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Published in final edited form as: Drug Alcohol Depend. 2024 Aug 13;263:112402. doi: 10.1016/j.drugalcdep.2024.112402

Monitoring illicit pentobarbital availability in the United States: A National Drug Early Warning System briefing

Joseph J Palamar a,*, Nicole D Fitzgerald b, Bruce A Goldberger c, Linda B Cottler d
PMCID: PMC11384643  NIHMSID: NIHMS2018228  PMID: 39173219

Abstract

Background:

Pentobarbital is a Schedule II/III short-acting barbiturate with limited medical use in humans. Veterinary professionals use pentobarbital to euthanize dogs, cats, and other companion animals. Pentobarbital is also utilized in capital punishment and small amounts are illegally shipped or diverted to assist in suicides. However, five kilograms of pentobarbital smuggled in from Mexico was recently seized by an organized crime drug enforcement task force (along with fentanyl, heroin, and cocaine), which may suggest a shift in illicit supply. We investigated potential indicators of illicit pentobarbital use or availability in the US to help determine whether this drug is becoming an emerging public health concern.

Methods:

The National Drug Early Warning System requested information on pentobarbital from its sentinel surveillance sites and collaborators and conducted a search of current literature.

Results:

In early 2024, multiple batches of counterfeit pills (e.g., pressed as “M30s” to represent oxycodone) confiscated near the Southwest border tested positive for pentobarbital plus combinations of fentanyl, fentanyl analogs, and xylazine. Other indicators suggest pentobarbital is being smuggled in powder form and possibly sold as another drug such as heroin. One national drug analysis program detected pentobarbital in 217 drug submissions from 2020 to 2023, and there were at least 12 fatal exposures linked to use from 2020 to 2022.

Conclusion:

Continued monitoring of illicit use and availability is needed as pentobarbital may continue to appear on the illicit market. Unknown exposure can occur if the drug is mixed into counterfeit pills or sold in powder form represented to be another drug.

Keywords: Pentobarbital, Barbiturates, Fentanyl, Drug adulteration, Drug surveillance

1. Introduction

Pentobarbital is a Schedule II/III potent and short-acting barbiturate. Its modern-day use in humans is limited to the treatment of persistent intracranial hypertension in intensive care units, although its use has been replaced by other more effective and safer drugs (Johnson and Sadiq, 2024). Pentobarbital is commonly used by veterinarians to euthanize dogs, cats, and other companion animals, and it is used in the US in an off-label manner including its use in capital punishment in some states (Death Penalty Information Center, 2024; Tanne, 2019). While some reports have focused on illicit pentobarbital use, primarily as a suicide aid (Cantrell et al., 2010; Solbeck et al., 2019; Waitz-Kudla et al., 2023; Witte et al., 2019), little is known regarding current illicit availability or use of this drug in the US.

Pentobarbital was originally marketed for human use in the US under the trade name Nembutal®. It was first synthesized by Abbott Laboratories in 1930 and was used for the treatment of insomnia, preoperative sedation, and emergency management of seizures (López-Muñoz et al., 2005). Its short-acting effects, however, include respiratory depression, bradycardia, hypotension, and syncope, and overdose can lead to compromised breathing, coma, and death (Johnson and Sadiq, 2024). Like other barbiturates such as phenobarbital, pentobarbital has a long history of misuse. By the mid-19th century, this class of drugs became widely overprescribed, diverted, and misused, and use was associated with nonfatal and fatal overdose (including suicides) (Barbiturate Abuse in the United States, 1973). In fact, in New York, there were at least 1165 deaths linked to barbiturate use between 1957 and 1963 (López-Muñoz et al., 2005). In 1971, there were at least 1082 barbiturate-related deaths in California (with 898 in Los Angeles County), accounting for 57 % of drug-related deaths (Barbiturate Abuse in the United States, 1973). Due to high risk of mortality among people who use, barbiturates such as pentobarbital have largely been replaced by benzodiazepines, which are perceived to be safer (Kripke, 2016). In recent years, barbiturate misuse has become less of a focus and has been omitted from many surveys, reducing our knowledge of their use.

