Polydrug Research Articles

Special Needs in Substance Use Treatment for Women Who Use Drugs: Social and Mental Health Factors

Women who receive substance use treatment have a particular classification of sensitivity to European drugs and drug use (according to the EMCDDA). The average level of women’s treatment is lower than men’s across Europe, while women’s abandonment is higher than men’s. The purpose of this study was to examine the factors associated with problems for women who use drugs, analyzing several psychological and social factors (gender, substance use, mental health, source of economic support, legal status, and abuse). Methodology: This was a quantitative study. Data on 2179 people receiving rehabilitation treatment were obtained from the EuropASI survey. The dependent variables in this study were (1) a patient’s known history of addiction and mental illness; (2) primary drug use; (3) drug use in their lifetime and the past month; (4) mood in their lifetime and the past month, physical condition, and sexual abuse history; (5) mental illness in their lifetime and the past month (including suicide attempts); (6) legal status in their lifetime and the past month; (7) and source of income in the past month and (8) and the number of patients. The factor of gender was taken as a dichotomous variable (male–female). The confidence interval used was 95%. Results: In summary, we found that women had consumed more alcohol, used more drugs, and suffered more from depression, anxiety, and suicidal ideation than men, both during their lifetimes and in the past month. In addition, women were more likely than men to be stigmatized for prostitution because their financial support came mainly from colleagues, friends, and family, as well as from prostitution. Finally, women had experienced more violence (emotional, physical, and sexual) during their lifetimes and in the last month than men. Conclusion: There appears to be a need to develop a comprehensive treatment network for addictive behaviors from a multifactorial perspective, including harm reduction, psychosocial support, and recovery programs; furthermore, targeting specific groups with special needs, such as women, especially those with mental health problems, women with alcoholism, and abused women, it also seems important to develop adaptive recovery programs within addictive behavior treatment networks.

Anxiety and Affective Symptoms Related to the Use of Classic Psychedelics: A Systematic Review.

There is a large and rapidly growing body of literature investigating the therapeutic effects of classic psychedelics in affective and anxiety disorders, but very few studies have examined the inverse of this, that is, the potential for psychedelics to inflict anxiety and affective symptoms. A systematic literature search was performed and 39 papers were included in the final review to qualitatively synthesize the current literature on anxiety and affective disorders related to the use of classic psychedelics. Persisting disorders were less frequent but generally occurred in individuals who presented with several risk factors (overdose, polydrug use, unstructured recreational setting, psychosocial stress, personal/familial psychiatric histories). When psychedelics were administered in clinical studies under the framework of psychedelic-assisted therapy, the incidence of enduring anxiety and affective symptoms was low. In most cases, acute transient anxiety emerged and resolved during the dosing session without the need for additional treatment interventions. The nuance of such cases is discussed, shedding light on the role of emotional catharsis in the therapeutic process. Several suggestions are proposed to enhance patient safety including strengthening the therapeutic alliance, ensuring adequate mental preparation, acclimating to high doses and providing on-going therapeutic support.

​​Solace of Substance​: Agency, Surrender, and Consolation in Addiction and Polydrug Use

Although preceding its association with substance use, early uses of the term ‘addiction’ signified intense attachment or ‘devotion’ to an activity or pursuit, indicating compromised autonomy, a necessary ‘culling’ of conflicting obligations, such as family and other concerns, and a potentially dangerous surrender (Lemon 2018). Recent advances in biomedical and neuroscientific understandings of addiction, as a relapsing neurological disorder, have sharpened notions of substance use as being outside of conscious control. Yet framing addiction in terms of individual, neurobiological predispositions towards addictive behaviour, continues to impact how we view agency, responsibility, and autonomy, even as substances are ascribed their own powerful agencies. Based on long-term ethnographic fieldwork with individuals and third sector services in south-east Scotland, this article attends to ambiguous notions of agency attributed to and by people who use substances, and to substances themselves. It asks how responsibility for recovery becomes divested onto individuals, and how a moral ‘devotion’ to one’s recovery is mandated by medical and judicial institutions. The article further highlights how dyadic and intimate relationships with heroin are emplaced within wider webs of relations, and how heroin itself is suffused with agency and intentionality: becoming at once a force for destruction and source of life-giving surrender.

