INSIDE a brightly lit shop in Amsterdam half a dozen people inspect the wares. Alongside the bongs, vibrators and heart-shaped key rings in its glass displays are rows of small silver packets emblazoned with names such as “Herbal Speed”, “Trip E” and “Liquid Bliss”. Four capsules of “Space Trips” will “take you to the moon and back” for €12.50 ($13.30). There are 160 coffee shops in this city where marijuana can be bought and smoked perfectly legally. But as these shiny packets bear witness, there is also a thriving market for “legal highs”, synthetic alternatives to drugs such as ecstasy or cocaine.

Humans have always sought to intoxicate themselves. For millennia they had only what could be reasonably easily coaxed from poppies, grapes, mushrooms and the like to help them in their endeavours. In the 19th century chemistry allowed the chemical compounds that had made such things worth seeking out to be purified and marketed. New drugs from the laboratory, such as ether and nitrous oxide, found a role in “laughing gas” parties and “ether frolics” well before they were pressed into medical service as anaesthetics.

The 20th century saw new drugs created from scratch: amphetamines, barbiturates, benzodiazepines and more. It also saw a far more spirited, if often fruitless, policing of the line between drugs-as-medicine and drugs-of-choice—a line that was in many cases drawn according to the sort of people who chose to use the drug, rather than any essential danger it posed. These prohibitions rarely improved public health or public order; but they did encourage some of those who served the markets on the wrong side of the line to investigate the potential of molecules similar to those in existing drugs but not yet subject to any sanction.

As the 21st century took off, so did the sale of these new drugs. At the turn of the century the UN Office on Drugs and Crime (UNODC) recognised only a handful of “new psychoactive substances” in use around the world. By 2008 the number was up to 26; by 2014 it was 452; in a UNODC report to be published this summer the total is expected to reach 700. Most do not stick around, appearing on the streets or in the head shops where drug paraphernalia is sold only for a few months; but 80 or so have spent years on the market. Never before has there been such an array of pills, gases and liquids available for people to swallow, inhale or inject.

New compounds such as those in that Amsterdam shop make up only a very small fraction of the global drugs trade. But in their profusion, in the way that they blur the distinctions between the legal and the illegal, and in the unintended consequences that can follow when one sort of high is traded for another, they offer a window into its future.

It is easier to set up a clandestine laboratory, or even a fully fledged pharmaceutical factory, than ever before. As a result the world now has an innovative infrastructure capable of developing synthetic variations on established druggy themes with ease, whether it is to circumvent laws on ecstasy in Europe or to meet the rocketing demand for opioids in America.

Bigger bangs

Almost all these new drugs are intended to replicate the effects of older stimulants, hallucinogens, depressants and the like. Yet their changed molecular structures mean that their effects are different—sometimes subtly so, sometimes dramatically and dangerously so. Some of them, in some circumstances, may well offer real as well as legal benefits with respect to the originals: a more enjoyable high, say, or a milder portfolio of side-effects. But two drugs which, in molecular theory, look quite similar can differ a lot in practice—with one more addictive, say, or easier to overdose on.

At the moment illicit manufacturers and drug-dealers do not know how people will react to the drug until it hits the market, and the full impact may not become visible for a long time afterwards. It is hard to see how to reduce the harm which can be done, let alone maximise possible benefits, in a world where prohibition remains a default, but ineffective, response to many broad categories of drug.

As the market for new psychoactives took off in the 2000s, the main selling point was that very prohibition: legal highs could be sold openly in head shops (which boomed as a result). According to Fiona Measham, a drug specialist at Durham University, the new highs were particularly appealing to 30-something professionals, such as teachers, who would lose their jobs if found with illegal substances.

In some places a new spirit of experimentation emerged, particularly among “psychonauts”, mostly educated young men, excited by the chance to ingest new substances and discuss their explorations with others. Earth, the pseudonymous co-founder of Erowid, an encyclopedic online resource on drugs and their effects, sees it as a modern-day equivalent of “Amazonian residents tasting the bark of various trees in combination with the leaves of every plant to test their effects.” In the 2010s the rise of the “dark web”, which can be accessed through encrypted browsers such as Tor, made the new synthetic drugs pretty easy to purchase even after the authorities got around to prohibiting them.

One result of this experimentation is that a handful of new drugs have been found to be just as good, if not preferable, to older illicit substances. Take mephedrone (4-methylmethcathinone), which became popular among European clubbers in the mid-2000s. Ecstasy (MDMA) was in short supply at the time, recalls Tibor Brunt at Trimbos, a drug-research centre in Utrecht, and what was available was of poor quality; mephedrone and 4-FA (4-fluoroamphetamine, another clubbing drug) were legal ways to fill the gap. According to a 2016 study from the Autonomous University of Barcelona, mephedrone users report “euphoria, stimulation, alertness, empathy, sociability, talkativeness, intensification of sensory experiences and light sexual arousal”, which makes it sound pretty much indistinguishable from MDMA.

