Emergence of Medetomidine in the Unregulated Drug Supply and Its Association With Hallucinogenic Effects

ABSTRACT

Introduction

The unregulated drug supply in the United States is rapidly evolving, and veterinary tranquillisers have emerged as adulterants of concern, especially in illicitly‐manufactured fentanyl. Following the proliferation of xylazine, medetomidine, a more potent sedative, has recently appeared in multiple US states. This study describes the characteristics of medetomidine samples from a national mail‐based drug checking program and aims to determine whether medetomidine is associated with hallucinogenic effects.

Methods

We conducted a retrospective analysis of 11,363 drug samples between December 2022 and April 2025. Samples were sent voluntarily by people who use drugs. Participant‐reported sensations and sample characteristics (e.g., colour, texture) were gathered at point‐of‐contact. Composition was analysed using gas‐chromatography mass spectrometry. We estimated adjusted prevalence ratios for hallucinations in medetomidine‐containing samples using generalised estimating equations.

Results

Medetomidine was identified in 278 samples (2.4%), with pronounced growth beginning June 2024. Medetomidine commonly appeared with fentanyl (58.8%) and/or xylazine (55.9%). Most samples were powders (85.3%). Among all 11,363 samples, those containing medetomidine in primary abundance (n = 136) were more likely to be associated with reported hallucinations (17.6%) compared to all other samples (1.2%; adjusted prevalence ratio: 11.95, 95% confidence interval 6.36, 22.44).

Discussion and Conclusions

Medetomidine is an emerging adulterant, although its risk profile is under‐described. Our findings suggest medetomidine may cause hallucinogenic effects, contradicting clinical use for preventing delirium in postsurgical settings. Unexpected hallucinations may serve as a sentinel signal for medetomidine's presence in local drug markets. Education is needed for people who use drugs and clinicians about novel adverse effects of medetomidine.

Summary.

• Medetomidine, a potent veterinary tranquilliser and human sedative, is emerging as a new adulterant in the unregulated drug supply in the United States.

• We analysed 11,363 drug samples through a national mail‐based drug checking program from December 2022 to April 2025.

• A total of 278 samples contained medetomidine, which commonly co‐occurred with fentanyl (58.8%) and/or xylazine (55.9%).

• Samples containing medetomidine were 12 times as likely to include reported hallucinations than other samples; contradicting clinical expectations.

• Hallucinations may be one signal of medetomidine's presence in local markets; education is needed for people who use drugs and providers about distinct presentations of this adulterant.

1. Introduction

The United States is experiencing a rapidly evolving unregulated drug supply, complicating efforts to protect people who use drugs from overdose and other health sequelae of substance use. Recent trends include the introduction of new psychoactive substances (e.g., nitazenes and synthetic cannabanoids), nontherapeutic fillers with uncertain safety profiles (e.g., bis(2,2,6,6‐tetramethyl‐4‐piperidyl) sebacate [BTMPS]), and of particular concern, xylazine, a veterinary tranquilliser co‐occurring with—and sometimes supplanting—fentanyl and other opioids in illicit drug markets [1, 2, 3].

There is an urgent need to identify and characterise new constituents of the unregulated supply in a timely manner in order to inform harm reduction practice and policy. In particular, people who use drugs should be adequately informed to assess the risk of substances they may knowingly or unknowingly ingest. Unfortunately, efforts to educate substance‐using communities often fail to keep pace with supply trends, owing in part to the mercurial nature of drug markets and, as importantly, the inertia of research dissemination pipelines [4, 5]. Xylazine presents one example: Although the adulterant had appeared in 38 states by 2019, its association with severe skin ulceration was not reported in the research literature, to our knowledge, until 2022 (cf. two studies identified skin ulcers as an adverse reaction shortly after xylazine's introduction to Puerto Rico in the late 2000s) [6, 7, 8, 9]. As laboratory‐based drug checking becomes formalised as an accessible harm reduction strategy—and prolific data source—it is incumbent upon researchers to characterise new drugs of consumption before they saturate markets and cause preventable harm.

