Where weed is legal in the US and in countries around the world — Quartz
By Andy Extance 6 September Andy Extance investigates the chemistry that has helped recreational drugs evade the law, and its consequences. It relates to a scientific project that he worked on at an Israeli company in the early s, seeking to control crop-eating pests. Perhaps the psychoactive molecule cathinone might be responsible, Zee and his colleagues theorised. Rather than directly killing the pests that ate them, they thought cathinone might make them jittery, rendering them easy targets for predators.
Therefore the researchers started hunting similar molecules that might do it better. Yet Zee also knew that the small chemical modifications that produced cathinone analogues might encourage more than just caterpillars to dance. Psychoactive substances developer Dr Zee synthesised the cathinone derivative mephedrone. Having enjoyed chewing khat leaves himself, Zee developed a large-scale method to produce cathinone, making kg. As with cathinone, once Zee had found a substance with enjoyable effects, he set about producing it in large scale and selling it for recreational use.
This molecule — 4-methylmethcathinone — would spread far beyond Israel, making headlines under the name mephedrone. Mephedrone is just the tip of the iceberg. Over originally legal highs have appeared since the mids , sending governments scrambling to react. This follows less comprehensive bans that erected barriers to certain parts of the analogue space psychonauts like Zee explore with their chemistry skills. NPSs pose serious questions about the science — particularly the chemistry — and philosophy of drug control.
Researchers like University of Hertfordshire pharmaceutical chemist Amira Guirguis are responding. When mephedrone infiltrated the UK in , Hertfordshire researchers tracked it — and found many other NPSs appearing. Gerona was developing a non-targeted analysis approach, just as mysterious substances started causing hospital admissions. Amira Guirguis is developing analytical techniques to help identify new psychoactive substances.
The media has reported their shocking effects widely, including sudden heart attacks after very small doses. One common issue is an increased burden on emergency services.
Spice varieties containing 11 different SCs led to call-outs, involving patients , and four deaths. The shape of the cavity in the lock — the receptor — means that only certain keys — or drugs — fit. Psychoactive drugs usually target receptors in nerve synapses, interfering with neurotransmitter molecules that influence our behaviour. They block or open receptor locks that control the release of neurotransmitters that in turn cause nerve signals.
Endocannabinoids unlock CB1 and CB2 and reduce the release of another neurotransmitter to regulate appetite, pain, mood and memory.
Huffman wanted to design molecules that might have medicinal effects through CB2, without unlocking CB1. His team made hundreds of molecules to explore the analogue space, and what they found has been pivotal in the spice explosion. One important insight is that cannabinoid receptors are unusually easy to unlock, as many different types of molecule will fit into them.
Another insight is that psychoactive drugs affect neurotransmitter release in a similar manner to how turning a tap controls water flow. Drugs that turn the tap part-way are known as partial agonists, whereas ones that turn it all the way open are full agonists.
It was therefore adopted by spice makers, becoming one of the first substances identified in then-legal highs. For example, she has looked at how readily SCs make mice go into a rigid trance, known as catalepsy. Wiley and her colleagues also found that four SCs block a protein ion channel that controls calcium, sodium and potassium flow to keep our hearts beating. JWH was the worst culprit for blocking it, and they say this could explain reported heart problems.
Synthetic cannabis suppliers often spray the substances onto plant matter, which can then be smoked. While many people do not think of cannabis as dangerous, SCs definitely are, she says. As well as the chemical difference between THC and SCs, cannabis also contains many other different compounds, with cannabidiol seeming to have a calming effect, for example.
Spice does look similar to cannabis as it is usually supplied in a form that people can roll up and smoke. But to achieve this, one or more SC powders — without cannabidiol — is usually dissolved in a solvent like acetone and sprayed onto dried herbs.
This makes SCs the most obvious remnant defying the ban in the UK. The difficulty in detecting spice leads to it being taken by people being tested for drug use in prison, in rehabilitation, or on court-mandated drug treatment orders.
It can readily be smuggled by soaking a piece of paper, like a letter, in an SC solution and letting it dry. Users then swallow or smoke the spice-soaked paper. Also, people are being spiked for non-payment of debts and other retaliation.
