Emergency department toxicology: ASSIST

Between November 2023 and February 2024, the ‘A Surveillance Study of Illicit Substance Toxicity’ (ASSIST) emergency department project made 496 detections of 40 different illicit drugs, in samples from 88 patients. The most commonly detected drug category was depressants (67% of detections), followed by opioids (13%). The most commonly detected individual drug was cocaine (11%), followed by desmethyldiazepam, temazepam and bromazolam (all 10%).

Background

The ASSIST study is conducted by the emergency department (ED) at the Queen Elizabeth University Hospital (QEUH) in NHS Greater Glasgow and Clyde (GGC). This project has been funded by the Scottish Government since August 2022.

The aim of the study is to monitor drug trends and associated clinical features through the use of prospective surveillance of ED attendances due to acute illicit drug toxicity. For the most unwell patients, the study performs full toxicological analysis through the biorepository-approved surplus sampling.

The study allows drug profiling and the identification of emerging drugs or changing trends to inform appropriate harm reduction measures and public health responses.

Data collection

The study collects anonymised data through the analysis of standard-of-care clinical data for patients attending QEUH ED due to illicit drug toxicity and surplus serum sample toxicology testing. Surplus serum samples are leftover blood samples, which were taken as part of usual care.

Each ED attendance is counted once in these data. If the same person presented more than once, each attendance would be a separate data point.

Drug detections presented here are of ‘illicit drugs’ only and were not prescribed to the individual.

Illicit drug definition

The use of the term 'illicit drug' encompasses any substance that is controlled. It excludes:

• legal substances, such as alcohol, nicotine, caffeine and paracetamol
• medications recently prescribed to the individual (e.g. if methadone is detected but the individual is prescribed methadone, it will not be included)
• drugs administered to the individual as part of treatment (by ambulance staff or in hospital).

Toxicology analysis of surplus serum samples

Detections presented are for the substance only. If a metabolite (compound produced when a drug breaks down in the body) is detected, it will be presented as the substance only. If the metabolite and substance are detected, it will also be presented as the substance only.

However, if a drug and a metabolite are both detected but the metabolite could also be a drug, we have included both as it is not possible to say which has been used, if not both.

Data from the study are presented in quarters, based on the date of ED presentation, and are provided in the table below:

Results

The first chart shows the most common drug categories detected in toxicology analysis of surplus serum samples between 17 August 2022 and 16 February 2024 (Q1 to Q6).

The results are shown as the total number of detections. They are broken down by the top five drug categories and presented by study quarter.

This stacked bar chart shows the percentage of detections of drug types within QEUH ED across six quarters - Q1 to Q6. The drugs are grouped into five categories (depressant, opioid, stimulant, cannabinoid and other (including dissociative and psychedelic drugs)). Percentage of detections by category is on the y axis and the time period is on the x axis. The most common category was depressants with 57%, 62%, 60%, 64%, 66% and 67% across the time series. The second most common was opioids with 17%, 18%, 16%, 16% ,15% and 13% across the time series.

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ASSIST hospital toxicology analysis: drug categories by study quarter

Summary

Historic trend

Between 17 August 2022 and 16 November 2023:

• The most commonly detected drug type was depressants, making up 62% of all detections, followed by opioids (17%). The most commonly detected individual drug was cocaine (11%).
• 72% of attendances were male and 28% were female.
• 76% of attendances were aged 44 and under. The most common age category was 25 to 34 years (30%), followed by 35 to 44 (27%) and 16 to 24 (19%).
• The most common outcomes were discharged to home (39%), ward (28%) and police custody (11%).

Update

For the most recent period (17 November 2023 to 16 February 2024):

• 288 individual ED attendances related to illicit drug use were identified.
• 88 attendances qualified for surplus sampling toxicology testing (as they were categorised as having a higher clinical severity of toxicity as per research inclusion criteria).

Drug type and category

Among the 88 samples analysed:

• There were 496 detections of 40 individual substances (found through the biological detection of the drug or its metabolite).
• The average number of drugs detected per sample was six.

