Medication and supplement pharmacokinetic changes following bariatric surgery: A systematic review and meta-analysis.

OBJECTIVES: To evaluate the impact of bariatric surgery on the pharmacokinetic (PK) parameters of orally administered medications and supplements. METHODS: Systematic searches of bibliographic databases were conducted to identify studies. Pooled effect estimates from different surgical procedures were calculated using a random-effects model. RESULTS: Quantitative data were synthesized from 58 studies including a total of 1985 participants. Whilst 40 medications and 6 supplements were evaluated across these studies, heterogeneity and missing information reduced the scope of the meta-analysis to the following medications and supplements: atorvastatin, paracetamol, omeprazole, midazolam, vitamin D, calcium, zinc, and iron supplements. There were no significant differences in PK parameters post-surgery for the drugs atorvastatin and omeprazole, and supplements calcium, ferritin, and zinc supplements. Paracetamol showed reduced clearance (mean difference [MD] = -15.56 L/hr, p = 0.0002, I2 = 67%), increased maximal concentration (MD = 6.90 µg/ml, p = 0.006, I2 = 92%) and increased terminal elimination half-life (MD = 0.49 hr, p < 0.0001, I2 = 3%) post-surgery. The remaining 36 medications and 2 supplements were included in a systematic review. Overall, 18 of the 53 drugs and supplements showed post-operative changes in PK parameters. CONCLUSION: This study demonstrates heterogeneity in practice and could not reach conclusive findings for most PK parameters. Prospective studies are needed to inform best practice and enhance patient healthcare and safety following bariatric surgery.

Broad evidence of xylazine in the UK illicit drug market beyond heroin supplies: Triangulating from toxicology, drug-testing and law enforcement.

BACKGROUND AND AIMS: Xylazine is a non-opioid sedative which has spread rapidly throughout the US illicit drug supply. This study aimed to describe the spread of xylazine throughout the UK illicit drug supply. METHODS: Xylazine detections in human biological samples were collated from toxicology laboratories operating in the United Kingdom with the date, location, case type, xylazine concentration and co-detected drugs (with quantifications where performed) detailed, where permitted, by the corresponding coroner. Drug-testing cases positive for xylazine were collated from the Welsh Emerging Drugs and Identification of Novel Substances (WEDINOS) drug-testing postal service with the date, location, purchase intent and co-detected drugs detailed. Drug seizures made by UK law enforcement were communicated by the Office for Health Improvement and Disparities with the date and location detailed. RESULTS: By the end of August 2023, xylazine was detected in 35 cases from throughout toxicology, drug-testing and drug seizure sources covering England, Scotland and Wales. There were no cases reported from Northern Ireland. Xylazine was detected in biological samples from 16 people. In most cases where full toxicology results were provided, xylazine was detected with heroin and/or a strong opioid (n = nine of 11), but this polydrug use pattern was not evident in all cases (n = two of 11), suggesting a wider circulation of xylazine in the UK illicit drug market beyond heroin supplies. Evidence from WEDINOS supports this claim, as all 14 drug samples (100%) submitted from across the UK contained xylazine; however, in none of these cases was heroin the purchase intent but rather counterfeit prescription medication tablets (n = 11 of 14), tetrahydrocannabinol (THC) vapes (n = two of 14) or white powder (n = one of 14). Additional evidence for the spread of illicit xylazine comes from five drug seizures made by law enforcement. CONCLUSIONS: Xylazine has penetrated the UK illicit drug market and is not limited to heroin supplies.

An evaluation of naloxone transit for opioid overdose using drones: A case study using real-world coroner data.

