Polysubstance Use Research Articles

Concurrent Mentions of Vaping and Alcohol on Twitter: Latent Dirichlet Analysis.

Co-use of alcohol and e-cigarettes (often called vaping) has been linked with long-term health outcomes, including increased risk for substance use disorder. Co-use may have been exacerbated by the COVID-19 pandemic. Social networking sites may offer insights into current perspectives on polysubstance use. The aims of this study were to investigate concurrent mentions of vaping and alcohol on Twitter (subsequently rebranded X) during a time of changing vaping regulations in the United States and the emergence of the COVID-19 pandemic. Tweets including both vape- and alcohol-related terms posted between October 2019 and September 2020 were analyzed using latent Dirichlet allocation modeling. Distinct topics were identified and described. Three topics were identified across 6437 tweets: (1) flavors and flavor ban (n=3334, 51.8% of tweets), (2) co-use discourse (n=1119, 17.4%), and (3) availability and access regulation (n=1984, 30.8%). Co-use discussions often portrayed co-use as positive and prosocial. Tweets focused on regulation often used alcohol regulations for comparison. Some focused on the perceived overregulation of vaping (compared to alcohol), while others supported limiting youth access but not at the expense of adult access (eg, stronger age verification over product bans). Across topics, vaping was typically portrayed as less harmful than alcohol use. The benefits of flavors for adult smoking cessation were also discussed. The distribution of topics across time varied across both pre- and post-regulatory change and pre- and post-COVID-19 pandemic declaration periods, suggesting shifts in topic focus salience across time. Co-use discussions on social media during this time of regulatory change and social upheaval typically portrayed both vaping and alcohol use in a positive light. It also included debates surrounding the differences in regulation of the 2 substances-particularly as it related to limiting youth access. Emergent themes from the analysis suggest that alcohol was perceived as more harmful but less regulated and more accessible to underage youth than vaping products. Frequent discussions and comparisons of the 2 substances as it relates to their regulation emphasize the still-evolving vaping policy landscape. Social media content analyses during times of change may help regulators and policy makers to better understand and respond to common concerns and potential misconceptions surrounding drug-related policies and accessibility.

Profiles of polysubstance use among people reporting past 12-month sleep-motivated nonmedical use of prescription tranquilizers/sedatives.

Nonmedical use of prescription tranquilizers/sedatives (NMUPTS) is associated with a 15-times increased likelihood of polysubstance use (PSU). This is correlated with an increased risk for use disorders and death, therefore, to inform prevention efforts, we identified PSU profiles among adults reporting sleep-related NMUPTS. National Survey on Drug Use and Health 2015-2019 participants with past 12-month sleep-related NMUPTS and use of an additional drug(s) (n = 2603) were studied. Latent class analyses identified unique latent profiles, and multivariable logistic regressions identified covariates associated with each profile. Alcohol (90.4%), tobacco (61.5%), and marijuana (55.5%) were most commonly reported, with an average of 3.6 additional substances. Two latent PSU profiles were identified: marijuana/alcohol/tobacco (MAT) (68.3%) and MAT + cocaine/hallucinogens/prescription drugs (MAT + CHPR) (31.7%). In comparison to those likely in the MAT profile, those likely in the MAT + CHPR profile had lower odds of being older than 18-25 years (26-34: adjusted odds ratio [AOR]: 0.5, 95% confidence interval [CI]: 0.3, 0.6; 35-49: AOR: 0.2, 95% CI: 0.1, 0.2; 50+: AOR: 0.1, 95% CI: 0.0, 0.1), female (AOR: 0.4, 95% CI: 0.3, 0.6), non-Hispanic Black (AOR: 0.5, 95% CI: 0.4, 0.8) or Hispanic in comparison to non-Hispanic White (AOR: 0.5, 95% CI: 0.4, 0.8), and to not have past 12-month insurance coverage (AOR: 1.7, 95% CI: 1.3, 2.3). Two PSU profiles were identified among people with NMUPTS, with noted variations in sociodemographic characteristics. In comparison to previous studies, sleep-related NMUPTS was associated with higher rates of stimulant use, suggesting stimulant use and sleep-related NMUPTS may be related.

Cannabis Vaping Among US Adults With Disabilities: Findings From the 2022 Behavioral Risk Factor Surveillance System.