One emerging substance of concern is medetomidine, a racemic mixture of levo‐ and dex‐medetomidine [10]. First identified in the unregulated supply in Maryland in mid‐2022 [11], medetomidine, like xylazine, is a potent veterinary tranquilliser; unlike xylazine, its active enantiomer (dexmedetomidine, commonly delivered as injectable Precedex, Pfizer, New York, USA) is an FDA‐approved α2‐adrenergic agonist used as a sedative, analgesic and anxiolytic in humans. Dexmedetomidine is widely used in hospital settings because it is not a controlled substance and is also used in veterinary medicine and biopharmaceutical research in animal models. Sublingual dexmedetomidine (Igalmi, BioXcel Therapeutics, New Haven, CT, USA) is additionally used in humans for management of agitation among adult patients with agitation due to schizophrenia or bipolar disorder.

Dexmedetomidine was developed to be a safer human sedative due to its purported lack of respiratory depressive effect and increased selectivity for the alpha‐adrenergic receptors. Interestingly, dexmedetomidine and xylazine were both developed in a cascade of medicinal chemistry attempts to improve on the sedative and addiction therapy potential of clonidine, an earlier α2‐adrenergic agonist [12]. Xylazine and dexmedetomidine have both been touted as selective α2‐adrenergic agonists, but this has recently been refuted for xylazine [13, 14]. In fact, xylazine has now been reported to have agonist activity at the kappa opioid receptor, 5‐HT₇ serotonin receptor, sigma 1 and 2 receptors, as well as the 3 α2‐adrenergic receptor subtypes [13, 14]. Current literature does not report any indications that dexmedetomidine is not selective for the alpha‐adrenergic system.

Given the complexity of xylazine's pharmacology, and growing concerns about prospective harms of medetomidine to human health alone or in combination with opioids [15, 16], there is a need for further validation of medetomidine's profile of effects and its presentation in community settings. The purpose of this study, therefore, is to characterise medetomidine and reported effects using data from a national drug checking service.

1.1. Study Rationale and Hypothesis

In October–November 2024, our team attended two harm reduction programs in Pennsylvania and Michigan to conduct a qualitative study of naloxone administration and overdose reversal behaviours in people who use drugs [17]. Several interview participants discussed a new constituent of the local drug supply, sometimes called ‘trippy dope’, that was described as inducing severe and troublesome visual hallucinations. These participants noted that ‘trippy dope’ was a relatively new phenomenon, appearing within the previous several months. This timeline roughly aligned with the proliferation of medetomidine in drug checking samples from both states. In consultation with harm reduction partners at both programs, we therefore formulated the following hypothesis:

Drug checking samples containing medetomidine are more likely to include reports of hallucinations than samples not containing medetomidine.

2. Methods

2.1. Study Design and Data Source

We conducted a retrospective analysis using data from a public drug checking service, the UNC Street Drug Analysis Lab. Analysis was restricted to samples with complete analysis by the lab between 7 December 2022, the first date of a positive medetomidine sample, and 11 April 2025, with at least one substance positively identified, comprising a total of 11,363 samples. The dataset included qualitative sample composition profiles identified using gas chromatography mass spectrometry (GCMS); all detected substances were positively identified using reference standards. Participant‐reported data included geographic location, collection method, expected substance and sample characteristics (sensations, colour and texture) recorded on a standardised data card filled out by program staff. Hallucinations were one of 12 closed‐ended response options for the sensation field on the data card and participants could expand on their selection(s) in a free text field (Appendix A) [18].

Because GCMS cannot distinguish between medetomidine and its individual enantiomers, the term medetomidine is used throughout this manuscript to refer to the compound as a whole.

2.2. Data Collection

Samples were submitted by health‐serving organisations including harm reduction programs, drug user unions, public health agencies and universities. Samples were collected as powders, pill fragments, swabs or used cottons, dissolved in acetonitrile solution and shipped to the drug checking lab with a prepaid return envelope. Sample collection and shipping followed established harm reduction exemptions under state‐controlled substance laws and federal regulations for small quantity hazardous materials.