At first the new drugs were often passed off as MDMA, but they soon came to be sold for what they were and their merits—for mephedrone, a shorter high and a more mellow comedown—appreciated. According to a 2014 paper by Mr Brunt and his colleagues, once 4-FA had become established 77% of users took it for its effects, not because of its legal status. This suggests that even though, this April, it became illegal in the Netherlands, it will still be widely taken, just as MDMA is.

Not many new psychoactives, though, earn a place in the market through merit-based competition. The origins of synthetic cannabinoids, which target the same aspect of brain chemistry as THC, the main active compound in marijuana, and fentanyl, an opioid, date back to the late 1950s and early 1960s, when the pharmaceutical industry was looking for new medicines of all sorts. Fentanyls found a niche in pain management; the early synthetic cannabinoids had “such a mind-blowing effect”, recalls David Nutt of Imperial College London, that the companies never took them to market. Today both are widely abused as more available, and more potent, substitutes for other drugs.

Synthetic cannabinoids sold in Europe and America as “Spice”, “K2” and “Black Mamba”, among other names, are mostly produced in China; in some cases their synthesis is perfectly legal. They are then shipped to Europe and America in the form of powders; there they are mixed with solvents and applied to dried leaves—tobacco, marshmallow and tomato are popular.

Successive attempts to crack down on them by governments have led producers to tinker with the molecular structures ever more, removing them ever further from THC. This makes them a far more heterogeneous group of drugs. According to Oliver Sutcliffe, a chemist at Manchester Metropolitan University, four different synthetic cannabinoids appeared in Manchester over a period of five weeks earlier this year, with the concentration of the active component in different batches varying by a factor of ten. But the drugs all looked identical.

The effects of these synthetic cannabinoids can be very different from those of ordinary cannabis. Some users start stumbling around zombie-like after taking them, though these catatonic effects typically wear off after 20 minutes or so. Some other effects—though not necessarily the high—can last a lot longer than those of cannabis, says Paul Dargan, a toxicologist at Guy’s and St Thomas’ Hospital in London. The drugs can cause convulsions; some have led to cardiac arrest. Unpleasant withdrawal symptoms are common.

Unsurprisingly, this is not very appealing to people with access to alternatives. In Amsterdam few of the head shops selling “legal” or “herbal” alternatives to ecstasy and stimulants find it worth their while to sell synthetic cannabinoids. A 2015 report from the Drug Policy Alliance, an NGO based in New York, found that arrests for synthetic cannabis in Colorado dropped by half when stores selling legal marijuana opened in 2014.

But synthetic cannabinoids do have their selling points. They are often strong; they are often cheap; and they don’t show up in urine tests. A listing on the dark web for “Dank Tobacco Spice” boasts that users can get high “in front of the police the Boss Your Mom The Judge Probation and Parole Officers and never get detected”. Synthetic-cannabinoid use is rife in those American homeless shelters in which urine samples are mandatory. They are also by far the most widely used drugs in British prisons, where a spate of recent riots has been linked to them. One person who works in those jails says that when he smells cannabis being smoked behind bars he immediately feels more at ease; not only will the inmates be less aggressive, but any symptoms will be far more predictable.

Dark matter

The rise of fentanyl followed a similar, but more deadly, trajectory. Illicit fentanyl first started to appear in the 1980s, according to Michael Evans-Brown of the European Monitoring Centre for Drugs and Drug Addiction in Lisbon. It was soon linked to a spate of deaths, and disappeared. Over the past five years, though, fentanyl and a range of relatives and lookalikes have made a comeback. Aggressively marketed pharmaceuticals such as OxyContin have led to an epidemic of opioid addiction in America, and those addicted sometimes turn to illegal opioids as an alternative to highly priced and sometimes strictly policed medical ones. As well as heroin, they can now get hold of as many as 30 variants of fentanyl (of which only 19 are controlled substances under federal law).

Fentanyl is powerful—50 to 100 times stronger than morphine. Some of its relatives are more potent yet. “If you are buying this for resale and selling it on as fentanyl I advise you cut this to ensure you do not harm your clients,” says a dark-web seller of one called carfentamil, and he is not kidding: a single gram of the stuff can make tens of thousands of doses, according to Mr Evans-Brown.

Such concentrated oomph means that lucrative quantities can be shipped in very small packages. In March an investigative report by the Globe and Mail, a Canadian newspaper, revealed that fentanyl was being shipped in from China inside silica-desiccant packets packaged with urine-test kits. Because the packets weighed less than 30 grams, Canadian border guards were not allowed to open them without getting the permission of the recipient.