BACKGROUND AND AIMS: Opioids are now the most cited class in fatal overdoses. However, the antidote for opioid overdose-naloxone-is not always readily available. Our aim was to evaluate the feasibility of naloxone transit via drone to provide rapid access at the point of care. METHODS AND FINDINGS: Real-world data pertaining to opioid overdoses, which occurred in the Teesside area of the UK 2015-2019, were extracted from the National Programme on Substance Abuse Deaths (NPSAD). The original locations of these opioid overdoses were used to compare the projected response times of ambulances with that of drones when considering the impacts of actual traffic and weather conditions, respectively; 58 cases were identified where a bystander-who could have called for and administered emergency naloxone-was likely present. RESULTS: In 78% of cases (n = 45/58) a class C1 commercial-off-the-shelf drone carrying naloxone could have reached the overdose location in 7 min-the benchmark time for the arrival of emergency services for Category 1 calls in England. With the implementation of recent advances in drone engineering, such as increased speeds and temperature-controlled cargo cradles, it is estimated that 98% of overdoses could have been reached in this timeframe (n = 57/58). Ambulances were able to reach a significantly lower number of cases in 7 min, even when considering best-case scenario traffic conditions (14%, n = 8/58, χ2 P < 0.001). CONCLUSIONS: This study provides proof-of-concept that, in the Teesside area of the UK, drones are more likely than ambulance to get naloxone to the site of an opioid overdose in 7 min.

New synthetic cannabinoids and the potential for cardiac arrhythmia risk.

Synthetic cannabinoid receptor agonists (SCRAs) have been associated with QT interval prolongation. Limited preclinical information on SCRA effects on cardiac electrogenesis results from the rapid emergence of new compounds and restricted research availability. We used two machine-learning-based tools to evaluate seven novel SCRAs' interaction potential with the hERG potassium channel, an important drug antitarget. Five SCRAs were predicted to have the ability to block the hERG channel by both prediction tools; ADB-FUBIATA was predicted to be a strong hERG blocker. ADB-5Br-INACA and ADB-4en-PINACA showed varied predictions. These findings highlight potentially proarrhythmic hERG block by novel SCRAs, necessitating detailed safety evaluations.

Trends in deaths following drug use in England before, during, and after the COVID-19 lockdowns.

Aim: This research aimed to describe how the characteristics of deaths following drug use changed during the COVID-19 pandemic in England, and how this can inform future strategy to support the health and social care of people who use drugs in future emergency scenarios. Method: All deaths reported to the National Programme on Substance Abuse Deaths which occurred between January 2018 and December 2021 inclusive were extracted for analysis. Exponential smoothing models were constructed to determine any differences between forecasted vs. actual trends. Key results: Following the first lockdown period in England there were significant increases in the proportion of people who died at home beyond the 95% confidence bounds of the exponential smoothing model and concurrent decreases in the proportion of people who died in hospital. Whilst the overall proportion of deaths attributable to opioids did not significantly deviate from the forecasted trend, there were significant increases in methadone-related deaths and decreases in heroin/morphine-related death beyond the 95% confidence bounds. The proportion of deaths concluded as suicide increased, as did those implicating antidepressant use. There were no changes in the proportion of deaths following use of other drug classes, alcohol use in combination with psychoactive drugs, or on decedent demographics (gender, age, and drug user status). A small number of deaths due to drug use had COVID-19 infection itself listed as a cause of death (n = 23). Conclusion: For people who use drugs, the impact of the restrictions due to the COVID-19 pandemic was greater than that of infection from the virus itself. The health and social care strategy for these people needs to be pre-emptively adapted to mitigate against the specific risk factors for fatal drug overdose associated with future emergency scenarios.

The first drug-related death associated with xylazine use in the UK and Europe.

BACKGROUND AND AIMS: On November 8th, 2022, the United States Food and Drug Administration (FDA) issued a statement alerting healthcare professionals to the increasing prevalence of xylazine in illicit drug overdoses in the country. Xylazine is a veterinary medicine with sedative, analgesic and muscle relaxant properties that is used as a heroin/fentanyl adulterant on the illicit drug market in North America. Here we report the first drug-related death associated with xylazine in the United Kingdom. METHODS: The National Programme on Substance Abuse Deaths (NPSAD) receives reports on drug-related deaths from coroners In England, Wales and Northern Ireland on a voluntary basis. The NPSAD was searched for cases with xylazine detections in cases received by December 31, 2022. RESULTS: One drug-related death associated with xylazine use was reported to NPSAD by December 31, 2022. The deceased was a 43-year-old male who was found dead at home with drug paraphernalia located at the property in May 2022. The post-mortem examination identified recent puncture wounds to the groin. Coronial documentation reports that the deceased had a history of illicit drug use. A number of drugs were detected by post-mortem toxicology and xylazine was implicated in death alongside heroin, fentanyl and cocaine. CONCLUSIONS: To the best of our knowledge, this is the first death associated with xylazine use reported in the UK, and even Europe, and indicates the entry of xylazine into the UK drug supply. This report highlights the importance of monitoring changes in illicit drug markets and the emergence of new drugs.

