. It took the recipe that had already been developed for research chemicals and added a new element: globalization.

JOHN BUCKLEY WALKS THROUGH a North London street, in his pocket a small key. A photographer’s satchel over his shoulder contains a series of identity documents and a printout of a lengthy email correspondence. He hopes he won’t need the papers, but it’s better to be safe than sorry.

The streets are busy enough to provide perfect urban anonymity, but even so, Buckley feels watched—followed, even. A year has passed since he last smoked a cigarette, but anxiety triggers the old familiar tug on his receptors; nicotine would smooth this tension out like a steam iron on a shirt cuff. Deep breaths instead. He turns, without breaking stride, through the glass door into the mailbox shop where, a few weeks before, he’d lied barefaced to the staff as he set up a bogus mailing address for a company that does not exist.

Buckley recognizes none of the workers today. He walks straight to the wall of corporate-gray mailboxes and opens number 203 with a fluid turn of the key. He expects a package that contains the products of weeks of meticulous planning and molecular-level precision. Instead, it’s empty.

One worker, a rangy guy with a Brazilian accent in a checked shirt with an asymmetrical east London fringe, sees his confusion and comes over, helpful, and gestures him to a back room, where there’s a wire cage filled with letters and boxes. They search together through perhaps 50 different packages looking for Buckley’s name, the colors of the courier, anything.

It’s several minutes until Buckley spots his name on a large plastic envelope. The Brazilian passes it to him; there are Chinese characters on it, and inside he can feel a small, square box. But he can’t open and check it, not here, so he walks out of the shop and jumps in a black cab home.

Safely indoors, I shed the persona of “John Buckley”, put my journalist’s press card, passport and paper trail back in its drawer, and tear open the envelope in haste. Inside the box lies a vacuum-sealed metallized bag, and inside that, a pair of small pinch-seal baggies. One of them contains a few grams of white powder.

It could be absolutely anything, one of several million compounds of different potencies and effects and toxicities. Or it could be sugar. There’s only one way to find out for sure.

MY JOURNEY, FROM MIKE POWER TO JOHN BUCKLEY, from investigative journalist to drug designer, started six weeks earlier. To understand exactly how access to designer drugs has changed—to see exactly how easy it is to commission, purchase and import powerful new compounds that are beyond the reach of the law—I decided to get one made myself.

I chose to focus on the Beatles’ drug, phenmetrazine: a nod to the cultural significance of Prellies and their illustrious user base. How easy would it be to get a legal version made? What procedures would it take, what roadblocks would be put in the way?

I phoned a contact with expertise in chemistry and asked if he could think of a simple molecular tweak that would produce a new version of phenmetrazine that would be totally legal. Yes, he said. The change would be trivial. What might its effects be? “A fantastic anorectic if you want to lose weight, and an effective stimulant.”

The search began for a laboratory that would make a one-off sample. I decided that I would present myself as a legitimate broker for a UK-based pharmaceutical firm. Taking on my new identity, I posted a buying request for the drug on various public websites that broker deals between individuals and small pharmaceutical manufacturers. Dozens of emails came back. Not all of them were genuine.

Some of these early responders were blatant scammers: Cameroon and Ukraine do have chemical industries, but those who work in them tend not to be able to offer large amounts of totally new, extremely rare drugs the very next day. My search headed to India, where three firms offered to synthesize the drug for me. On closer examination, though, none of them seemed up to the task—and they were all asking for very large sums of money, well beyond the actual value and difficulty of the compounds we were requesting. One priced the job as high as $10,000.

After weeks of constant searching for a decent lab, one of my contacts sent me the URL of a site in Shanghai that, on the surface of things, has nothing to do with legal highs, analog drugs, or any gray-market activity. They sell organic chemicals on international markets to people in many industries, and offer pharmaceutical drugs to legitimate importers.

But insiders in China who prefer to remain anonymous say there is little accountability or oversight of the chemical industry there. Once they are licensed, operators are seldom monitored, a scenario that has led to dozens of high-profile public health scares, including 300,000 children falling sick as a result of melamine being added to milk, and so-called “date rape” drugs appearing in Australian children’s toys.