On April 1, 2024, the US Drug Enforcement Administration (DEA) published a press release announcing a 50-count indictment of individuals involved in a drug smuggling ring (US DEA, 2024a). Specifically, from December 2018 through April 2020, the individuals allegedly operated in southern Texas and distributed drugs that were smuggled in from Mexico, with drugs distributed in multiple states including Texas, Louisiana, Florida, Georgia, Tennessee, Illinois, California, Colorado, and Washington. Among large quantities of fentanyl, cocaine, and heroin seized by the organized crime drug enforcement task force, five kilograms of pentobarbital were also seized (US DEA, 2024a). It was further reported that the pentobarbital was sold as heroin (Rowland, 2024). After the publication of the press release, we at the National Drug Early Warning System (NDEWS) were contacted by a reporter who asked about the illicit pentobarbital situation in the US. In response to this request, we investigated potential indicators of illicit pentobarbital use and availability in the US to help determine whether this drug may represent an emerging public health concern.

2. Methods

NDEWS monitors novel drug trends in the US with a particular focus on new psychoactive substances (Cottler et al., 2020). We aim not only to rapidly detect signals of new drug trends, but also to rapidly disseminate information regarding these signals to inform public health response. We oversee various initiatives, including an early warning network which currently includes 16 sentinel sites representing various cities and states throughout the US. Sentinel site directors are typically department of health employees, research professors, or law enforcement officials with access to relatively rapid information regarding emerging drug trends. We also work closely with various organizations including the National Survivors Union, NPS Discovery at the Center for Forensic Science Research & Education (CFSRE), and the High Intensity Drug Trafficking Areas (HIDTA) program, with some of their directors or leading representatives serving on our Scientific Advisory Group.

In response to the reporter’s request about illicit pentobarbital use in the US, we conducted a rapid review of potential indicators of illicit pentobarbital use and availability, including queries to our early warning network, a review of the current literature, and a review of existing data (Fig. 1). This process is modeled in part after the European Monitoring Centre for Drugs and Drug Addiction’s (EMCDDA) trendspotter study methodology, which is intended to complement traditional monitoring approaches by mapping and describing new or emerging drug trends (EMCDDA, 2018). Queries to our early warning network included a survey sent to our sentinel site directors, collaborators at CFSRE and HIDTA, and the National Survivors Union, which is a national grassroots coalition of people with lived drug experience. The following week in our Weekly Briefing email newsletter (https://ndews.org/publications/ndews-weekly-briefings), we also asked our subscribers (currently over 4700) if they were aware of illicit pentobarbital use in their area. In addition to contacting experts in our network, we also requested additional information on the seizure mentioned in the initial press release from the public relations contact (by telephone, as no other means of contact was provided), and we submitted Freedom of Information Act (FOIA) requests to the US DEA and to US Customs and Border Protection (CBP). Specifically, on April 30, 2024, we submitted a FOIA to CBP requesting a list of CBP seizures of pentobarbital from 2020 through 2024, including the date, port/city/state and number of grams/kilograms seized. A FOIA request was also sent to the DEA on May 6, 2024, requesting the number of recorded instances of prescription pentobarbital diversion within the same time period.

Fig. 1.

Fig. 1.

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NDEWS procedure to rapidly collect data on pentobarbital.

We conducted reviews of the current published literature and existing datasets from systems known to monitor drug use and/or drug exposure trends, focused on pentobarbital use/exposures in the US from 2020 through 2024. A list of sources is included in Fig. 1, and although this was not a formal systematic review, we followed many recommendations included in the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Searches were conducted within PubMed using the terms “pentobarbital and overdose”, “pentobarbital and death”, “pentobarbital and suicide”, “pentobarbital and poisoning”, “pentobarbital and misuse”, “pentobarbital and abuse”, “pentobarbital and heroin”, “pentobarbital and fentanyl”, “pentobarbital and seizure”, “pentobarbital and DEA”, “pentobarbital and CBP”. These terms were repeated using the term “Nembutal” instead of “pentobarbital”. While relevant reports of any age were of interest (e.g., to inform us about the history of use), to qualify for our surveillance analysis, results had to be from the US, published in English, and published within 2020–2024. We focused on the epidemiology of use and exposures rather than medical use. We also conducted similar searches in Google News for pentobarbital-related news media and press releases from 2020–2024.

