ORIGINAL RESEARCH article

Front. Pharmacol., 29 January 2026

Sec. Neuropharmacology

Volume 16 - 2025 | https://doi.org/10.3389/fphar.2025.1708335

Legislating novel psychoactive substances: lessons from 15 years of UK mortality data (2007-2022)

  • 1. Institute of Pharmaceutical Sciences, King’s College London, London, United Kingdom

  • 2. Retired, London, United Kingdom

  • 3. National Programme on Substance Use Mortality, London, United Kingdom

Abstract

Background:

Novel Psychoactive Substances (NPS) emerged in the early 2000s as chemically designed alternatives to circumvent laws which internationally control drugs. There is limited evidence that NPS are produced in the UK, whereas China has long been recognised as a primary source of NPS. This study aimed to evaluate the relative impact of UK, Chinese, and UN legislative controls on the availability of NPS in the UK, as evidenced by post-mortem detections of NPS in deaths.

Methods:

Deaths reported to the National Programme on Substance Use Mortality (NPSUM) which occurred 2007–2022 were extracted for analysis. Drugs from the three major substance classes–opioids, stimulants and cannabinoids–which were detected in these deaths were categorised according to their control status as either classical substances (i.e., those under international control prior to 2007), NPS controlled in China, or other NPS.

Findings:

Across all three drug classes, detections of classical substances dominated throughout the study period. Detections of NPS opioids–primarily fentanyl analogues–peaked in 2017, NPS stimulants–notably cathinones–in 2015, and synthetic cannabinoid receptor agonists in 2018 and 2021. Whilst UK legislative controls (the Misuse of Drugs Act 1971, Temporary Class Drug Orders, the Psychoactive Substances Act 2016) were generally implemented first, reductions in NPS detections were more closely associated with the introduction of Chinese legislations - in particular the 2021 Chinese generic ban on synthetic cannabinoids which resulted in an almost complete disappearance of these compounds in UK deaths in 2022.

Conclusion:

The findings of this study indicate that the most effective way to reduce NPS availability in the UK is via legislation in producer countries, as evidenced by substantial declines in their detections in deaths following their control in China. This reliance on international controls places the UK in a vulnerable position, as its domestic drug landscape is being shaped largely by the pace and scope of independent international legislations. To achieve and maximise effectiveness, UK drug policy needs to integrate harm reduction measures alongside the introduction of legislative controls, whilst also encouraging international efforts to bring in global control of problem materials.

Highlights

  • Producer-country controls appear to be more effective than domestic legislation.

  • UK demand-side drug policy interventions appear to have had limited impact.

  • Control of NPS may be driving substitution to more harmful substances.

Introduction

Novel psychoactive substances (NPS) are drugs that have been newly designed to mimic the effects of traditional controlled substances (e.g., opioid, stimulants) (). They pose significant health risks due to their unknown potencies, toxic effects, and lack of pre-clinical and clinical testing (). There is very little evidence that NPS are manufactured within the United Kingdom (UK), with the UK NPS market instead supplied by imports of materials synthesised overseas: China has long been recognised as a primary source of NPS (; ; ; ; ; ), with the products of its extensive and proficient chemical industry infrastructure now readily available to the rest of the world by means of internet trading and rapid postal delivery services (; ; ).

Legal controls on NPS

Controls on NPS have been progressively introduced as new materials have emerged and evidence of their harms has accumulated (). Individual countries are responsible for legislative control of drugs within their jurisdiction. Additionally, there is overarching international drug control co-ordinated by the United Nations (UN), intended to provide a globally consistent approach (; ; ). UN guidance on materials for control are required to be enacted into national legislations of member states (; ; ).

UN guidance on regulation of NPS

The UN operates three major international Conventions addressing drug control: the 1961 Convention on Narcotic Drugs; the 1971 Convention on Psychotropic Substances; the 1988 Convention against Illicit Traffic in Narcotic Drugs and Psychotropic Substances (; ; ). These are updated annually by the UN Commission on Narcotic Drugs (CND), based on recommendations from the World Health Organisation’s (WHO) Expert Committee on Drug Dependence (ECDD). Since 2015, the annual extensions of the Conventions’ lists have primarily concerned NPS and their precursors.

UK legislative control of NPS

The UK as a UN member state is obliged to place substances listed in the three international drug Conventions under national drug control. The UK has also controlled many additional psychoactive substances which are considered to represent a hazard to human health (; ).