Opioid-related deaths during hospital admissions or shortly after discharge in the United Kingdom: A thematic framework analysis of coroner reports.

BACKGROUND: People who use heroin and other illicit opioids are at high risk of fatal overdose in the days after hospital discharge, but the reasons for this risk have not been studied. METHODS: We used the National Programme on Substance Abuse Deaths, a database of coroner reports for deaths following psychoactive drug use in England, Wales, and Northern Ireland. We selected reports where the death occurred between 2010 and 2021, an opioid was detected in toxicology testing, the death was related to nonmedical opioid use, and death was either during an acute medical or psychiatric hospital admission or within 14 days after discharge. We used thematic framework analysis of factors that may contribute to the risk of death during hospital admission or after discharge. RESULTS: We identified 121 coroners' reports; 42 where a patient died after using drugs during hospital admission, and 79 where death occurred shortly after discharge. The median age at death was 40 (IQR 34-46); 88 (73%) were male; and sedatives additional to opioids were detected at postmortem in 88 cases (73%), most commonly benzodiazepines. In thematic framework analysis, we categorised potential causes of fatal opioid overdose into three areas: (a) hospital policies and actions. Zero-tolerance policies mean that patients conceal drug use and use drugs in unsafe places such as locked bathrooms. Patients may be discharged to locations such as temporary hostels or the street while recovering. Some patients bring their own medicines or illicit opioids due to expectations of low-quality care, including undertreated withdrawal or pain; (b) high-risk use of sedatives. People may increase sedative use to manage symptoms of acute illness or a mental health crisis, and some may lose tolerance to opioids during a hospital admission; (c) declining health. Physical health and mobility problems posed barriers to post-discharge treatment for substance use, and some patients had sudden deteriorations in health that may have contributed to respiratory depression. CONCLUSION: Hospital admissions are associated with acute health crises that increase the risk of fatal overdose for patients who use illicit opioids. Hospitals need guidance to help them care for this patient group, particularly in relation to withdrawal management, harm reduction interventions such as take-home naloxone, discharge planning including continuation of opioid agonist therapy during recovery, management of poly-sedative use, and access to palliative care.

A case-control study of antipsychotic use and pneumonia-related mortality in the United Kingdom.

BACKGROUND AND AIM: There is increasing evidence linking antipsychotic use with pneumonia, but limited evidence of an effect on pneumonia-related outcomes such as mortality. In this study, we aimed to examine the association of pneumonia-related death with specific antipsychotic exposure. METHOD: Deaths analysed were those reported to a UK-based drug-related deaths database, the National Programme on Substance Abuse Deaths (NPSAD), between 1997 and September 2020. We conducted a case-control study with cases defined as pneumonia-related deaths and controls as cases with alternative causes of death. Cases were analysed by considering drugs detected at post-mortem (PM) and by drugs prescribed to the deceased at the time of their death with calculated odds ratios (ORs) adjusted to account for confounders. RESULTS: There were 2467 PM cases and 40,128 controls; 1818 prescribed cases and 28,018 controls. Second generation antipsychotics (SGAs) were robustly associated with an increased risk of pneumonia-related death compared with those not prescribed or taking antipsychotics (PM detection adjusted OR [AOR] 1·34 [95% CI 1·15-1·55]; prescribed AOR 1·28 [95% CI 1·11-1·49]). First generation antipsychotics had no clear association with death from pneumonia (PM detection AOR 1·06 [95% CI 0·77-1·47]; prescribed AOR 0·91 [95% CI 0·71-1·17]). Amongst SGAs, olanzapine was associated with an increased risk of death due to pneumonia (PM detection AOR 1·49 [95% CI 1·22-1·82]; prescribed AOR 1·44 [95% CI 1·18-1·76]) as was quetiapine (PM detection AOR 1·34 [95% CI 1·07-1·66]; prescribed AOR 1·28 [95% CI 1·01-1·64]). CONCLUSION: Olanzapine and quetiapine were found to increase the risk of pneumonia-related death in this NPSAD sample to a clinically important extent.