Of the 496 detections, the following drugs were the most common:

• cocaine: 55 (11% of detections, 63% of samples)
• desmethyldiazepam: 50 (10% of detections, 57% of samples)
• temazepam: 50 (10% of detections, 57% of samples)
• bromazolam: 49 (10% of detections, 56% of samples)
• etizolam: 38 (8% of detections, 43% of samples)
• oxazepam: 38 (8% of detections, 43% of samples)
• cannabis (tetrahydrocannabinol): 25 (5% of detections, 28% of samples)
• diazepam: 22 (4% of detections, 25% of samples)
• morphine: 19 (4% of detections, 22% of samples)

Please note: desmethyldiazepam, temazepam and oxazepam are all benzodiazepine drugs but can also be found as a metabolite of diazepam and other benzodiazepines.

The chart below shows the most common depressant drug detected in toxicology analysis of surplus serum samples between 17 August 2022 and 16 February 2024 (Q1 to Q6). The percentages are of all detections.

This line chart shows the percentage of detections of specific depressant drugs within QEUH ED across six quarters - Q1 to Q6. Percentage of detections is on the y axis and the time period is on the x axis. The most common depressant drug in Q1, Q2, Q5 and Q6 was desmethyldiazepam (Q1; 10%, Q2; 8%, Q5; 11%, Q6; 10%). The most common depressant drug in Q4 was bromazolam (Q4; 10%). This was the third quarter in which xylazine was detected.

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ASSIST hospital toxicology analysis: depressant drugs by study quarter

Depressants were the most common drug category, making up 67% of detections (334).

• Benzodiazepines were detected 296 times (60% of all detections):
  • In total, 12 different types of benzodiazepines were detected, including bromazolam (10%) and etizolam (8%).
  • Desmethyldiazepam made up 10% of all detections, down from 11% in Q5.
• Gabapentinoids were detected 30 times (6% of all detections, from 5% in Q5). Of these detections, 14 were gabapentin and 16 were pregabalin.
• There were four detections of xylazine (1%).

This line chart shows the percentage of detections of specific opioid drugs within QEUH ED across six quarters - Q1 to Q6. Percentage of detections is on the y axis and the time period is on the x axis. The most common opioid drug across the time series was heroin/morphine (Q1: 4%, Q2: 5%, Q3: 6%, Q4: 5% , Q5: 5% and Q6; 4%). Nitazenes were detected for the first time in Q4 (seven detections) and increased to 2% of detections (16 detections) in Q5. They were detected 8 times in Q6. Detections of noscapine decreased from 3% in Q1 to 0% in Q5 and increased to 1% in Q6.

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ASSIST hospital toxicology analysis: opioid drugs by study quarter

Opioids were the second most common drug category, making up 14% of detections (90).

• There were 19 detections of heroin/morphine (4%), 7 for methadone (1%) and six for codeine (1%).
• There were eight detections of nitazenes (1%).

Stimulants were the third most common drug category, making up 12% of detections (58).

• The most common stimulant was cocaine, making up 11% of detections (55).

Further findings

Complete clinical data were available for 288 attendances for the most recent period (17 November to 16 February 2024):

• 71% of attendees were male (205) and 30% were female (83).
• 19% (55) of attendees were aged 16 to 24 years and 22% (63) were aged 25 to 34.
• 58% of attendees were aged 35 years and over, with 34% (97) aged 35 to 44, 19% (55) aged 45 to 54 and 5% (14) aged 55 years or older.

This stacked bar chart shows the percentage of QEUH ED ASSIST attendees by age group across six time periods - Q1 to Q6. Percentage of attendees is on the y axis and the time period is along the x axis. The most common age group in Q1, Q2 and Q4 was 25 to 34 years (34%, 34% and 29% respectively). In Q3, patients aged 25 to 34 years and 35 to 44 were equally common (both 29%). The most common age group in Q5 and Q6 was 35 to 44 years (30% and 34% respectively).