Validation of Serum Tetrahydrocannabinol Assay and Its Clinical Application

Abstract Background The widespread use of marijuana across all age groups in the United States, driven by the legalization of recreational and medical cannabis, has underscored the need for accurate measurement of tetrahydrocannabinol (THC) and its metabolites in blood specimens. This requirement spans both legal and medical contexts, prompting the development of precise diagnostic tools. Methods We developed a high-throughput liquid chromatography-tandem mass spectrometry (LC-MS/MS) assay, utilizing a straightforward protein precipitation extraction method to quantify THC and its metabolites: THC, 11-OH-THC, THC-COOH, cannabidiol (CBD), and THC-COOH glucuronide. The assay was rigorously validated for precision, linearity, stability, carryover, and quality assurance to ensure its reliability and accuracy for clinical use. Results Precision studies demonstrated a coefficient of variation ranging from 1.7% to 4.9%. The analytical measurement range was established at 1-100 ng/mL for THC, CBD, and 11-OH-THC, 5-500 ng/mL for THC-COOH, and 10-1000 ng/mL for THC glucuronide, accommodating the broad spectrum of THC/metabolite concentrations observed in our patient cohort. Carryover from all analytes were negligible (<0.01%). Sample stability was confirmed for up to two weeks at -20°C and through three freeze-thaw cycles. Despite a median THC concentration of 5 ng/mL in a limited sample size (N=44), high concentrations of THC and its metabolites correlated with trauma-related incidents and a history of polysubstance abuse in emergency department admissions. Conclusions The LC-MS/MS assay offers superior sensitivity and specificity compared to traditional immunoassays for cannabinoid detection, effectively distinguishing between THC and its metabolites. Its implementation will offer an advanced approach for analyzing the prevalence and clinical implications of THC and metabolite levels in various patient populations, including trauma, pediatric patients, and organ transplant candidates.

Systematic review: The relationship between gabapentinoids, etizolam, and drug related deaths in Scotland.

In recent years Scotland has been experiencing a disproportionally high number of drug related deaths compared to other European countries, causing significant individual, societal and economic burden. A possible cause of this is the increase in average number of substances involved in Scottish drug related deaths, as well as the changing pattern of substances involved. Opioids, cocaine, and alcohol have been consistently involved in the culture of drug use in Scotland, however recently National Records Scotland have identified that designer benzodiazepines such as etizolam, and prescription drugs such as gabapentinoids are increasingly being detected in Scottish toxicology reports. A systematic literature review following PRISMA guidelines was conducted through searching PubMed and Google Scholar to identify peer-reviewed articles published in English between 2013 and 2023 that investigated Scottish population data on gabapentinoids and etizolam to establish their contribution to the rise in Scottish drug related deaths. 18 studies were included in the review. A high use prevalence of etizolam and gabapentinoids in Scotland has been identified, with both substance-related deaths showing recent increase, marked since 2015. This pattern is replicated in the Scottish prison system. There has also been a significant increase of gabapentinoids prescriptions in Scotland. Polydrug use was identified as the most common determinant of both etizolam and gabapentinoids related adverse effects and fatality in Scotland, especially concurrent opioid use. The results indicate the literature on individual characteristics of Scottish at-risk users of gabapentinoids and etizolam is limited, however the data shows both substances are being used by older cohort, with adverse effects seen more in older women.