Potency not only makes smuggling easier: it makes dealing more profitable. According to an official from America’s Drug Enforcement Administration, quoted in the House of Representatives earlier this year, a kilo of heroin can be purchased for roughly $6,000 and sold wholesale for $80,000 before fetching a few hundred thousand dollars on the street. The price for a kilo of fentanyl might be $3,500-5,000; stretched out into 16-24kg of product it might be worth $1.6m.

The potency makes overdosing very easy, and fentanyl overdoses are harder to treat than those of other opioids. In 2015 over 9,000 people in America died from a synthetic opioid overdose. In Ohio, one of the worst-affected states, fully 62% of those who recently died from a heroin or fentanyl overdose had been prescribed at least one opioid painkiller in the previous seven years.

The response of rich-world authorities has mostly been more bans. Initially governments outlawed one substance after another, playing a game of whack-a-mole with producers, who would add molecular tweak after molecular tweak. “We have created a hydra phenomenon,” says Kenneth Tupper, of the British Columbia Centre on Substance Use. “You cut off the head of the beast and eight more pop up.”

As a result, broader laws have also been put in place. In 2010 Ireland introduced a blanket ban. In America the Synthetic Drug Abuse Prevention Act of 2012 banned “cannabimimetic agents”, as defined by the effects they have on the brain. Last year Britain passed a sweeping piece of legislation which outlaws anything that has “psychoactive effects”—altered perceptions of time and space; hallucinations; changes in alertness; enhanced empathy; drowsiness—along the lines of those provided by older illicit drugs.

These broader bans have not worked much better. In Ireland head shops closed down but the use of these drugs did not: according to a Eurobarometer survey, some 22% of those aged between 15 and 24 had taken a new synthetic drug in 2014, compared with 16% in 2011. In British prisons the price of Spice and its variants has actually come down since the ban was put in place, defying the rules of the market, according to one person who works in them. Some bans may have done real harm. A 2016 report from the Beckley Foundation, a British research and lobby group, suggests that the government’s addition of mephedrone to the schedule of controlled substances in 2010 may have led to a brief rise in deaths from cocaine.

Light and darkness

An alternative approach is to try and stamp out the drugs at their source. In 2015 China regulated 116 synthetic drugs, including several fentanyl derivatives; in March this year it added four more to its list. Yet in the same year the UNODC found that over a hundred new drugs had been synthesised. And suppressing fentanyl in China may just push it elsewhere: drug cartels in Mexico have incentives to try and find scientists to synthesise these drugs, considering the profit margins. American politicians also talk of clamping down on international post in order to try to detect these drugs more effectively; but it is doubtful that this will catch all of the fentanyl making its way into the country, especially as it can be carried on people rather than in parcels. Such a policy is more likely to lead to ever more inventive ways for dealers to smuggle it in, and to increase the incentives for discovering variations that are as potent as possible.

A more enlightened response would be to explore the possibility that some of these drugs might, in some settings, be comparatively benign, and that if that is the case then making them more easily available might make sense. New Zealand—where, given the distance from other drug markets, new synthetics are particularly popular—looked at such an approach in 2013 with a plan to regulate, rather than to simply prohibit, some new drugs. The rules allowed manufacturers of new psychoactive substances to apply for permits; if after a year-long clinical trial their drugs were found to be “low risk”, they would be allowed to sell them to people over the age of 18. Yet this soon fell foul of other legal problems, with an anti-vivisection society successfully lobbying to ensure that the drugs in question, unlike those intended for medical use, could not be tested on animals. Robbed of ways of demonstrating a compound’s safety, the plan stalled.

In theory, the profusion of new drugs, and of psychonauts willing to try them, offers an opportunity to rethink various aspects of drug policy. The wheat could be sorted from chaff, drugs with lower risks distinguished from those with higher risks, compounds with possible medicinal merit singled out for further development. In practice, though, as long as prohibition dominates the responses, the opportunities for new knowledge will be scarce—perhaps more so than ever. Mr Nutt, a former British government adviser and a critic of current policy, complains that the sweeping British ban has made the study of psychoactive substances harder. It also means that academic research groups may find that drugs in their laboratories which were previously perfectly legal have become illegal, further hindering research.

The boom in synthetic drugs has given consumers more choice; some of its products may be genuine improvements on their predecessors in some settings. But it has also provided dangerous and poorly understood products to people who are often already marginalised. A willingness to re-examine current policies would reap dividends. At present, though, the new substances add to the confusions and contradictions of the old system—which, in the case of American federal law, treats the fentanyl which is killing thousands as less of an issue than marijuana.

Correction (May 22nd): A previous version of this briefing referred to the British Columbia Centre on Substance Abuse. It is, in fact, the British Columbia Centre on Substance Use. Apologies.