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Attendances by age

ED outcome records show:

• 119 (41%) patients were discharged home
• 74 (26%) were admitted to a ward
• 42 (15%) were taken into police custody
• 34 (12%) self-discharged
• 15 (5%) were admitted to an intensive care unit, high-dependency unit, critical care unit or died
• less than five were recorded as ‘unknown’ or ‘other’.

Clinical severity outcome (after 28 days) recorded:

• 270 patients were discharged following the attendance
• less than five patients either died or remained an inpatient following the attendance
• outcomes for 13 patients were ‘unknown’.

Additional information

Public Health Scotland (PHS) was provided with these data by QEUH, NHS GGC.

The ASSIST trial is registered with Clinical Trials UK (ID: NCT05329142).

Ethical approval has been granted by the West of Scotland Research Ethics Service (IRAS ref: 313616, REC ref: 22/WS/0047) and surplus sampling methodology through Biorepository Ethics (ref: 22/WS/0020).

The West of Scotland Safe Haven research database hosts the electronic clinical data under IRAS ref: 321198 or REC ref: 22/WS/0163.

This study is sponsored by NHS GGC Research and Innovation and is funded by the Scottish Government.

The testing has been carried out by the LGC group (external website). LGC analyse pseudonymised samples using mass spectrometry and screen against a database of over 3,500 analytes. This testing can detect drugs and metabolites, but this analysis does not imply that specific drugs were implicated in harms.

Further information on the study can be found at Clinical Trials (external website).

Post-mortem toxicology testing for controlled substances

In Q4 of 2023, the most common drug types detected in post-mortem toxicology were opioids (70%) and benzodiazepines (58%). The percentage of deaths where cocaine was detected remained stable at 36% (37% in Q3 of 2023). It continued to be the most commonly detected individual substance, followed by heroin/morphine (29%), methadone (29%), diazepam (27%), and bromazolam (22%).

Background

All sudden or unexpected deaths in Scotland are subject to investigation by the Crown Office and Procurator Fiscal Service (COPFS) to determine the cause of death and the need for criminal proceedings. In order to inform these decisions, the COPFS commissions post-mortem toxicology and pathology services across Scotland.

This analysis is based on data from toxicology testing conducted at post-mortem for sudden and unexplained deaths. It is not limited to deaths involving controlled drugs and includes suicides and natural deaths where there is no previous medical history.

Post-mortem toxicology testing is carried out by two services in Scotland:

• The Scottish Police Authority Forensic Services (SPA FS) covers deaths occurring in the west, east and parts of the north of Scotland.
• The Department of Clinical Biochemistry at NHS Grampian covers deaths in the far north and north-east of Scotland.

The inclusion of data on deaths in the far north and north-east of Scotland (the areas covered by NHS Grampian) from January 2022 onwards, means that the figures presented after that point cover the whole of Scotland and are different from publications released before October 2023.

This report includes two new periods of data:

• Remaining outstanding data for September 2023, completing data for Q3 of calendar year 2023; and
• 1 October to 31 December 2023, representing data for Q4 of 2023. This period is the most recent data discussed below.

The range of substances routinely analysed is extensive and includes the detection of alcohol, prescribed medicines and controlled drugs. The data within this report will develop further as other new or emerging drugs are added to toxicology screening.

The charts below show the prevalence of controlled substances detected in deaths which were subject to post-mortem toxicology screening. Drug detections were assigned to specific time periods based on the calendar year quarter of death. As indicated by the line on the chart, data for 2020 and 2021 are based on deaths in the west, east and parts of the north of Scotland. From January 2022, the data include all areas in Scotland. Throughout the time series, the sum of the percentages for each quarter exceeds 100% due to the widespread detection of multiple substances in deaths (multiple controlled drugs were detected in 96% of deaths in Q4 2023).

The first chart below provides an indication of controlled drugs detected at post-mortem, in deaths occurring between 1 January 2020 and 31 December 2023.