Samples were prepared then analysed on a Thermo Scientific Q Exactive GC Orbitrap GC–MS System with a TriPlus RSH Autosampler with electron ionisation. Xcalibur Qual Browser Version 4.5.445.18 (ThermoFisher, Bremen, Germany) was used to analyse raw GCMS output. Substances were identified using mass spectral libraries and classified as ‘primary’ or ‘trace’ in abundance. Trace substances were defined as those with ≥ 5% peak height area relative to the most abundant substance. Complete lab analysis methods, including reference libraries, are described elsewhere [19].

2.3. Measures

The unit of analysis was a drug sample. The primary outcome was participant‐reported hallucinations. The primary exposure of interest was the positive identification of medetomidine in abundance per sample.

2.4. Covariates

Substance covariates were selected using a model‐driven approach: Substances were included if they were associated with both medetomidine presence and independently associated with hallucinations in preliminary bivariate analyses. Substances were then grouped based on pharmacological class and/or to address sparse data bias based on an a priori threshold of ≥ 5 co‐occurrences of hallucinations with medetomidine. Among 410 unique substances identified in the dataset, 23 co‐occurred with medetomidine in a reported hallucination. Only one substance (bromazolam, a benzodiazepine) was excluded, as it did not meet the a priori threshold and could not be grouped pharmacologically. Substance covariates selected for the model were: xylazine, fentanyl, fentanyl precursors/impurities (4‐ANPP, 1,3‐diacetin, despropionyl p‐fulorofentanyl), other opioids (buprenorphine, heroin, 6‐monoacetylmorphine, N‐phenethyl‐N‐phenylpropionamide, p‐fluorofentanyl), local anaesthetics (procaine, lidocaine, tetracaine, bupivacaine), stimulants (methamphetamine, cocaine, caffeine) and nonpsychoactive fillers (quinine, acetaminophen, dimethyl sulfone, BTMPS).

Additional covariates were considered for the model using forward variable selection and the quasi‐information criterion. These variables were the number of substances per sample (including abundant and trace, to account for polysubstance complexity), region (Northeast, Midwest, South, West) and time (i.e., year). The number of substances and region improved model fit and were included. Year was excluded as only one medetomidine‐associated hallucination occurred prior to 2024.

2.5. Statistical Analysis

We used generalised estimating equations with a log link and Poisson distribution to estimate adjusted prevalence ratios (aPR). The model accounted for clustering by county using an exchangeable correlation structure. All hypothesis tests were two‐sided. Statistical significance was assessed at the p < 0.05 level. Multicollinearity was assessed using variance inflation factors; no covariates exceeded a variance inflation factor of 5. All analyses were conducted in Python 3.10 using the statsmodels, pandas and mlxtend packages in a Deepnote environment.

2.6. Sensitivity Analysis

Participant‐reported sensations were recorded on 52.2% of data cards. Because it was unclear whether blanks indicated the substance was not consumed, there was a lack of sensations, or the question was not asked, a sensitivity analysis was conducted, including only samples with any recorded sensations (hallucinations or otherwise).

2.7. Preregistration

The study protocol was preregistered at https://osf.io/4agfx.

3. Results

Between 7 December 2022 and 11 April 2025, 11,363 samples were analysed by GCMS. Primary collection methods were spatula (56.3%), swab (10.9%), pill (8.3%), scoop (5.4%) or cotton (3.8%). Medetomidine was identified in 278 samples (2.4%), including 136 in primary abundance (1.2%). Pronounced growth in the prevalence of positive samples began around June 2024 (Figure 1, xylazine as comparator molecule).

FIGURE 1.

Top: Percentage of samples containing xylazine and medetomidine, December 2022–April 2025. Bottom: Total samples received (blue line) and number of originating state (grey bars) per month.

Medetomidine was identified in primary abundance in seven US states during the analysis period (New York, Pennsylvania, North Carolina, Michigan, Ohio, Florida, Virginia) (Appendix B). Medetomidine‐containing samples were most often white and in powder form (Table 1). Commonly endorsed sensations included ‘sedating’ (32.4%), ‘stronger’ (25.0%), ‘unpleasant’ (16.9%), ‘weird’ (13.2%) and ‘more down’ (11.0%). Sample donors most often expected samples to contain fentanyl (86.9%), xylazine (42.3%) and/or heroin (23.1%).