UK drug controls are primarily enacted by the Misuse of Drugs Act 1971 (the MDA ()). In addition to specific substances, the MDA also includes generic controls on families of psychoactive substances with a common core chemical structure intended to control ‘designer drugs’ – variants of controlled drugs chemically ‘designed’ so as to avoid specifically worded legislative controls ().

From 2009, as NPS began to emerge, a series of substance-specific and generic controls were brought into effect by means of additions to the MDA (e.g., synthetic cannabinoid receptor agonists [SCRAs], cathinones) (). However, such MDA additions took time to implement as evidence of substance-related harms needed to be gathered. The MDA was therefore supplemented by the use of emergency Temporary Class Drug Orders (TCDOs), introduced in November 2011 to permit more rapid control of NPS whilst their potential harms were more fully evaluated ().

However, as both the MDA and TCDOs require the identification of specific substances (or families of substances) to bring them under control, this proved a significant limitation to the control of rapidly emerging NPS. In response, the Psychoactive Substances Act 2016 (the PSA) was brought into effect in late May 2016 (). The PSA includes provisions to prevent the importation, distribution, and sale of any psychoactive substances which were outside the scope of the MDA and TCDO controls, unless specifically exempted (). This had the immediate effect of outlawing the open sale of NPS through commercial outlets such as ‘head shops’ and internet vendors ().

Chinese legislative control of NPS

China is also a UN member state and therefore a signatory of the three major international drug Conventions (; ; ). Similarly to the UK, China has also enacted a series of additional controls on a large number of specified NPS (; ) as well as a broad generic ban on fentanyl derivatives in May 2019 () and a set of generic controls on many SCRA structural families in May 2021 ().

Evolution of NPS

As substance-specific legislative controls have been introduced, NPS producers have rapidly adjusted their products or developed new NPS based on core structures not yet addressed by international or national controls (; ; ; ). This iterative process of new NPS, substance-specific legal controls, and rapid replacement by further NPS has become a game of “cat and mouse” or “whack-a-mole” (; ).

Study aim and method of investigation

In this study we aimed to evaluate the relative impact of UK, Chinese and UN control measures on NPS available on the UK illicit drug market. This evaluation was based on the most serious adverse effect of NPS, as evidenced by post-mortem detections of NPS in deaths from England, Wales and Northern Ireland recorded by the National Programme on Substance Use Mortality (NPSUM) over a 15-year period, from 2007 to 2022.

Methods

National programme on substance use mortality (NPSUM)

The NPSUM receives voluntary reports from over 85% of English, Welsh, Northern Irish and Islands’ (Jersey, Guernsey, Isle of Man) coroners on deaths related to psychoactive drugs. A death is referred to a coroner if it has an unknown cause, is violent or unnatural, sudden, and unexplained, occurred during an operation or before the person came out of an anaesthetic, or potentially caused by an industrial disease or poisoning (). Toxicology tests are requested dependent upon individual case circumstances at the discretion of the coroner and consulting pathologist.

A range of documents comprise coronial inquest files, although this varies from case to case. Typically, the coroner has access to: statements from witnesses, family and friends; General Practitioner (GP) records (if the deceased is registered with one); reports from first responders (e.g., police, emergency services); hospital emergency departments and clinical ward reports; psychiatric and substance abuse team reports; as well as post-mortem and toxicology reports. Information from these reports is transposed into the relevant data fields on the NPSUM database as either numerical variables or string text, as appropriate. All drugs detected by toxicological testing of post-mortem samples are entered on the NPSAD database, except for caffeine and nicotine (and metabolites thereof).

The King’s College London Biomedical and Health Sciences, Dentistry, Medicine and Natural and Mathematical Sciences Research Ethics Subcommittee re-confirmed in August 2025 that NPSUM does not require research ethics committee review as all subjects are deceased.

Case identification

A retrospective study design was used to identify all cases with detections of opioids, stimulants, or cannabinoids in post-mortem tissue (e.g., blood, urine, vitreous humor, stomach contents, liver, skeletal muscle) which occurred in the 15-year period 2007–2022 and were reported to the NPSUM by 1 November 2024. These three drug classes were chosen as the majority of additional controls enacted by the UK, China and UN have focused upon substances from within these classes (; ; ; ; ; ). Sub-analysis was then performed on cases with detections of opioids, stimulants, or cannabinoids which had been controlled in China between 2015 and 2021 either directly via legislation introduced by the Council of China, or indirectly via their addition to the International Drug Control Conventions by the UN Commission on Narcotic Drugs.

