"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.

"Since around 2008, there has been a dramatic growth in the NPS market as globalisation and new technologies, such as the internet, have allowed them to be produced, sold and supplied on an industrial scale. Between 2009 and 2018, 119 countries and territories reported the emergence of 892 different NPS to UNODC, through the UNODC Early Warning Advisory on NPS (UNODC, 2019b). In Europe, more than 730 NPS have appeared on the drug market since monitoring began in 1997, with around 90 % of these being detected between 2008 and 2018 (EMCDDA, 2019b).

"Cathinone and its derivatives are closely related to the phenethylamine family (which includes amphetamine and methamphetamine), but with a lower potency than the latter.¹³ They are characterised by the presence of a ?-keto group on the side chain of the phenethylamines. Cathinone, the principal active ingredient in the leaves of the khat plant (catha edulis), can be considered as the prototype from which a range of synthetic cathinones have been developed.

"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).

"In the operating guidelines on the early warning system, EMCDDA [European Monitoring Centre on Drugs and Drug Addiction] made it explicit that 'the term ‘new’ did not refer to newly invented, but rather ‘newly misused’' substances as 'most of the drugs in question were first created many years ago.'²⁰ In fact, investigations into the potential use of piperazines as anthelmintic have been reported in scientific literature since the early 1950s.²¹ Yet they only started to emerge as a health problem in several countries in the decade 2001-2010.

"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 creation of new substances to exploit loopholes in drug control legislation has been a problem since the international drug control system was first established. The proliferation of such substances in recent decades was influenced by the work done by Ann and Alexander Shulgin on phenethylamines⁸ and tryptamines⁹ in the 1960s and the 1970s. The Shulgins reported over 230 psychoactive compounds that they had synthesized and evaluated for their psychedelic and entactogenic potential.