Cocaine Use Research Articles

Colony-stimulating factor 2 (CSF2) as a gut microbiome dependent immune factor that alters molecular and behavioral responses to cocaine in male mice

Cocaine use disorder is a condition that leads to tremendous morbidity and mortality for which there are currently no FDA-approved pharmacotherapies. Previous research has demonstrated an important role for the resident population of bacteria of the large intestine, collectively dubbed the gut microbiome, in modulating brain and behavior in models of cocaine and other substance use disorders. Importantly, previous work has repeatedly shown that depletion of the gut microbiome leads to increased cocaine taking and seeking behaviors in multiple models. While the precise mechanism of these gut-brain signaling pathways in models of cocaine use is not fully clear, and intriguing possibility is through gut microbiome influences on innate immune system function. In this manuscript we identify the cytokine colony stimulating factor 2 (CSF2) as an immune factor that is increased by cocaine in a gut microbiome dependent manner. Peripherally injected CSF2 crosses the blood–brain barrier into the nucleus accumbens, a brain region central to behavioral responses to cocaine. Treatment with peripheral CSF2 reduces acute and sensitized locomotor responses to cocaine as well as reducing cocaine place preference at high doses. On a molecular level, we find that peripheral injections of CSF2 alter the transcriptional response to both acute and repeated cocaine in the nucleus accumbens. Finally, treatment of microbiome depleted mice with CSF2 reverses the behavioral effects of microbiome depletion on the conditioned place preference assay. Taken together, this work identifies an innate immune factor that represents a novel gut-brain signaling cascade in models of cocaine use and lays the foundations for further translational work targeting this pathway.

Illicit cocaine and opioid drug-related maxillofacial trauma: a 10-year review of a state-wide database of all hospitals admissions

The aim of this study was to investigate the characteristics of illicit cocaine and opioid drug-related facial trauma and determine whether the presence of cocaine or opioid drug use in facial trauma patients influenced the cause of injury, morbidity, or management. A retrospective observational cohort study was performed using records from a state-wide database of all patients who presented to a Victorian hospital with a facial fracture between 2004 and 2014. Data collected included demographics, concomitant opioid and cocaine use, mechanism of injury, facial injuries, and management. Statistical analysis was done using chi-square test, Student's t tests, binary logistic regression analysis, and multivariable linear regression analysis. Results were considered statistically significant if P < .05. A total of 54,613 patient presentations for facial trauma were analyzed with 363 patients in the cocaine and opioid-related group, and 54,250 patients in the nondrug-related group. Patients with illicit drug use were more likely to have facial fractures caused by interpersonal violence when compared with nondrug users (47.9% vs 23.5%, OR = 2.23, P < .001). Opioid and cocaine users had 0.3 more total fractures per presentation, which included more midface and skull fractures, and more facial lacerations (P < .001). There was no statistically significant difference in the need for surgical management between the two groups. Opioid and cocaine affected patients also on average had a longer hospital stay of 3.4 days and required 0.9 more allied health inputs during their admission when compared with nondrug users (P < .05). This effect was similarly reflected when controlling for confounding variables (P < .001). Concomitant cocaine or opioid use in facial trauma patients leads to more violence-related injuries with higher morbidity and healthcare costs.

The activity-regulated cytoskeleton-associated protein (Arc) functions in a cell type- and sex-specific manner in the adult nucleus accumbens to regulate non-contingent cocaine behaviors.

Repeated cocaine use produces adaptations in brain function that contribute to long-lasting behaviors associated with cocaine use disorder (CUD). In rodents, the activity-regulated cytoskeleton-associated protein (Arc) can regulate glutamatergic synaptic transmission, and cocaine regulates Arc expression and subcellular localization in multiple brain regions, including the nucleus accumbens (NAc)-a brain region linked to CUD-related behavior. We show here that repeated, non-contingent cocaine administration in global Arc KO male mice produced a dramatic hypersensitization of cocaine locomotor responses and drug experience-dependent sensitization of conditioned place preference (CPP). In contrast to the global Arc KO mice, viral-mediated reduction of Arc in the adult male, but not female, NAc (shArcNAc) reduced both CPP and cocaine-induced locomotor activity, but without altering basal miniature or evoked glutamatergic synaptic transmission. Interestingly, cell type-specific knockdown of Arc in D1 dopamine receptor-expressing NAc neurons reduced cocaine-induced locomotor sensitization, but not cocaine CPP; whereas, Arc knockdown in D2 dopamine receptor-expressing NAc neurons reduced cocaine CPP, but not cocaine-induced locomotion. Taken together, our findings reveal that global, developmental loss of Arc produces hypersensitized cocaine responses; however, these effects cannot be explained by Arc's function in the adult mouse NAc since Arc is required in a cell type- and sex-specific manner to support cocaine-context associations and locomotor responses.

