"Depressant NPS encompass two main types of CNS depressants: opioids, which cause analgesia, euphoria, drowsiness, and sedation (eg, fentanyl analogues); and benzodiazepines, which have sedative, anxiolytic, hypnotic, muscle-relaxant, and anticonvulsant effects (eg, etizolam, phenazepam).¹⁵ These NPS can be sold under their own name, but have also been detected as counterfeit prescription medicines (eg, in tablets or capsules), or adulterated with or sold as more established illicit drugs (eg, in powder form).¹⁶ They are mostly swallowed, snorted, or injected.

"Hallucinogen NPS are a diverse group of substances that alter an individual’s awareness of their surroundings, as well as their thought processes and perception, which can lead to substantial distortions of reality. They can be divided into two main types: dissociatives, which induce euphoria alongside a feeling of weightlessness and detachment from the body; and classic hallucinogens, which produce altered perception,¹⁵ causing cognitive and visual disturbances and an altered state of consciousness.

"Stimulant NPS are drugs with similar effects to amphetamine, cocaine, and 3,4-methylenedioxymethamphetamine (MDMA), which result in increased alertness, energy, confidence, and sociability, and suppression of appetite and fatigue (eg, mephedrone, methylone, α-PVP).¹⁴ They are typically in a powder, capsule, tablet, liquid, or crystal form, and are primarily consumed by swallowing or snorting, as well as by injecting."

"Synthetic cannabinoid receptor agonists (hereafter synthetic cannabinoids) are a chemically diverse group of synthesised compounds that often act on similar receptors to those acted on by Δ-9-tetrahydronnabinol in cannabis. Powders are typically dissolved in solvent, sprayed on inert plant material and then smoked, and are often sold as commercial mixtures (eg, Spice, Kronic).¹² Other forms and routes of administration include ingestion of pills or powders, and vaping using solutions containing synthetic cannabinoids.

"Clinical and public health responses to date have focused on acute toxicity from NPS. This attention has grown in previous years with the increased reportings of overdose associated with NPS in several countries.

"Data on 27,338 overdose deaths that occurred during July 2016–December 2017 were entered into SUDORS, and 152 (0.56%) of these decedents tested positive for kratom on postmortem toxicology (kratom-positive). Postmortem toxicology testing protocols were not documented and varied among and within states.

"Synthetic cathinones are related to the parent compound cathinone (Figure 1), one of the psychoactive principals in khat (Catha edulis Forsk). Cathinone derivatives are the β-keto (βk) analogues of a corresponding phenethylamine. The group includes several substances that have been used as active pharmaceutical ingredients (API) of medicinal products, e.g. amfepramone (diethylpropion; Figure 2). Since the mid-2000s, unregulated ring-substituted cathinone derivatives have appeared in the European recreational drugs market.

"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).