Studies have demonstrated that people with disabilities are more likely to use cannabis than people without disabilities. However, less is known about novel forms of use, such as cannabis vaping, in this population. We examined the correlates of cannabis vaping among people with disabilities and the association between cannabis vaping and the frequency of cannabis use in any form. We used data from the 2022 Behavioral Risk Factor Surveillance System to examine the association between disabilities and past-month cannabis vaping, as well as the number of days that cannabis was used in the past month, among US adults. We used weighted multivariable logistic and modified Poisson regression models with incidence rate ratios to examine the associations. The prevalence of cannabis vaping was higher among adults with any disability (4.6%) than among adults without disabilities (2.8%); adults with only cognitive disabilities had the highest prevalence (8.2%). Daily nicotine vaping (adjusted odds ratio [AOR] = 6.04; 95% CI, 4.14-8.80), former cigarette smoking status (AOR = 1.67; 95% CI, 1.25-2.25), and being aged 18-24 years (vs ≥65 y) (AOR = 11.07; 95% CI, 7.05-17.38) were associated with higher odds of cannabis vaping among adults with any disability. Disability status modified the relationship between cigarette smoking and cannabis vaping (P < .001). Additionally, among adults with disabilities, the rate of cannabis-use days was higher among adults who vaped cannabis (adjusted incidence rate ratio = 1.28; 95% CI, 1.19-1.36) than among adults who did not vape cannabis. Among adults with disabilities, nicotine consumption by vaping was associated with cannabis vaping. Our findings highlight the need for interventions that reduce the risk of polysubstance use (ie, nicotine and cannabis) in this population.

Lidocaine Patches After Cesarean Sections: A Randomized Control Trial

ObjectivesLidocaine patches are a common topical analgesic therapy but have not been thoroughly investigated in the surgical or obstetric literature. We sought to investigate the impact of adding topical lidocaine patches to routine post-cesarean pain management on patients’ post-cesarean pain scores and opioid use. Study DesignThis is a prospective randomized subject blinded controlled trial of patients undergoing cesarean delivery at a single institution. Individuals were excluded if they had three or more cesarean sections, abdominoplasty, history of abdominal hernia repair with mesh, active polysubstance use, or history of opiate use disorder with current medication-assisted treatment. Patients were randomized via a 1:1 randomization scheme to a placebo patch or lidocaine patch. Baseline maternal characteristics were collected. The primary outcome was mean visual analog pain scores (0-10). Our secondary outcome was total morphine equivalents used over the post-operative hospital stay. Pre- and post-study surveys were performed to evaluate subject's prior analgesia use (including opioids) and patient experience in the study. ResultsA total of 100 patients were randomized and 93 had complete data for analysis (46 placebo group, 47 treatment group). Groups had similar baseline characteristics (age, BMI, ethnicity, surgical time, and estimated blood loss). Mean maximum post-operative pain score by visual analog scale did not differ between placebo or lidocaine patch groups on post-operative day 1 (p=0.3), day 2 (p=0.9), day 3 (p=0.07), or day 4 (p=0.09). Mean post-operative pain score by visual analog scale did not differ between placebo or lidocaine patch groups on post-operative day 1 (p=0.7), day 2 (p=0.6), day 3 (p=0.2), or day 4 (p=0.5). In the post-study survey, 0% of the respondents in the lidocaine patch group reported disruption of their care and 63% reported desired use of lidocaine patch in the future. ConclusionsThe addition of lidocaine patches did not significantly decrease the maximum or average post-operative pain scores via visual analog scale after cesarean sections. More research is needed into non-opioid pain management strategies in the post-operative period in obstetric care.

Preadolescent individual, familial, and social risk factors associated with longitudinal patterns of adolescent alcohol, cannabis, and other illicit drug use in a population-representative cohort.

The aim of this exploratory study was to identify developmental patterns of adolescent concurrent alcohol, cannabis, and other illicit drug use and their preadolescent individual, familial, and social risk factors in a population-representative cohort from the province of Quebec, Canada (N = 1,593; 48.4% male). Age 12-17 years self-reports of alcohol, cannabis, and other illicit drug use were collected. Latent growth modeling was used to analyze developmental patterns of single- or polysubstance use (SU/PSU), and multinomial regression examined their association with risk factors assessed at age 10-12 years. Five developmental patterns were revealed, including nonusers (12.8% sample) and four classes reflecting different levels of SU/PSU (5.8%-37.5%), varying in severity based on onset, frequency, and type of substances used. Boys and girls were similarly represented throughout SU/PSU patterns. In comparisons with nonusers, several preadolescent risk factors were associated with increasing severity of SU/PSU. Possibly indexing fearlessness/disinhibition, low internalizing symptoms were common to all adolescent users. An earlier onset of substance use and increasing use of substances throughout adolescence were linked with having deviant peers for all user classes but later-onset users. Preadolescents manifesting externalizing problems and exposed to family adversity in addition to the above risk factors showed the earliest onset and most frequent adolescent SU/PSU, especially those also exposed to less appropriate parenting. Consistent with the developmental model of substance use, the nature, number, and severity of preadolescent risk factors distinguished between the type and severity of SU/PSU patterns in adolescence and call for a consistent strategy of universal, selective, and indicated preventive interventions. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Expanding access to addictions care: Implementation of a 24-hour healthcare provider support line in British Columbia, Canada