The sort of mannerisms people portray are seen as entertainment. The prisoners I speak to will say that spice is the number one drug problem in prison. None of them have a good word to say about it.
So why do they use it? Part of the answer is that prisoners, like homeless people, are more likely to have psychological problems, explains Ian Hamilton , a mental health and addiction researcher at the University of York in the UK. Quite often they use drugs to keep a lid on that.
Consequently, researchers have proposed reforming mandatory drug testing to reduce harm. BDP deals with clients per year, with around half on opiates like heroin, and some homeless people taking heroin and crack have also started taking spice , she says. But Davenport goes on to explain that BDP sees two other main groups of NPS users, albeit small, who might be at university or have full-time jobs. The second group are psychonauts who, perhaps because they adopt the same cautious approach as Shulgin and Zee, usually only come to BDP in extreme circumstances.
A lot of our people taking a few NPSs get into the habit of taking one thing for an experience, another thing to perk them up, and another to get through exams. That really affects your mental health. The emergence of such substances inevitably forced official responses. Then, it emulated Ireland and Poland in introducing legislation designed to control all psychoactive substances. But is it working? In the UK, production and supply of legal highs were banned on 26 May A main concern about the PSA is its broad scope.
This cover-all approach also means that effectively you reduce the incentive for chemists to create new substances to get around the Misuse of Drugs Act. Nearly people had been arrested under the Act, and four jailed. In this regard, the PSA has been a success, Wadsworth says.
However Wadsworth questions whether closing down websites is the ultimate goal. The worry is that sales would simply move to other markets, such as street-level drug dealing or the cryptomarkets — underground markets without regulation.
It refers to how crackdowns on drugs in one place tend to shift the problem somewhere else. NPSs replay this game of whack-a-mole in the realm of chemistry. One reason ecstasy purity was low in and was due to mass seizures of the starting material safrole in Cambodia.
Prisoners adopting spice after their cannabis use was prohibited is another example. Now spice dealers have less motivation to care. NPS sellers who wanted to continue trading have popped up again, after relocating their websites to places like Spain, she adds.
Similarly, she has seen little change in NPS prices, other than an increase for mephedrone. So we have to focus on people who are supplying them, importing them, making them, or places where they cause the biggest misery, in open drug markets, through links with organised crime and physical harms. Nevertheless, the UK police has been working with postal services to get more options to detect small quantities of material, Bray adds.
Other efforts include work between the EU and China, according to Bray, leading the Chinese government to introduce controls on hundreds of substances in and This has led to a definite reduction in the flow of substances coming into the UK from China, according to Bray.
Dr Zee has first-hand experience of how new laws have influenced the international NPS trade. He started looking at working with a Chinese supplier in on compounds that were later banned. However, he says he has successfully fought cases with customs about his imports in Slovakia, the Czech Republic, Switzerland, the Netherlands, Spain and Portugal. However, the process is like a fast-forward version of how conventional industrial chemists explore structure—activity relationships, trying to design medicinal molecules by tweaking their structures.
Yet responding to such risks by pushing psychoactive substances into the criminal world drives sellers towards the strongest products, he adds. Faced with the risk of getting caught, they transport as little as possible.
Chemists like Guirguis have seen evidence for this: And even tiny structural differences can also cause big detection challenges, especially with highly selective colour-changing immunoassays used by probation officers and in prison.
Chemical colour tests that are used for a wide range of drugs, for example using the Marquis reagent, have the opposite problem, Guirguis adds. A yellow colour might mean cathinone itself, or any slightly modified related substance. Cutting agents or other adulterants can also mask the NPS signal when using handheld vibrational spectroscopy techniques. Guirguis and her University of Hertfordshire colleagues have however been able to identify 29 out of 60 NPSs using a handheld Raman spectroscopy approach.
Yet because there is often no reference standard to compare entirely new substances against, developing such tests is difficult. Gerona therefore started working with Sam Banister at nearby Stanford University. Using the same kind of small changes from existing molecules that clandestine chemists might, Banister has made up to potential SCs and metabolites for reference.