Research and analysis

Amendment to ACMD report – Use and harms of xylazine, medetomidine and detomidine: 21 October 2025 (accessible)

Updated 21 October 2025

ACMD Chair: Prof Owen Bowden-Jones
NPS Committee Secretary: Yetunde Animashawun
1st Floor (NE), Peel Building
2 Marsham Street
London
SW1P 4DF

ACMD@homeoffice.gov.uk

Rt Hon Sarah Jones MP
Minister of State (Minister for Crime and Policing)
2 Marsham Street
London
SW1P 4DF

21 October 2025

Dear Minister

Re: Amendment to ACMD report – Use and harms of xylazine, medetomidine and detomidine

• In February 2024 the Advisory Council on the Misuse of Drugs (ACMD) reviewed the use and harms of xylazine and, given the reports of detections and related harms from North America, recommended that it should be added to Class C of the Misuse of Drugs Act 1971. This was in spite of the fact that at that time there was no significant evidence of detection, use or reported harms of xylazine in the UK. Since xylazine has legitimate use as a veterinary medicine, the ACMD recommended that it should be placed in Schedule 4 Part 1 of the Misuse of Drugs Regulations 2001 (as amended) [ACMD Report 2024].

• Subsequent evidence now shows that xylazine has entered the UK drug market and is a growing concern. More recent surveillance has also confirmed wider penetration of the drug, with 35 detections across toxicology reports, law enforcement seizures, and drug-checking services between 2022 and 2023 in England, Scotland, and Wales [Copeland 2024].

• At that time the ACMD also reviewed the structurally and pharmacologically related compounds detomidine and medetomidine. The ACMD review noted that there was no evidence of use or harms of these compounds in the UK at that time and no significant use or detection elsewhere. Therefore, the ACMD recommended that no further action in relation to detomidine or medetomidine was required at that time, although the report recommended that responsible agencies be vigilant for the appearance of these compounds [ACMD Report 2024].

• Since that recommendation, through ongoing horizon scanning, the ACMD has become aware of increased use and associated harms related to medetomidine in North America where, following controls being placed on xylazine, it has appeared as replacements intended to synergistically extend/enhance the effects of opioids in the illicit drug supply [Palamar 2024; Murphy 2025; Nayani 2025; Nham 2025; Rettger 2025]. Medetomidine has now been identified in the UK illicit drug supply, and the ACMD therefore instigated a re-review of medetomidine, along with detomidine, to determine whether they should also be added to the Misuse of Drugs Act 1971.

• Below is a summary of the further review by the ACMD xylazine, medetomidine and detomidine working group on the potential for increased use and harms of medetomidine and detomidine, together with the ACMD’s recommendations in light of these findings.

• Pharmacology: Detomidine and medetomidine, like xylazine, are non-selective α-2 adrenoceptor agonists that activate both central and peripheral α-2 adrenoceptors. Activation of central (brain) α2A adrenoreceptors will lead to sedation and hypotension, whereas activation of peripheral (small diameter blood vessel smooth muscle) α2B adrenoreceptors will lead to peripheral vasoconstriction. Medetomidine is reported to be a significantly more potent α- 2 adrenoceptor agonist compared to xylazine (approximately 200 times more potent). As with xylazine, the sedative effects of detomidine and medetomidine would not be reversed by naloxone. However, often medetomidine has been detected in combination with opioids and any response to naloxone is likely to be due to the reversal of the associated opioid toxicity.

• Current legal status in the UK: In the UK, both detomidine and medetomidine are prescription only veterinary medicines (POM-V) licensed for sedation and/or use as pre-medication prior to use of anaesthetics. There are 18 detomidine and 15 medetomidine veterinary medicinal products authorised for use in the UK for use in horses/cattle and dogs/cats respectively. Only dexmedetomidine, one of the stereoisomers of medetomidine, is approved by the Medicines and Health care products Regulatory Agency (MHRA) for human use, as a sedative for use by infusion in critical care areas. Although detomidine and medetomidine are not currently controlled under the Misuse of Drugs Act, 1971, given that they are licensed for use as sedatives and/or anaesthetics in veterinary medicine and that the stereoisomer dexmedetomidine is licensed for human use as a sedative, they are likely to be subject to the provisions of the Psychoactive Substances Act 2016 because of these known psychoactive effects in animals.

