New Psychoactive Substances (including kratom, synthetic cannabinoids, synthetic opioids, synthetic cathinones, and more).

Related Chapters:
Entheogens and Psychedelics

Chapter Sections:
Synthetic Opioids (e.g. Fentanyl)
Synthetic Cathinones (Mephedrone, Methylone)
Salvia Divinorum
Synthetic Cannabinoids
Others - New psychoactive substances are being developed at a rapid rate

Page last updated June 10, 2020 by Doug McVay, Editor.

11. Synthetic Opioids, Including Fentanyl

"With a total of 38 different opioids reported, the number of synthetic opioids has grown rapidly in Europe since the first substance was reported in 2009. In fact, most of these substances have been reported for the first time during the past two years, with 9 reported in 2016 and 13 during 2017. Although they play a small overall role in Europe’s drug market, many of the new opioids are highly potent substances that pose a risk of life-threatening poisoning because an overdose can cause respiratory depression (slowing down of breathing), which can lead to respiratory arrest (stopping breathing) and death. The public health importance of this risk is reflected in the fact that most deaths involving illicit opioid use are caused by respiratory depression (White and Irvine, 1999). Of particular concern are the new fentanils. These substances currently dominate this group, with a total of 28 reported since they first appeared in 2012.

"Reflecting their small share of the market as well as their high potency, new opioids accounted for only around 2% of the total number of seizures of new substances and about 0.2% of the total quantity reported to the EU Early Warning System during 2016. New opioids are found mainly in powders but also in tablets and, since 2014, liquids. For the most part, seizures are dominated by fentanils. There were around 1,600 seizures of new opioids reported by law enforcement during 2016, of which 70% were related to fentanils. These included 7.7 kg of powders (of which 60% contained fentanils), approximately 23,000 tablets (of which 13% contained fentanils) and 4.5 litres of liquids (of which fentanils accounted for 96% of the total). Some of these liquids are from seizures made by police and customs of nasal sprays, which appear to be growing in popularity as a way of using these substances."

European Monitoring Centre for Drugs and Drug Addiction (2018), Fentanils and synthetic cannabinoids: driving greater complexity into the drug situation. An update from the EU Early Warning System (June 2018), Publications Office of the European Union, Luxembourg.

12. Fentanyl in the Context of New Psychoactive Substances

"Since 2012, a total of 28 new fentanils have been identified on Europe’s drug market. This includes eight substances that were reported for the first time in 2016 and 10 during 2017. During this period, there has also been a large increase in seizures reported by customs at international borders and police at street-level (Figure 4) (see also ‘Reducing the risk of occupational exposure to fentanils’, page 11). While the picture differs widely across Europe, 23 countries have reported detections of one or more of these substances (Figure 5) (2). Reports to the EMCDDA of fatal poisonings have also increased substantially from some countries (EMCDDA, 2016a; EMCDDA, 2017a,b,c,d,e,f,g; EMCDDA, 2018a,b).

"It appears that most shipments of new fentanils coming into Europe originate from companies based in China. Production in illicit laboratories, including in Europe, has also been reported occasionally. Typically, production of fentanyl and other fentanils is relatively straightforward, which adds to the challenges in responding to these substances.

"Like other new substances, one of the reasons behind the increase in these fentanils is that they are not controlled under the United Nations drug control conventions. This means that in many countries they can be manufactured and traded relatively freely and openly — a situation which has been exploited by entrepreneurs and crime groups using companies based in China to make the substances. The fentanils are typically shipped to Europe by express mail services and courier services. From here, they are then sold as ‘legal’ replacements for illicit opioids on the surface web and on the darknet. Unknown to users, they are also sold as heroin or mixed with heroin and other illicit opioids. Occasionally they have also been used to make fake medicines and, less commonly, sold as cocaine (see ‘Fentanils in fake medicines and cocaine’, page 12).

"Fentanils have been found in a variety of physical and dosage forms in Europe. The most common form is powders, but they have also been detected in liquids and tablets. Depending on the circumstances, seizures of powders have ranged from milligram to kilogram quantities. They may be relatively pure, especially when seized coming into the European Union. They may also be mixed with one or more substances. In the latter case, these include commonly used cutting agents (such as mannitol, lactose and paracetamol), as well as heroin and other fentanils/opioids. To a much smaller degree, other drugs, such as cocaine and other stimulants, have also been detected in mixtures with fentanils in Europe. During 2016, more than 4.6 kg of powder containing fentanils was reported, while almost 4.5 litres of liquid and around 2 900 tablets were also reported. Less commonly, fentanils have also been found in blotters and plant material. In these cases, there may be no indication that they contain fentanils, which could pose a risk of poisoning to people who use them."