7504 A Case of Methicillin Sensitive Staphylococcus Aureus Thyroiditis

Abstract Disclosure: K. Patel: None. P. Kachhadia: None. S. Khan: None. F. Akanbi: None. A. Abu Limon: None. S.A. Aldasouqi: None. Introduction: Acute suppurative thyroiditis refers to bacterial infection of the thyroid gland. It is rare as the thyroid gland is typically protected from infection due to isolation of the gland from neighboring structures as well as its rich blood supply and adequate lymphatic drainage. It shares characteristics with subacute and autoimmune thyroiditis which make for difficult diagnosis. Here we present a case of acute suppurative thyroiditis in the setting of methicillin sensitive staphylococcus aureus (MSSA) bacteremia. Case Presentation: We have a 45 year old gentleman with a history of polysubstance abuse who was admitted after a drug overdose. He was being treated for rhabdomyolysis and approximately ten days after admission he became febrile with Tmax 103.3 Farenheit with a sore throat and dysphagia. Workup showed leukocytosis, ESR 86 mm/h [0-15], CRP 45.5 mg/dL [0-1], blood cultures with MSSA, negative viral upper respiratory panel, throat culture, Syphilis and HIV testing. He had a positive Hepatitis C antibody without a detectable viral load. Echocardiogram ruled out vegetations. He was treated with cefazolin. CT neck was obtained and showed thyroid enlargement. Subsequent ultrasound showed heterogeneous echotexture and increased color flow and a left inferior pole nodule 2.3 x 2.1 x 2.0 cm. Thyroid labs showed TSH 0.16 [0.35 - 4.01 u[IU]/mL,] Free T4 3.91 ng/dL [0.61 - 1.37], TPO <0.3. The nodule was biopsied and endocrinology was consulted. On exam thyroid was nontender. He was started on beta blockers and thyroid labs were monitored. TSI and TRAB were negative. TSH, Free T4 and Free T3 improved to normal range. Nodule biopsy results showed benign follicular cells with abundant acute inflammation suggestive of an abscess. Metronidazole was added after biopsy results. Post antibiotic therapy, CRP improved to 1.7 mg/dL. Discussion/Conclusion: Incidence of acute suppurative thyroiditis has been published as occurring <1% of all thyroid diseases. One systematic review found 200 cases reported from January 2000 to January 2020. Prior case reports have described acute suppurative thyroiditis in adult patients with prior thyroid gland pathology or an immunocompromised state and some demonstrated a correlation with intravenous drug users. The most common culprits include Staphylococcus spp, Streptococcus spp, Salmonella spp, Escherichia spp. Management includes antimicrobial therapy and/or needle aspiration. Non-responders can undergo incision and drainage of abscess or thyroidectomy. Mortality was reported in about 8% of the reported 200 cases. In our patient, his history of drug use and Hepatitis C likely made him prone to infection. Although there was no description of pus during biopsy, pathology suggested acute inflammation. This along with elevated inflammatory markers led to the diagnosis. This case highlights an uncommon but potential cause of thyroiditis. Presentation: 6/3/2024

7493 A Case Report of Recurrent Hypoglycemia With Polysubstance Abuse With Rhabdomyolysis and Capillary Glucose Monitoring Dilemma

7493 A Case Report of Recurrent Hypoglycemia With Polysubstance Abuse With Rhabdomyolysis and Capillary Glucose Monitoring Dilemma

A Rare Coexistence: Minimal Change Disease and Guillain-Barre Syndrome in a Patient with Polysubstance Abuse

A Rare Coexistence: Minimal Change Disease and Guillain-Barre Syndrome in a Patient with Polysubstance Abuse

A Rare Coexistence: Minimal Change Disease and Guillain-Barre Syndrome in a Patient with Polysubstance Abuse

A Rare Coexistence: Minimal Change Disease and Guillain-Barre Syndrome in a Patient with Polysubstance Abuse

Psychedelic-related deaths in England, Wales and Northern Ireland (1997–2022)