Existing datasets included in this review consisted of annual and/or quarterly reports published between 2020 and 2024 from the National Poison Data System (NPDS), which collects data on poisonings reported by individuals or medical staff (Gummin et al., 2021, 2022, 2023); the Toxicology Investigators Consortium (ToxIC), which collects data from participating sites and provides toxicology consultations for healthcare facilities (Amaducci et al., 2023; Love et al., 2022; Spyres et al., 2021); and the DEA Toxicology Testing Program (DEA TOX), which tests the contents drugs submitted to their program (US DEA, 2023). With respect to national survey data, we focused on reports from Monitoring the Future (MTF) (which focuses on drug use among high school seniors) (Miech et al., 2023b) and the National Survey on Drug Use and Health (NSDUH) (which is a survey of noninstitutionalized individuals ages ≥12) (Substance Abuse and Mental Health Services Administration, 2023). In addition to data summarized in published reports, we requested information on pentobarbital seizures from HIDTA, which collects data on law enforcement seizures throughout all US states, and we used the new DEA National Forensic Laboratory Information System (NFLIS) public data query system (NFLIS, 2024) to search for (unweighted) count data regarding the number of submissions testing positive for pentobarbital in 2020–2023 at the national and state level.

All searches were conducted between April and July 2024 by two authors, and relevant search results were compared and summarized. This analysis related only to published data and reports from NDEWS affiliates and sentinel site directors and did not involve newly collected data. As such, this research was exempt from review from the University of Florida institutional review board.

3. Results

With respect to our sentinel site network, all 16 sites replied and five were able to provide information regarding trends in illicit use. Our Texas sentinel site director provided details regarding recent pentobarbital seizures. Specifically, information was provided regarding pills seized in Texas that were pressed as counterfeit oxycodone or alprazolam and found to contain various barbiturates—not only pentobarbital, but also phenobarbital and butalbital. In early February, a pill pressed to represent an “M30” (counterfeit oxycodone) pill was found to contain fentanyl, pentobarbital, xylazine, and acetaminophen. Relatedly, our colleague from CFSRE sent us their recent report, published in February 2024, regarding the contents of six exhibits of 40 counterfeit “M30” oxycodone pills seized at the Southwest border (CFSRE, 2024). Of the 40 total seized counterfeit pills, pentobarbital was detected in 16 pills from two distinct exhibits, in addition to fentanyl, para-fluorofentanyl, xylazine, metamizole, acetaminophen, and an assortment of fentanyl and para-fluorofentanyl synthesis precursors.

Our site director in Kentucky reported that between 2021 and mid-2024, there was at least one pentobarbital-related death, but data use restrictions do not allow them to report specific numbers when there are fewer than five cases. Our San Diego site director reported that there were three pentobarbital-related suicides between January 2022 and May 2024. Our site director of Duluth, Minnesota reported that there was one pentobarbital-involved death in 2018, three in 2019, and two in 2020, and he noted that there have been no detections through their biosurveillance program, possibly due to its absence in their testing panel. Our Chicago site director informed us of a recent federal indictment in Chicago charging a Mexican individual with importing pentobarbital into the US to serve as a suicide drug (US Attorney’s Office, Northern District of Illinois, 2024). Specifically, in May 2024, an individual was charged with operating an online drug business to facilitate the sale and distribution of pentobarbital in the US to individuals seeking to commit suicide (US District Court, Northern District of Illinois, Eastern Division, 2016, 2024). Legal documents note that Western Union records suggest that the individual possibly sold the drug to dozens of people between 2013 and 2016, and deaths of multiple buyers were linked to use of this product, including deaths in Illinois and California. Our connection at the National Survivor’s Union suggested that a related organization in Texas found that people purchase pentobarbital illegally online or on the dark web.

The US DEA provided us with the requested data on pentobarbital diversions. Between 2020 and 2023, there were 259 thefts or other types of losses reported to the US DEA, with a total of 68,485 mL reportedly diverted. Specifically, 30.9% (n=80) of diversions were reported thefts (e.g., employee theft, burglary), while 69.1% (n=179) were other types of losses (e.g., lost in transit). The majority of diversion was from practitioners (52.9%, n=137), followed by diversion from distributors (37.1%, n=96). Table 1 presents a breakdown of reported diversions by business type and loss type. In particular, practitioners had the highest level of loss via theft (51.8%), with employee theft (or suspected employee theft) and break-in/burglary being the most commonly reported types of theft. CBP did not provide us data per our FOIA request by the time of publication, for information on pentobarbital seizures, and the DEA press office did not respond to our questions regarding formulation of the drug seized, whether it was a single seizure or multiple, or whether it was sold as heroin as mentioned in a media report.