In the vast majority of cases, NPS detections were made from preserved blood and urine samples. UK toxicology laboratories typically screen for drugs using an immunoassay or a multi-analyte liquid chromatography–mass spectrometry (LC–MS) screening technique (). The samples then proceed to confirmatory testing using either an LC–MS/gas chromatography–mass spectrometry (GC–MS) or high-resolution accurate mass (HRAM) analysis ().

Data analysis

Software: Data analysis were performed using IBM® SPSS™ Statistics for Windows version 31, with visualisations constructed using Microsoft Excel 365.

Statistics: Given the time-series nature of the data and the close temporal proximity of when the UK, Chinese and UN NPS legislations were introduced, formal statistical testing was deemed to not be appropriate. The analyses are therefore descriptive, focusing on the temporal relationship between NPS detections in deaths and when the various NPS legislations were introduced.

Results

This study has been subdivided into three broad categories: opioids, stimulants, and cannabinoids. In the tables (Tables 1–3), the substances listed within each category have been segmented according to whether or not they were considered ‘classical’ substances. Classical substances are those that were under international control prior to the start of the study period (i.e., 2007). All other substances within each drug class have then been further segmented as to if and when they became controlled by China, and coloured coded as to when each was controlled by the UK, China and UN either in response to international guidance being issued or by means of a country-specific additional control.

TABLE 1

DrugYear
2007200820092010201120122013201420152016201720182019202020212022
Classical opioids
  Alfentanil00101112024234713
  Buprenorphine86111512122736413452638210410198
  Codeine214227321270257258284279282307286387354367420386
  Dextropropoxyphenea42212010548531211031
  Dihydrocodeine131140136103128101103105129112100130146157146134
  Dihydromorphine0000000000030140
  Dipipanone8592421300111100
  Etonitazene0000000000000045
  Fentanyl751311181831264452866372595153
  Hydrocodone124215514351524514833
  Levorphanol0000001110020010
  Meptazinol2401010010150233
  Methadone380369437390446345353331398382401478577856826793
  Morphine/Heroin10291089130581267267767484499099193111171380130312951298
  Oxycodone191724263136473862516674748083106
  Oxymorphone0000000042114720
  Pentazocine0010000000000000
  Pethidine6281301231002001
  Remifentanil0000000000020111
  Tramadol9483125130182157208194198183173199224240205223
NPS opioids controlled in China in 2015
  4-Fluorobutyrylfentanyl0000000010620000
  Acetylfentanyl0000000020500100
  AH-79210000003100000000
  Butyrfentanyl0000000000611000
  Ocfentanil0000000000101000
NPS opioids controlled in China in 2017
            Carfentanil00000000015100000
            Furanylfentanyl0000000000610000
  U-47,7000000000001000000
NPS opioids controlled in China in 2019
 2-Fluorofentanyl0000000002000000
 Cyclopropylfentanyl0000000000320000
 Despropionyl fentanyl0000000000331100
 Fluorofentanyl (unspecified)0000000001010000
 Methoxyacetylfentanyl0000000000170210
NPS opioids controlled in China in 2021
  Isotonitazene00000000000010172
Other opioids
  Brorphine0000000000000010
  Etodesnitazene0000000000000012
  Kratom/Mitragynine0000042041001011
  N-Pyrollidino etonitazene0000000000000048
  Protonitazene0000000000000001
  Tapentadol00000022125815131020
  Unidentified synthetic opioid0000000000010000

Detections of opioids in deaths reported to the NPSUM 2007–2022 subdivided by type (classical opioids; NPS opioids controlled in China in 2015, 2017, 2019, 2021; other opioids) and colour coded with year and jurisdiction of control according to the Colour Wheel of Drug Policy (yellow: UN; blue: UK; red: China; orange: UN and China; green: UN and UK; purple: UK and China; grey: UN, UK and China).

a

Considered as a licensed medication as previously licensed and prescribed.