I made an approach to the lab during Chinese business hours, and I heard back within an hour. “First, can I know the application of this compound your client use?” asked the person on the other end. “I just want to make sure it is legal application. We can do custom synthesis of this simple chemical surely. But if you can give synthesis route, it will be very good for us and we can save some time for this project.”

I replied, “We are doing basic animal research into the compound’s putative analgesic properties. Based upon its expected effect on monoamines, we believe it will have fairly potent analgesic effects, whilst causing minimal cardiovascular strain. Our intention is to use it as a proof of concept for a new type of analgesic for dogs.”

My online identity for this character and for his company are bare bones: nothing but a webmail address. My cover explanation is that I am designing a painkiller—yet phenmetrazine, the clear progenitor of this recipe, is not known to have any analgesic qualities. To anyone who cares to look, my story is blatantly false. But the lab does not seem to care.

We agree on a price and discuss quality control standards. The lab eventually agrees to send over data that will, they say, confirm they have created a drug with the makeup I require. The report will be based on high-pressure liquid chromatography, which chemists use to match a sample to library of known compounds, and nuclear magnetic resonance, which can reveal the structure of a molecule, regardless of whether it has been studied previously.

Next we agree payment—a few hundred dollars. Rather than an untraceable cash transfer such as Western Union, or an anonymous crypto currency such as Bitcoin, we opt for a simple bank transfer. Delivery is agreed by a well-known courier firm.

Two weeks later I receive another email. The compound is ready, though it is currently a liquid. Purity stands at around 93.7 percent; to purify it to 98 percent will reduce yield. I’m happy to accept that loss, as it will never be consumed. I request that it be salted into a solid, powder form using hydrochloric acid. I receive the qualitative data from the firm by email. The NMR readings feature the long, jagged peaks that suggest the existence of the drug. Now that it meets the stringent purity demands of “my client,” I agree: it’s time to ship it.

But how? Technically, we are doing nothing illegal, so we needn’t smuggle it, or even disguise it. At this stage, though, I have no guarantee beyond the lab’s word that they have carried out the work as instructed; they could easily send me an illegal drug instead of the one I have asked for. And while the point of this substance is that it is legal to bring it into the UK, this is not a mainstream importing job. I cannot help feeling the paranoia of a novice: what screening do customs officers and law enforcement do to track unidentified substances that are being sent across their borders?

I ask for an Material Safety Data sheet, standard paperwork that should accompany any chemical sample in the post. They do not have one—unsurprising, since the chemical is so rare. The unspoken truth hangs in the complicit silence between us: we both know this a modification of an illegal drug, and that it is designed for recreational, not medical purposes.

To get around this, the lab offers to send it hidden in a book: an unusual offer from a company claiming to make and distribute entirely legal substances. But I know that one of the most common ways that small-scale smugglers are detected is when a drug is packed inside an object too cheap or trivial to be posted internationally. Who aside from a rare books dealer would spend $100 sending a book from China to London? Instead, I tell the chemist to simply mark it as documents, to be delivered to a London postal dropbox that I have set up in the fictitious company’s name.

Over the next few days I scan the courier’s site nervously watching the package’s progress from Shanghai and out of the country. Paranoia affects would-be drug designers and importers as much as users: after all, while they usually operate legally, their cat-and-mouse game happens at the fringes of the law, not the center—labeling them as not for human consumption—for example. But a few days later my package arrives in the UK, ready for collection.

A legal highs vendor would now offer the drug privately to a select number of influential bulletin-board posters, and ask them to review the drug online. Building hype, creating a market, they would then start selling the compound, but the process of testing and legislating means the British government would be powerless to intervene for at least a few months—perhaps even up to a year. They could sell this drug for $130 a gram, or, to make more money, press it into tablets.

Instead, I send it by registered mail to Andrew Westwell, a medicinal chemist at Cardiff University, who will analyze its contents.

What he doesn’t know, of course—what nobody really knows about any research chemical—is what the long-term implications of taking the drug would be.

WESTWELL, WHO DESIGNS, synthesizes, and analyzes new drugs for the treatment of breast cancer, is also a member of the WEDINOS group that tracks and traces new recreational drugs in Wales.