European Monitoring Centre for Drugs and Drug Addiction (2018), Fentanils and synthetic cannabinoids: driving greater complexity into the drug situation. An update from the EU Early Warning System (June 2018), Publications Office of the European Union, Luxembourg.

13. Growth of Fentanyl on the Illegal Market

"Alongside their legitimate uses as medicines and in research, the fentanils also have a long history of illicit use as replacements for heroin and other controlled opioids. Between 1979 and 1988, more than 10 fentanils that had been made in illicit laboratories were detected on the drug market in the United States (Henderson, 1991). The first was alpha-methylfentanyl, followed by substances such as 3-methylfentanyl and 4-fluorofentanyl. Typically, they were sold as heroin or ‘synthetic heroin’. Together, these substances were involved in more than 100 deaths, mostly in the state of California. Later, in the mid-2000s, illicitly manufactured fentanyl was sold as heroin or in mixtures with heroin, and was responsible for outbreaks of overdoses that involved hundreds of deaths in the eastern United States (Schumann et al., 2008). It appears that, with the exception of Estonia, where 3-methylfentanyl and fentanyl were responsible for an epidemic of fatal poisonings during this time, these substances caused limited problems elsewhere in Europe (Berens et al., 1996; de Boer et al., 2003; Fritschi and Klein, 1995; Kronstrand et al., 1997; Ojanperä et al., 2008; Poortman-van der Meer and Huizer, 1996).

"Over the past few years, there has been a large increase in the availability of fentanils in the United States, Canada and Europe (Gladden et al., 2016; US CDC, 2015). This has been driven by the opioid epidemics in North America, interest in selling these substances in Europe and broader changes in the illicit drug market."

European Monitoring Centre for Drugs and Drug Addiction (2018), Fentanils and synthetic cannabinoids: driving greater complexity into the drug situation. An update from the EU Early Warning System (June 2018), Publications Office of the European Union, Luxembourg.

14. Synthetic Cannabinoids

"Synthetic cannabinoids, also known as synthetic cannabinoid receptor agonists, are a group of drugs that mimic the effects of a substance found in cannabis called tetrahydrocannabinol (THC). THC is responsible for many of the psychoactive effects of cannabis which give that feeling of being ‘stoned’ or ‘high’ (Gaoni and Mechoulam, 1964; Huestis et al., 2001; Pertwee, 2005a; Pertwee, 2014). These effects are caused by activating a receptor in the brain called the cannabinoid receptor type 1 (CB1 receptor) (Huestis et al., 2001; Pertwee, 2014). The receptor is part of a signalling system in the body called the endocannabinoid system, which helps regulate, among other things, behaviour, mood, pain, appetite, sleep and the immune system (Pertwee, 2015).

"Similar to the fentanils, the synthetic cannabinoids were originally developed by scientists to study the body, provide insights into disease and help develop new medicines (Pertwee, 2005b; Reggio, 2009). Around the mid-2000s, they began to appear in Europe in products called ‘Spice’ that were sold as ‘legal’ replacements to cannabis. In these products, powders containing synthetic cannabinoids were mixed with plant material which could then be smoked as cigarettes (‘joints’) (Auwärter et al., 2009; EMCDDA, 2009; Jack, 2009). Since then, 179 cannabinoids have been identified on the drug market in hundreds of different products (Figure 7). The products are commonly referred to as ‘herbal smoking mixtures’, ‘Spice’, ‘K2’, ‘synthetic cannabis’ and ‘synthetic marijuana’. Most of the synthetic cannabinoid powders are made in China, with the final products made in Europe.

"Because synthetic cannabinoids work in a similar way to THC, many of their effects are similar to those of cannabis (Auwärter et al., 2009). Most prominently, they are able to create the feeling of being ‘stoned’. This includes relaxation, euphoria, lethargy, depersonalisation, distorted perception of time, impaired motor performance, hallucinations, paranoia, confusion, fear, anxiety, dry mouth, bloodshot eyes, tachycardia (an abnormally fast heart rate), nausea and vomiting. In some cases, these effects appear to be much more pronounced and severe than those produced by cannabis (Ford et al., 2017; Zaurova et al., 2016)."