A Fatal Case Report of Barium Chloride Toxicity.

Barium is an alkaline earth metal whose toxicity is dictated by its compounded salt form: barium sulfate is insoluble and safe to ingest, but other barium salts (chloride, carbonate, sulfide, oxide and acetate) are bioavailable and therefore toxic when ingested. There have been 49 previous reports of fatal intoxications following barium consumption: 38 deemed accidental in nature, 8 suicidal, 1 homicidal and 2 of undetermined intent. In this report, we detail the first intentional fatal self-poisoning with barium chloride to be reported in the UK, along with a review of the surrounding literature. This is the first case to report quantified levels of barium in blood and vitreous humor, and by providing details of sample collection, storage and processing, this case will aid in future interpretations.

The role of thalamic group II mGlu receptors in health and disease.

The thalamus plays a pivotal role in the integration and processing of sensory, motor, and cognitive information. It is therefore important to understand how the thalamus operates in states of both health and disease. In the present review, we discuss the function of the Group II metabotropic glutamate (mGlu) receptors within thalamic circuitry, and how they may represent therapeutic targets in treating disease states associated with thalamic dysfunction.

Can cannabis kill? Characteristics of deaths following cannabis use in England (1998-2020).

BACKGROUND: Cannabis is the most widely used illegal drug but is rarely considered a causal factor in death. AIMS: This study aimed to understand trends in deaths in England where cannabinoids were detected at post-mortem, and to evaluate the clinical utility of post-mortem cannabinoid concentrations in coronial investigations. METHODS: Deaths with cannabinoid detections reported to the National Programme on Substance Abuse Deaths (NPSAD) were extracted and analysed. RESULTS: From 1998 to 2011, on average 7% of all cases reported to NPSAD had a cannabinoid detected (n = 110 deaths per year), rising to 18% in 2020 (n = 350). Death following cannabis use alone was rare (4% of cases, n = 136/3455). Traumatic injury was the prevalent underlying cause in these cases (62%, n = 84/136), with cannabis toxicity cited in a single case. Polydrug use was evident in most cases (96%, n = 3319/3455), with acute drug toxicity the prevalent underlying cause (74%, n = 2458/3319). Cardiac complications were the most cited physiological underlying cause of death (4%, n = 144/3455). The median average Δ9-tetrahydrocannabinol post-mortem blood concentrations were several magnitudes lower than previously reported median blood concentrations in living users (cannabis alone: 4.3 µg/L; cannabis in combination with other drugs: 3.5 µg/L). CONCLUSIONS: Risk of death due to cannabis toxicity is negligible. However, cannabis can prove fatal in circumstances with risk of traumatic physical injury, or in individuals with cardiac pathophysiologies. These indirect harms need careful consideration and further study to better elucidate the role cannabis plays in drug-related mortality. Furthermore, the relevance of cannabinoid quantifications in determining cause of death in coronial investigations is limited.

Adverse experiences resulting in emergency medical treatment seeking following the use of lysergic acid diethylamide (LSD).