BackgroundPsychedelic drugs are increasingly visible in society once more, but their risks and adverse effects have received less attention than perhaps they should. While fatalities associated with psychedelics appear rare, a systematic approach to characterising their aetiology is required to inform harm minimisation efforts. AimsThis study aimed to analyse prevalence and characteristics of psychedelic-related deaths in England, Wales, and Northern Ireland, between 1997 and 2022. MethodsWe analysed coroner reports submitted to the National Programme on Substance Use Mortality where psychedelic serotonergic agonist drugs were involved in the death, and conducted a thematic framework analysis to explore potential factors associated with their occurrence. ResultsWe identified 28 cases where psychedelics were implicated (75 %, N = 21) or potentially implicated (25 %, N = 7) in the death; 19 of these involving psychedelic tryptamines (LSD 39 %, N = 11; Psilocybin 21 %, N = 6; DMT 7 %, N = 2), and 9 psychedelic phenethylamines (incl. NBOMes 18 %, N = 5). Most deaths were deemed accidental by the coroner (86 %, N = 24), including both traumatic injuries and drug toxicities; most cases involved multiple implicated drugs (68 %, N = 19); and most of the deceased were under 30 years of age (82 %, N = 23). Thematic framework analysis identified nine themes in the deaths across three categories. ‘Polysubstance use’ was the most common theme (82 % of cases, N = 23/28), followed by a suboptimal ‘physical environment’ (70 % of cases where this information was available, N = 14/20). ConclusionsThe profound and often unpredictable effects of psychedelics pose a unique profile of risks and adverse reactions. Nevertheless, psychedelic-related deaths remain very rare in comparison to other recreational drugs, and frequently involve polydrug use. Implications for harm reduction and policy are discussed.

High lifetime prevalence of regular nitrous oxide use in French medical students

ABSTRACT Background: Although nitrous oxide (N₂O) is increasingly misused recreationally, its use and risks among medical students who have professional access to it are rarely explored. Objectives: To investigate the recreational use of N₂O among medical students in Paris Region (France). Methods: This cross-sectional study used an online questionnaire distributed in 2022 through social networks, to all medical students (undergraduate student from the 2nd year of medical studies to residents until the end of the residency) from the six medical universities in Paris Region. We collected demographic characteristics, patterns of N₂O consumption, co-consumptions, and N₂O training (academic course or self-training). Factors associated with N₂O consumption and complications were analyzed using multivariable logistic regressions. Results: The questionnaires of 444 students (mean age: 25.9 years (SD = 2.69), 75.5% female, and 63.74% residents) were analyzed. Recreational N₂O consumption was reported by 71.85% of students and 20.50% consumed at least monthly. N₂O consumption was associated with being a resident (versus undergraduate student) (adjusted OR (aOR) = 3.07[1.45–6.72]; p < .01), receiving training on N₂O (aOR) = 3.13[1.84–6.24]; p < .01), and consumption of cannabis (aOR = 18.21[3.47–104.26]; p < .01), ecstasy (aOR = NA, p = .048) and poppers (aOR = 13.9[2.64–77.94]; p < .01). Complications (mainly dizziness, paresthesia and burns) were reported in 8.15% of students consuming N₂O. They were associated with consuming more than 10 balloons per intake (aOR = 6.04[1.32–25.00); p < .01) and inversely associated with receiving training (aOR = 0.35[0.14–0.86]; p = .01). Conclusions: Almost three-quarters of medical students experienced recreational N₂O consumption, particularly with poly-drug use. Given that complications were associated with high consumption and lack of education, risk training and screening for N₂O consumption could be beneficial.

The Rise of Bromazolam in Postmortem Cases from Travis County, Texas and Surrounding Areas: 2021-2023.

As novel psychoactive substances (NPS) have continued to emerge over the last decade, NPS benzodiazepines have likewise increased in prevalence. They pose an evolving threat to public health and safety with regard to postmortem cases, particularly when used in combination with opioids. Bromazolam was first detected in Travis County, Texas (TX) in April 2021. Given the recent onset of the fentanyl epidemic in this region, the international rise of bromazolam, and increased reports of "benzo-dope", a retrospective study was conducted to characterize bromazolam-positive deaths in Travis County and surrounding counties from 2021-2023. Bromazolam was identified in 112 deaths from 2021-2023, accounting for 1.57% of cases submitted for toxicology testing (n=7,129). During that interval, a 7.5-fold increase was observed in postmortem bromazolam-related drug toxicities from 2021 (n=7) to 2023 (n=53). Fatalities primarily occurred in males in their early-30's. Postmortem concentrations ranged from 21-220 ng/mL, with mean (median) concentrations of 69.4 ± 48.4 (53.5) ng/mL. Polydrug use was present in 99% of bromazolam-positive deaths with co-occurrence with other drugs and drug classes widely varying over time. Bromazolam was attributed as the sole cause of death in one case with a postmortem blood concentration of 23 ng/mL. Polydrug use in bromazolam-related drug toxicities commonly involved fentanyl (82%), methamphetamine (41%), and cocaine (28%). Similarly, cases where bromazolam was an incidental finding and non-contributory to the cause of death often involved methamphetamine (38%), alprazolam (33%), and cocaine (33%). In light of the significant increase in fentanyl-related deaths in Travis County, the increasing prevalence of bromazolam accompanying fentanyl was particularly alarming due to the heightened risk of toxicity when used in combination. Identifying and evaluating bromazolam-related deaths clarifies the impact of bromazolam on this population, promotes awareness, and aids in identifying meaningful harm reduction strategies to decrease bromazolam-related morbidity and mortality.