Table 1.

Nationwide thefts and other losses of pentobarbital reported to the US Drug Enforcement Administration by business and loss type, 2020–2023 (n=259 diversions).

Business Loss type Frequency % of
total
Practitioners Total thefts/other losses 137 52.9
Total thefts 71 (51.8%)
Employee theft (or suspected) 38
Break-in/burglary 24
Robbery 6
Customer theft (or non-employee) 2
Hijacking of transport vehicle 1
Total other losses 66 (48.2%)
Disaster (e.g., fire, weather) 25
Lost in transit 22
Packaging discrepancy 19
Distributors Total thefts/other losses 96 37.1
Total thefts 0 (0.0%)
Total other losses 96 (100.0%)
Lost in transit 68
Packaging discrepancy 28
Reverse distributors Total thefts/other losses 11 4.2
Total thefts 3
Customer theft (or non-employee) 3
Total other losses 8
Packaging discrepancy 5
Lost in transit 3
Researchers Total thefts/other losses 7 2.7
Total thefts 1 (14.3%)
Employee theft (or suspected) 1
Total other losses 6 (85.7%)
Lost in transit 4
Disaster (e.g., fire, weather) 1
Packaging discrepancy 1
Mid-level practitioners Total thefts/other losses 4 1.5
Total thefts 2 (50.0%)
Employee theft (or suspected) 1
Break-in/burglary 1
Total other losses 2 (50.0%)
Disaster (e.g., fire, weather) 2
Hospitals Total thefts/other losses 4 1.5
Total thefts 3 (75.0%)
Employee theft (or suspected) 3
Total other losses 1 (25.0%)
Lost in transit 1
Exporters Total thefts/losses 0 0.0
Teaching institutions Total thefts/losses 0 0.0
Pharmacies Total thefts/losses 0 0.0
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Our review of the current published peer-reviewed literature from 2020 through July 2024 yielded 102 PubMed results, of which 95 were unrelated to the epidemiology of pentobarbital use and/or exposures. Among the seven articles of interest, six involved cases outside of the US (four in Japan, two in Australia) and were thus excluded. The single remaining report was a case study of an elderly woman in Florida who overdosed after taking pentobarbital and secobarbital (with no reason for use reported) (Katz et al., 2021). A search of Google News for media reports related to pentobarbital published between 2020 and 2024 identified 56 deduplicated results, five of which were published outside of the US. Forty-two articles were related to pentobarbital’s use for capital punishment in several US states, while six articles involved its use in veterinary settings for euthanasia, including four published in 2021 describing a widespread shortage affecting veterinarians. Three articles published in June 2024 concerned the recent federal indictment in Chicago described by our Chicago site director. Additionally, through collaboration with the reporter who initially asked us about pentobarbital use, we were also directed to a well-publicized case in 2019 in which someone smuggling purported fentanyl off the coast of Oregon ingested pentobarbital and experienced a nonfatal overdose (United States Attorney’s Office: District of Oregon, 2020), which was unsuccessfully reversed with naloxone (United States v. Stirling, 2020). The substance he ingested was later determined to be pentobarbital, and his vessel was found to contain plastic-wrapped bricks of pentobarbital along with more than seven gallons of liquid methamphetamine (United States Attorney’s Office: District of Oregon, 2020).