The chart shows the percentage of forensic toxicology cases testing positive for controlled substances (opioids, benzodiazepines, gabapentin and pregabalin, cocaine). The percentage of cases is on the y axis and the calendar year and quarter of death, between Q1 of 2020 (1 January to 31 March) and Q4 of 2023 (1 October to 31 December), is on the x axis. The most commonly detected drug types were opioids and benzodiazepines. The percentage of deaths positive for opioids has gradually decreased since Q2 of 2020, to 70% in Q4 of 2024. Benzodiazepines were present in 74% of deaths in Q2 of 2020, but have gradually decreased over time, and have been present in 51% to 61% of deaths in each quarter since Q2 of 2022. Since Q1 of 2022, the percentage of deaths involving gabapentin and pregabalin has been relatively stable, averaging 31% per quarter. The percentage of deaths where cocaine was present increased markedly during Q2 of 2020 (to 38%), but otherwise remained relatively stable to Q1 of 2023 (averaging 29%). Detections recently increased from 29% of deaths in Q1 of 2023 to 36% of deaths in Q4 of 2023.

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Forensic toxicology cases testing positive for controlled substances

The following charts provide an indication of specific opioids and benzodiazepines detected at post-mortem, in deaths occurring between 1 January 2020 and 31 December 2023.

The chart shows the percentage of forensic toxicology cases testing positive for specific opioids (heroin/morphine, fentanyls, methadone, buprenorphine and nitazenes). The percentage of cases is on the y axis and the calendar year and quarter of death, between Q1 of 2020 (1 January to 31 March) and Q4 of 2023 (1 October to 31 December), is on the x axis. Heroin/morphine has been the most commonly detected opioid since Q3 of 2021 – the percentage of deaths testing positive for heroin/morphine followed a gradual decreasing trend from 43% in Q1 of 2020 to 29% in Q4 of 2023. Methadone detections reached 45% in Q2 of 2020, after which they gradually decreased to 23% in Q3 of 2022. Since then, methadone detections have slightly increased (29% in Q4 of 2023). Deaths with buprenorphine present remained relatively low and stable throughout the time series (averaging 6%). There was a gradual increase in the percentage of cases where fentanyls were detected from 1% in Q1 of 2022 to 5% in Q4 of 2023 nitazene-type opioid substances (detected for the first time in Q1 of 2022) have increased slightly but remained uncommon, detected in 2% of deaths in Q4 of 2023.

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Forensic toxicology cases testing positive for specific opioids

The chart shows the percentage of forensic toxicology cases testing positive for specific benzodiazepines (diazepam, etizolam, clonazolam and bromazolam). The percentage of cases is on the y axis and the calendar year and quarter of death, between Q1 of 2020 (1 January to 31 March) and Q4 of 2023 (1 October to 31 December), is on the x axis. Diazepam has been the most commonly detected benzodiazepine since Q2 of 2022. Diazepam detections were stable for most of the time series, averaging 24% until Q3 of 2022, when there was a marked increase to 35%. Diazepam was detected in 27% of deaths in Q4 of 2023. Bromazolam (detected for the first time in Q1 of 2022) has increased sharply and was detected in 22% of deaths in Q4 of 2023. Etizolam was the most common benzodiazepine detected for some time, averaging 51% between Q2 of 2020 and Q2 of 2021. Since then, etizolam detections have decreased to 6% in Q4 of 2023. Temazepam detections were relatively stable (averaging 5%) until Q1 of 2022. Detections then increased and remained stable (9% in Q4 of 2023). Deaths with clonazolam present increased and peaked at 12% in Q3 of 2021, before falling to low levels from early 2022 (2% in Q4 of 2023).