BACKGROUND: Recreational lysergic acid diethylamide (LSD) use is growing in popularity amid increasing research interest on psychedelics and their possible therapeutic potential yet; the potent psychotropic effects of LSD may result in adverse reactions and behaviour. AIMS: This study aimed to investigate the 12-month incidence and nature of LSD-related adverse experiences resulting in emergency medical treatment (EMT) seeking in an international sample of people reporting LSD use. METHODS: We use data from the 2017 Global Drug Survey - a large anonymous online survey on patterns of drug use conducted between November 2016 and January 2017. RESULTS: Out of 10,293 past-year LSD users, 102 (1.0%) reported seeking EMT, with a per-event risk estimate of 0.2%. Younger age, comorbid mental health conditions and higher frequency of use were associated with increased risk of EMT seeking. The most common symptoms were psychological, including anxiety, panic and confusion, with the most common explanatory factors cited by respondents being poor 'setting' and 'mindset'. Most responders reported feeling back to normal within 24 h, but 11 participants experienced persistent issues after 4 weeks. CONCLUSION: The results suggest that LSD is a relatively safe drug in recreational settings. Adverse reactions are typically short-lived, self-limiting and psychological in nature. Sub-optimal set and setting were commonly reported as suspected contributory factors. Within clinical settings, patient screening, preparatory sessions and supervision should reduce these acute risks considerably.

Fatalities associated with gabapentinoids in England (2004-2020).

The gabapentinoids were reclassified as Schedule II medications and Class C drugs in the UK in 2019 due to their potential misuse. In this study we examined deaths following gabapentinoid use in England reported to the National Programme on Substance Abuse Deaths. A total of 3051 deaths were reported (gabapentin: 913 cases; pregabalin: 2322 cases [both detected in 184 cases]). Prescribed and illicitly obtained gabapentinoids accounted for similar proportions of deaths (gabapentin illicit 38.0%, prescribed 37.1%; pregabalin illicit 41.0%, prescribed 34.6%). Opioids were co-detected in most cases (92.0%), and co-prescribed in a quarter (25.3%). Postmortem blood gabapentinoid concentrations were commonly (sub)therapeutic (65.0% of gabapentin cases; 50.8% of pregabalin cases). In only two cases was gabapentinoid toxicity alone attributed in causing death. Gabapentinoids alone rarely cause death. Clinically relevant doses can, however, prove fatal, possibly by reducing tolerance to opioids. Doctors and patients should be aware of this interaction. Gabapentinoid-opioid co-prescribing needs urgent revision.

The First Fatal Intoxication with 3-MeO-PCP in the UK and a Review of the Literature.

The phencyclidine derivative 3-methoxyphencyclidine (3-MeO-PCP) is a potent dissociative hallucinogen. Sought for recreational use as a novel psychoactive substance, it can also induce acute psychological agitation and pathophysiological cardiorespiratory effects. Due to the harms associated with its use, 3-MeO-PCP was added to the "Green List" of materials covered by the 1971 Convention on Psychotropic Substances as a Schedule II substance by the United Nations Commission on Narcotic Drugs in April 2021. There have been 15 previous reports of fatal intoxications following 3-MeO-PCP use, but only one was attributable to 3-MeO-PCP intoxication alone. In this report, we detail the first fatality due to 3-MeO-PCP intoxication to be reported in the UK, along with a review of the surrounding literature. While the blood concentrations associated with 3-MeO-PCP toxicity and fatality remain unclear, by providing details of sample collection and storage conditions, this case will aid in future interpretations. Furthermore, this case suggests that 3-MeO-PCP toxicity may be exacerbated by exercise. Users of 3-MeO-PCP should be cautioned against its use as a "club drug" or in a similar setting where elevations in heart rate, body temperature and blood pressure may occur.

Highlighting the hidden dangers of a 'weak' opioid: Deaths following use of dihydrocodeine in England (2001-2020).