We also reviewed existing data published by systems known to monitor drug use and/or drug exposure trends in the US between 2020 and 2024. Annual NPDS reports, which describe many fatal drug exposures (poisonings) reported to poison centers, reported on 12 fatal pentobarbital exposures in 2020–2022, with five in 2020, three in 2021, and four in 2022 (Gummin et al., 2021, 2022, 2023). Of the 12 reported fatal exposures, eight were reported as suspected suicides, two as adverse reactions, and two for unknown reasons; the ages of patients ranged from 26 to 91 years, and several cases involved other substances present in addition to pentobarbital (three involving benzodiazepines, two involving prescription opioids, and one involving amphetamine). The annual ToxIC Registry reports suggest that in 2020–2022, 20 cases involving barbiturate exposure were reported (five in 2020, five in 2021, and ten in 2022), although pentobarbital data are collapsed with data from other barbiturates such as butabarbital, butalbital, and phenobarbital (Amaducci et al., 2023; Love et al., 2022; Spyres et al., 2021). Pentobarbital was not noted in any DEA TOX quarterly or annual reports published between 2020 and 2024. With respect to national survey data on the prevalence of drug use in the US, MTF reported that in 2023, past-year prevalence of reported use of “sedatives (barbiturates)” reached a historic low of 1.5% (Miech et al., 2024), with estimated use in 2020, 2021, and 2022 being 2.4%, 1.8%, and 2.0%, respectively. However, as discussed more below, this category included example drugs from benzodiazepine and Z-drug classes, which likely influenced these estimates of use. NSDUH no longer queries nonmedical pentobarbital/Nembutal use, and there were fewer than five type-in mentions of lifetime use of pentobarbital in 2020–2022 (Center for Behavioral Health Statistics and Quality [CBHSQ], 2021, 2022, 2023).

Finally, regarding illicit availability, NFLIS drug submission data suggest that in 2020–2023, 217 drug submissions tested positive for pentobarbital—72 in 2020, 65 in 2021, 61 in 2022, and 19 in 2023. In 2020–2023, submissions from 29 states tested positive for pentobarbital. Ohio had the highest number of submissions (n=36), followed by Florida (n=23) and California (n=17). According to HIDTA, there have been 18 law enforcement seizures of pentobarbital recorded since 2010, and one was recorded in 2013 (reported to contain 60 dosing units) and one in early 2024 (reported to contain 259 dosing units).

4. Discussion

We at NDEWS have established a potential signal that illicit pentobarbital availability has begun to expand in the US, and through this report, we summarize the most relevant literature and present the most up-to-date information regarding illicit use and availability. While the five kilograms of pentobarbital seized that led to this research is relatively small compared to the amount of other drugs commonly seized in the US (Palamar et al., 2021, 2022), we discovered some important information about current illicit use and availability this drug. Pentobarbital may be present as an adulterant in or replacement for another drug, which can lead to unintentional exposure. For example, there was the well-publicized incident of a smuggler using the drug thinking it was fentanyl and then overdosing (United States Attorney’s Office: District of Oregon, 2020). While naloxone is now widely used to reverse fentanyl overdoses, the naloxone administered was unsuccessful in reversing this overdose (although the individual did survive) (United States v. Stirling, 2020). This is also alarming as the drug may be sold as other drugs such as heroin (Rowland, 2024). Further, in early 2024, some batches of counterfeit “M30” pills were found to contain a mixture of pentobarbital, fentanyl and its analogs, and sometimes other drugs such as xylazine (CFSRE, 2024). Unintentional exposure to pentobarbital through adulteration of other drug products can be dangerous to consumers, particularly when these products contain other substances such as fentanyl that can also potentially depress respiration. Although it may be unlikely that a counterfeit pill will contain a full gram of pentobarbital (which is considered a toxic dose for an adult), death has been found to occur after use of 2–10 g (Johnson and Sadiq, 2024). It is possible to be rapidly unintentionally exposed to a gram or more especially if sniffed in powder form or if multiple counterfeit pills containing the drug are taken.

Annual publications from toxicology networks such as NPDS and ToxIC suggest that exposures (particularly that lead to hospitalization or death) appear to be rare. However, it is unknown to what extent people have been unknowingly exposed and did not experience a severe outcome or hospitalization. Statistics based on medical examiner and coroner data are also lacking, although there have been some studies focusing on cases of suicides involving use of pentobarbital (Cantrell et al., 2010; Solbeck et al., 2019; Waitz-Kudla et al., 2023; Witte et al., 2019). A recent study noted increases in suicides involving use of this drug between 2011 and 2016 based on a review of medical examiner data (Cantrell and McIntyre, 2017). An investigation of suicide scenes in Canada found that there is often evidence of receipt of the drug via mail order or internet purchase, often from Mexico or China (Solbeck et al., 2019). Drugs investigated from suicide scenes are typically in liquid form (in vials) or in the form of white powder. Vials are typically from Mexico (with labels printed in Spanish), with brand names such as Sedalphorte and Pisabental. White powders are often intentionally mislabeled as “potassium formate” or “fumaric acid” on the package and/or on the customs paperwork.