Prevalence and Patterns of Drug Use Among People in Al-Najaf Governorate, Iraq

Background: After a series of instability Iraq confronted in the past decades, the drug abuse issue has grown and is now a complex national concern where the rise in drug transshipment through the country and neighbor countries accompanies noticeable increased consumption of drugs especially those associated with transnational criminal networks such as amphetamines. This is a descriptive cross-sectional epidemiological study conducted in Al-Najaf governorate from January to March 2024, qualitative data based on the correction institutions of the Ministry of the Interior using a non-probability sample since lack of precise sample frame or data about the real prevalence or rate of the problem. The study recruited 288 drug users all between 20-64 years, 31(10.8%) were females and 257(89.2%) were males (49%). 237 (82%) of the drug users of young adults between 20 to 40 years old. The objective was to investigate personal history and examine the extent and patterns of the abuse of drugs, using a structured questionnaire designed and modified after reviewing relevant studies. The study found that the majority of the participants smoked nicotine throughout their lifetime as 60.8% smoked hookah, 15% smoked e-cigarettes and 86% smoked cigarettes with about 75% current heavy smokers, 51% of participants used alcohol as lifetime prevalence with more than 32% used it weekly. A large percentage: 88% abused more than one type of illicit drug with amphetamine stimulants (methamphetamine and fenethylline) as the most commonly abused illicit drugs among the majority of the participants. The lifetime prevalence of prescription drug use was 86%. 60% used more than one method of administration, while 8% used drugs by injection. The study concluded that a large percentage of the study participants were polydrug abusers with extensive patterns of use which revealed the complex status of which stresses a holistic approach to managing the problem. Conclusion: The study concluded that a large percentage of the study participants were polydrug abusers with extensive patterns of use which revealed the complex status of which stresses a holistic approach to manage the problem.

A novel method for the simultaneous determination of drugs of abuse, ethyl glucuronide and synthetic opioids in human hair through a single digestion, purification and analysis in LC-MS/MS

Polydrug use is a serious health and social problem worldwide. Over the past several years, there has been an increasing tendency to combine narcotics, alcohol, sedatives, and/or stimulants. To the traditional drugs of abuse and alcohol, an increase of new abuse drugs such as synthetic opioids has been added. In the current study, the development and validation of an innovative and fast analytical procedure has been presented to determine drugs of abuse, ethyl glucuronide and synthetics opioids in 30 mg of human hair through a single digestion, purification and analysis in LC-MS/MS. A combine simple preparation of hair sample followed to a single chromatographic run of 10 min has been proposed. A full validation for 54 target analytes for the parameters of selectivity, linearity, limit of detection, limit of quantification, accuracy, precision, matrix effects, recovery, and dilution integrity was successful completed. The method was linear in different ranges with r values of at least 0.990; the value to the validated LLOQ values were in the range 0.1–100 pg/mg. The method offered satisfactory precisions (CV<15 % and accuracy ± 20 %). In conclusion, a significant reduction in the overall times of the analytical procedure and the reduction of consumables costs make this method extremely advantageous and undoubtedly useful in routine laboratory workflow analyses and open the way to the prospect of a further implementation which also includes other classes of xenobiotics.