TABLE 2

DrugYear
2007200820092010201120122013201420152016201720182019202020212022
Classical stimulants
  Amphetamine10599886810485120106140133137140178203196164
  Cathine0310010111121071
  Cathinone0410110011001121
  Cocaine4274223412322362643353985025977569381228137113791779
  DMT0000000000000001
  Fenproporex0100000000000000
  Methamphetamine6633671011811151725374337
  Methylphenidate0101001052360788
  MDMA7140813214345405964737998994231
  MDA0100011000100011
  MDEA0000100011001522
  N-Ethylamphetamine0000010000000011
  Para-methoxyamphetamine000142433410000200
  Phentermine1000010100000010
  Pyrovalerone0001000000000100
NPS stimulants controlled in China in 2015
  2-AI0000000101011111
  2-Methoxyphenidine00000006125000000
  3-MMC0000000000010100
  3-Trifluoromethylphenylpiperazine432214533000000110
  4-Fluoroamphetamine0010010021001000
  4-Fluoromethamphetamine0000000000001000
  5-MAPB0000001100000000
  5-MeO-DALT0001001100000000
  5-MeO-DiPT0000001000000000
  Alpha-PHP00000000001116164
  Alpha-PVP0000000248011033
  AMT0000235530000000
  Benzylpiperazine9172513583000000100
  Butylone0000001030301000
  Clephedrone0000000022000000
  Desoxypipradrol0003000000000000
  DOC0000100000100000
  Ethylone0000001230000100
  Ethylphenidate000000320101010010
  Flephedrone0002230020000000
  Fluoromethcathinone0000002210000000
  MCPP0000001000111233
  MDAI0000210000000000
  MDPBP0000100000000000
  MDPV0009411110000010
  Mephedrone0074625253032347454382
  Methedrone0002300000000012
  Methiopropamine000004816186100010
  Methylone0002049310100200
  Pentedrone0000010000000000
NPS stimulants controlled in China in 2016
  4-Methylethcathinone000051413652130000
  PMMA0000136000000100
NPS stimulants controlled in China in 2018
  4-Chloroethcathinone0000000000220000
  4C-PVP0000000000100000
  4-MEAPP0000000000300000
  Dibutylone0000000000102500
  Ephylone0000000001421000
  MDPHP000000000011151347
  Mexedrone0000000027100010
  Naphyrone0001000100000000
  N-Ethylhexedrone0000000000100000
  Pentylone0000100000000100
NPS stimulants controlled in China in 2021
  1,2-Diphenidine0000000211000000
  3-FPM0000000062101010
  3-MeO-PCP0000000000000100
  Eutylone0000000000000400
Other stimulants
  2-C-I0000001000000000
  3-FMC0000100000000000
  4-Ethylphenethylamine0000001000000001
  4-Fluoromethylphenidate0000000000001000
  4-Methylamphetamine0000122500000000
  5/6-APB0000143111000000
  5-IAI0000010101000000
  Aminoindane unspecified0000000011000000
  Atomoxetinea0000000001000000
  Benzedrone0000000000000001
  CPP1000101000021547
  Desoxy-D2PM0000001000000000
  DOI0000001000000000
  EAPB0000000101000000
  Fluorocathinone0000000010000000
  Fluoropiperazine0010000000000000
  Ibogaine0010000000000000
  Methcathinone unspecified0001100000000000
  Methoxypiperamide0000000011000000
  Modafinila0010000101324143
  Phenylpiracetamb0000000000100000
  Tryptamine unspecified0010000000000110

Detections of stimulants in deaths reported to the NPSUM 2007–2022 subdivided by type (classical stimulants; NPS stimulants controlled in China in 2015, 2016, 2018, 2021; other stimulants) and colour coded with year and jurisdiction of control according to the Colour Wheel of Drug Policy (yellow: UN; blue: UK; red: China; orange: UN and China; green: UN and UK; purple: UK and China; grey: UN, UK and China).

a

Psychoactive medications not subject to the PSA.

b

Shown to act on CNS receptors but not formally tested for psychoactivity at time of writing so cannot be considered banned under the PSA

TABLE 3

DrugYear
20122013201420152016201720182019202020212022
Cannabis (THC)148201171216241289370463518511512
NPS synthetic cannabinoids controlled in China in 2015
  5F-AMB00000003110
  5F-APINACA02352000000
  5F-PB-2201331012100
  AB-CHMINACA00120000000
  AB-FUBINACA0010314193310
  AB-PINACA00001000050
  AKB-4800100000000
  AM-220110000000000
  AM-223310000000000
  MDMB-CHMICA00052400000
  STS-13500300000000
NPS synthetic cannabinoids controlled in China in 2018
  5F-ADB0000837505311
  ADB/AMB/EMB-FUBINACA00000440030
NPS synthetic cannabinoids controlled in China in 2021
  4F-ABUTINACA00000000290
  4F-AKB-4800000000010
  4F-MDMB-BICA000000006222
  4F-MDMB-BINACA0000003161820
  5F-EMB-PICA00000000020
  5F-MDMB-PICA0000001221430
  5F-MMB-PICA00000001000
  ADB-4en-PFUPPYCA00000000010
  ADB-4en-PINACA00000000010
  ADB-BUTINACA000000000331
  ADB-HEXINACA00000000030
  APP-BINACA00000010000
  BB-2200010000000
  MDMB-4en-PINACA00000001141237
            MMB-CHMICA00001100000
Other synthetic cannabinoids
  ADB-INACAa00000000001
  CHPIATAb00000000002
Unspecified SCRA00021980010

