New psychoactive substances: a review and updates, Abu Shafi et al., 2020

New psychoactive substances: a review and updates

Abu Shafi, Alex J. Berry, Harry Sumnall, David M. Wood and Derek K. Tracy

Therapeutic Advances in Psychopharmacology, 2020, Vol. 10, 1–21.

Doi : 10.1177/2045125320967197


Abstract :

New psychoactive substances (NPS) are a heterogeneous group of substances. They are associated with a number of health and social harms on an individual and societal level. NPS toxicity and dependence syndromes are recognised in primary care, emergency departments, psychiatric inpatient and community care settings. One pragmatic classification system is to divide NPS into one of four groups: synthetic stimulants, synthetic cannabinoids, synthetic hallucinogens and synthetic depressants (which include synthetic opioids and benzodiazepines). We review these four classes of NPS, including their chemical structures, mechanism of action, modes of use, intended intoxicant effects, and their associated physical and mental health harms. The current challenges faced by laboratory testing for NPS are also explored, in the context of the diverse range of NPS currently available, rate of production and emergence of new substances, the different formulations, and methods of acquisition and distribution.

Keywords : laboratory testing, new psychoactive substances, NPS, synthetic cannabinoid receptor agonists, synthetic hallucinogens, synthetic opioids, synthetic stimulants



New psychoactive substances (NPS) are a complex and diverse group of substances often known as either designer or synthetic drugs, or by the more popular but misleading colloquial term of ‘legal highs’.1,2 They tend to be either analogues of existing controlled drugs and pharmaceutical products or newly synthesised chemicals, created to mimic the actions and psychoactive effects of licensed medicines and other controlled substances. 3–5 By their number, nature and composition, NPS pose significant challenges for drug consumers, clinicians – both in drug services and, more broadly, researchers, forensic toxicologists, healthcare systems and drug control policy globally – and have been described as a ‘growing worldwide epidemic’.6,7

The United Nations Office for Drugs and Crime (UNODC) has defined NPS as ‘substances of abuse, either in a pure form or a preparation, that are not controlled by the 1961 Single Convention on Narcotic Drugs or the 1971 Convention on Psychotropic Substances, but which may pose a public health threat’.8 However, definitions of NPS can vary between countries, reflecting differences in national legislation, rather than pharmacological or structural classification. Although some former NPS have been subject to international control under the UN Conventions (e.g.mephedrone in 2015; the synthetic cannabinoid ADB-FUBINACA in 2019), different approaches have been taken to legal control at national level.2,9,10 This has included the use of existing controlled drug legislation, new NPS-specific legislation, or extension of generic public health and medicines legislation. In the United Kingdom (UK), for example, the Psychoactive Substances Act 2016 introduced legislation that made it an offence to produce, supply, offer to supply, possess with intent to supply, possess on custodial premises, import or export psychoactive substances, but did not make it an offence to possess for personal use outside of a custodial setting.11 In principle this created a ‘blanket ban’ of all current and future NPS (with certain exemptions). However, the legislation has been criticised for the imprecise definition of psychoactivity, its blanket nature covering compounds with quite differing harm profiles, difficulties in enforcement,
and exemptions that meant that popular NPS such as nitrous oxide can still be purchased. 4,12,13 Early evaluation of the Act suggested that whilst the availability of NPS had decreased, there was no evidence of a reduction in NPS-related harms.14

By 2018, a total of 892 individual NPS, reported by 119 countries, were being monitored by the UNODC early warning system,15 and by the end of 2018, over 730 NPS had been notified to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA).16 The rapid proliferation at which new NPS have emerged on the global drugs market is unparalleled,17 and it was estimated that at its peak in 2015, new NPS appeared at a rate of at least one new substance per week.18 The number of new NPS detections has decreased in recent years and, in addition, the nature of the market has changed, with a relative decrease in the number of new stimulants and synthetic cannabinoids detected, and an increase in the numbers of new opioids and benzodiazepines available.16 The rapidly changing profile of the NPS market raises concerns over uncertainty and ambiguity regarding their chemical, metabolic and toxicity profiles, and the associated physical, social and mental health harms.19–21