BackgroundMorbidity and mortality related to substance use have risen to catastrophic levels in North America, and treatment services are often difficult to access. In response, the province of British Columbia (BC), Canada, launched a province-wide addiction medicine support phone line that offers clinicians immediate access to phone consultation with an addictions medicine expert. The service operates 24/7 is accessible to any clinician in the province seeking assistance with an addiction-related question. We describe an evaluation of the reach and perceived impact of the service over its first two years.MethodsThe 24/7 Addiction Medicine Clinician Support Line was evaluated prospectively from June 2020 to April 2022. All provider-to-provider encounters were included. Data was collected from two primary sources: health provider demographic information collected at the time of consultation, and optional clinician surveys conducted after the consultation was complete. Descriptive data are presented as numerical values and percentages.ResultsOver the 22-month evaluation period, 1,279 consultations were requested by 631 distinct care providers across British Columbia. The service averaged 15 calls per week across the province, and 51.5% of calls were made outside of business hours. Physicians made the majority of calls to the service (n = 865, 67.6%), followed by nurse practitioners (n = 162, 12.7%). Among those who completed a follow-up survey (n = 258 calls, 20.2% total calls), 81.8% (n = 211) were “very” or “extremely” satisfied with the consultation. Of these respondents, 65.5% (n = 169) reported that the consultation led to the provision of better care for their patient, with 58.1% (n = 150) initiating a new prescription and 22.1% (n = 57) reporting expedited treatment for their patient. The consultation area of focus was most commonly opioid use (n = 417; 59.6%), followed by polysubstance use (n = 98; 14.0%).ConclusionsThe impact of the 24/7 Addiction Clinician Support Line was widespread, and the service increased accessibility to evidence-based addictions treatment across a range of care settings. Clinicians expressed a high degree of satisfaction with the service. To our knowledge, this province-wide program is the first of its kind in North America, offering a scalable and adaptable model to support access to evidence-based addictions care in under-resourced settings.

Association between mental and physical health with poly-substance use among adults in 33 U.S. states

Abstract Leveraging national data from 33 states in the U.S. for adults 18 and over (N = 347,060), from the 2020-2022 Behavioral Risk Factor Surveillance System (BRFSS), we investigated the association between current self-reported physical and mental health outcomes and substance use, focusing on alcohol, nicotine, cannabis, and all combinations of poly-substance use. Specifically, we conducted multiple weighted linear regression analyses using self-reported outcomes for poor mental and physical health in the last 30 days to examine seven mutually exclusive combinations: alcohol (A) only, nicotine (N) only, cannabis (C) only, A+N, A+C, N+C, and A+N+C. We adjusted for race, sex, age group, education level, and marital status in our analyses. For poor mental health, mean number of days ranged from 3.49 (SD = 7.07) for A-only to 10.39 (SD = 11.54) for N+C and for poor physical health, means ranged from 2.38 (SD = 6.24) to 7.17 (10.61) for N+C. All adjusted β coefficients were significant for poor mental health days, notably with the three highest being 4.36 (95%CI: 3.72-5.00) for C-only, 5.68 (95%CI: 5.06-6.30) for N+C, and 5.27 (95%CI: 4.76-5.79) for A+N+C. For poor physical health, all adjusted β coefficients were significant except for A+N, with the two highest being 2.88 (95%CI: 2.31-3.45) for C-only, 3.16 (95%CI: 2.62-3.69) for N+C, and 1.83 (95%CI: 1.54-2.11) for N-only. Recent poly-substance use containing nicotine and cannabis was both associated with 5+ days of poorer mental health and 3+ days of poorer physical health. Overall, our findings hold implications for informing future policy discourse, shaping public health campaigns, and designing educational initiatives aimed at the link between mental health and substance use. Understanding the dynamics of poly-substance use involving the three most commonly utilized substances globally among adults is critical for crafting targeted interventions. Key messages • Recent poly-substance use (alcohol, nicotine, and cannabis) is related to poorer mental and physical health in the past 30-days. • Recent nicotine and cannabis co-use is associated with 5+ days of self-reported poorer mental health and 3+ days of physical health.

