Polysubstance Use and Overdose Visualized via Maps: Opioids

Polysubstance (combinations of substances) abuse and overdose deaths now surpass mono-substance abuse and overdose deaths. Several international and governmental organizations such as the WHO (World Health Organization), CDC (Centers for Disease Control and Prevention), several of the Institutes of the NIH (National Institutes of Health), Regulators, and Enforcement Agencies, among others, track and provide a valuable source of statistical information about drug (prescription and illicit) (mis)use and overdose. The information is disseminated free to stakeholders and the general public for use. Although the numeric presentations of the data are helpful and adequate for professionals, the non-expert and the visual learner often find visual representation more clear and more compelling. With this in mind, the aim of this study was to present polysubstance use and overdose using visual maps of the available data. This article considers the opioids.

Co-Occurring Polysubstance Use and Physical Disease of Persons with Mental Disorders in Residential Treatment Program

The purpose of this study was to describe the prevalence of co-occurring polysubstance use and to examine the differences in physical disease between polysubstance users and single/no substance users with mental disorders. This retrospective cross-sectional study included 1949 clinical records of psychiatric patients from 11 residential treatment programs between 2007 and 2011. Demographic variables, psychiatric diagnoses, and data on substance use and physical disease were obtained from the clinical records. Chi-square analyses were used to examine substance use difference in the prevalence of each physical disease category. This study found that the prevalence of co-occurring polysubstance use was 53.5%. Chi-square analyses identified that co-occurring polysubstance users reported more respiratory, digestive, musculoskeletal, and HIV/AIDS diseases but less endocrine diseases than single/no substance users. Therefore, integrated treatment programs for treating patients with co-occurring substance use and physical disease should be developed and expanded for this high-risk group.

Polysubstance Use and Overdose Visualized via Maps: Amphetamines and Cocaine

Abuse of drug substances and resultant overdose deaths are no longer very straightforward—viz., attributable to a single chemical entity of known purity. The reality is that most overdose deaths involve polysubstance use (i.e., the use of combinations of substances). Further, the combinations are often of unknown purity, and even of unknown composition. Overdose deaths are at all-time highs. The depressing statistics are monitored and reported by several international and governmental organizations such as the WHO (World Health Organization), CDC (Centers for Disease Control and Prevention), several Institutes of the NIH (National Institutes of Health), Regulators, and Enforcement Agencies (e.g., DEA). The information is disseminated for free for review and use. But it is our observation that although numeric presentation is helpful and adequate for professionals, the non-expert and the visual learner often find a visual representation clearer and compelling. With this in mind, we present the “gestalt” of polysubstance use and overdose using available maps of the data. The previous article in the series considered the opioids. This one considers amphetamines and cocaine, and places the rise in opioid-associated overdose deaths in the context of other abused drugs.

Commentary: “Ockham’s Razor” Doesn’t Apply to “Opioid” Overdose Death

Polysubstance Abuse (PSA) greatly complicates an attempt to implicate a single drug as sole cause of an overdose death. Since PSA now occurs in the majority of cases of drug overdoses, many or most overdose deaths are polysubstance overdose deaths. And since many of the substances involved in a polysubstance Overdose Death (POD) are Central Nervous System (CNS) depressants, many of which can cause overdose death themselves, or synergistically with opioids, it is somewhat puzzling that prescription opioids have been singled out as the cause of these deaths—without reference to PSA. This is particularly puzzling in light of the fact that the issues of PSA and POD have been recognized and discussed in the literature since at least the 1960’s and before. We therefore here consider the question: are we facing an “opioid” crisis or, instead, a “polysubstance crisis”? And we wonder if the issue has been over-simplified, to the detriment of the individuals affected, and to society more broadly. There is a need for an “agnostic” respiratory stimulant that can reverse polysubstance-induced respiratory depression.