• International control: Detomidine and medetomidine are considered as veterinary medicines, and would therefore be subject to appropriate national veterinary prescription requirements, rather than as Controlled Drugs, in different countries. Dexmedetomidine is a prescription only medicine and therefore would be subject to the relevant national human medicines regulations.

• Detomidine acute toxicity: The previous ACMD review of xylazine and related compounds published in 2024 identified four published reports of detomidine-related acute toxicity from the Republic of Ireland (2), Finland (1), and Scotland (1) [Reid 1994; Pohjalanien 2001; Cummins 2005; Hannah 2010]. In two cases, the exposure was to a mixture of detomidine with the analgesic butorphanol, which could have contributed to some of the drowsiness described [Reid 1994; Hannah 2010]. There have been no further published reports since that review. Those four reports were of two males and two females, aged between 26 and 36 years old, who were hospitalised, with three accidental and one self-harm related exposures. The route of exposure was by injection in three, and dermal absorption in one. All were drowsy, although none had associated respiratory depression; two had bradycardia, one had hypotension and one had hypertension. All four required only a brief period of observation and none required endotracheal intubation.

• Medetomidine acute toxicity: At the time of the ACMD review of xylazine and related compounds, there were no published reports of acute toxicity related to medetomidine. Since the review, however, there have been a number of reports of the detection of medetomidine in patients presenting to healthcare services in North America with suspected acute opioid toxicity [Murphy 2025; Nayani 2025; Nham 2025; Rettger 2025]. These are summarised below:

  • Chicago, Illinois, USA: Three male patients with opioid use disorder presented to emergency medical services with suspected opioid toxicity, with partial response to naloxone administration. Subsequent analysis of serum samples detected medetomidine with i) fentanyl; ii) fentanyl, heroin and xylazine; and iii) fentanyl and xylazine [Nayani 2025].

  • Chicago, Illinois, USA: The US Centres for Disease Control and Prevention (CDC) reported an outbreak of 178 overdoses involving medetomidine. The CDC defined specific criteria for classifying the degree of certainty that an overdose was related to medetomidine: confirmed (12 cases in which medetomidine was detected in blood analysis), probable (26 cases in which medetomidine detected on drug sample analysis or the patient responded to naloxone and had bradycardia) or suspected (140 cases in which the patient responded to naloxone or did not respond but had bradycardia). In all the confirmed cases, in addition to medetomidine (blood concentrations ranged from 0.7 to 63.7 microgram/L), fentanyl and diphenhydramine were detected in all cases, and in the majority of cases one or more other drug was also detected. Patients were predominately males, aged 45-64 years old and the most commonly reported clinical feature was bradycardia [Nham 2025].

  • Philadelphia, Pennsylvania, USA: A retrospective case series described the clinical features of eleven individuals presenting to an emergency department with suspected opioid overdose. Medetomidine was detected as part of a wider public health surveillance project involving screening of de-identified blood samples between April and May 2024 in patients presenting with atypical features in the setting of presumed opioid toxicity. Whole blood medetomidine concentrations ranged from 1.2 to 16 microgram/L; all blood samples also contained fentanyl and xylazine and one or more other adulterants or drugs. Although all patients had bradycardia (median (IQR) 41 (38-44) beats/min) there was no correlation between medetomidine, fentanyl or xylazine concentrations and the degree of bradycardia. The median (IQR) duration of the bradycardia was 3.4 (2.7- 9.3 hours); there was a suggestion of a relationship between the duration of bradycardia and medetomidine concentrations, but the authors concluded the sample size was too small to draw any firm conclusion [Murphy 2025].

  • Worcester, Massachusetts, USA: Detection of medetomidine in two patients with suspected opioid toxicity responsive to naloxone: i) male in his 40s with medetomidine detected alongside cocaine, fentanyl, ketamine and xylazine; and ii) detection of medetomidine in a female in her 30s, together with cocaine, diazepam, fentanyl, ketamine and xylazine [Rettger 2025].

• Chronic toxicity of detomidine and medetomidine: There have been reports of chronic ulceration related to the use of heroin, fentanyl and other opioids that contain xylazine [ACMD report 2024] As medetomidine and detomidine have the same pharmacological actions that are postulated to contribute to the development of the xylazine-related ulceration, there remains the potential that these may have the same effects. So far, however, there have been no reports of skin ulceration related to the use of detomidine or medetomidine.