Severity and Number of Substances Used are Independently Associated with Antiretroviral Therapy Adherence Over Time among People with HIV in the Current Treatment Era.

Substance use is associated with decreased antiretroviral therapy (ART) adherence among people with HIV (PWH). Adherence plays a significant role in mediating the negative effects of substance use on HIV suppression and is a principal modifiable patient-level factor in improving HIV suppression and reducing ART drug resistance. Understanding substance use and ART adherence, particularly with rapidly changing substance use epidemiology and ART regimens, is vital to improving HIV care. Among 10,557 PWH (2010-2021) from 8 academic clinical sites nationally we examined longitudinal associations of substance use severity and number of substances used (measured using AUDIT-C and modified ASSIST) with patient-reported ART adherence (visual analog scale). Alcohol (68% any use, 18% unhealthy use [AUDIT-C > 4 men, > 3 women]), marijuana (33%), and methamphetamine (9%) use were most reported. Polysubstance use was common (32%). Both higher severity substance use and higher number of substances used were associated with lower ART adherence. Severity of methamphetamine use had the strongest dose-response association with ART adherence (low severity [ASSIST 1-3]: -3.05%, 95% CI: -4.23%, -1.87%; moderate [ASSIST 4-26]: -6.20%, 95% CI: -7.08%, -5.33%; high [ASSIST > 26]: -10.77%, 95% CI: -12.76%, -8.78%). Severe substance use, especially methamphetamine, and higher number of illicit drugs used were associated with declines in adherence at levels that were likely clinically meaningful in the modern era of ART. Findings support integrating substance use care with HIV care and potential benefits of harm reduction strategies for improving adherence such as encouraging lower levels of substance use and fewer number of substances used.

Exploring Human Misuse and Abuse of Veterinary Drugs: A Descriptive Pharmacovigilance Analysis Utilising the Food and Drug Administration’s Adverse Events Reporting System (FAERS)

Introduction: Evidence suggests an increasing misuse of veterinary medicines by humans. This study aims to analyse Adverse Events (AEs) associated with selected veterinary products using the Food and Drug Administration Adverse Events Reporting System (FAERS). Methods: A descriptive pharmacovigilance analysis was conducted on AEs related to 21 drugs approved for human and/or animal use. Results: A total of 38,756 AEs, including 9566 fatalities, were identified. The United States reported the highest number of cases (13,532), followed by Canada (2869) and the United Kingdom (1400). Among the eight drugs licenced exclusively for animals, levamisole, pentobarbital, and xylazine were most frequently reported. Reports predominantly involved males (57%) from the 18–64 age group, with incidents related mainly to overdose, dependence, and multi-agent toxicities. Unmasking techniques revealed ‘intentional overdose’ as the primary reaction. Polysubstance use was evident in 90% of the drugs, with benzodiazepines/Z-drugs and opioids as common co-used classes. Conclusions: Veterinary medications are increasingly infiltrating the illicit drug market due to their pharmacological properties. This trend highlights the need for heightened vigilance and awareness to prevent further public health risks associated with the adulteration of illicit substances with veterinary products like xylazine and pentobarbital.

Occurrence of Stigmatizing Documentation Among Hospital Medicine Encounters With Opioid-Related Diagnosis Codes: Cohort Study.

Physician use of stigmatizing language in the clinical documentation of hospitalized adults with opioid use is common. However, patient factors associated with stigmatizing language in this setting remain poorly characterized. This study aimed to determine whether specific demographic factors and clinical outcomes are associated with the presence of stigmatizing language by physicians in the clinical documentation of encounters with opioid-related ICD-10 (International Statistical Classification of Diseases, Tenth Revision) codes. Hospital encounters with one or more associated opioid-related ICD-10 admission diagnoses on the hospital medicine service during the 2020 calendar year were analyzed for the presence of stigmatizing language in history and physical and discharge summaries. Multivariable adjusted logistic regression models were used to determine associations of age, race, gender, medication for addiction treatment use, against medical advice discharge, homelessness, comorbid polysubstance use, comorbid psychiatric disorder, comorbid chronic pain, cost, and 30-day readmission with the presence of stigmatizing language. A total of 221 encounters were identified, of which 64 (29%) encounters had stigmatizing language present in physician documentation. Most stigmatizing language was due to use of "substance abuse" rather than the preferred term "substance use" (63/66 instances). Polysubstance use and homelessness were independently associated with the presence of stigmatizing language (adjusted odds ratio [aOR] 7.83; 95% CI 3.42-19.24 and aOR 2.44; 95% CI 1.03-5.90) when controlling for chronic pain and other covariates. Among hospital medicine encounters with an opioid-related diagnosis, stigmatizing language by physicians in clinical documentation was common and independently associated with comorbid polysubstance use and homelessness.