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Forensic toxicology cases testing positive for specific benzodiazepines

Summary

• The most commonly detected drug types were opioids and benzodiazepines, averaging 71% and 58% respectively between January 2022 to December 2023.
• The most commonly detected individual drug in the last three quarters was cocaine (averaging 37%). Before Q2 of 2023, the most common individual drug was heroin / morphine.
• Multiple drugs were detected in 629 (96%) of 654 deaths in Q4 of 2023.
• The following drugs or drug types were most commonly detected in deaths from Q4 of 2023:
  • opioids: 458 (70%)
  • benzodiazepines: 380 (58%)
  • cocaine: 235 (36%)
  • heroin/morphine: 189 (29%)
  • methadone: 189 (29%)
  • gabapentin and pregabalin: 188 (29%)
  • diazepam: 175 (27%)
  • bromazolam: 143 (22%)

Stimulants

• For the third quarter in a row, the most commonly detected drug was cocaine.
• The percentage of deaths where cocaine was detected was relatively stable until Q1 of 2023 (averaging 29%), with the exception of an isolated increase in Q2 of 2020 (38%). Detections recently increased from 29% of deaths in Q1 of 2023 to 36% of deaths in Q4 of 2023.

Opioids

• The percentage of deaths where opioids were detected has gradually decreased from a peak of 82% in Q2 of 2020, to 70% in Q4 of 2023:
• Heroin/morphine detections decreased from a peak of 45% in Q2 of 2020 to 29% in Q4 of 2023 (35% in Q3).
• Methadone detections reached 45% in Q2 of 2020, before gradually decreasing to 23% in Q3 of 2022. Since then, methadone detections have increased slightly (29% in Q4 of 2023).
• Buprenorphine detections remained low and stable (detected in an average of 6% of deaths throughout the time series).
• There was a gradual increase in the percentage of cases where fentanyl-type opioids were detected, from around 1% prior to Q2 of 2022, to 5% in Q4 of 2023.
• Nitazene-type opioids (detected for the first time in Q1 of 2022) have increased slightly but remained uncommon, detected in 2% of deaths (12) in Q4 of 2023 (also 2% in Q3 (12)).

Depressants

• Benzodiazepines were present in 74% of deaths in Q2 of 2020, but have gradually decreased over time, and have been present in 51% to 61% of deaths in each quarter since Q2 of 2022.
• Diazepam has been the most commonly detected benzodiazepine since Q2 of 2022. Since then, detections have fluctuated between 25% and 35%. Detections decreased to 27% in Q4 of 2023 (from 35% in Q2).
• Detections of bromazolam increased sharply throughout 2022, replacing etizolam as the most commonly detected ‘street’ benzodiazepine from Q1 of 2023 onwards. Bromazolam was detected in 22% of deaths in Q4 of 2023.
• Etizolam was the most common benzodiazepine detected for some time, before detections fell to 6% of deaths in Q4 of 2023.
• Temazepam detections were relatively stable (averaging 5%) until Q1 of 2022, when there was an increase to 9%. Since then, the percentage of temazepam detections have remained broadly similar (9% in Q4 of 2023).
• Clonazolam detections increased and peaked at 12% in Q3 of 2021, before decreasing to low levels from Q1 of 2022. In Q4 of 2023, clonazolam detections were 2% (from <1% in Q3 of 2023).
• Since Q1 of 2022, the percentage of deaths involving gabapentin and pregabalin has been relatively stable, averaging 31%.
• Xylazine (detected for the first time in Q3 of 2023) was detected in less than 1% of deaths (3) in Q4 of 2023 (from 1% (5) in Q3 of 2023). However, this is likely to be an undercount and should be interpreted with caution, as detections of xylazine in Q4 of 2023 may be subject to change once further testing information becomes available.

More detailed descriptions of historical changes can be found within our previous reports.

Additional (provisional) data

It is important to note that the information presented within this section is based on incomplete data. It is therefore provisional and subject to change once further toxicology data becomes available.

Data presented within this report has been based on the latest and most complete period for which toxicology data were available. However, in this section, more recent data (partial data for January 2024) is included to provide an early indication of emerging trends or detections of new substances.

Where available, provisional data received for January 2024 indicated the following:

• Deschloroetizolam (a ‘street’ benzodiazepine) was detected for the first time.
• There were a small number of nitazene and xylazine detections, but these continued to be relatively uncommon (<5).

Additional information

PHS was provided with post-mortem toxicology testing data for deaths occurring in the west, east and parts of the north of Scotland by Forensic Medicine and Science at the University of Glasgow and SPA FS.