• Detomidine and medetomidine dependency: There have been case reports of xylazine dependency and associated withdrawal in regular long- term users of xylazine [Ehrman-Dupre 2022, Mulders 2016] and online survey reports of withdrawal in individuals using opioids thought to contain xylazine [Spadaro 2023]. There has been one report of 165 individuals hospitalised for fentanyl withdrawal in three different Philadelphia health systems between September 2024 and January 2025, where the withdrawal was complicated by profound autonomic dysfunction (severe hypertension and tachycardia) which did not respond to medications previously effective in managing fentanyl and xylazine withdrawal [London 2025]. The symptoms, however, were responsive to dexmedetomidine. In 43 patients treated in one health system, analytical screening of urine collected within 72 hours of admission and prior to the administration of dexmedetomidine detected the medetomidine metabolite 3-hydroxy-medetomidine (43 patients), the fentanyl metabolite norfentanyl (43 patients) and xylazine (29 patients). It has been postulated that as medetomidine is 200 times more potent than xylazine, that individuals may be at risk of developing dependency more rapidly and that the subsequent withdrawal will be more severe with medetomidine compared to xylazine. Currently, however, there is no clinical or drug treatment service level data to support this increased risk of dependency and/or withdrawal. To date, there have been no reports of dependency and/or withdrawal related to the use of detomidine.

• Social harms: The acute toxicity described with exposure to detomidine and medetomidine involves drowsiness and coma. Therefore, there is the potential that individuals may be exposed intentionally to detomidine and/or medetomidine by other individuals with the intent of causing sedation to facilitate crimes such as robbery, assault and sexual assault. There is also the potential that detomidine and medetomidine may increase the risk to the individual and the public when an individual is driving under the influence of detomidine or medetomidine.

• Detection of detomidine/medetomidine in the UK: To evidence the identification and prevalence of detomidine and medetomidine in the UK, the ACMD’s New Psychoactive Substances (NPS) Committee wrote to stakeholders in April 2025 requesting available data on their detections.

  • Whilst analytical laboratories are able to detect the presence of medetomidine in biological and/or other samples, methods are not currently in place to separate and identify the two stereoisomers. In principle, laboratories could achieve this through chiral separation techniques, and published methods are now available [Walton 2025]. These approaches are not widely implemented due to practical limitations, including the additional time, cost, and resources required. Moreover, laboratories must operate in compliance with ISO 17025 and LAB 51 standards, which adds further constraints on adopting new analytical procedures.

  • Developing the capability to routinely separate medetomidine stereoisomers would be advantageous, particularly when analysing ante- or post-mortem samples from patients who may have received dexmedetomidine therapeutically. Without stereoisomer separation or additional contextual information (e.g. a record of medications administered during clinical care, analysis of samples taken before therapeutic dexmedetomidine use, or examination of drugs recovered from the individual), the findings are likely to be reported simply as ‘medetomidine’, and it will not be possible to determine whether the detection reflects therapeutic dexmedetomidine use, the intentional use of an illicit drug adulterated with medetomidine, or medetomidine itself. They are usually not able to differentiate between the two stereoisomers to determine if the analyte is racemic medetomidine or one of the individual stereoisomers. This may be of importance when analysing ante- or post-mortem blood and other samples from patients where dexmedetomidine may have been given therapeutically since this would be detected and reported as “medetomidine”. In these circumstances without further information (e.g. summary of medication administered as part of clinical care, analysis of samples from prior to the therapeutic administration of dexmedetomidine or analysis of drugs found on the individual), it may not be possible to determine if this was the detection of therapeutic use of dexmedetomidine or the intentional use of an illicit drug adulterated with medetomidine, or medetomidine itself.

  • The MHRA have reported that there were two spontaneous fatal yellow card reports relating to dexmedetomidine in 2023; no further information is available on the circumstances relating to these reports and whether they related to therapeutic use. Additionally, the MHRA last received notifications of intent (NOIs) to import dexmedetomidine on 5 May 2020.

  • The Office for Health Improvement and Disparities (OHID, launched in October 2021 as a part of the Department of Health and Social Care, with the aim of tackling health inequalities across England and Wales, reported detection of medetomidine in three illicit drug samples analysed in 2025 at the time of the data request: i) London, February 2025: purchased as heroin and found to contain medetomidine; ii) South West England, March 2025: purchased as heroin and found to contain caffeine, clozapine, codeine, nitazenes, benzodiazepines, heroin, isotocyanazene, medetomidine and paracetamol; and iii) South East England, June 2025: purchased as heroin and found to contain benzodiazepines, caffeine, heroin, ketamine, paracetamol, medetomidine, nitazenes and xylazine.