A case of Russell body gastritis associated with psychiatric disorder

Abstract Introduction/Objective Russell body gastritis is a benign and rare entity characterized by infiltration of lamina propria with plasma cells stuffed with spherical eosinophilic cytoplasmic inclusions known as Russell bodies which represent immunoglobulins. Russell bodies accumulate due to dysfunction in secretion pathway of plasma cells. Plasma cells with Russell bodies are also termed Mott cells. Although exact etiology is unknown, but it can be seen in association with other conditions like mucosa associated lymphoid tissue (MALT) lymphoma, multiple myeloma and plasmacytoma. This condition most commonly affects the antrum and may present as erythema or sometimes nodular lesion. Definitive diagnosis is based on histology. Methods/Case Report A middle-aged male with past medical history significant for polysubstance use disorder, bipolar disorder, and osteoarthritis was evaluated for bleeding per rectum and dyspepsia in the setting of chronic nonsteroidal anti-inflammatory drugs (NSAID) and ethanol use. Physical examination was remarkable for an external hemorrhoid and complete blood count showed anemia. Upper GI endoscopy and colonoscopy was performed. Patchy erythema was seen in antrum and duodenal bulb, and colonoscopy was unremarkable. Microscopic examination showed numerous plasma cells with Russell bodies (Mott cells) in the lamina propria and mild chronic inflammation in gastric mucosa. H. Pylori was negative by immunohistochemistry (IHC). Plasma cells were polyclonal and positive for CD138, and negative for cytokeratin which excluded plasmacytoma and signet-ring adenocarcinoma, respectively. Patient was placed on proton pump inhibitor therapy and discharged. Results (if a Case Study enter NA) Russell body gastritis can be seen in patients with and without H. Pylori infection. Cytokeratin, kappa and lambda immunohistochemistry stains, and gene rearrangement studies may be needed to exclude frequent lesions that may enter in the differential diagnosis. Long term effects and clinical significance of russell bodies accumulation is yet to be determined. Conclusion Russell body gastritis is a rare morphologic variant of chronic gastritis that may enter in the differential diagnosis with other more serious lesions. A careful morphologic examination and occasionally IHC stains / molecular studies are needed to make the correct diagnosis.

Pattern of Psychoactive Substance Use in Sierra Leone: A Descriptive Retrospective Study

Background Substance use, and pattern of consumption varies across population and may, within a particular population, show temporal variations in accordance with changing fads. Understanding the pattern of substance use in a population is key to any programme of demand reduction. Thus, we studied a consecutive series of patients with substance use disorders in our facility, aiming to determine the patient profile and pattern of substance use. Methods Hospital’s digital register was consulted and data of patients who were seen over a 16-months period, and who had diagnosis of ‘alcohol and substance use disorder’ were retrieved and analyzed. Results Seven hundred and nineteen patients were treated for substance use disorder over a 16-months period. Age of patients ranged from 16 to 69 years with mean age (SD) of 28.7(9.2) years. Majority were males (91%), single (87%) and had been to secondary or tertiary school with or without graduation. Fifty nine percent (421/719) of the patients admitted being on ‘Kush’, 49% on alcohol, 47% on cannabis, 11% on tramadol and 5.6% on cocaine. About 71% of the patients were poly-substance users while 29 percent were on one agent. Alcohol, ‘Kush’ and cannabis were the most common preferences of those who use more than one agent. Conclusions Substance use disorder in Freetown was most prevalent in young, adult, secondary school educated males. ‘Kush’ was the most common agent of abuse and frequency of polysubstance use is high. Understanding the factors responsible for low substance use among females in the population might point to some preventive control measures.

Detection of serum alterations in polysubstance use patients by FT-Raman spectroscopy