Detections of cannabinoids in deaths reported to the NPSUM 2007–2022 subdivided by type (cannabis [THC]; NPS synthetic cannabinoids controlled in China in 2015, 2018, 2021; other synthetic cannabinoids) and colour coded with year and jurisdiction of control according to the Colour Wheel of Drug Policy (yellow: UN; blue: UK; red: China; orange: UN and China; green: UN and UK; purple: UK and China; grey: UN, UK and China).

a

A “no-tail” SCRA, precursor so is not covered by generic legislations in China or the UK., Psychoactivity not yet proven so is not subject to the PSA.

b

Has an acetamide linkage so is not covered by the 2021 Chinese generic SCRA, control.

Opioids

Deaths with detections of opioids rose in the latter 5 years of the study (2018-2022) with an average of 560 deaths per year over 2007–2017, rising to 1,458 deaths in 2022 (Figure 1A). Classical opioids accounted for the majority of detections in these deaths (Figure 1B; Table 1).

FIGURE 1

There were no detections of NPS opioids before 2013 (Figures 1B, 2; Table 1). During the subsequent 10-year period, 2013 to 2022, within a total of 24,662 detections of opioids, 254 (1.0%) referred to NPS opioids. NPS opioid detections peaked in 2017 when there were 82 (3.8% of that year’s total detections), primarily driven by a cluster of detections of carfentanil (51 detections, 2.4% of the total).

FIGURE 2

Five NPS opioids were controlled in China in 2015, four due to specific controls enacted by the Council of China (4-fluorobutyrylfentanyl, acetylfentanyl, butyrfentanyl and ocfentanil) and one due to a UN directed control (AH-7921; Figure 2A; Table 1). Whilst detections of AH-7921 ceased following its ban, the other four NPS opioids controlled in China in 2015 persisted on the UK drugs market, with a peak of 18 detections in deaths occurring in 2017 before disappearing altogether in 2021. These four of NPS opioids had already been controlled for several years in the UK under the MDA (Table 1).

Three further waves of controls on NPS opioids were introduced in China in 2017, 2019, and 2021, with detections of the substances controlled reducing following their enaction (Figures 2B–D). All of the NPS opioids controlled by these Chinese legislations had already been controlled in the UK for several years under the MDA (Table 1).

Stimulants

Note: In this study, the ‘Ecstasy’ drugs, MDA, MDMA and MDEA, are not regarded as NPS as they were internationally controlled in 1985, 1986, and 1990 respectively (; ; ). During the study period, there was a marked contribution (69 cases) from para-methoxyamphetamine (PMA) detections. This material has been under international control since 1986 (; ; ), well before the period of interest, and is therefore not regarded here as an NPS. The closely related para-methoxy methamphetamine (PMMA) contributed a small number of reports (n = 11) concurrent with the PMA reports. PMMA has long been a controlled drug in the UK by virtue of the UK’s 1977 generic control on phenethylamine derivatives (). However, as it was not brought under international control until 2016 (; ; ), it is treated here as an NPS.

Deaths with detections of stimulants reported to the NPSUM have been steadily rising since 2013, with an average of 436 deaths per year over 2007–2012, rising to 1,581 deaths in 2022 (Figure 3A). Classical stimulants–and then mainly cocaine–accounted for the majority of detections in these deaths (Figure 3B; Table 2): in 2014, cocaine represented 59.3% of stimulant detections, which has risen to 86.4% of detections in 2022.

FIGURE 3

There were a total of 927 NPS stimulant detections within the study period, representing 6.0% of total stimulant detections. These reached a peak of 114 in 2015, but in the subsequent years in the study, 2016 to 2022, the average number of stimulant NPS detections dropped to approximately 40 per year.