  • Eurofins laboratories reported that in the analysis of bulk drug samples, medetomidine was detected in 18 powder samples analysed in 2025 at the time of the data request. There was no differentiation between racemic medetomidine and its two stereoisomeric forms. This detection of medetomidine was alongside the detection of one or more other drugs: i) clozapine, caffeine and paracetamol; ii) heroin and other nitazenes; iii) heroin, paracetamol and caffeine; and iv) clozapine, caffeine, paracetamol, levamisole and phenacetin.

  • The National Crime Authority (NCA) reported the detection of medetomidine in the analysis of nine seized powder “heroin” samples; there was no differentiation between racemic medetomidine and its two stereoisomeric forms. Nitazenes were also detected in these samples.

  • There have been very few telephone enquiries to the National Poisons Information Service (NPIS) regarding these substances. There have been a total of 8 calls to the NPIS related to medetomidine between 2019 and 2025, with no significant increase in calls over time (2019 – 1 call, 2023 – 1 call, 2024 – 3 calls, 2025 – 2 calls). No further information is available on these enquiries in regards to the circumstances of use, clinical features observed, or patient outcomes. There have been no telephone enquiries concerning detomidine. Online and app TOXBASE® accesses for medetomidine and dexmedetomidine are summarised in the Table below; there is no specific TOXBASE® page for levomedetomidine. As medetomidine is a licensed veterinary medicine and dexmedetomidine is a licensed human medicine, it is not possible to determine whether these TOXBASE® accesses relate to accidental or intended (including recreational) human exposures to the compounds. However, by the time of the data request, there had already been a sharp increase in the number of TOXBASE® accesses related to medetomidine compared to dexmedetomidine in 2025. There was no information available on TOXBASE® accesses for detomidine at the time of this report.

Table 1. National Poisons Information Service (NPIS) TOXBASE® accesses for medetomidine and detomidine from 2019 to April 2025.

	2019	2020	2021	2022	2023	2024	2025
Medetomidine	27	10	25	35	28	20	254
Dexmedetomidine	15	14	20	20	26	24	36
Detomidine	24	15	16	17	14	7	9

• The following stakeholders confirmed that they have not had any detections, cases of toxicity and/or deaths of detomidine or medetomidine in the UK up to the time of the data request: Border Force, Crown Office and Procurator Fiscal Service (COPFS and NHS Grampian), Emerging Drugs and Technology (EDAT) Project (previously known as the Forensic Early Warning System (FEWS) Project), EU-MADNESS, European Drug Emergencies Network Plus (Euro-DEN Plus) project, Identification Of Novel psychoactive substances (IONA) study, Laboratory of the Government Chemist (LGC), MANchester Drug Analysis and Knowledge Exchange (MANDRAKE), National Programme on Substance Use Mortality (NPSUM), National Records of Scotland (NRS), Northern Ireland Statistics and Research Agency (NISRA), Office of National Statistics (ONS), Public Health Scotland - Rapid Action Drug Alerts and Response (PHS-RADAR), Scottish Police Authority, Scottish Prison Service, TIC TAC Communications, Welsh Emerging Drugs and Identification of Novel Substances (WEDINOS). It is possible that this lack of reported detections by these stakeholders is in part due to lack of routine screening of samples for detomidine and/or medetomidine.

Conclusions

• When xylazine and the related compounds, detomidine and medetomidine, were reviewed by the ACMD in 2024, there was considered to be insufficient evidence of use or associated harms in the UK or elsewhere to recommend that either detomidine or medetomidine should be controlled under the Misuse of Drugs Act, 1971.

• Since the publication of the ACMD recommendations, the ACMD has become aware of the increasing evidence of the detection of medetomidine, along with associated acute harms and risk of dependency and severe withdrawal syndromes, in North America. There has been a significant increase in detections and reports following the control of xylazine in North America, suggesting that this control led to medetomidine substitution in the drug market as a result.

• In addition, although the numbers of detections of medetomidine in the UK remain low, there have been several reports in 2025 of medetomidine being detected in drug samples by a number of different forensic science providers and other sources in the UK.