Substance use disorders pose significant health risks and treatment challenges due to the diverse interactions between substances and their impact on physical and mental health. The chemical effects of multiple substance use on bodily fluids are not yet fully understood. Therefore, this study aimed to investigate the chemical changes induced by a combination of substances compared to a control group. Analysis of FT-Raman spectra revealed structural alterations in the amide III, I, and C = O functional groups of lipids in subjects treated with opioids, alcohol and cannabis (polysubstance group). These changes were evident in the form of peak shifts compared to the control group. Additionally, an imbalance in the amide-lipid ratio was observed, indicating perturbations in serum protein and lipid levels. Furthermore, a 2D plot of two-track two-dimensional correlation spectra (2T2D-COS) demonstrated a shift towards dominance of lipid vibrations in the polysubstance use groups, contrasting with the predominance of the amide fraction in the control group. This observation suggests distinct molecular changes induced by multiple substance use, potentially contributing to the pathophysiology of substance use disorders. Principal Component Analysis (PCA) was utilized to visualize the data structure and identify outliers. Subsequently, Partial Least Squares Discriminant Analysis (PLS-DA) was employed to classify the polysubstance use and control groups. The PLS-DA model demonstrated high classification accuracy, achieving 100.00 % in the training dataset and 94.74 % in the test dataset. Furthermore, receiver operating characteristic (ROC) analysis yielded perfect AUC values of 1.00 for both the training and test sets, underscoring the robustness of the classification model.This study highlights the quantitative and qualitative changes in serum protein and lipid levels induced by polysubstance use groups, as evidenced by FT-Raman spectroscopy. The findings underscore the importance of understanding the chemical effects of polysubstance use on bodily fluids for improved diagnosis and treatment of substance use disorders. Moreover, the successful classification of spectral data using machine learning techniques emphasizes the potential of these approaches in clinical applications for substance abuse monitoring and management.

Risk Factors for Late-Onset Psychosis: A Case-Control Study.

The onset of schizophrenia occurs after the age of 40 in up to 20% of cases. We aim to depict risk factors for first-episode psychosis after the age of 40 by comparing late-onset psychosis (LOP) patients to healthy age-matched controls. In this case-control study using electronic health records, 142 individuals aged 40-65 years with an encounter for a first episode of psychosis between 2013 and 2021 were included. Four controls (N = 568) were matched to each case on age, sex, race, and year of encounter. Potential risk factors for the primary analysis were captured via structured data and text-mining of medical notes. Conditional logistic regression models were used to assess the odds of LOP with potential risk factors. After adjusting for all variables in the main analysis, odds for LOP were increased by immigration (OR 3.30, 95% CI, 1.56-6.98), depression (OR 3.58, 95% CI, 2.01-6.38), anxiety (OR 2.12, 95% CI, 1.20-3.75), cannabis use (OR 3.00, 95% CI, 1.36-6.61), alcohol use disorder (OR 5.46, 95% CI, 2.41-12.36), polysubstance use (OR 4.22, 95% CI, 1.30-13.7), severe trauma (OR 2.29, 95% CI, 1.08-4.48), and caregiver burden (OR 15.26, 95% CI, 3.85-60.48). Life stressors along with the effects of substance use and other psychiatric conditions may confer some risk to the development of LOP. Replication is required in independent prospective studies. Further research is necessary to truly parse out which of these factors belong on the causal pathway.

Bidirectional associations between sleep and cannabis and alcohol (co-)use in daily life.

Poor sleep is common in the context of cannabis use, but experimental and daily-life studies provide mixed evidence for whether cannabis use helps or disturbs same-night sleep. Despite a high prevalence of co-use of alcohol and cannabis, most studies of cannabis use and sleep do not consider alcohol use. We sought to add to this literature by examining associations between cannabis and sleep in the context of alcohol co-use and to examine these associations bidirectionally using ecological momentary assessment. Participants were 88 adults reporting cannabis use at least 3×/week and simultaneous alcohol and cannabis use at least 2×/week. For 14 days, participants completed morning surveys assessing hours slept and perceived sleep quality from the night before. In morning surveys, random surveys, and substance-specific surveys, participants also reported on alcohol and cannabis craving, use, and amounts. Primary results from multilevel models demonstrated that cannabis use was not independently associated with sleep (duration or quality). However, cannabis use attenuated alcohol's negative effects on sleep quality. Results question the utility of cannabis use to improve sleep but highlight the attenuated negative effects of alcohol as a potential reinforcer of alcohol-cannabis co-use. Future work should continue to consider polysubstance use and integrate additional self-report and objective measures of sleep health to further clarify how cannabis use affects sleep.

Epigenetic and Genetic Profiling of Comorbidity Patterns among Substance Dependence Diagnoses.