In addition to illegal importation of the drug, veterinary clinics have been documented as another source of access to pentobarbital for illicit use. Euthasol® is a common trade name, but other brands such as Fatal-Plus® and Sleepaway® are also carried by many veterinary clinics to anesthetize or euthanize animals (Crellin and Katz, 2016). A recent analysis of distribution of controlled substances to veterinary teaching institutions found that pentobarbital was the most available controlled substance by weight, with the total weight of pentobarbital distribution peaking in 2011 at 69.4kg (Piper et al., 2020). However, there was a reported shortage of pentobarbital for veterinarians in the US and Canada in 2021 (Cooney and Titcombe, 2022). Perhaps in response to requests from manufacturers, controlled availability of pentobarbital, which is overseen by the US DEA, recently increased (US DEA, 2024b). In 2024, pentobarbital now has the fourth-highest established production quota for a Schedule II drug (40.0 M grams), after oxycodone (53.7M grams), thebaine (57.1M grams), and methylphenidate (53.3M grams). Although the production quota has increased, as noted, some pentobarbital has been found to be diverted to be used for suicide (Crellin and Katz, 2016; Witte et al., 2019). The US DEA requires clinics to immediately report thefts of the drug (US DEA, 2022b), and through our FOIA request, we learned that there have been 259 thefts or other types of losses of pentobarbital reported to the US DEA between 2020 and 2023. Slightly below a third (30.9%) of diversions were reported thefts (e.g., employee theft, burglary), while the majority (69.1%) were other types of losses (e.g., lost in transit). The majority of diversion was from practitioners, and, within this business type, the majority of diversion (51.8%) was via theft—driven by employee theft and burglary. While we did not receive data regarding type of practice (e.g., veterinary), a small study of veterinarians recently found that 30% of those interviewed leave their pentobarbital unlocked at least part of the time (Waitz-Kudla et al., 2023). Theft is likely of greatest concern, as theft may suggest diversion for misuse; it is unknown how other types of losses (e.g., pentobarbital lost in transit) affect illicit availability of the drug.

While there is a lack of information on diversion of pentobarbital products from clinics, drug seizure data help inform us regarding possible availability on the illicit market. Only two seizures of the drug have been reported to HIDTA since early 2023. However, drugs seized by HIDTA-affiliated agencies typically do not extensively test drugs seized so it is possible that pentobarbital was seized but mixed in with more common drugs such as heroin. There were 214 drug submissions to NFLIS in 2020–2023 which tested positive for the drug, and Ohio had the highest number of submissions, followed by Florida and California. However, there are no publicly available data regarding the weight or form of the drug (e.g., liquid vs. powder).

With respect to self-report, there is currently a major lack of survey data focusing on pentobarbital or on barbiturates in general, but given the decline in nonmedical availability and barbiturate use in recent decades, it is understandable that major surveys no longer query use. For example, through 2014, NSDUH asked about overall nonmedical barbiturate use and included Nembutal, Pentobarbital, Seconal, Secobarbital, and Butalbital as examples (CBHSQ, 2015), but beginning in 2015, NSDUH stopped asking about barbiturates and instead began focusing more on benzodiazepines and Z-drugs (CBHSQ, 2017). There is still a type-in option for lifetime use of drugs not specifically queried but such open-ended responses have been found to lead to severe underreporting of use (Palamar et al., 2015). MTF estimated that 1.5% of high school seniors used “sedatives (barbiturates)” in 2023 (Miech et al., 2024). However, MTF’s definition of barbiturates (which varies across its six different survey forms) has changed over the years—especially since the early 2000s. MTF used to ask solely about barbiturates and list examples of ‘street’ names such as “downs”, “downers”, “goofballs”, “yellows”, “reds”, “blues”, and “rainbows” (Johnston et al., 2001) (with “yellows” or “yellow jackets” a common ‘street’ name for yellow Nembutal capsules (US DEA, 2022a)), but over time the survey instead asked about “sedatives including barbiturates”, and ‘street’ terms were replaced with various combinations of barbiturate names and brands (e. g., phenobarbital, Tuinal, Nembutal, and Seconal) and combinations of names of benzodiazepines and Z-drugs including Dalmane, Seconal, Ambien, Lunesta, Sonata, Restoril, Halcion, Intermezzo, and Zolpimis (Miech et al., 2023a). As such, current and recent prevalence likely refers more to non-barbiturate drugs, and overreporting, especially in more recent years, is also a possibility. Considering shifts in the definition of barbiturates, prevalence of nonmedical barbiturate use among high school seniors was highest (16%) in 1976 and dropped to 3% in 1992 and remained low thereafter (Miech et al., 2023b).