Safety of Stress Testing With Cocaine Use

Safety of Stress Testing With Cocaine Use

Modeling impaired insight after drug use in rodents.

Impaired insight in substance use disorder has been argued to reflect a global deficit in using cognitive models to mentally simulate possible future outcomes. The process of mentally simulating outcomes allows us to understand our beliefs about their causes, that is, to have insight and thereby avoid potentially negative outcomes. However, work in humans cannot address whether impaired insight and its neural/neurochemical sequalae are present prior to the development of a substance use disorder, a consequence of substance use, or a combination of both. This is because baseline measurements prior to drug use are not possible in humans. However, if these changes can be directly caused by drug use, then in animal models, a history of drug use should cause impairments in behavioral tasks designed to assess such inferences. Focusing on cocaine use, here we will review several lines of research from our laboratory that have tested this question using learning-theory tasks designed to isolate insight. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

The Efficacy of GLP-1 Agonists in Treating Substance Use Disorder in Patients: A Scoping Review.

Substance use disorder (SUD) continues to be a leading cause of morbidity and mortality with limited treatments. There is interest in expanding the use of GLP-1 agonists in treating SUD. However, evidence for safety and efficacy in humans is limited. This review aims to bridge the existing knowledge gap by establishing a baseline of literature in this area to inform future trials and clinical practice. Our inclusion criteria were English peer-reviewed manuscripts reporting on use of GLP-1, GIP, and/or glucagon receptor agonists in treatment of SUDs, excluding case studies. The literature search was performed in accordance to PRISMA guidelines. Five studies were included in this review examining the use of this medication in tobacco use disorder, alcohol use disorder, and cocaine use disorder. No studies regarding substance withdrawal syndrome were identified. The included studies varied widely in terms of patient selection, dose/formulation of GLP-1 agonists, and follow-up. The results of this scoping review are mixed, with 3 studies demonstrating positive results and 2 studies finding no efficacy of this medication on SUD outcomes. It is premature to prescribe this medication off-label to patients. Further research is needed to determine the efficacy of GLP-1 agonists in treating SUD.

Large Intra-Coronary Thrombus Induced by Cocaine Use

Large Intra-Coronary Thrombus Induced by Cocaine Use

Readmission and Dropout in Outpatient Centers: An Analysis of Real-World Data in Patients with Dual-Diagnosis

AbstractSubstance use disorder treatment faces challenges such as dropout, relapse, and readmission. This study aims to identify factors associated with readmission and those influencing dropout among dual diagnosis (DD) patients (those with both a substance use disorder and another psychiatric disorder) attending outpatient addiction centers. Retrospective cohort study using the electronic health records of 8383 outpatients diagnosed with DD. Bivariate analysis and regression analysis were applied to control for the variables. Age, incarceration for 30 days prior to admission, and specific patterns of consumption increased the likelihood of readmission. Specifically, individuals who reported no substance use in the 30 days before admission or those diagnosed with an opioid or cocaine use disorder were particularly susceptible to readmission. Of the dual diagnoses, patients with personality disorders were more likely to be readmitted. In relation to dropout, opioid dependence and frequency of use were associated with a higher probability of dropout. Patients with poorer adherence to treatment and previous readmissions were also more likely to drop out. Enhancing treatment adherence and reducing dropout and readmission rates poses a challenge in managing patients with DD. Leveraging electronic health records offers enhanced ecological validity concerning the outpatient treatment requirements for such patients. Therapeutic adherence, alongside specific sociodemographic variables and consumption patterns, emerges as pivotal factors in this context. Identifying and understanding these variables facilitates the customization of outpatient treatment strategies to better meet the needs of patients with comorbidities.