European Monitoring Centre for Drugs and Drug Addiction (2018), Fentanils and synthetic cannabinoids: driving greater complexity into the drug situation. An update from the EU Early Warning System (June 2018), Publications Office of the European Union, Luxembourg.

15. Effects of Synthetic Cannabinoids More Severe and Can Include Fatal Poisoning

"The reasons for the more pronounced psychoactive effects and severe and fatal poisoning seen with synthetic cannabinoids are not particularly well understood, but at least two factors are likely to be important: the high potency of the substances and the unintentionally high doses that users are exposed to.

"Firstly, studies have found that many of the cannabinoids sold on the drug market are much more potent than THC (behaving as so-called ‘full agonists’). This means that even at very small doses they can activate the CB1 receptor much more strongly than THC (Banister et al., 2016; Ford et al., 2017; Longworth et al., 2017a,b; Reggio, 2009; Tai and Fantegrossi, 2017). It is worth noting that little is known about the effects of synthetic cannabinoids on other signalling systems in the body, which may also explain some of the effects of these substances.

"Secondly, the process for mixing the synthetic cannabinoids with the plant material to make smoking mixtures (which are the most common way of using these substances) can lead to dangerous amounts of the substances in the products. This is because producers have to guess the amount of cannabinoids to add, while the mixing process makes it difficult to dilute the cannabinoids sufficiently and distribute them consistently throughout the plant material. This can result both in products that contain toxic amounts of the substances in general, as well as in products where the cannabinoids are clumped together, forming highly concentrated pockets among the plant material (Figure 9) (Ernst et al., 2017; Frinculescu et al., 2017; Langer et al., 2014, 2016; Moosmann et al., 2015; Schäper, 2016). These issues are made worse because the products are smoked (or vaped), allowing the substances to be rapidly absorbed into the bloodstream and to reach the brain, where they cause many of their effects.

"The combination of these two factors makes it difficult for users to control the dose that they are exposed to. This can lead them to unintentionally administer a toxic dose (see ‘Other risks related to synthetic cannabinoids and smoking mixtures’, page 18). Accounts from patients and people who witness poisonings suggest that in some cases a small number of puffs from a joint have been sufficient to cause severe and fatal poisoning."

European Monitoring Centre for Drugs and Drug Addiction (2018), Fentanils and synthetic cannabinoids: driving greater complexity into the drug situation. An update from the EU Early Warning System (June 2018), Publications Office of the European Union, Luxembourg.

16. New Psychoactive Substances (NPS) Defined

"To better serve policymaking at the regional and international levels, the term “new psychoactive substances” or NPS was coined. The Commission on Narcotic Drugs introduced this term at the international level in its resolution 55/1 of 16 March 2012.
"The term 'new psychoactive substances' had been legally defined earlier by the European Union as a new narcotic or psychotropic drug, in pure form or in a preparation, that is not scheduled under the Single Convention on Narcotic Drugs of 1961 or the Convention on Psychotropic Substances of 1971, but which may pose a public health threat comparable to that posed by substances listed in those conventions (Council of the European Union decision 2005/387/JHA).
"That legal definition is now widely used and has also been adopted by the EMCDDA.18"

UNODC, World Drug Report 2013 (United Nations publication, Sales No. E.13.XI.6), p. 60.

17. Worldwide Growth in Novel Psychoactive Substances

"Between 2008 and 2015, a total of 644 NPS had been reported by 102 countries and territories to the UNODC early warning advisory on NPS. The emergence of NPS was reported for the first time in 2015 in Kyrgyzstan and Mauritius. In 2015, the early warning advisory also registered the emergence of NPS in previous years in Belarus, Serbia, South Africa and Tajikistan. The majority of countries and territories that reported the emergence of NPS up to December 2015 were from Europe (41), followed by Asia (30), Africa (16), the Americas (13) and Oceania (2).

"The NPS market continues to be characterized by a large number of new substances being reported. Although data collection for 2015 is still in progress, 75 new substances have been reported to UNODC for the first time, compared with a total of only 66 in 2014. Between 2012 and 2014, most substances reported for the first time belonged to the group of synthetic cannabinoids. The data reported for 2015 so far show a different pattern: first, 20 synthetic cathinones (a group of substances with stimulant effects similar to cocaine or methamphetamine) were reported for the first time — almost as many as synthetic cannabinoids (21); and second, 21 'other substances' (substances not belonging to any of the major groups identified in previous years) were reported for the first time, including synthetic opioids (e.g. fentanyl derivatives) and sedatives (e.g. benzodiazepines).