TABLE 1.

Characteristics of samples containing medetomidine in primary abundance (n = 136).

	n (%)
Sensations a
Sedating	44 (32.4)
Stronger	34 (25.0)
Hallucinations	24 (17.6)
Unpleasant	23 (16.9)
Weird	18 (13.2)
More down	15 (11.0)
Normal	8 (5.9)
Long	6 (4.4)
Weaker	5 (3.7)
Other	10 (7.4)
Unknown/not specified	40 (29.4)
Textures a
Powder	116 (85.3)
Chunky	24 (17.6)
Dull	12 (8.8)
Flaky	9 (6.6)
Other	11 (8.1)
Unknown/not specified	17 (12.5)
Colour a
White	47 (34.6)
Brown	13 (9.6)
Tan	10 (7.4)
Grey	7 (5.1)
Blue	7 (5.1)
Other	22 (16.2)
Unknown/not specified	45 (33.1)
Expected substance(s)
Fentanyl	114 (83.8)
Xylazine	55 (40.4)
Heroin	31 (22.8)
Benzodiazepine	8 (5.9)
Ketamine	3 (2.2)
Medetomidine	3 (2.2)
BTMPS	2 (1.5)
Opioids (unspecified)	2 (1.5)
M30	1 (0.7)
Nitazene	1 (0.7)
Crack cocaine	1 (0.7)
Procaine	1 (0.7)
Methamphetamine	1 (0.7)
Cocaine	1 (0.7)
Unknown/not specified	13 (9.6)
Region
Northeast	99 (72.8)
Midwest	20 (14.7)
South	17 (12.5)
West	0

^a Includes values with count ≥ 5.

Most medetomidine‐positive samples also contained fentanyl (58.8%) and/or xylazine (55.9%) (Table 2). Including trace substances, GCMS identified a median of eight substances in medetomidine‐containing samples (range: 2–17) compared with a median of three substances in all other samples (range: 1–19) (Table 3).

TABLE 2.

Co‐occurring substances found in primary abundance in medetomidine‐positive samples (n = 136).

Substance a	n (%)
Fentanyl	80 (58.8)
Xylazine	76 (55.9)
4‐ANPP	55 (40.4)
Procaine	55 (40.4)
Lidocaine	42 (30.9)
BTMPS	34 (25.0)
Caffeine	34 (25.0)
Heroin	30 (22.1)
Tetracaine	27 (19.9)
Acetaminophen	25 (18.4)
Diphenhydramine	16 (11.8)
6‐monoacetylmorphine	12 (8.8)
Dimethyl sulfone	11 (8.1)
Bromazolam	9 (6.6)
Cocaine	8 (5.9)
Bupivacaine	8 (5.9)
Despropionyl p‐fluorofentanyl	8 (5.9)
1,3‐Diacetin	7 (5.1)
P‐fluorofentanyl	7 (5.1)
Promethazine	6 (4.4)
Quinine	5 (3.7)
Methamphetamine	5 (3.7)
All others	35 (25.7)

^a Includes values with count ≥ 5.

TABLE 3.

Measures of central tendency for number of unique substances identified per sample (N = 11,363).

	Median (range)	Mean (SD)
Including abundant substances only
Medetomidine‐positive samples	5 (2–14)	5.38 (2.12)
Medetomidine‐negative samples	2 (1–13)	2.34 (1.76)
Including trace and abundant substances
Medetomidine‐positive samples	8 (2–17)	8.24 (2.89)
Medetomidine‐negative samples	3 (1–19)	3.53 (2.92)

Note: p values for group comparisons were calculated using permutation tests (50,000 iterations) for median and mean differences. All comparisons yielded p < 0.001.