4.1. Limitations

Aside from the limitations discussed above, it should be noted that pentobarbital involvement in poisonings may be underreported or under-detected since laboratory testing in the hospital does not universally include barbiturates. More specific testing in hospitals is required to assess exposure to pentobarbital. Also, there is a lack of data on thefts of pentobarbital-containing products (e.g., from veterinary clinics) and there are no publicly available data from the US Centers for Disease Control and Prevention (CDC) on pentobarbital-related mortality. Much of the overdose and mortality-related information we were able to access was based on published case studies in which the drug was found to be linked to suicide.

4.2. Conclusions

Recent seizures of powders and pills containing pentobarbital may serve as an early warning signal of increased prevalence of pentobarbital in the illicit drug supply, complicating overdose risk mitigation for people who use drugs, overdose prevention efforts, and responses from medical providers. Pentobarbital mixed with or sold as other drugs such as heroin or fentanyl can place people who use at particular risk. With respect to drug checking, pentobarbital test strips are available singly or in combination with other drugs detection tests. The strips can be incorporated into current field-testing modalities if pentobarbital adulteration becomes widespread. In addition, a subset of CDC Overdose Data to Action (OD2A): LOCAL jurisdictions implemented a new drug product and paraphernalia checking program strategy in 2023 (US Centers for Disease Control and Prevention, 2024). While point-of-care Fourier transform infrared spectroscopy (FTIR) analysis is an effective tool for the identification of pentobarbital in the field, laboratory-based tests utilizing gas chromatography-mass spectrometry and liquid chromatography-mass spectrometry are preferred. Revisiting use of this drug should be considered including improved testing for barbiturates such as pentobarbital in clinical, forensic, and law enforcement settings to inform national data.

Acknowledgments

J. Palamar is funded by the National Institutes of Health (NIH) (R01DA057289), as is L. Cottler (U01DA051126). N. Fitzgerald is a T32 postdoc through T32DA031099.

Role of funding source

Research reported in this publication was supported by the National Institute on Drug Abuse of the National Institutes of Health under Award Numbers U01DA051126, R01DA057289, and T32DA031099. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. We would also like to thank the following individuals from our NDEWS network: Sarah Howell, Brett Rowland, Alex Krotulski, Thomas Carr, Caty Simon (and the rest of the National Survivors Union), Dayong Lee, Matthew Myers, Caleb Banta-Green, Devika Bhatia, Phillip Coffin, Dana Quesinberry, Ellenie Tuazon, Alexandra Harocopos, Annick Borquez, Mary Mackesy-Amiti, Heidi Israel, Lee Hoffer, Mary-Lynn Brecht, Lisa Wiederlight, James Cunningham, and Nate Wright.

Footnotes

CRediT authorship contribution statement

Joseph J. Palamar: Writing – review & editing, Writing – original draft, Visualization, Software, Investigation, Funding acquisition, Formal analysis, Data curation, Conceptualization. Nicole D. Fitzgerald: Writing – review & editing, Writing – original draft, Investigation, Formal analysis, Data curation. Bruce A. Goldberger: Writing – review & editing, Writing – original draft, Investigation. Linda B. Cottler: Writing – review & editing, Writing – original draft, Investigation.

Declaration of Competing Interest

J. Palamar has consulted for the Washington-Baltimore High Intensity Drug Trafficking Area program. The authors have no other potential conflicts to declare.

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