Malignant Catatonia in the Setting of Acute Methamphetamine and Cocaine Intoxication.

Malignant catatonia is a potentially lethal neuropsychiatric syndrome characterized by psychomotor abnormalities and autonomic instability. Patients with this syndrome require immediate treatment. Various psychiatric conditions and nonpsychiatric medical problems can trigger malignant catatonia. Use of psychostimulant drugs, including methamphetamine and cocaine, has not been previously reported to precipitate malignant catatonia. This case concerns a 35-year-old man hospitalized for psychosis due to methamphetamine and cocaine intoxication. He developed malignant catatonia the day after admission. He was treated with lorazepam for malignant catatonia, and his blood pressure was controlled with clonidine. Over 7 days, his condition resolved, and his mental status and vital signs returned to baseline. He was discharged to the community in stable condition and has returned to his baseline functional status. He remains free of catatonia and has maintained abstinence from methamphetamine and cocaine. Acute intoxication with psychostimulant drugs is a possible trigger for malignant catatonia, and administration of high potency first-generation antipsychotics in this setting may increase the risk. Patients hospitalized for stimulant intoxication should be monitored for signs and symptoms of catatonia, and D2 receptor antagonist medications should be used with caution in this population. Our case supports the potential role of altered dopamine and norepinephrine signaling in the pathogenesis of malignant catatonia. The patient provided written and verbal consent to publish the information in this case report.

Substance Use Among Illinois Farmers

Background: People in agriculture face unique stressors and occupational hazards, and relatively little is known about substance use in this population. The purpose of this study was to describe substance use among farmers in Illinois. Methods: We conducted a mail survey of Illinois farmers that included the Brief ASSIST to assess substance use for lifetime and past three-month use of ten different substances. The survey also included questions about farming characteristics, mental health, stress, coping, social support, and demographic characteristics. We used chi-square and non-parametric tests to assess group differences. Results: Alcohol, tobacco, cannabis, and sedatives were most reported as used for a lifetime and in the past three months. About three-quarters of the sample had recently used alcohol. Recent tobacco use was associated with not being married, less education, and less concern about climate-related farm stress. Recent sedative use was associated with greater concern about isolation-related farm stress. People who reported multiple substance use were at a greater risk for suicide and were more likely to meet the criteria for generalized anxiety disorder. None of the participants reported recent use of cocaine, heroin, inhalants, or hallucinogens. Conclusion: Specific social and cultural aspects of farming and farm communities may contribute to substance use among people working in agriculture. Future research can help to better understand this intersection and make recommendations for programs and resources to promote adaptive coping strategies.

Prospective Intergenerational Associations between Parents’ and Children’s Illicit Substance Use During Adolescence

Objective Intergenerational studies have identified relations between adolescents’ and their future offspring’s cannabis and alcohol use, but rarely have examined the association for other illicit drug use. Given the low prevalence of such use in community populations, we pooled data from three prospective intergenerational studies to test this link. Method Participants were 1,060 children of 937 parents who had been repeatedly assessed since early adolescence. Children and parents reported on their use of cocaine, stimulants, hallucinogens, sedatives/tranquilizers, and opiates/narcotics from ages 10 to 18 years. Intergenerational similarities in any versus no use of these drugs were formally modeled using logistic regression. Patterns also were descriptively analyzed. Results Parent illicit substance use was associated with significantly higher odds of child use (adjusted odds ratio [95% confidence interval] = 2.682 [1.328–5.416], p = 0.006). However, intergenerational continuity was modest; 87% of children whose parent used illicit drugs in adolescence did not use such drugs, and 77% of parents of children who used illicit drugs had not themselves used these drugs during adolescence. Conclusions The use of illicit substances by parents during their teenage years poses a risk for their offspring’s similar behaviors. However, the discontinuity of these behaviors across generations implies children are largely resilient to or protected from this risk, and conversely that other aspects of parents’ and children’s experiences or characteristics may be more powerful risks for children’s illicit drug use than this transgenerational influence.