• In light of the increase in detections and associated harms related to medetomidine in North America, along with the small number of detections in the UK in 2025 and given the likelihood of further increases of use and associated harms in the UK, the ACMD advises that control of medetomidine via the Misuse of Drugs Act, 1971 is now necessary. This would also result in control of dexmedetomidine via the Act, as this would capture all stereoisomers.

• There is no further evidence of increased detection or harms related to detomidine, beyond what was considered in the ACMD 2024 review. It should be noted that detomidine and medetomidine are structurally related to xylazine, and have similar pharmacological actions. Although there does not appear to be an increase in detections or harms related to detomidine, there remains a potential for detomidine to be used as a substitute for xylazine and/or medetomidine. For this reason, the ACMD advises that detomidine is also controlled via the Misuse of Drugs Act, 1971.

• The potential harms of detomidine and medetomidine will be similar to xylazine, and therefore are broadly equivalent to other sedatives such as benzodiazepines, zopiclone or pregabalin, as such the ACMD recommends both compounds are listed in Class C of the Misuse of Drugs Act, 1971, similar to xylazine.

• Since the ACMD does not wish to hamper the legitimate human use of dexmedetomidine or veterinary medicine use of detomidine or medetomidine, similar to xylazine, the ACMD would recommend listing in Schedule 4 Part 1 of the Misuse of Drugs Regulations 2001 as this does not require Controlled Drug prescription requirements, safe custody arrangements or drug registers.

• Currently laboratories and analytical services do not differentiate between the different stereoisomers of medetomidine. We would suggest that there is an increase in the capability of these services to be able to differentiate between the stereoisomers of medetomidine.

Recommendation 1

Although there remains limited evidence of detection and/or harms related to both detomidine and medetomidine in the UK currently, given the reported increase in detection and associated harms in North America and the increasing detections of medetomidine in the UK, similar to xylazine, the ACMD would now recommend that both detomidine and medetomidine are added to Class C of the Misuse of Drugs Act 1971. As both have legitimate use as veterinary medicines, they should be placed in Schedule 4 Part 1 of the Misuse of Drugs Regulations 2001 (as amended).

Lead: Home Office.

Measure of outcome: The inclusion of the detomidine and medetomidine in Class C of the Misuse of Drugs Act 1971 and Schedule 4 Part 1 of the Misuse of Drugs Regulations 2001.

Recommendation 2

Information should be provided in an appropriate format to the general public (such as FRANK, DAN 24/7 and ‘Know the Score’) and to harm reduction services on the potential that heroin, fentanyl and other illicit drugs may contain medetomidine and detomidine, and should include the unwanted health effects of these compounds. Users and those coming into contact with them (e.g. emergency department staff, ambulance staff, drug treatment staff), should be aware that the sedative effects of using “drugs” containing both heroin, fentanyl or another opioid and detomidine or medetomidine may not fully respond to use of naloxone, and other supportive measures in the community or in hospital may be required.

Lead: Department for Education, Office for Health Improvement and Disparities, Local Government Association, Association of Directors of Public Health, Chief Medical Officers in England, Wales, Scotland and Northern Ireland, National Poisons Information Service, FRANK, DAN 24/7 (Betsi Cadwaladr University Health Board), Know the Score (Scotland).

Measure of outcome: Information available for the general public, including those with lived experience, healthcare professionals and others working with potential users. Updating information on FRANK, DAN 24/7, Know the Score and TOXBASE ®.

Recommendation 3

Responsible agencies need to be vigilant and monitor for xylazine and medetomidine, which are being used to augment the UK opioid market, as well as detomidine which has the potential for future misuse. This can be done by analysis of seized or submitted drug samples, especially seized heroin and other opioid samples, and analysis of patient toxicology and post mortem samples. Analytical laboratories and services should routinely include medetomidine and detomidine in their screening panels, particularly where opiates have been detected and develop methods for stereoisomer separation of medetomidine to distinguish between licit and illicit use. These data can then be collected, collated and monitored by the relevant public health agencies in the UK and reviewed by the Office for Health Improvement and Disparities newly established Early Warning System.

Lead: Office for Health Improvement and Disparities (OHID), Public Health Wales, Public Health Scotland, Public Health Agency Northern Ireland, Laboratory Service Providers

Measure of outcome: Information on the frequency and amount of detomidine, medetomidine and xylazine being used to augment the UK opioid market provided to the ACMD by the Office for Health Improvement and Disparities, and the equivalents in the devolved administrations.