In 2015, the Council of China controlled 116 NPS, 30 of which were stimulants detected in deaths reported to the NPSUM. Whilst 22 of these 30 substances were already controlled in the UK under the MDA (Table 2), it was not until this Chinese legislation was introduced in October 2015 that a considerable drop in detections of these 30 substances was observed (Figure 4A) – however, this drop does also somewhat coincide with the introduction of the PSA in the UK in May 2016. The only exception to this was in detections of alpha-PHP which briefly resurged in 2021 (n = 16).

FIGURE 4

Three further waves of controls on NPS stimulants were introduced in China in 2017, 2018, and 2021. Whilst detections of these NPS stimulants decreased following introduction of these controls (Figures 4B–D), in some instances decreases were apparent prior to their implementation (e.g., 4-methylethcathinone was controlled in 2016 but detections markedly decreased from 2013; 3-FPM was controlled in 2021 but detection markedly decreased from 2015). All of the NPS stimulants controlled by these Chinese legislations had already been controlled in the UK either under the MDA or PSA (Table 2).

Cannabinoids

Deaths with detections of cannabinoids reported to the NPSUM have been steadily rising since 2015, with an average of 149 deaths per year over 2007–2014, rising to 521 in 2022 (although peaking in 2020 at 571 deaths; Figure 5A). Once again, the ‘classical’ cannabinoid detections predominated–in this instance THC as the major psychoactive constituent of cannabis (Figure 5B). The NPS cannabinoids detected are all compounds that fall within the synthetic cannabinoid receptor agonist (SCRA) drug class.

FIGURE 5

There were no detections of SCRAs before 2012 (Figures 6A–D; Table 3). A total of 488 detections of 30 different SCRAs were reported to the NPSUM over the study period, first peaking in 2018 with 87 detections and then again in 2021 with 112 detections, before drastically falling in 2022 to 14 detections (from 12 deaths; Figure 6D; Table 3). Six SCRAs accounted for 63.5% of these detections: 5F-MDMB-PINACA (also known as 5F-ADB) 21.5%, MDMB-4en-PINACA 16.8%, AB-FUBINACA 9.0%, 5F-MDMB-PICA 8.2%, 4F-MDMB-BINACA 8.0% and ADB-BUTINACA 7.0%.

FIGURE 6

The first SCRAs were controlled in China in 2015, following which detections of those controlled dropped, except for AB-FUBINACA (Figure 6A; Table 3). Of the 11 SCRAs which were controlled in China in 2015 and which were detected in deaths, only two were already controlled in the UK under the MDA (Table 3).

Two further waves of controls on SCRAs were introduced in China in 2018 and 2021, with the 2021 legislation detailing a generic control on compounds featuring the skeleton SCRA structure. Detections of 5F-ADB and ADB/AMB/EMB-FUBINACA decreased following their control in China in 2018 (Figure 6B), as did detections of other SCRAs that had subsequently emerged following introduction of the 2021 generic SCRA control (Figure 6C). All of the SCRAs controlled by these latter Chinese legislations had already been controlled in the UK under the PSA (and many subsequently under the MDA; Table 3).

Discussion

In this study we have provided the first systematic evaluation of the relative impacts of UK, Chinese, and UN legislative controls on the availability of NPS in England, Wales and Northern Ireland, evidenced by their post-mortem detections in deaths following psychoactive drug use. By linking toxicological evidence to the introduction of drug control legislations across these jurisdictions, we were able to infer which regulatory controls were most effective in influencing the most negative effect (i.e., death) of NPS available on the UK drug market.

‘Classical’ substances remain the dominant drivers of drug-related mortality

A consistent finding across the three drug classes studied–opioids, stimulants and cannabinoids–is that classical substances were detected in the vast majority of deaths, eclipsing those with involvement of NPS. This illustrates that whilst NPS attract significant attention due to their novelty, unpredictable harms, and the challenges that they pose for regulators (; ; ; ; ), drug-related mortality continues to be driven by established, widely available substances (). Legislative controls on NPS have therefore not reduced overall demand for psychoactive substances, but rather reshaped the composition of the illicit drug market with a renewed consumption of classical substances.

UK vs. Chinese legislative impacts

Whilst the majority of UK legislative controls on NPS were enacted earlier than either the Chinese or UN equivalents, they appear to have had limited impact on the appearance of NPS in deaths. Instead, reductions in NPS detections correlated more with the introduction of Chinese controls. This is consistent with the central role that Chinese manufacturing and export networks are thought to hold in supplying the global NPS market (; ; ; ; ; ).