Street adolescents in low income setting exposed to hepatitis B and C, and disadvantaged by lifestyle: a Togolese cross-sectional study

BackgroundIn Togo, few data are available on viral hepatitis in street adolescents, a vulnerable population due to their lifestyle. The aim of this study was to describe the lifestyle of street adolescents (sexual practices and drug use), to estimate the prevalence of hepatitis B and C viruses, and to describe their HBV immunization profile in Togo.MethodsA cross-sectional study was conducted in Lomé (Togo) in July 2021. Street adolescents aged between 13 and 19 years were included. A questionnaire was used to document lifestyle. ELISA tests were performed for Hepatitis B surface antigen (HBsAg), Hepatitis B core and surface antibodies (anti-HBc, anti-HBs), and antibodies against hepatitis C virus (anti-HCV).ResultsA total of 299 adolescents (5.4% female) with a median age of 15 years (IQR: 14–17) were included. Of these, 70.6% (211/299) were sexually active and 70.6% (149/211) had not used a condom during their last sexual intercourse. Drug use was reported by 42.1% of the adolescents. The most used substances were cannabis (39.0%), cocaine (36.6%), glue solvents (19.5%), and tramadol (11.4%). However, cocaine use may have been overestimated due to information bias. Current HBV infection (HBsAg+) was detected in 3.7% (95%CI: 1.9–6.5) of the adolescents. Isolated anti-HBc + was present in 5.3%. All three HBV markers (HBsAg, anti-HBs, and anti-HBc) were negative in 71.6% of adolescents. Anti-HCV was detected in 4.7% of adolescents.ConclusionNearly one in 10 street adolescents has markers for HBV contact/current infection, and approximately 72% of street adolescents may still be infected with HBV, as they have no HBV markers. HCV is also circulating in this population. Given the reported high-risk sexual practices and high levels of drug use, there is an urgent need to develop integrated strategies to prevent infections, including HBV, and drug dependence in this population.

Substance Use Disorder as Risk Factor for Intubation in Angioedema: A Nationwide Cohort Study.

Individuals with angioedema (AE) are at high risk for airway compromise and often require endotracheal intubation. Patient factors predisposing one to airway compromise are not well described. The objective of this study is to examine whether substance use disorder (SUD) in patients with AE is associated with need for airway intervention. This population-based retrospective cohort study compared AE patients with SUD versus propensity-matched control groups. Outcomes were hospitalization, intubation, and tracheotomy. Using the TriNetX National Database, this study included 28,931 patients with SUD and 117,509 patients without SUD who presented with AE. Among patients with AE, those with each subtype of SUD (alcohol, cannabis, cocaine, tobacco, and opioids) were found to have higher risk of severe AE compared to propensity-matched non-SUD cohorts. Rate of hospitalization after cohort matching ranged from 20.4% for tobacco use disorder to 30.4% for cocaine use disorder, all significantly higher than the 8.0% in a population without SUD. Each SUD subtype was associated with a higher rate of intubation compared with matched non-SUD groups, with cannabis use disorder having the highest relative risk (RR) of 3.67 (95% CI: 2.69-5.02). Tobacco (RR = 2.45, 95% CI: 1.79-3.34) and alcohol (RR = 2.82, 95% CI: 1.73-4.58) use disorders were both associated with significantly higher risk of tracheotomy. These data suggest that patients with SUD, regardless of subtype, and after propensity matching for demographics and comorbidities are at higher risk for adverse outcomes when presenting with AE. This study highlights clinically relevant predictors of airway compromise. Level 3 Laryngoscope, 2024.

T46 - A Longitudinal Analysis of Time in Buprenorphine Treatment States and Stratification by Hazardous Alcohol Use, Cocaine Use and Alcohol or Cocaine Use Disorders Among People With HIV

T46 - A Longitudinal Analysis of Time in Buprenorphine Treatment States and Stratification by Hazardous Alcohol Use, Cocaine Use and Alcohol or Cocaine Use Disorders Among People With HIV

The positive reinforcing effects of cocaine and opposite-sex social contact: roles of biological sex and estrus.