This study investigated the genetic and epigenetic mechanisms underlying the comorbidity patterns of five substance dependence diagnoses (SDs; alcohol, AD; cannabis, CaD; cocaine, CoD; opioid, OD; tobacco, TD). A latent class analysis (LCA) was performed on 31,197 individuals (average age 42±11 years; 49% females) from six cohorts to identify comorbid DSM-IV SD patterns. In subsets of this sample, we tested SD-latent classes with respect to polygenic burden of psychiatric and behavioral traits and epigenome-wide changes in three population groups. An LCA identified four latent classes related to SD comorbidities: AD+TD, CoD+TD, AD+CoD+OD+TD (i.e., polysubstance use, PSU), and TD. In the epigenome-wide association analysis, SPATA4 cg02833127 was associated with CoD+TD, AD+TD, and PSU latent classes. AD+TD latent class was also associated with CpG sites located on ARID1B , NOTCH1 , SERTAD4, and SIN3B , while additional epigenome-wide significant associations with CoD+TD latent class were observed in ANO6 and MOV10 genes. PSU-latent class was also associated with a differentially methylated region in LDB1 . We also observed shared polygenic score (PGS) associations for PSU, AD+TD, and CoD+TD latent classes (i.e., attention-deficit hyperactivity disorder, anxiety, educational attainment, and schizophrenia PGS). In contrast, TD-latent class was exclusively associated with posttraumatic stress disorder-PGS. Other specific associations were observed for PSU-latent class (subjective wellbeing-PGS and neuroticism-PGS) and AD+TD-latent class (bipolar disorder-PGS). We identified shared and unique genetic and epigenetic mechanisms underlying SD comorbidity patterns. These findings highlight the importance of modeling the co-occurrence of SD diagnoses when investigating the molecular basis of addiction-related traits.

8431 Triphasic response of pituitary stalk post anoxic injury in a mechanically ventilated patient

Abstract Disclosure: P. Henriquez Feliz: None. H. Neizer: None. E. Alshdifat: None. F. Abdulkarim: None. T. Mazhude: None. T. Zahra: None. Introduction: A phenomenon may manifest wherein the pituitary undergoes a triphasic response following an inciting event. Phases include diabetes insipidus (DI) followed by Syndrome of inappropriate Antidiuretic Hormone (ADH), and finally a recurrence of DI. Research has established that this is a common complication to neurosurgical interventions but there are limited reports following anoxic brain injury. This case demonstrates a potential pituitary stalk injury after an anoxic brain injury. Case: Unknown 30 year old male found by EMS with pulseless electrical activity cardiac arrest likely from polysubstance use. Returned of spontaneous circulation after 30 minutes in the emergency department. Total downtime unknown. Managed by Intensive Care Unit. Scans were negative. Initial blood work showed eunatremia with a specific gravity (sg) 1.068 and serum osmolarity (Sosm) 311. Eventually, developed hypernatremia, 163 mmol/L, and a urine osmolarity (Uosm) of 428 mosm, raising concern for central DI (CDI). Responded to hypotonic fluids not requiring desmopressin at that time. On day 10, developed severe hyponatremia 113 mmol/L with a Uosm of 774, suggesting ADH mediated response or excessive free water intake. Sodium normalized after managed with fluid restriction. On day 16, patient developed hypernatremia, 178 mmol/L, and Uosm of 869 mosm. Suggestive of CDI recurrence. Treated with desmopressin and hydrocortisone. Discussion: Changes in water-electrolyte balances may occur after anoxic brain injury. The mechanism is believed to arise from axonal shock due to disruptions in vascular supply leading to unregulated release of ADH from degenerating posterior pituitary, causing oliguria and hyponatremia, and subsequent permanent DI from loss of neurons. These stages may last 5-7 days on initial phase, and the second phase can extend anywhere from 2-14 days. In this case, phases one and two lasted four and three days, respectively. It is important to acknowledge that timelines may vary based on management initiation and recognition of transition between stages. CDI treatment involves hypotonic fluids with desmopressin. Our patient was initially managed with free water due to low suspicion for CDI. During shift towards suspected second phase, Uosm increased, urine output and sodium dropped significantly. However, it is uncertain whether this was due to axonal injury causing SIADH or a consequence of hypotonic fluids causing increased response of ADH. As predicted during triphasic response, patient became oliguric with a net negative fluid balance of &amp;gt;10L and Uosm of 869. Therefore, desmopressin was started with good response. Further follow up was unattainable as neurological status deteriorated preceding to brain death. Most cases reported showed hypoattenuation lesion of posterior pituitary on MRI; MRI would have been required to determine if there was injury to the pituitary in this case. Presentation: 6/2/2024