For NPS opioids, UK controls appear to have been largely ineffective, whereas the controls of these substances in China in 2017, 2019 and 2021 correspond with sharp reductions in their detection. An exception to this was the 2015 Chinese opioid controls, which were followed by a persistence of four non-pharmaceutical fentanyl analogues in deaths up until 2021. This anomaly could be due to a number of reasons, including that the 2015 controls represented one of the earliest and largest waves of Chinese NPS legislation () which may not have been enforced as comprehensively as subsequently introduced controls, that these fentanyl analogues may have been produced outside of China, or stockpiled materials within the UK. These explanations remain speculative however, in the absence of direct evidence. With regards to NPS stimulants, a similar pattern is evident: whilst the UK had already controlled the majority of cathinones under the MDA, there was only a marked drop in detections after China controlled many stimulant NPS in 2015. The clearest evidence of Chinese legislative impact was observed with cannabinoid NPS as the 2021 generic ban on SCRAs virtually eliminated the presence of these compounds in UK deaths within the year, reducing detections from over 100 to just 14 by 2022. In contrast, the earlier UK controls on SCRAs via the MDA and PSA had limited impact on the appearance of successive generations of SCRAs.

Taken together, these findings suggest that controlling NPS at their point of origin is more effective than restricting access and availability at the point of demand. This raises a pertinent and pressing question for future UK drug policy on emergent NPS: how can the UK move beyond a reactive position–dependent upon which NPS emerge from producer countries–to more proactively reduce the harms inflicted by the substances which ultimately reach its market?

Unanticipated consequences of NPS controls on market shifts

Prior to the implementation of the PSA, deaths with detections of cocaine were comparatively lower, suggesting that some NPS stimulants may be associated with a lower incidence of lethal toxicity than cocaine. Indeed, a number of pre-clinical studies have found several stimulant NPS–and particularly cathinone derivatives–to exert weaker dopaminergic activities when compared with cocaine (; ; ; ). Following the ban of stimulant NPS under the PSA, stimulant users appear to have returned to classical substances–and in particular cocaine–which was followed by a sharp rise in cocaine detections in deaths. A similar pattern was observed in Germany following the introduction of the Neue-psychoaktive-Stoffe-Gesetz (NpSG) in 2016 –legislation which generically controlled NPS rather than individual substances similar to the PSA–as there was a marked decline in the detection of NPS (; ; ) suggestive of a reduction in their domestic availability. However, subsequent studies have indicated that many German NPS users returned to using classical substances (; ), thus mirroring what was observed in the UK. This trend is illustrative of a recurring theme across drug markets which has been termed the ‘potency paradox’ (; ) in which restrictions on one substance/class of substances may be leading unintentionally to increased harms by steering users towards more potent alternatives. Indeed, the control of ketamine in the UK as a Class C substance in 2006 (and subsequently as a Class B substance in 2014) () was followed by the appearance of methoxetamine and diphenidines (; ), which were marketed as legal replacements to ketamine, but possess greater potency and longer duration of action (; ; ) leading them to be associated with more severe toxicological outcomes (). A related phenomenon is now playing out within the opioid drug class: although in this analysis NPS opioids represented only a fraction of detections, the subsequent widespread arrival of nitazenes in the UK in 2023 () after the end of the study period (note: the UK and China both implemented generic controls on nitazenes in 2025 (; ), however, it is not yet possible to assess the impact of these controls via analysis of drug deaths) has been linked to restrictions on less potent within-class alternatives (e.g., fentanyl analogues) and reduced heroin availability from Afghanistan (). Together, these findings highlight a central drug policy dilemma: whilst prohibition can reduce availability of NPS, it may also be a driver towards other more harmful substances, illustrating the need for complementary harm reduction strategies to be delivered alongside the implementation of legislative controls.

