By Sam Craft, Michael Dunn, Dan Vidler, Jane Officer, Ian S. Blagbrough, Christopher R. Pudney, Graeme Henderson, Ahmed Abouzeid, Pual I. Dargan, Michael Eddleston, Jamie Cooper, Simon L. Hill, Clair Roper, Tom P. Freeman and Simon H. L. Thomas.
Novel psychoactive substances (NPS) are a broad range of drugs that are not controlled by the United Nations international drug conventions, but may pose a threat to public health. Previously marketed as ‘legal highs’ or ‘designer drugs’, NPS are often structural analogues of conventional illicit drugs or medicinal products designed to mimic their effects while evading legal control. Their prevalence in the general population is low, with ~0.5% of those ages 16 to 59 reporting past year use in the United Kingdom (UK) in 2019. However, NPS are often considerably more harmful than the drugs they were designed to mimic and pose a significant challenge to health-care services. In 2020, the Office for National Statistics (ONS) recorded 137 deaths involving NPS use in the United Kingdom. In 2017, data from the three UK hospitals reporting to the European Drug Emergencies Network (EURO-DEN) show that patients reported NPS use in 15% of all drug-related hospital emergency presentations. Definitions and classifications of NPS vary between data collection systems, but those most commonly encountered are benzodiazepines, cathinones, and synthetic cannabinoid receptor agonists (SCRAs).
With over 200 different compounds currently being monitored by the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA), SCRAs are the largest group of NPS, and in recent years they have been involved in the greatest proportion of deaths and emergency hospital presentations. Although structurally diverse, SCRAs elicit their effects via interaction with the endocannabinoid system, typically acting as full agonists at CB1 and CB2 receptors. The main psychoactive compound of cannabis, delta-9-tetrahydrocannabinol (THC), is a partial CB1 and CB2 receptor agonist, and comparatively SCRAs show considerably greater potency and binding affinity at these receptors.
The individual SCRAs most commonly encountered have changed with time, presumably to evade national and international legislative changes. In the United Kingdom, following classification under consecutive amendments to the Misuse of Drugs Act (MDA)—first in 2009 and then in 2013—novel groups of compounds with structural modifications that circumvented these controls quickly emerged with a general increasing trend in potency. In response, and in attempt to end the open sale of SCRAs and other ‘legal highs’ in high-street retailers, the United Kingdom introduced the Psychoactive Substances Act (PSA) on the 26th May 2016 to be used alongside the MDA. Whereas the MDA controls individual or small groups of compounds according to chemical structure, the PSA made illegal the importation, production, and supply (but not possession, except in custodial settings) of all psychoactive substances (not already controlled under the MDA), although with several named exemptions including alcohol, nicotine and licensed medications. Alongside this, a third amendment to the MDA in December 2016 (although based on recommendations made by the Advisory Council for the Misuse of Drugs [ACMD] in 2014) increased the scope of the generic definition of SCRAs to include the then emerging third generation compounds that were controlled as Class B substances in line with the compounds already scheduled, thereby extending sanctions beyond those covered by the PSA (including penalties for possession).
In 2018, the UK Home Office conducted a review into the effectiveness of the PSA. The report concluded that although ending the open sale and reducing use of NPS within the general population, SCRAs (and other NPS) had been integrated into the illicit market and use had increased within vulnerable populations, such as the homeless or those in prison. More recently, a multidisciplinary study interviewing SCRA users and various stakeholders (e.g. emergency services, outreach engagement workers etc.) outlined several detrimental impacts of the PSA on the UK SCRA market, which the authors conclude have increased the risk of individual and societal harm. This is supported by mortality data from the ONS and National Program on Substance Abuse Deaths (NPSAD), which show that since the PSA, the number of deaths where SCRAs are implicated and/or detected at post-mortem have increased.
Data from hospital presentations can also provide important insight into the nature and epidemiology of SCRA related harm; however, there is currently a lack of routinely collected, systematic data of this kind in the UK or elsewhere. Data from the National Poisons Information Service, a service for clinicians seeking advice for the diagnosis/management of individual cases of poisoning, has demonstrated that telephone enquiries citing NPS exposure have decreased since the enactment of the PSA, however, the impact on the number of enquiries citing SCRA exposure specifically was not reported. Poison centre data have several limitations and are not representative of the true number of clinical exposures or hospital admissions, see Wood et al. Previous studies analysing data from individual hospitals in Edinburgh and London have reported that the number of NPS-related toxicity presentations did not significantly change following the implementation of the PSA, although in London, there were changes in the types of NPS involved and the number of SCRA-related presentations had increased in the year after its implementation. However, confirmatory toxicological analysis is not typically available in acute clinical settings, and previous studies have relied on details of drug exposure reported by the patient (or witness). This is unreliable because there may be substantial variability in the composition of NPS products that may not be known to the user, and patients may report SCRAs when they have not been used or fail to report them when they have. Therefore, without analytical confirmation, clinical data may not accurately reflect trends in SCRA related harm.
The Identification of Novel Psychoactive Substance (IONA) study has been collecting clinical data and biological samples from patients attending emergency departments across the UK with severe toxicity associated with suspected NPS use since 2015. By conducting time series analysis using IONA data, we aimed to examine trends in the number of hospital presentations for severe acute toxicity involving analytically confirmed SCRA exposure before and after the implementation of the PSA between July 2015 and December 2019. For comparison, we also examined trends in the number of non-SCRA drug toxicity presentations during the same period.