Changing trends in anabolic-androgenic steroid use within Scottish prisons: Detection, prevalence, and quantitation.

Anabolic-androgenic steroids (AASs) are a subclassification of image performance enhancing drugs (IPEDs). While AAS use is most prevalent among people in athletics, there is also high lifetime prevalence of AAS use among prisoners. This study reports the qualitative detection of AASs in seized samples from the Scottish prisons from 2019-2023. Additionally, methods were developed for the quantitative analysis of AASs using gas chromatography-mass spectrometry (GC-MS) and applied to 61 samples of tablets or powders seized from Scottish prisons between July 2022 and July 2023. Since 2022, there has been an increase in AAS detections in the Scottish prisons. Oxymetholone was the most prevalent AAS, followed by metandienone (methandrostenolone, methandienone), methyltestosterone, oxandrolone, mestanolone (methylandrostanolone), stanozolol, and androstenedione. Multiple AASs were found in 21 samples and 10 samples contained other drugs, including amitriptyline, sertraline, zopiclone, mirtazapine, sildenafil, etizolam, Δ9-tetrahydrocannabinol, and the synthetic cannabinoid MDMB-INACA. Most AAS samples were tablets (77.0%), although they were also detected in powders, herbal material, e-cigarettes, and a fragmented soap bar-type sample. There was a large variation in the concentration of AASs in the tablets and powders seized from the Scottish prisons, demonstrating AASs are another highly variable component of the polydrug use situation in prisons, the effects of which need to be examined further.

A quantitative LC-MS/MS method for investigation of polysubstance use involving heroin and cocaine

Concurrent use of heroin and cocaine (known as the “speedball”) prevails among substance use disorder populations, especially in opioid-dependent individuals, with severe consequences and a high fatality rate. Little is known about the patterns and correlations of the concurrent use of heroin and cocaine. It is vital to investigate such a polydrug use in both humans and animals to uncover concomitant toxicity and the cause of fatal overdose (death). In this study, we aimed to shed some light on the role of cocaine in the etiology of heroin-related deaths in the context of molecular pharmacokinetics (PK). For the purpose, a high-performance liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) method for simultaneous determination of heroin, cocaine, and their metabolites in whole blood was developed and fully validated in accordance with the US Food and Drug Administration (FDA) and European Medicines Agency (EMA) guidelines. Then, this method was used to analyze heroin, cocaine, and their metabolites in blood from the rats intraperitoneally administered non-lethal 10 mg/kg heroin or 20 mg/kg cocaine alone, or their combination that is lethal with a proximal mortality of 33 %. The obtained results from the rats that experienced the lethal toxicity revealed that the concurrent use of heroin and cocaine significantly increased the risk of fatality from overdose. Heroin significantly slowed down the elimination of cocaine and its main metabolites in blood, while cocaine significantly enhanced heroin metabolism from 6-monoacetylmorphine (6-MAM) to morphine. Similar elimination half-lives for other heroin metabolites were observed. These findings are reported for the first time in this study, facilitating our understanding of the polysubstance metabolism and severe consequences produced by the polydrug use.

The rising use of cognitive enhancement drugs and predictors of use during COVID-19: findings from a cross-sectional survey of students and university staff in the UK.