"A growing number of NPS are reported every year by a large number of countries and territories throughout the world. NPS that have an established presence in the market include ketamine (reported by 62 countries and territories), khat (reported by 56), JWH-018 (reported by 50), mephedrone (reported by 49) and methylone (reported by 47).227 Other NPS are transient in nature and are only reported by a small number of countries and territories for a couple of years."

United Nations Office on Drugs and Crime, World Drug Report 2016 (United Nations publication, Sales No. E.16.XI.7), p. 56.

18. Prevalence of NPS Use Among Young People in England and Wales

"According to the Crime Survey for England and Wales,238 over the period 2014-2015, 279,000 adults (0.9 per cent of the population aged 16-59) reported the use of NPS. Among young adults (ages 16-24), the prevalence of NPS use was much higher (2.8 per cent), the majority of the users being young men. Herbal smoking mixtures were the most commonly used form of NPS, with 61 per cent of the population aged 16-59 reporting their use. According to Public Health England,239 the number of individuals 'presenting to treatment' for a 'club drug' or NPS more than doubled, from 2,727 to 5,532, between the financial years 2009-2010 and 2014-2015. The largest increase was recorded for mephedrone — from 953 in the period 2010-2011 to 2,024 in the period 2014-2015. Compared with the previous period, the prevalence of past-year use of mephedrone in England and Wales in the financial years 2014-2015 remained stable at 1.9 per cent for young adults and 0.5 per cent for adults, which is similar to the prevalence of past-year use of amphetamines (0.6 per cent) and higher than that of LSD (0.4 per cent) or heroin (0.1 per cent).240"

United Nations Office on Drugs and Crime, World Drug Report 2016 (United Nations publication, Sales No. E.16.XI.7), p. 60.

19. Prevalence of New Psychoactive Substances (NPS) Among US Youth

"In the United States, there are indications of an increase in NPS use among certain user groups between 2009 and 2013; the prevalence of lifetime use of a 'novel psychoactive substance' among the population aged 12-34 was 1.2 per cent in 2013.235 There are signs of declining use of synthetic cannabinoids among secondary school students in the United States. The prevalence of past-year use of synthetic cannabinoids among twelfth-grade students decreased from 11.4 per cent in 2011 to 5.2 per cent in 2015.236 This is associated with an increase, over the same period, in the perceived risk of taking synthetic cannabinoids among the same group. The use of NPS with stimulant effects (reported as “bath salts“) among twelfth graders remained stable at 1 per cent in 2015. The prevalence of the use of synthetic cannabinoids among eighth, tenth and twelfth graders has declined to the lowest levels since the collection of such data began. However, the large amount of synthetic cannabinoids seized between 2012 and 2014 (more than 93 tons) and the large number of calls to poison centres for problems related to the use of synthetic cannabinoids (3,682 in 2014 and 7,779 in 2015)237 indicate the continued presence and use of this NPS group in the United States."

United Nations Office on Drugs and Crime, World Drug Report 2016 (United Nations publication, Sales No. E.16.XI.7), p. 60.

20. Emergency Room Visits Related to NPS Use

"In the United States, the first report on synthetic cannabinoids from the Drug Abuse Warning Network revealed that an estimated 11,406 visits of the approximately 2,300,000 emergency department visits that involved drug use in 2010 were specifically linked to synthetic cannabinoids. Three quarters of these emergency department visits involved patients aged 12 to 29 (75 percent or 8,557 visits), of which 78 percent were male, and in the majority (59 percent) of these cases, no other substances were involved. The average patient age for synthetic cannabinoids-related visits was 24 years, while it was 30 years for cannabis. Overall, synthetic cannabinoid-related visits were concentrated in the younger age groups: 75 percent of the visits involved patients aged 12 to 29, with 33 percent of the patients aged 12 to 17. In comparison, 58 percent of cannabis-related visits involved patients aged 12 to 29, with 12 percent in the 12 to 17 age group.173"

UN Office on Drugs and Crime, "The Challenge of New Psychoactive Substances: A Report from the Global SMART Programme" (Vienna, Austria: UNODC Laboratory and Scientific Section, March 2013), p. 38.