“Looks like you have a sample of high purity,” he says, after analyzing my mystery drug. “Whoever you were dealing with in China have clearly done a professional job. The synthesis and production is not a trivial task, and requires someone with substantial expertise in synthetic organic chemistry. They also likely have access to good database facilities that will help them design a chemical literature–based synthesis for similar-looking chemicals.”

He attaches a copy of his lab’s results: they match, millimeter for millimeter, peak for peak, the version sent by the Chinese lab—showing that the original chemists had access to expensive nuclear magnetic resonance equipment that is normally reserved for pharmaceutical firms or academic research labs.

So they succeeded in delivering a legal analog of an illegal drug. But such a substance, ordered over email by a random name with nothing more than a Gmail account and a postal address, seems clearly intended to get people high, rather than form any part of legitimate research. So what does the lab have to say for itself? What do they do to ensure that their customers are legitimate, or that the recipes they cook up are above board? The answer, it seems, is very little.

I contact the lab to reveal that I am a journalist. At first they misunderstand what I tell them, and think we are accusing them of producing an entirely illegal substance.

“We didn’t check the job carefully,” admits the manager by email. “From now on we will check if the new molecular is legal before we reply to customer.”

But what about the identity of the buyer? What level of screening do they run before making a drug? “We can’t check,” he claims. Many legitimate buyers will use private email addresses, or have business details that his company cannot confirm from overseas. It doesn’t make sense for them to check the credentials of paying customers.

So what about the offer to smuggle the sample to us? If the drug he was making was entirely legal, why did he offer to ship it hidden inside a book? He claims it was merely a service offered to avoid unnecessary hassle at customs—a helping hand to genuine pharmaceutical companies, who may want to get an edge over their competitors.

“If our customer requires a sample in a hurry, we can understand their position but you can’t,” he writes. “Time is very precious … If other company finish effect test and apply patent before your company, all the work you have done will become zero.”

Yet he has already admitted that did not run enough checks to know whether the substance was legal or not. This is, he suggests, because chemistry is “a very varied subject.”

So if the professional chemist can’t—or won’t—tell me whether he really knows what it is he’s making, can Westwell at least tell me what effect the drug might have?

“It is notoriously difficult to predict how a drug structure modification will affect potency, activity, or toxicology. If we could make these types of predictions with any degree of certainty, fiendishly difficult areas like drug discovery and drug development would become so much more straightforward,” he says. “However, this is a simple modification to a substance with a fairly well-documented history… it would be reasonable to extrapolate—with a hefty dose of caution—that the psychoactive properties of phenmetrazine would be preserved in this new substance.”

What he doesn’t know, of course—what nobody really knows about any research chemical—is what the long-term implications of taking our drug would be.

And here lies the problem. We can ban drugs. But we can’t ban chemistry, and we can’t ban medical research.

BECAUSE THE LEGAL SYSTEM HAS no way to cope with the constant evolution of research chemicals, the biggest dangers for users aren’t capture and punishment. Instead, many experts fear that even the slightest chemical modification can cause unexpected and undesirable effects. Consider a substance like thalidomide, the entirely legal anti-morning sickness drug prescribed in the 1950s and 1960s, mainly around Europe. Many thousands of women were given the drug during pregnancy and around 10,000 of them gave birth to children with stunted limbs or without limbs at all. This was because the drug’s developers had not isolated and tested it adequately: one version is a relatively safe sedative and nausea treatment, but the other causes serious birth defects. Now, precisely because of scandals like thalidomide, legitimate drugs now have to undergo a battery of tests and study before they become available to the public. But legal highs are rarely tested at all.

John Ramsey is a clinical toxicologist who has for over a decade specialized in novel psychoactive substances at St. George’s Hospital in London. Ramsey buys drugs online and tests them and identifies them for police and health services across the UK, and has become Britain’s foremost expert in the identification of new drugs, with a collection of over 29,000 samples. He fears the emergence of a truly toxic chemical: a gray-market equivalent of thalidomide, bought for the high and used widely—but dangerous in ways that cannot be foreseen.

“It’s impossible preemptively to ban them all,” he says. “We find them, test them and the government drafts laws guessing at all the possible generic variations that can be made. Then the manufacturers just change the formula again. There are simply too many, and too many variations.”