BACKGROUND: Dihydrocodeine (DHC) is considered a 'weak' opioid, but there is evidence of its increasing misuse in overdose deaths. This research aims to analyse trends in DHC-related deaths in England relevant to source and dose of DHC, and decedent demographics. METHODS: Cases from England reported to the National Programme on Substance Abuse Deaths (NPSAD) where DHC was identified at post-mortem and/or implicated in death between 2001 and 2020 were extracted for analysis. RESULTS: 2071 DHC-related deaths were identified. The greatest number of deaths involved illicitly obtained DHC and a significant increase in these deaths was recorded over time (r = 0.5, p = 0.03). However, there was a concurrent decline in the implication rate of DHC in causing death (r = -0.6, p < 0.01). Fatalities were primarily due to accidental overdose (64.8%) and misuse was highly prevalent in combination with additional central nervous system depressants (95.3%), namely illicit heroin/morphine and diazepam. In contrast, when DHC was obtained over-the-counter (OTC) suicide mortality accounted for almost half of the deaths (42.5%). Differences in polysubstance use were also identified, with less heroin/morphine and benzodiazepine co-detection, but increased OTC codeine co-detection. CONCLUSIONS: DHC misuse in England is increasing. The pharmacological consideration of DHC as a 'weak' opioid may be misinterpreted by users, leading to accidental overdosing. There is an urgent need to understand increasing polypharmacy in overdose deaths. Additionally, suicides involving DHC is a potential cause for concern and a review of OTC opioid-paracetamol preparations is necessary to determine whether the benefits of these medications continue to outweigh the risks of intentional overdose.

Synthetic Cannabinoid-Related Deaths in England, 2012-2019.

Aim: To identify drug-related death trends associated with synthetic cannabinoid receptor agonists (SCRAs) reported to the National Programme on Substance Abuse Deaths (NPSAD) from England. Design: Case reports from NPSAD (England) where a SCRA was detected in post-mortem tissue(s) and/or implicated in the death were extracted, analyzed, and compared against non-SCRA-related deaths that occurred over the same time period (2012-2019). Findings: One hundred sixty-five death SCRA-related reports were extracted, with 18 different SCRAs detected. Following the first death in 2012, a subsequent sharp increase in reporting is evident. Acute SCRA use was the underlying cause of death in the majority of cases (75.8%) with cardiorespiratory complications the most frequently cited underlying physiological cause (13.4%). SCRA users were predominantly found dead (68.6%), with a large proportion of those witnessed becoming unresponsive described as suddenly collapsing (81.6%). Psychoactive polydrug use was detected in 90.3% of cases, with alcohol the most commonly co-detected (50.3%), followed by opioids (42.2%), benzodiazepines/Z-drugs (32.1%), stimulants (32.1%, [28.5% cocaine]), and cannabis (24.8%). Compared to all non-SCRA-related NPSAD deaths occurring over the same time period, SCRA-related decedents were more predominantly male (90.3% vs. 72.0%; p<0.01), and lived in more deprived areas (p<0.01). While a comparatively significant proportion of decedents were homeless (19.4% vs. 4.1%), living in a hostel (13.3% vs. 2.3%) or in prison (4.9% vs. 0.2%) at time of death (all p<0.01), the greatest majority of SCRA-related decedents were living in private residential accommodations (57.6%). Conclusions: This is the largest dataset regarding SCRA-related mortalities reported to date. Reporting of SCRA-related deaths in England have increased considerably, with polydrug use a specific concern. Lack of effective deterrents to SCRA use under current UK legislation, compounded by limited knowledge regarding the physiological impacts of SCRA consumption and their interaction with other co-administered substances are contributory factors to the occurrence of SCRA-related mortalities in an increasingly deprived demographic.

Group II metabotropic glutamate receptor (mGlu2 and mGlu3 ) roles in thalamic processing.