Hallucinations were reported in 17.6% of samples containing medetomidine overall (n = 24) and 25.0% of such samples with recorded sensation data, as compared with 1.2% and 2.3% in the overall dataset. Adjusting for covariates, samples containing medetomidine were significantly more likely to be associated with hallucinations compared with other samples, with an aPR of 11.95 (95% confidence interval [CI] 6.36, 22.44) (Table 4). Among covariates, selected nonpsychoactive fillers (aPR 0.41, 95% CI 0.24, 0.70) and fentanyl precursors and impurities (aPR 0.46, 95% CI 0.22, 0.96) were associated with lower prevalence of hallucinations. Hallucinations were significantly more common overall in the Northeast, South and Midwest compared with the West during the study period. Model results were robust to sensitivity analysis, though attenuated (aPR 9.11, 95% CI 4.81, 17.23) (Appendix C). In free response, participants described medetomidine‐related hallucinations as ‘intense’, ‘trippie [sic] like DMT’, ‘psychedelic’ and ‘dissociative seeming’ (Appendix D).

TABLE 4.

Adjusted prevalence ratios of hallucination reports by sample characteristics.

Covariate	aPR	95% CI
Substance(s)
Medetomidine	11.95*	(6.36, 22.44)
Fentanyl	0.78	(0.48, 1.27)
Xylazine	1.41	(0.81, 2.45)
Nonpsychoactive fillers	0.41*	(0.24, 0.70)
Local anaesthetics	1.59	(0.90, 2.79)
Other opioids	1.00	(0.56, 1.79)
Stimulants	0.76	(0.47, 1.22)
Fentanyl precursors/impurities	0.46*	(0.22, 0.96)
Number of substances	0.96	(0.90, 1.02)
Region (Ref: West)
Northeast	2.02*	(1.00, 4.08)
South	5.44*	(2.94, 10.08)
Midwest	3.87*	(1.72, 8.71)

Abbreviations: aPR, adjusted prevalence ratio; CI, confidence interval.

^* p < 0.05.

4. Discussion

In this paper we characterise the increasing presence of an emerging tranquilliser adulterant in the unregulated drug supply in multiple regions of the United States. We identified 278 samples containing medetomidine, including 136 in primary abundance. Medetomidine was found to co‐occur with multiple substances, most commonly fentanyl, 4‐ANPP (a fentanyl byproduct), xylazine, local anaesthetics (e.g., procaine) and various nonpsychoactive cuts.

Participants commonly reported that medetomidine‐containing samples induced sedation, which aligns with its pharmacodynamic profile [20]. However, reports of hallucinations—which were common in these samples but rare in the broader dataset—belie clinical expectations. Psychosis is not a documented adverse effect in the FDA labelling for Precedex [21]. In fact, dexmedetomidine may be administered perioperatively to reduce risk of postoperative delirium during cardiac and noncardiac surgery [20, 22, 23, 24, 25]. Nonetheless, the effects of dexmedetomidine on postoperative delirium remain a subject of debate, with at least one retrospective study suggesting increased, rather than decreased, postoperative risk [26]. Notably, in one case report of a woman with polysubstance use, dexmedetomidine was determined to induce delirium and agitation in an increasing dose–response manner, and symptoms only ceased after discontinuation [27].

Though our results suggest medetomidine is a likely culprit behind reported hallucinations, the mechanism is unclear given the relative absence of these effects in clinical safety profiles or the medical literature. It is possible that the side effects of unregulated medetomidine arise from the racemic mixture where clinical populations are only exposed to dexmedetomidine. Though classified as pharmacologically inactive, levomedetomidine in high doses has been demonstrated in animal studies to attenuate the sedative and analgesic effects of dexmedetomidine and enhance bradycardia [28]. It is possible that levomedetomidine may also have psychoactive side effects in humans, although the drug has not been adequately clinically evaluated. Related α2‐adrenergic agonists such as clonidine and guanfacine have been associated with hallucinations and delirium in multiple case studies and clinical trials [29, 30, 31, 32, 33, 34]. To further complicate matters, clonidine has also been successfully used to treat hallucinations in patients with schizophrenia [35, 36]. The potential for noradrenergic implication in medetomidine‐induced hallucinations is clear but certainly requires more careful study.