Strengths and limitations

This study has both strengths and limitations. A strength of this study is that it used routinely collated post-mortem toxicology data from the NPSUM, covering over 85% of coronial jurisdictions in England, Wales and Northern Ireland. This has provided a unique, mortality-based perspective of the NPS market, which is arguably one of the most clinically-relevant outcomes. However, the voluntary nature of reporting means that not all deaths, and therefore NPS detections, will have been captured. Furthermore, NPS toxicology screens are not requested in every case subject to coronial investigation, differ in terms of the screening library between laboratory operators, and will have happened at a particularly low incidence in the earlier years of the study when awareness of NPS was not as widespread. This may therefore have significantly impacted upon when NPS were first detected, as if not screened for they will not have been reported. However, as our analyses primarily focus on when NPS ceased to be detected in relation to legislative changes - by definition, such substances must have been previously included in analytical screens. The linking of mortality data to legislative implementations across multiple jurisdictions has allowed for stronger inference on the likely impact of different regulatory implementations. However, causality cannot be inferred with certainty: whilst temporal associations between NPS controls in China and reduced detections are strong, other market forces will have also contributed (e.g., law enforcement strategy, changing user preferences, price shifts). In this regard, it is important to note that NPS legislation introduced in India was not included as an additional variable in this analysis, despite India’s growing role as a producer of NPS (). This is because the legislations directing control of specific NPS in India were introduced either at the same time or after the same compounds had been directed for control under the UN Conventions, so that India, as a signatory of the Conventions, was obliged to enact controls (; ; ; ; ; ). Finally, as this analysis focused only on deaths, it has not captured trends in non-fatal NPS use. However, a recent UK study on acute recreational drug toxicity presentations in London which compared two time-points (2016/17 vs. 2019/20) had complementary findings to the present study as they observed a reduction in cathinone detections but no significant change in SCRA detections between these two timepoints (). This suggests that trends in non-fatal NPS toxicity presentations broadly reflect those observed in the mortality data.

Conclusion

The findings of this study indicate that the most effective way to reduce NPS availability in the UK is via legislation in producer countries, as evidenced by substantial declines in their detections in deaths following their control in China. UK interventions–despite enabling national law-enforcement activity and often being enacted earlier–had limited impact, highlighting the restricted influence of consumer country legislation in a globalised market. This reliance on international controls places the UK in a vulnerable position, as its domestic drug landscape is being shaped largely by the pace and scope of independent international legislations. To achieve and maximise effectiveness, UK drug policy needs to integrate harm reduction measures alongside the introduction of legislative controls, whilst also encouraging international efforts to bring in global control of problem materials. Without this combined approach, the cycle of NPS emergence, prohibition, and displacement will continue to undermine public health.

Statements

Data availability statement

Original data can be obtained from the corresponding author upon reasonable request. Requests to access these datasets should be directed to .

Ethics statement

The requirement of ethical approval was waived by The King’s College London Biomedical and Health Sciences, Dentistry, Medicine and Natural and Mathematical Sciences Research Ethics Subcommittee for the studies on humans because NPSUM research does not require ethics committee review as all subjects are deceased. The studies were conducted in accordance with the local legislation and institutional requirements. Written informed consent for participation was not required from the participants or the participants’ legal guardians/next of kin in accordance with the national legislation and institutional requirements. The human samples used in this study were acquired from Pathologists who submitted samples to a toxicology laboratory for testing as part of the coronial investigation into the deaths. Written informed consent was not obtained from the individual(s) for the publication of any potentially identifiable images or data included in this article because all subjects are deceased so consent does not apply.

Author contributions

KR: Data curation, Visualization, Validation, Formal Analysis, Investigation, Writing – review and editing. RT: Investigation, Writing – review and editing, Conceptualization, Writing – original draft. CC: Formal Analysis, Resources, Writing – review and editing, Validation, Project administration, Writing – original draft, Visualization, Data curation, Methodology, Investigation, Conceptualization, Supervision.

Funding

The authors declare that financial support was received for the research and/or publication of this article. KLR is supported by a Society for the Study of Addiction PhD studentship.

Conflict of interest

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Generative AI statement

The authors declare that no Generative AI was used in the creation of this manuscript.

Any alternative text (alt text) provided alongside figures in this article has been generated by Frontiers with the support of artificial intelligence and reasonable efforts have been made to ensure accuracy, including review by the authors wherever possible. If you identify any issues, please contact us.

Publisher’s note

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.

References

Summary

Keywords

novel psychoactive substances, drug policy, international drug control, opioids, stimulants, cannabinoids

Citation

Rock KL, Treble R and Copeland CS (2026) Legislating novel psychoactive substances: lessons from 15 years of UK mortality data (2007-2022). Front. Pharmacol. 16:1708335. doi: 10.3389/fphar.2025.1708335

Received

18 September 2025

Revised

24 October 2025

Accepted

20 November 2025

Published

29 January 2026

Volume

16 - 2025

Edited by

Taoufik Ghrairi, Tunis El Manar University, Tunisia

Reviewed by

Heather Barkholtz, University of Wisconsin-Madison, United States

Tobias Zellner, Technical University of Munich, Germany

Updates

Copyright

© 2026 Rock, Treble and Copeland.

This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

*Correspondence: Caroline S. Copeland,

Disclaimer

All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.

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