BACKGROUND AND PURPOSE: As the thalamus underpins almost all aspects of behaviour, it is important to understand how the thalamus operates. Group II metabotropic glutamate (mGlu2 /mGlu3 ) receptor activation reduces inhibition in thalamic nuclei originating from the surrounding thalamic reticular nucleus (TRN). Whilst an mGlu2 component to this effect has been reported, in this study, we demonstrate that it is likely, largely mediated via mGlu3 . EXPERIMENTAL APPROACH: The somatosensory ventrobasal thalamus (VB) is an established model for probing fundamental principles of thalamic function. In vitro slices conserving VB-TRN circuitry from wild-type and mGlu3 knockout mouse brains were used to record IPSPs and mIPSCs. In vivo extracellular recordings were made from VB neurons in anaesthetised rats. A range of selective pharmacological agents were used to probe Group II mGlu receptor function (agonist, LY354740; antagonist, LY341495; mGlu2 positive allosteric modulator, LY487379 and mixed mGlu2 agonist/mGlu3 antagonist LY395756). KEY RESULTS: The in vitro and in vivo data are complementary and suggest that mGlu3 receptor activation is largely responsible for potentiating responses to somatosensory stimulation by reducing inhibition from the TRN. CONCLUSIONS AND IMPLICATIONS: mGlu3 receptor activation in the VB likely enables important somatosensory information to be discerned from background activity. These mGlu3 receptors are likely to be endogenously activated via 'glutamate spillover'. In cognitive thalamic nuclei, this mechanism may be of importance in governing attentional processes. Positive allosteric modulation of endogenous mGlu3 receptor activation may therefore enhance cognitive function in pathophysiological disease states, such as schizophrenia, thus representing a highly specific therapeutic target. LINKED ARTICLES: This article is part of a themed issue on Building Bridges in Neuropharmacology. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v179.8/issuetoc.

Recreational ketamine-related deaths notified to the National Programme on Substance Abuse Deaths, England, 1997-2019.

BACKGROUND: Ketamine is a phencyclidine derivative with dissociative anaesthetic properties. Increasing numbers of individuals in England take ketamine recreationally. Information on deaths arising from such use in England is presented. METHODS: Cases were extracted on 31 January 2020 from the National Programme on Substance Abuse Deaths database, based on text searches of the cause of death, coroner's verdict and positive toxicology results for the terms 'ketamine' or 'norketamine'. FINDINGS: During 1997-2005, there were <5 deaths p.a. in which ketamine was implicated. Numbers increased until 2009 (21), plateauing until 2016; thereafter, deaths have risen to about 30 p.a. Decedents' characteristics (N = 283): male 84.1%, mean age 31.2 (SD 10.0) years, employed 56.5%, drug use history 79.6% and living with others 60.3%. Ketamine was detected with other substances in most cases. Main (74.6%) underlying cause of death was accidental poisoning. Ketamine may have impaired judgement in other cases. CONCLUSIONS: Although controlled, recreational ketamine use and related fatalities continue to increase. Consumers need to be more aware of the potentially fatal risks they face.

Deaths from novel psychoactive substances in England, Wales and Northern Ireland: Evaluating the impact of the UK psychoactive substances act 2016.

BACKGROUND: 'Legal highs' began appearing in the UK in the mid-2000s. Whilst many of these substances were controlled under the 1971 Misuse of Drugs Act, novel compounds and new variants of controlled compounds were continuously being introduced to the recreational drug market. The Psychoactive Substances Act (PSA) was therefore implemented in 2016 as a blanket ban on all novel psychoactive substances (NPS). AIM: To evaluate the impact of the PSA on deaths following NPS use in England, Wales and Northern Ireland. METHODS: Cases reported to the National Programme on Substance Abuse Deaths where death had occurred 3 years pre- or post-implementation of the PSA were extracted. Cases with NPS detected at post-mortem were analysed and compared against cases non-NPS cases. RESULTS: 293 deaths with NPS detected were identified; 91 occurring before the PSA and 202 afterwards, indicating an 222.0% post-PSA increase. Contrastingly, non-NPS drug-related death case reporting increased by only 8.0%. Synthetic cannabinoid, anxiolytic/sedative and stimulant NPS were detected in the largest proportions of deaths pre-PSA; post-PSA stimulant NPS detections reduced whilst synthetic cannabinoid and anxiolytic/sedative detections increased.Post-PSA, average decedent age increased significantly (mean age pre-PSA 34.4 ± 10.8 vs post-PSA 38.3 ± 9.4), and they were significantly more likely to have been living in deprived areas (pre-PSA 50.0% vs post-PSA 65.9%). CONCLUSIONS: Reporting of deaths following NPS use has risen despite introduction of the PSA. Whilst deaths amongst younger individuals and those living in more affluent areas has reduced, additional approaches to prohibition are needed to curb their persistence in deprived demographics.