It is also possible that hallucinations occur only at high doses. If illicit drug suppliers are replacing xylazine or supplementing fentanyl with medetomidine, then many people who use drugs may be purchasing and ingesting supratherapeutic doses of medetomidine, perhaps in amounts that are orders of magnitude greater than clinically indicated. As opioids and α2‐adrenergic agonists exhibit cross‐tolerance to sedation, it is possible that people who use fentanyl are desensitised to sedation from medetomidine while still predisposed to other known or unknown adverse effects [37, 38]. Future studies should investigate how the pharmacology of medetomidine might contribute to hallucinogenic effects, particularly given that reports of hallucinations associated with xylazine—a pharmacologically related adulterant—were rare in our sample.

Importantly, hallucinations were not reported in most medetomidine samples, suggesting that pharmacology alone cannot explain these adverse reactions. More research would be needed to determine how various factors contribute to differential risk, including individual characteristics (e.g., neurobiological vulnerability, substance use history) and/or drug‐related factors (e.g., drug–drug interactions, route of administration).

Although medetomidine can be identified by technicians using specialised equipment (e.g., GCMS, infrared absorption spectroscopy) or by harm reduction participants using test strips, these technologies are not readily available to every person who uses drugs. Sensation data may provide a useful proxy indicator of drug adulteration in a constantly evolving unregulated supply. We found that hallucinations were reported in 17.6% of medetomidine‐containing samples but only 1.2% of samples overall. Hallucination reports could be one sentinel signal of medetomidine's introduction into local markets, just as pervasive and enduring wounds, often of the extremities, are among the first indicators of xylazine adulteration in an area [3, 39, 40]. Zibbell et al. argued for ‘sensory discernment strategies’ during the market transition from heroin to fentanyl [41]. The authors found that people who use opioids were able to discern fentanyl from heroin based on appearance, psychoactive effects (e.g., shorter time to withdrawal) and sensations (e.g., pins and needles) [41]. In the absence of drug checking technology, such inferential strategies may be necessary to keep people who use drugs educated about the potential presence of novel adulterants in local supplies.

Much remains unknown about the potential harms of medetomidine to the health of people who use drugs. Preliminary evidence suggests that bradycardia and hypertension are common sequelae of street medetomidine consumption [10], and repeated use may lead to severe withdrawal symptoms, including tachycardia, hypertension, agitation, tremor and vomiting [42, 43]. As with xylazine‐adulterated fentanyl, medetomidine‐involved overdoses and medetomidine‐induced withdrawal may present with different symptoms than those involving opioids alone. And as with xylazine, it is still unclear how responsive medetomidine will be to opioid overdose antagonists. Nonetheless, current clinical practice dictates naloxone should be administered in any suspected opioid overdose in community settings, and rescue breathing should be especially emphasised where α2‐adrenergic agonists may be involved [44]. Medical providers, first responders, harm reduction practitioners and people who use drugs should be educated about signs of medetomidine involvement, as optimal responses to overdose and/or withdrawal may differ from fentanyl and other opioids [44].

Our study has some limitations. Findings pertaining to prevalence should be interpreted with caution. Samples are submitted voluntarily, and it is possible that substances with unique appearances, tastes and/or sensations are more preferentially submitted for testing. The drug checking service also receives more samples from certain states (e.g., Washington, New York and North Carolina) than others (Appendix E); our results are not indicative of geographical trends. Sensations are presented as closed‐response options on the sample data card and are likely inexhaustive. Relatedly, hallucinations are also not defined for participants, and so the construct validity of this variable is unclear, specifically the lack of detail on visual versus auditory hallucination. However, notes on cards and common usage of the word hallucination in the context of our service users strongly favours semantic usage to mean visual hallucinations; several participants characterised reactions as visual hallucinations or psychedelic effects.

Our cross‐sectional design precludes causal inferences about the relationship between medetomidine and hallucinations. The temporal relationship between substance use and reported effects cannot be confirmed from our data, and individual factors such as tolerance, concurrent substance use or underlying medical conditions may influence the occurrence of hallucinations.

Regarding laboratory analysis, quantitative results are not available, and the threshold for primary abundance (≥ 5% peak) may have influenced results. Relatedly, our model cannot account for the dosage of drug consumed by sample donors. Finally, it cannot be inferred from GCMS alone whether positive samples contained a racemic mixture of medetomidine or its active enantiomer, dexmedetomidine. An answer to this question will be necessary to determine whether hallucinations are an under‐described sequela of dexmedetomidine administration, or whether these findings present insight into the human impacts of veterinary formulations.