The potential dangers of untested synthetics are not theoretical. In June 2012, Elijah Stai, a 17-year-old from Park Rapids, Minnesota, took several packets of an unidentified white powder from a friend, mixed them into melted chocolate, and ate the result. No dose was measured.

The powder was 25i-NBOME, a psychedelic originally created to help trace the biochemical pathways that may play a role schizophrenia and depression. But, after being carefully documented in papers by David Nichols, it had been copied and sold online as a legal high.

A single gram of 25i-NBOME contains up to 10,000 doses; it is as potent as a chemical weapon in the wrong hands. Stai overdosed, convulsed and battered his head on the floor. He died the following morning. He was the second victim in a week; the other was 18-year-old Christian Bjerk, who lived 150 miles away in Grand Forks. His friend Wesley Sweeney, who had gotten the drug from the same place as Stai, laid it out like lines of cocaine on a table at a party.

A typical line of a powdered drug might contain around one hundred milligrams—for Bjerk, that was enough for a thousand-fold overdose. He died quickly in the street. Sweeney was found naked and incoherent in a park: once he recovered, he was tried and jailed for twelve and a half years for supplying the drugs that killed his friend, even though they were ostensibly legal.

The drugs had been purchased from a website run by 28-year-old Charles Carlton, who lived over 1,400 miles away in Katy, Texas. Carlton had never met his customers, of whom he had thousands, and his website, MotionResearchCo, was meticulous in enforcing the strictures of the U.S. Analog Act: these chemicals, it said, were not for human consumption. Carlton bought his 25i-NBOME from a Chinese lab. Carlton also imported chemicals from China, the UK, Austria, Poland, Greece, Spain, and Canada: he was charged with conspiracy to import a misbranded drug and faces possible life imprisonment.

Dr. Adam Winstock, an addictions psychiatrist in London, suggests that wider society is not ready for the greater availability of novel research chemicals that are coming on sale. “The Internet parachuted in these new drugs,” he says. “That meant there was no way for people to accurately discuss correct and safer use around things like dosage and onset of action. Government action and blurring of legislation means we can’t tell people that effectively. It should be on the label.”

The men who pioneered so many research chemicals are themselves ambivalent. Alexander Shulgin, now 88, is exhibiting signs of dementia, but has argued in the past that deaths from drugs are a “sad event” but that all drugs, from MDMA to aspirin, carry risks if taken incorrectly. Meanwhile, David Nichols, who retired from his role at Purdue’s chemistry department in 2012, says the growth of unregulated, untested legal highs is a deeply negative consequence of drug laws.

“It bothers me,” he admits. “When I used to talk about psychedelic research, the one thing you could say was these drugs do not kill people and that they are not addictive. But then when I started seeing people killed by this irresponsible marketing and use, this was not something I intended.”

It is clear that others are co-opting his medical research into psychedelics and other potent drugs, and using them in ways he finds uncomfortable—despite the fact that his celebrity status in the drug community means such a response is now predictable. So why did he carry on his research? His answer is surprising.

“I have this hidden fantasy that some day, a drug will appear that will have a profound effect on humankind and it will make them stop causing wars and killing each other and gassing each other and destroying society. What if someone came up with a drug that was wildly popular, as popular as ecstasy, but had no side effects, and did not kill? It’s probably an impossible drug. But as a consequence of taking this drug, [people] suddenly realized that all humans are part of one organism, and that when you kill one person you are killing yourself, and that the earth is our lifeboat, and we are destroying it. What if a drug could produce an experience like that? I have fantasized that if it were possible to make a drug like that, I’d sure like to make it in my lab.”

David Caldicott is more pessimistic. From a medical and cultural perspective, he says, the constant flood of new drugs is wearying and poses new and unmanageable risks for clinicians and users alike.

“What is intrinsically dangerous is that there is no gentle build into the market, where in the past when a new drug appeared, we had a chance to gain medical knowledge about it. There are an infinite number of drugs on the market simultaneously, and no sort of body of knowledge. The society that is consuming these drugs has not had time to assimilate them,” he says. “Rather than any one of us trying to track the evolution of a single drug, people like me are now faced with this tsunami of different agents.”

