18 March 2021

Researchers are involved in the campaign to make designer drugs illegal as quickly as possible. Henrik Gréen investigates how new psychoactive substances act, and why some designer drugs are more lethal than others.

white phentanyl powder in small bag.In 2017, around 100 people died in Sweden from poisoning by such substances. The work of the LiU researchers helped to get rid of such phentanyl analogues from the market. Photo credit Darwin Brandis

The corona pandemic has led to increased internet-based trade in illegal drugs, according to the United Nations Office on Drugs and Crime (UNODC). Many people are worried that a downturn in the economy following the crisis will stimulate the use and sale of drugs.

“We see that internet sales have increased dramatically during the pandemic. We suspect that the trade in new psychoactive substances has also increased”, says Henrik Gréen, professor of forensic science at the Department of Biomedical and Clinical Sciences, and researcher at the National Board of Forensic Medicine.Henrik Green.Henrik Green. Photo credit Magnus Johansson

“Designer drugs”, or “legal highs” as they are also known, are psychoactive substances that affect the brain in a similar manner as illegal drugs. But since the legislation relating to drugs classification is based on the exact chemical structure of the substance, it takes some time before a new variant can be classified as a narcotic.

“Previously, when drugs were sold from one person to another, the threshold for young and inexperienced people to test psychoactive substances was probably higher. Today, you can get hold of them with just a computer”, says Henrik Gréen.

The ease of obtaining designer drugs is not the only problem. Since there is a period in which it is not illegal to possess the new psychoactive substances, some people believe that taking them is not harmful. This is not the case.

“You have no idea about how toxic these substances are, what happens in the body at different doses, or the effects you experience when you take them. It’s like playing Russian roulette with your life”, says Henrik Gréen.

Can form toxic breakdown products

Henrik Gréen and his colleagues deal with around 50 new substances every year. The first thing that happens is that the police or customs service somewhere in the world confiscates a substance and sends it to a laboratory to find out what it is. If it turns out to be a previously unknown substance, a warning is distributed to national and international government agencies.Henrik Gréen and Niclas Björn.Henrik Gréen and Niclas Björn. Photo credit Magnus Johansson

In the lab, researchers start to investigate how the new substance interacts with receptors in the brain. Does it activate receptors that give a feeling of intoxication, and does it produce dependency? The results are part of the scientific information that the Public Health Agency of Sweden needs to be able to classify the new substance as a narcotic, and in this way make its sale illegal. It takes between six months and a year from a new substance entering Sweden until it is removed from the (legal) market, while many substances remain available on the illegal market.

The researchers also determine the period during which a urine or blood sample must be taken in order to prove the presence of the substance before the body manages to get rid of it. They identify the breakdown products, or metabolites, that are formed when the substance is broken down by the body. The forensic laboratory can then include the metabolites in the analysis methods.

An important aspect of the research is to determine how the drugs function, so that we understand why they are dangerous and how an overdose can be treated. If the substance affects the receptors in the brain that heroin and morphine activate, it can cause breathing to stop.

“We have also identified several substances that form toxic breakdown products. Highly toxic cyanides, for example, can be released in the body when the substance is metabolised by the liver. The chemists who develop such new psychoactive substances sometimes add a chemical group that no-one would ever conceive of using in medical pharmaceuticals, since they can form dangerous breakdown products”, says Henrik Gréen.

Helped to get rid of illegal drugs

A couple of years ago, designer drugs similar to the narcotic fentanyl were in circulation. In 2017, around 100 people died from poisoning by such substances. Several substances were classified as narcotics in December of the same year. Several highly publicised trials have been held of people charged with selling these types of drug.Chemical structure of four phentanyl analogues.Many of the new psychoactive substances differ by a single atom. This small difference can change the properties of the substance dramatically. The fentanyl analogues in the figure differ in strength by a factor of approximately 700. Photo credit Henrik Gréen

“Fentanyl now is nearly completely gone from the market, due to a large extent to our research and how the police, prosecutor’s office and government agencies have worked against it”, says Henrik Gréen.

He is driven by a combination of chemistry, biology and care for society.

“The big question, of course, is: ‘How can we get designer drugs away from the illegal market?’ We try to predict which variants of psychoactive molecules can turn up next. In the best case, we can have them classified as narcotics before they come onto the market, and in this way reduce the number of deaths. We focus on removing those that are really, really dangerous, such as the fentanyl analogues.”

Translated by George Farrants

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