8165 A Case Of Rhabdomyolysis-Induced Hypocalcemia And Hypercalcemia

Abstract Disclosure: A. Desai: None. A.L. Izzi: None. B. Flores Chang: None. A. Sajan: None. Introduction: Rhabdomyolysis is a syndrome characterized by muscle breakdown and the release of intracellular muscle contents into circulation. It is associated with electrolyte abnormalities and acute renal failure that can lead to prolonged hospitalization. We report a case of persistent hypercalcemia from recovery of acute renal failure and severe rhabdomyolysis. Case Description: A 47-year-old man with past medical history of polysubstance use initially presented with opiate-induced acute encephalopathy and respiratory failure. He developed severe rhabdomyolysis during the hospital course leading to acute renal failure requiring hemodialysis with hypocalcemia. The initial labs showed corrected calcium 6.2 mg/dL [9.2-11.0], ionized calcium 3.48 mg/dL [4.65-5.28], creatinine kinase level was &amp;gt;72,600 U/L [38-174], BUN 110 mg/dL [8-23], creatinine 7.8 mg/dL [0.6-1.2], and GFR 7 ml/min/BSA. His renal function improved over the next several days in the hospital. The serum creatinine improved to 4 mg/dL, BUN 49 mg/dL and GFR 20 ml/min/BSA respectively after couple of intermittent dialysis sessions. Six days after the last hemodialysis session, patient developed severe hypercalcemia with corrected calcium values ranging from 13.5 to 14.7 mg/dL and ionized calcium 7.41 mg/dL. Labs showed PTH 10 pg/mL [15-65], 1,25-dihydroxyvitamin D &amp;lt;10.0 pg/dL [21-65] and 25-OH Vitamin D levels 15.3 ng/ mL [30-96], which is consistent non-PTH medicated hypercalcemia. The 24-hour urine calcium was 696 mg [0-300 mg/24 hrs, 2900 cc]. PTH-related peptide was not collected. He was treated with intermittent doses of calcitonin and a single dose of pamidronate when the calcium levels were &amp;gt;13 mg/dL. Hypercalcemia resolved in eleven days after initially noted to have hypercalcemia. The corrected calcium improved to 10.1 mg/dL on the day of discharge. Discussion:Severe rhabdomyolysis is associated with acute kidney injury. The initial hypocalcemic phase during rhabdomyolysis is due to entry of calcium into damaged myocytes and deposition of calcium salts in damaged muscle. This is seen in the oliguric phase of acute kidney injury. After the recovery of rhabdomyolysis, the polyuric phase persists during renal recovery. During this time, up to one third of patients may have rebound hypercalcemia due to massive muscle calcium release. As per case reports the hypercalcemia phase lasts from 8 days to 3.5 months. In our case, the patient initially developed hypocalcemia in the oliguric phase of acute kidney injury from rhabdomyolysis. He developed hypercalcemia in the polyuric phase of renal recovery. The hypercalcemia resolved with intravenous hydration, calcitonin and pamidronate. Rhabdomyolysis is a rare cause for both hypocalcemia and hypercalcemia. Our case highlights the biphasic calcium response associated with rhabdomyolysis in the setting of renal impairment and recovery. Presentation: 6/1/2024

Consumption of oxycodone prevents oxytocin from attenuating alcohol intake in rats

Alcohol and opioid polysubstance use (PSU) is common and often accompanied by higher trait anxiety. Oxytocin decreases anxiety, alcohol- and opioid-seeking and -taking but has not been assessed in the context of PSU. Here we developed a rat model of sequential oxycodone and alcohol PSU to examine the relationship between anxiety, alcohol and oxycodone intake, and the efficacy of systemic oxytocin to attenuate alcohol intake. Male and female Sprague-Dawley rats were assessed for baseline anxiety-like behavior using acoustic startle and the elevated plus maze (EPM). Rats were then given 2-bottle choice access to oxycodone and/or water for 6-hr/day for 7 days, followed by 2-bottle choice access to alcohol (20% v/v) and/or water for five 24-hr sessions across 10 days. Next, monosubstance (oxycodone- or alcohol-alone) rats continued to have access to only one substance/day while PSU rats had access to oxycodone and water for 3-hr, followed by alcohol and water for 6-hr. After 12 days, rats were tested in the EPM 20 hours after alcohol access to examine withdrawal-related anxiety. Next, oxytocin (0, 0.3 or 1.0 mg/kg IP) was administered following the oxycodone/water session, 30 minutes prior to alcohol access. Rats received intragastric oxycodone (2 mg/kg) or water followed by intragastric alcohol (2 g/kg) and blood was collected to determine blood alcohol levels. Elevated baseline anxiety-like behavior was accompanied by reduced alcohol intake. Consumption of oxycodone did not alter alcohol intake but resulted in less anxiety-like behavior during withdrawal and prevented oxytocin from attenuating alcohol intake. Oxytocin (1 mg/kg) reduced alcohol intake in the alcohol-only condition, an effect that persisted for days after a single oxytocin administration. Rats that received oxycodone prior to non-contingent alcohol displayed higher blood alcohol levels than those that did not. These results support the necessity for the testing of medications for substance use in rodent models of PSU.

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.