In late 2022, post-mortem toxicology services for the west, east and parts of the north of Scotland were transferred from the University of Glasgow to the Scottish Police Authority Forensic Services (SPA FS). During the period of transition, tests were completed by other laboratory testing sites in the UK. Although testing has now been moved to SPA FS, these testing sites continued to provide support in 2023 and data from both SPA FS and outsourced sites have been included in this report.

Data on deaths occurring in the far north and north-east of Scotland from January 2022 onwards, was supplied by the Department of Clinical Biochemistry at NHS Grampian.

The table shows the total number of deaths testing positive for controlled substances, for each calendar year and quarter.

New drugs (e.g. bromazolam, desalkylgidazepam, nitazene-type opioids and xylazine) were detected for the first time when screening was expanded or testing was outsourced to other laboratories. These drugs may have been present before this time but were not being tested for. Data for substances including nitazenes and bromazolam are considered to be more robust and reliable from January 2023 onwards. Xylazine is not currently routinely tested for. These data will develop further as new or emerging drugs are added to routine toxicology screening by the SPA FS and NHS Grampian.

Detailed interpretation of the levels of drugs found present, drug interactions, co-morbidities, or other factors relating to death, are outside the scope of this analysis. This analysis does not imply that specific drugs were implicated in deaths nor that deaths were classified as ‘drug-related’, and it does not include consideration of wider causes of death.

It should be noted that increases observed in specific substances within this report may be due to differences in toxicology test approaches (e.g. detection of concentration levels of a particular drug) between outsourced laboratories and previous screening. This may result in increases in substance detection. Further data will be required and monitored to determine the impact of any differences in toxicology screening across laboratories.

Additionally, it is important to note that small numbers of detections for specific substances may result in large percentage differences between quarters. Where it is felt that data should be interpreted with caution due to small numbers, the number of detections has also been provided for context.

As some of the data received from other laboratory testing sites did not include date of death, other date variables have been used as a proxy to improve data completeness and enable the inclusion of these deaths within this report. Two separate date variables have been used to approximate date of death information, where this information was unavailable:

1. Date of the case being received or sent to other labs for toxicology testing.
2. Date of toxicology test being completed.

Similarly, as date of death was unavailable for those tests conducted by the Department of Clinical Biochemistry at NHS Grampian, the date when the case was received from the Crown Office and Procurator Fiscal Service has been used instead.

These dates listed above have been used in the analysis as they are considered to provide a close approximation to the month and year of death. It is anticipated that missing information on date of death will be improved over time, as further information becomes available.

Drug seizures in Scottish prisons

The Scottish Prisons Non-Judicial Drug Monitoring Project is a collaboration between the Scottish Prison Service and the Leverhulme Research Centre for Forensic Science at the University of Dundee (external website). The project tests drug seizures made across the Scottish prison estate in order to understand the changing characteristics of synthetic drugs, including synthetic cannabinoids, often referred to as 'spice'.

Analysis of the drug seizures in Scottish prisons from November 2023 to January 2024 is ongoing and is not included in this report. We anticipate the updated data will be available for the next release in July 2024.

Since the last quarterly report, we have received data for a limited number of samples for the latest period (1 August to 31 October 2023):

• 33 samples were tested. 27 contained an illegal substance and six contained nicotine.
• Synthetic cannabinoids were the most prevalent drug type. They were detected in 36% of samples (12), compared to 33% between January and July 2023.
• MDMB-INACA was the most common synthetic cannabinoid (four detections), followed by MDMB-4en-PINACA (three).
• In the latest period, only two samples contained a benzodiazepine (diazepam, alprazolam). Please note that due to the limited number of samples received for testing since August 2023, these detections do not fully represent all benzodiazepine seizures in this reporting period. Between January and July 2023, benzodiazepines were detected in 16% of samples, with bromazolam being the most common.
• The most common sample type was powder (30%), followed by tablets and e-cigarettes (both 24%). Synthetic cannabinoids were detected in 50% of e-cigarettes.

Complete data to July 2023 are available in a previous quarterly report.