"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.

"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).

"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).

"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’.

"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.

"Reflecting consumer demand, the market in new benzodiazepines appears to have grown over the past few years. The EMCDDA is currently monitoring 23 of these substances, including six that were reported for the first time in 2016 and three during 2017. While the overall number of seizures reported by law enforcement during 2016 decreased compared with 2015, the quantity reported increased. More than half a million tablets containing new benzodiazepines such as diclazepam, etizolam, flubromazolam, flunitrazolam and fonazepam were reported during 2016 — which was about 70 % more than in 2015.

"Reflecting their use as legal replacements for cocaine, amphetamine and other controlled stimulants, there were more than 23 000 seizures of synthetic cathinones reported from across Europe in 2016 (Figure 3). These account for almost one-third of the total number of seizures of new substances over the year, and amounted to almost 1.9 tonnes, making synthetic cathinones the most commonly seized new psychoactive substances by quantity in 2016. The EMCDDA is currently monitoring 130 of these substances, including 14 that were reported for the first time in 2016 and 12 during 2017.

"By the end of December 2017, the EMCDDA was monitoring more than 670 new substances that have appeared on Europe’s drug market over the past 20 years. This total includes 51 substances that were reported for the first time during 2017 (Figure 1), namely 13 opioids, 12 cathinones, 10 cannabinoids, 4 phenethylamines, 3 benzodiazepines, 2 tryptamines, 1 arylcyclohexylamine, 1 arylalkylamine, 1 piperidine/pyrrolidine and 4 substances that do not belong to these other groups.

(Toxic Effects of Kratom) "During the past 3 years, there have been an increasing number of case reports^15,17,29 describing unusual adverse reactions in patients who had been using kratom or kratom-based products. The acute adverse effects of kratom experienced by many users appear to be a direct result of kratom's stimulant and opioid activities.6,9,11,30,31 Stimulant effects may manifest themselves in some individuals as anxiety, irritability, and increased aggression. Opioid-like effects include sedation, nausea, constipation, and itching.

(Analgesic and opioid-like effects of Kratom) "In Southeast Asia, kratom has long been used for the management of pain and opium withdrawal.^6,9-11,14 In the West, kratom is increasingly being used by individuals for the self-management of pain or withdrawal from opioid drugs such as heroin and prescription pain relievers.^20,27 It is these aspects of kratom pharmacology that have received the most scientific attention.