5. Conclusion

In this study, we describe characteristics of a novel α2‐adrenergic agonist in the unregulated drug supply in the United States. We find that medetomidine is significantly associated with reported hallucinations, a finding at odds with clinical and pharmacological expectations. Hallucinogenic effects, along with the sedation typical of α2‐adrenergic agonists, may be unique signals of trends in local markets toward medetomidine adulteration. Resources permitting, harm reduction providers and participants should continue to use drug checking technologies to empower informed consumption decisions, and medical providers should remain alert to the presentation of medetomidine‐involved overdose and withdrawal as more is learned about this new adulterant.

Author Contributions

Each author certifies that their contribution to this work meets the standards of the International Committee of Medical Journal Editors. Adams L. Sibley: conceptualisation, methodology, formal analysis, writing – original draft. Madigan L. Bedard: conceptualisation, writing – original draft, writing – reviewing and editing. Samuel Tobias: conceptualisation, methodology, writing – reviewing and editing. Brooke A. Chidgey: conceptualisation, writing – reviewing and editing. Irina G. Phillips: conceptualisation, writing – reviewing and editing. Alice Bell: conceptualisation, writing – reviewing and editing. Nabarun Dasgupta: conceptualisation, methodology, formal analysis, data curation, writing – reviewing and editing.

Ethics Statement

This investigation was reviewed by the UNC Office of Human Research Ethics and deemed exempt from human subjects research.

Conflicts of Interest

The authors declare no conflicts of interest.

Appendix A. Sample Collection Data Card

Appendix B. Medetomidine‐Positive Samples Received by State, 11 December 2022–1 April 2025

State	Trace and primary abundance	Primary abundance only	Total samples received
New York	140	65	2058
Pennsylvania	50	34	321
North Carolina	36	14	1600
Michigan	20	7	913
Ohio	19	13	147
Florida	6	2	261
Virginia	3	1	52
Oregon	1	0	623
Colorado	1	0	589
Wisconsin	1	0	124
New Mexico	1	0	433
Total	278	136	7121

Appendix C. Sensitivity Model

Covariate	aPR	95% CI
Substance(s)
Medetomidine	9.11*	(4.81, 17.23)
Fentanyl	0.75	(0.48, 1.17)
Xylazine	1.25	(0.74, 2.10)
Nonpsychoactive fillers	0.37*	(0.21, 0.65)
Local anaesthetics	1.49	(0.87, 2.57)
Other opioids	0.96	(0.55, 1.67)
Stimulants	0.67	(0.41, 1.10)
Fentanyl precursors/impurities	0.44*	(0.21, 0.93)
Number of substances	0.95	(0.89, 1.01)
Region (Ref: West)
Northeast	1.97	(0.91, 4.28)
South	3.57*	(2.07, 6.17)
Midwest	3.10*	(1.55, 6.23)

Abbreviations: aPR, adjusted prevalence ratios; CI, confidence interval.

^* p < 0.05.

Appendix D. Free Text Sensation Descriptions in Samples With Medetomidine in Primary Abundance

1. Made dizzy and felt weird like not right for dope feelings

2. [Blank]

3. Paralysis, doesn't seem like opioid

4. Person was very tired for days, trippie like DMT; incoherent for hours. was with several peers and they all were very scared