Preclinical studies report that drug use and social contact mutually influence the reinforcing effects of one another. Most of these studies have used same-sex dyads exclusively, and the role of factors related to biological sex and hormonal fluctuations are not well understood. The purpose of this study was to examine the reinforcing effects of cocaine and social contact with an opposite-sex partner in male and female rats, and how these effects are modulated by ovarian hormones. Male and female rats were trained in a nonexclusive choice procedure in which cocaine and social contact with an opposite-sex partner were simultaneously available on concurrent progressive ratio schedules of reinforcement. To examine the effects of ovarian hormones related to estrous cycling, Experiment 1 used naturally cycling, gonadally intact females, whereas Experiment 2 used ovariectomized females, and estrus was artificially induced with exogenous hormones. In both experiments, cocaine and social contact functioned as robust reinforcers, and there were no significant effects of biological sex or estrus status of the females. The positive reinforcing effects of both cocaine and social contact increased as a function of cocaine dose, indicating that contingent cocaine administration increases the reinforcing effects of social contact. These data suggest that cocaine use among opposite-sex partners may enhance factors that contribute to social bonding.

T63 - Association of Prescribed Oral Stimulants on Cocaine Use Among Patients Enrolled in Opioid Agonist Treatment: A Retrospective Longitudinal Cohort Study

T63 - Association of Prescribed Oral Stimulants on Cocaine Use Among Patients Enrolled in Opioid Agonist Treatment: A Retrospective Longitudinal Cohort Study

Treatment Seeking Nitrous Oxide Users in Addiction Care: A Comparison with Cocaine Users on Clinical and Treatment Characteristics

Introduction: Over the past decade, frequent use of large quantities of nitrous oxide (N2O) has become more common in the Netherlands. Although N2O poses several negative health consequences for a subgroup of problematic N2O users, there is a lack of knowledge on what characterizes these intensive users. This study therefore aims to provide the demographic and substance use characteristics and experiences during treatment of treatment seeking problematic N2O users and to compare this with a matched group of treatment-seeking problematic cocaine users. Methods: A retrospective chart review was performed of patients who were referred for treatment of problematic N2O use at a large Dutch addiction care facility from January 2020 to September 2022, extracting demographics, pattern of use and follow-up data. Additionally, a subgroup of N2O users was propensity-score matched (1:1) with a subgroup of treatment seeking problematic cocaine users, both groups excluding users with substance use disorders or frequent use of substances other than N2O and cocaine, respectively. Results: 128 patients with a N2O use disorder were included in the total sample and a subgroup of 77 N2O-only users was propensity-score matched on age and sex to 77 cocaine-only users. N2O users were typically young (mean age 26.2 years), male (66.4%), unmarried (82.9%), with a low education level (59.0%) and born in the Netherlands (88.2%), with parents born in Morocco (45.3%). N2O was used intermittently (median 10 days/month, IQR 4.0–17.5 days) and often in very large quantities (median 5 kg [ca. 750 balloons] per average using day, IQR 2–10 kg). Compared to the patients with a cocaine use disorder, matched N2O users were lower educated, more often from Moroccan descent, and less likely to be alcohol or polysubstance users. Despite receiving similar treatments, N2O users were twice as likely to discontinue treatment before completion compared to cocaine users (63 vs. 35%, p = 0.004). Conclusion: Treatment-seeking problematic N2O users are demographically different from treatment-seeking problematic cocaine users and are much more likely to dropout from psychological treatment. Further research is needed into the needs and other factors of problematic N2O users that relate to poor treatment adherence in problematic N2O users.

Dynamic alterations in gene co-expression networks and gene-transcript associations characterize co-morbidities in cocaine use disorder.