Certainly, the clinical impact is disturbing. Usually, doctors in emergency care diagnose and treat based on classic symptoms of overdose from different drugs. But now, the indicators they rely on for delivering the right treatment no longer apply. Some drugs on the market create symptoms usually associated with wildly different drug categories.

“The impact of this is that you can be led down the wrong path very quickly,” he says. “This is one of the problems with the NBOME-series of drugs. You can think patients are presenting with a simple stimulant psychosis, and then suddenly you’re dealing with a case of serotonin syndrome. That’s confusing and dangerous as far as the medical profession is concerned because the assumptions about the drugs we’re treating are probably no longer correct. We have thrown out the textbook. We are forced to wing it with every single drug overdose.”

“Let’s see drugs as an illness, and prohibition as an antibiotic. If you treated any illness with the same antibiotic for 50 years, medical people would be stunned if resistance hadn’t developed.”

WHILE I WAS CARRYING OUT this investigation, the legal highs industry reinvented itself along exactly the same lines that “John Buckley” did. Following a ban on the NBOME series of drugs in the UK, a simple new replacement came to the market: NBOH. It is a set of hallucinogens related to the original work by Nichols, but with a shorter duration and, users say, a more gentle and enjoyable effect.

In August 2013, meanwhile, British websites claimed to have bought an entirely new class of drug to the market—one based on LSD. To the Internet drug scene, this is a seismic development. The vendors claim to have synthesized two new LSD analogs, one of which has the same potency as its parent, while the other is even stronger. They are, according to the man who first synthesized them, “as safe as LSD” and one of them, according to someone who tested the product, is “everything LSD wishes it was, but isn’t.” Initial testing by an independent analyst suggests that at least one of the compounds is exactly what the vendors claim.

There is no let-up. In late September, a Shulgin drug called 2CB, lauded by his testers for its aphrodisiac and aesthetic effects, was modified and made available legally at around $65 a gram.

So, how easy is it to design and commission a new legal drug based on a banned one? For the most part you cannot simply tweak cocaine, add a molecule and dodge the law—most countries are wise to this, and their rules are tightly-written, expert affairs focused on well-known narcotics. But outside of headline drugs, as I showed, it is simple enough to scan medical literature and look for new compounds that could intoxicate. The resulting drug will, most likely, be legal—though whether the result will be pleasant or not will only be discovered by a process of human trial and error. I passed my drug along to John Ramsey at St. George’s to be logged into TICTAC, a database that is used by law enforcement and healthcare professionals. We do not know precisely what my legal drug will do: It may be incredibly unpleasant—but it will be active and, with the right marketing, could potentially sell by the truckload.

And here lies the problem. We can ban drugs. But we can’t ban chemistry, and we can’t ban medical research. There are an almost infinite number of different drugs and substitutions that are possible, and a combination of circumstances have radically increased the public’s ability to access and alter them. The openness of the Web, China’s prominence as both a manufacturer and exporter, the ability of laypeople to study organic chemistry, the availability of research, improved technology and falling prices—these have all come together to create an unusual, explosive, effect.

I am a rank amateur by comparison to my contacts in the chemical underworld, who dedicate their lives to creating these novel psychoactive substances. And just 20 years ago, this experiment would have been impossible for anyone except a skilled chemist. Yet I was able to complete it in a matter of weeks.

David Caldicott laughed as we discussed the ramifications of the deal I made as “John Buckley.”

“This is concierge drug design, outsourcing all the risk and hard work. It’s like room service drug design, ordering from a menu.”

What can we do about it? The drugs and the technology and the culture have all mutated to take advantage of their environment, but our policies have remained static for many decades. Instead of constricting supply, drug laws focused on a group of well-known chemicals have simply pushed users towards new and increasingly dangerous forms of chemical stimulation. And now attempts to enforce the law simply encourage greater, riskier innovation—and no one now knows where that will take us.

Caldicott offers an analogy: “Let’s see drugs as an illness, and prohibition as an antibiotic. If you treated any illness with the same antibiotic for 50 years, medical people would be stunned if resistance hadn’t developed.”

This story was written by Mike Power, edited by Bobbie Johnson, fact-checked by Kristen French, and copy-edited by Tim Heffernan. Jack Stewart narrated the audio version. The illustrations were done by Tim Marrs.

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