Using Umbilical Cord Tissue to Identify Prenatal Exposure to Fentanyl and Other Commonly Abused Drugs

Background: Prenatal exposure to fentanyl may lead to Neonatal Abstinence Syndrome (NAS), a constellation of symptoms observed when newborns begin withdrawing from addictive substances such as opioids. The use of umbilical cord tissue segments (UC) for newborn toxicology has been increasing due to its apparent long detection window, sensitivity, and ease of collection. However, very little has been reported in the literature concerning the prevalence of in utero exposure to fentanyl and co-exposure with other commonly abused substances. Specific aim: The specific aims of this retrospective study are twofold. We will report prevalence of neonatal exposure to fentanyl for a nationwide high-risk population using UC submitted to a national reference laboratory for routine forensic toxicology analysis and the co-exposure patterns observed for these fentanyl-exposed neonates. Methods: A secondary analysis was performed using historical data for UC received between January 1, 2020 and December 31, 2020 for routine forensic toxicology analysis. Results: During the study period, our laboratory received 23,104 UC for analysis and 9667 (41.8%) of those UC were positive for at least one drug. The prevalence of fentanyl detection was 1.9% (n = 429). Of these 429 specimens there were 407 UC where both fentanyl and norfentanyl were detected. There were 14 UC where only fentanyl was detected and 8 UC where only norfentanyl was detected. When detected, the median concentrations of fentanyl and norfentanyl were 4029 pg/g (IQR: 1696, 9230 pg/g) and 10,756 pg/mg (IQR: 3925, 25,288 pg/g), respectively. Of the 429 positive fentanyl and/or norfentanyl UC, 33 (7.7%) were only positive for fentanyl and/or norfentanyl. Of the 396 polypositive UC, morphine was the highest co-exposure with 243 UC (56.6%) being positive for both fentanyls and morphine. The second most prevalent co-exposure observed was methamphetamine/amphetamine (n = 173;40.3%) followed by cannabinoids (n = 113;26.3%) and benzoylecgonine (cocaine metabolite;n = 106;24.7%). Conclusions: Nonmedical use of fentanyl is an alarming trend in this country including this maternal demographic reported here. Fentanyl was typically found with other commonly abused substances.

Commentary: New Complications Make Treatment of “Opioid” Overdose Challenging

The “opioid crisis” has had a tremendous impact not only on its victims, but also on the practice of medicine, pain patients, and society in general. Unfortunately, efforts to “stem the tide” have not been successful at reducing overdose deaths. Counterbalancing the many ardent efforts to eliminate overdose deaths (such as the current widespread availability and use of opioid-receptor antagonists such as naloxone) is influx of the illicit fentanoids (i.e., fentanyl and analogs). In addition to their high-potency, the fentanoids differ in surprising ways from more “traditional” opioids such as morphine and heroin. This uniqueness contributes to a reduced effectiveness of opioid receptor antagonists in the treatment of opioid overdose. Further greatly complicating overdose treatment is polysubstance abuse (e.g., an opioid plus a benzodiazepine). The non-opioid in the combination is not responsive to an opioid-recep- tor antagonist, which imparts additional challenges. Thus, the new reality introduces complications that negatively impact efforts to reverse “opioid” overdose. New approaches to improve outcomes in individuals who experience respiratory depression due to fentanoid-induced or polysubstance-induced over- dose are needed. Approaches that harmonize with the new reality, perhaps something like a non-opioid “agnostic” pharmacologic ventilatory stimulant, would provide a welcome addition to the current choices.

Fatal Overdoses Involving Carfentanil:A Case Series

Carfentanil,an ultrapotent analog of fentanyl,has invaded the street drug market,unbeknownst to many heroin users.About 10,000 times more potent than morphine,it was initially suspected that 20μg of the substance was lethal.In this case series,we present 17 confirmed carfentanil overdoses in Michigan,with a primary focus on the concentration levels.Through a retrospective review,each public death reported in Oakland County,Michigan,with a subsequent toxicology report was investigated for suspected carfentanil use.To characterize each fatality,the autopsy results were collected,including the postmortem findings at scene and the decedent’s medical and social history.Carfentanil levels were measured through liquid chromatography and tandem mass spectrometry(LC-MS-MS)by National Medical Services(NMS)Laboratories.Our case series found postmortem carfentanil concentrations as low as 10 ng/mL,with a mean concentration of 0.387 ng/mL.Ultimately,there are implications on law enforcement,first responders,and health care providers when dealing with this emerging illicit substance,and there is an alarmingly high mortality rate associated with the abuse of carfentanil.