The use of psychoactive substances to increase cognitive performance while studying has been termed 'pharmacological cognitive enhancement' (PCE). In previous years, several large-scale national surveys have focused on their use by students at university, including drug types, prevalence rates, and predictive factors. The recent coronavirus pandemic brought about widespread structural changes for UK universities, as students were forced to adapt to home-based learning and in many cases reduced academic support. No study has yet focused primarily on the impact of pandemic social restrictions on PCE in students and academic staff, and whether personality and demographic factors reveal user profiles that predict use during the pandemic period. A convenience sample of 736 UK students and staff aged 18-54 (M = 22.2, SD = 5.2) completed a cross-sectional survey assessing PCE prevalence rates, polydrug use, perceived effects, academic self-efficacy and personality during the first year of social restrictions (March 2020 - February 2021) compared with the previous year (March 2019 - February 2020). There was a significant self-reported rise in the use of all drug types (all ps < 0.001) during social restrictions, particularly with Modafinil (+42%), nutraceuticals (+30.2%) and microdose LSD (+22.2%). Respondents also indicated stronger PCE effects for all substances, except alcohol, in comparison to the previous year. Polydrug use with modafinil and other prescription stimulants increased the most during social restrictions. Personality factors and gender identity reliably predicted PCE use and lower agreeableness was often the strongest predictor, followed by identifying as male and lower conscientiousness. Academic self-efficacy and student/academic staff status were not consistent predictors. This is the first survey of UK students to investigate PCE during coronavirus social restrictions and to assess predictive factors. Findings reveal a rise in PCE use and polydrug use which we suggest is because of increased pressures on students created by the lockdown and reduced access to university resources.

Relationship between family history of mandatory boarding school experiences and suicide risk in US reservation-based Native American youth: a cross-sectional analysis

IntroductionSuicide is a leading cause of death among Native American youth and adolescents in the USA. A myriad of factors have been correlated with risk for suicide ideation (SI)/suicide attempt...

Structure-Activity Relationships of the Fentanyl Scaffold: Identification of Antagonists as Potential Opioid Overdose Reversal Agents.

Opioid-related overdoses account for almost half of all drug overdose deaths in the United States and cause more preventable deaths every year than car crashes. Fentanyl, a highly potent mu opioid receptor (MOR) agonist and its analogues (fentalogues) are increasingly found in illicit drug samples, both where the primary drug of abuse is an opioid and where it is not. The prevalence of fentalogues in the illicit drug market is thought to be the primary driver of the increased number of opioid-related overdose deaths since 2016. In fact, fentanyl and its analogues are involved in more than 70% of opioid-related overdoses. The standard opioid overdose rescue therapy naloxone is often insufficient to reverse opioid overdoses caused by fentalogue agonists under current treatment paradigms. However, the pharmacology of many fentalogues is unknown. Moreover, within the fentalogue series of compounds, it is possible that antagonists could be identified that might be superior to naloxone as opioid overdose reversal agents. In this report, we explore the pharmacology of 70 fentalogues and identify compounds that behave as MOR antagonists in vitro and demonstrate with one of these reversals of fentanyl-induced respiratory depression in the mouse. Such compounds could provide leads for the development of effective agents for the reversal of opioid overdose.

Polysubstance puzzle: A case report on alcohol, pregabalin, cyproheptadine, and dexamethasone dependence

This case report explores the intricate landscape of polysubstance dependence, focusing on a 24-year-old male presenting with concurrent reliance on alcohol, pregabalin, cyproheptadine, and dexamethasone. This unique case underscores the complexities inherent in diagnosing and managing overlapping substance use disorders, emphasizing the need for thorough assessment and comprehensive intervention strategies. With substance dependence representing a significant global health concern, this report contributes valuable insights to the scientific literature by elucidating the multifaceted dynamics of polysubstance misuse. A 24-year-old male of asthenic built, with a history of alcohol consumption for 8 years initiated by peer pressure and escalated by life stressors, presented with depressive symptoms and reliance on multiple substances. His main concerns included mood disturbances, fatigue, and decreased appetite. Clinical evaluation revealed depressive features, substance dependence, and comorbidities associated with polysubstance misuse. Notably, he self-medicated with pregabalin for its euphoric effects, consumed cyproheptadine and dexamethasone to alter his body weight, and relied on alcohol as a coping mechanism. Treatment involved pharmacotherapy and motivational enhancement therapy, resulting in significant improvement and subsequent abstinence from all substances. This case underscores the complexities encountered in diagnosing, treating, and managing polysubstance dependence, exemplified by the dependencies on alcohol, pregabalin, cyproheptadine, and dexamethasone within a single patient. A comprehensive treatment approach incorporating detoxification, tapering, and psychological counseling facilitated significant progress. Achievements included successful abstinence from alcohol and notable reductions in cravings for pregabalin, cyproheptadine, and dexamethasone.