Individuals with cocaine use disorder (CUD) who attempt abstinence experience craving and relapse, which poses challenges in treatment. Longitudinal studies linking behavioral manifestations in CUD to the blood transcriptome in living individuals are limited. Therefore, we investigated the connection between drug use behaviors during abstinence with blood transcriptomics. We conducted a comprehensive longitudinal study involving 12 subjects (9 males, 3 females) with CUD and RNA sequencing on blood collected at a drug-free baseline, and 3, 6 & 9 months thereafter. We categorized subjects into 2 responder groups (high-low) based on scores of drug use variables, and 3 responder groups (low-intermediate-high) on days of abstinence. We investigated differential expression and gene-transcript associations across responder groups at each time point. Lastly, we examined genes that are both co-expressed and showed dynamic expression with time. Genes with significant transcript associations between high and. intermediate days of abstinence at 9 months were notably enriched for cannabis use disorder, drinks weekly, and coronary artery disease risk genes. Time-specific gene co-expression analysis prioritized transcripts related to immune processes, cell cycle, RNA-protein synthesis, and second messenger signaling for days of abstinence. We demonstrate that abstinence reflects robust changes in drug use behaviors and the blood transcriptome in CUD. We also highlight the importance of longitudinal studies to capture complex biological processes during abstinence in CUD.

Perineuronal Nets in the Rat Medial Prefrontal Cortex Alter Hippocampal-Prefrontal Oscillations and Reshape Cocaine Self-Administration Memories.

The medial prefrontal cortex (mPFC) is a major contributor to relapse to cocaine in humans and to reinstatement in rodent models of cocaine use disorder. The output from the mPFC is potently modulated by parvalbumin (PV)-containing fast-spiking interneurons, the majority of which are surrounded by perineuronal nets. We previously showed that treatment with chondroitinase ABC (ABC) reduced the consolidation and reconsolidation of a cocaine conditioned place preference memory. However, self-administration memories are more difficult to disrupt. Here we report in male rats that ABC treatment in the mPFC attenuated the consolidation and blocked the reconsolidation of a cocaine self-administration memory. However, reconsolidation was blocked when rats were given a novel, but not familiar, type of retrieval session. Furthermore, ABC treatment prior to, but not after, memory retrieval blocked reconsolidation. This same treatment did not alter a sucrose memory, indicating specificity for cocaine-induced memory. In naive rats, ABC treatment in the mPFC altered levels of PV intensity and cell firing properties. In vivo recordings from the mPFC and dorsal hippocampus (dHIP) during the novel retrieval session revealed that ABC prevented reward-associated increases in high-frequency oscillations and synchrony of these oscillations between the dHIP and mPFC. Together, this is the first study to show that ABC treatment disrupts reconsolidation of the original memory when combined with a novel retrieval session that elicits coupling between the dHIP and mPFC. This coupling after ABC treatment may serve as a fundamental signature for how to disrupt reconsolidation of cocaine memories and reduce relapse.

Assessing daily patterns in stimulant use during the COVID-19 pandemic in Melbourne, Australia using wastewater analysis

During the COVID-19 pandemic, one of Australia’s biggest cities, Melbourne, experienced three major isolation (“lockdown”) periods in 2020 (160 days) and in 2021 (111 days) which makes it one of the most locked down cities world-wide. This study assessed how the pandemic affected temporal trends in methamphetamine, MDMA and cocaine consumption using wastewater-based epidemiology. Daily samples were collected for most of 2020 and 2021 (n = 660 days). Concentrations were measured using direct-injection LC-MS/MS and back-calculated to consumption estimates. Results indicate that methamphetamine use was increasing before the first lockdown and decreased after the end of the first lockdown in 2020. Methamphetamine trends appeared to have remained steady throughout the second lockdown period before increasing steeply after it ended. For most of 2020, cocaine use remained steady, with an increase after the second lockdown. MDMA use decreased after the start of the first lockdown and remained steady throughout most of 2020 and 2021. In comparison to 2020, trends in 2021 were less variable and stimulant use did not appear to be as associated with COVID-19 restrictions. Overall, this study was able to show the impact of lockdown periods and the related social restrictions on illicit stimulant use. Environmental ImplicationIllicit drugs are hazardous chemicals, of concern both to humans and the environment. While studies have been undertaken to understand their temporal trends, this work utilizes wastewater-based epidemiology and daily sampling to provide a comprehensive understanding of the impact of the COVID-19 pandemic on the use of methamphetamine, MDMA and cocaine on one of the most locked-down cities in the world. Understanding the consequences of this significant intervention on illicit drug use could provide valuable insights into its potential environmental impact.