5. Bad

6. Like being really drunk + speedy, auditory and visual hallucinations then pass out

7. Knocked out

8. Very strong

9. Lethargic, dissociative seeming, long lasting down

10. Burned when injecting, black out

11. Sleepy

12. Numb lips and hands anxiety, heart rate up, chest hurt

13. Head tingle, low blood pressure, upset diarrhoea, restless legs (body), headache

14. Dissociative, tranq

15. Felt like a bad anxiety attack

16. Weird

17. Lots of sweating

18. Less opioid, more tired, knocked out

19. Visual hallucinations then passed out quickly

20. Trippy

21. Foggy, rooted in place

22. Bad reaction

23. Tranq/hallucinate, weakness

24. After 15 min hits hard. Vivid nightmares for 8 h

25. Fainting, shortness of breath, paralysis, hearing in and out

26. Blood pressure spiked

27. Shitty

28. DK

29. High lasted 24 h., out of it, felt psychedelic

30. Head is in the dirt

31. Knocking people out

32. Odd smell, heavily sedating

33. Unusual. Hallucinations when sniffed

34. Heavy sedation, no rush

35. Stroke like symptoms

36. Nausea, dizziness, sweat, intense hallucinations. Did not feel like opiate

Appendix E. Summary of Coverage of UNC Drug Checking Services

State	Programs	Samples	Counties	Earliest sample	Latest sample
Washington	14	3946	13	17‐Nov‐22	5‐May‐25
New York	29	2058	44	27‐Jan‐22	2‐May‐25
North Carolina	43	1600	56	26‐Jan‐22	5‐May‐25
Michigan	8	913	15	11‐Oct‐22	29‐Apr‐25
California	17	800	13	9‐Jan‐23	5‐May‐25
Oregon	5	623	8	30‐Aug‐22	30‐Apr‐25
Colorado	4	589	5	19‐Jul‐23	5‐May‐25
New Mexico	6	433	11	22‐Nov‐22	5‐May‐25
Pennsylvania	9	321	10	11‐Feb‐22	22‐Apr‐25
Florida	10	261	15	7‐Jun‐23	30‐Apr‐25
Texas	7	180	13	27‐May‐22	28‐Apr‐25
Ohio	9	147	10	3‐Jan‐23	22‐Apr‐25
Tennessee	6	141	13	17‐Jul‐22	9‐May‐24
Wisconsin	6	124	8	18‐Apr‐23	28‐Apr‐25
Minnesota	1	74	4	6‐Nov‐24	2‐May‐25
Virginia	5	52	3	21‐Apr‐23	25‐Apr‐25
Maine	3	46	5	3‐Feb‐23	28‐Apr‐25
Arizona	6	44	6	18‐Jul‐22	3‐Apr‐24
Nevada	1	35	1	26‐Jan‐23	29‐Apr‐25
South Carolina	7	24	4	11‐Feb‐22	11‐Oct‐24
Indiana	2	24	5	16‐Mar‐23	24‐Jul‐24
Georgia	7	14	6	21‐Apr‐22	14‐Apr‐25
Massachusetts	4	14	4	28‐Aug‐23	15‐Nov‐24
Illinois	3	13	1	27‐Mar‐23	2‐May‐25
New Jersey	3	9	3	12‐Jun‐23	6‐Feb‐25
Missouri	1	8	1	27‐Aug‐24	10‐Mar‐25
Connecticut	1	8	2	28‐Aug‐23	7‐Nov‐24
Alabama	1	5	1	26‐Aug‐24	26‐Aug‐24
Hawaii	1	5	1	28‐Apr‐25	28‐Apr‐25
Montana	2	4	2	28‐Nov‐22	4‐Feb‐25
Delaware	1	4	1	20‐Aug‐24	22‐Aug‐24
Oklahoma	1	3	2	17‐Jul‐23	8‐Sep‐23
District of Columbia	1	2	1	1‐May‐25	2‐May‐25
Mississippi	1	2	1	23‐Apr‐23	23‐Apr‐23
Vermont	1	2	1	25‐Feb‐25	25‐Feb‐25
West Virginia	1	2	1	21‐Apr‐23	21‐Apr‐23
Kentucky	1	1	1	28‐Oct‐24	28‐Oct‐24
New Hampshire	1	1	1	19‐Feb‐25	19‐Feb‐25
Idaho	1	1	1	3‐Jan‐24	3‐Jan‐24
Louisiana	1	1	1	10‐Nov‐23	10‐Nov‐23
Rhode Island	1	1	1	21‐Apr‐23	21‐Apr‐23

Sibley A. L., Bedard M. L., Tobias S., et al., “Emergence of Medetomidine in the Unregulated Drug Supply and Its Association With Hallucinogenic Effects,” Drug and Alcohol Review 44, no. 7 (2025): 1896–1906, 10.1111/dar.70024.

Data Availability Statement

The data that support the findings of this study are available from the corresponding author upon reasonable request.