History Of Cocaine Research Articles

Replication and extension of the subregion selectivity of glutamate-related changes within the nucleus accumbens associated with the incubation of cocaine-craving

Cue-elicited drug-seeking behavior intensifies with the passage of time during withdrawal from drug taking and this “incubation of cocaine-craving” involves alterations in nucleus accumbens (NA) glutamate transmission. Here, we employed a combination of in vivo microdialysis and immunoblotting approaches to further examine changes in biochemical indices of glutamate transmission within NA subregions that accompany the incubation of cocaine-craving exhibited by male rats with a 10-day history of 6-h access to intravenous cocaine (0.25 mg/infusion). Immunoblotting on whole cell lysates from the core subregion (NAc core) revealed interactions between cocaine self-administration history, withdrawal and drug cue re-exposure for Homer2a/b, mGlu1, and GluN2b expression, as well as indices of Akt and ERK activity. With the exception of PKCε phosphorylation, most protein changes within the shell subregion (NAc shell) depended on drug cue re-exposure and cocaine history rather than varying in a consistent time-dependent manner. Reduced basal extracellular glutamate content was apparent only in the NAc core of cocaine-experienced rats during protracted (30 days) withdrawal and this was accompanied by a markedly blunted capacity of the mGlu1/5 agonist DHPG to elevate glutamate levels within this subregion. Finally, over-expressing neither Homer1c nor Homer2b within the NAc core during protracted cocaine withdrawal altered the magnitude of cue-elicited responding, its extinction or cocaine-primed reinstatement of drug-seeking behavior. The present findings are consistent with the extant literature implicating changes in Group 1 mGlu receptor function within the NAc core subregion as central to incubated cocaine-craving and provide further evidence against a major role for Homer proteins in gating incubated cocaine-craving. Further, our results provide novel correlational evidence implicating elevated Akt and blunted ERK activity within the NAc core as potential contributors to the expression of incubated cocaine-craving, worthy of future investigation.

Endogenous Regulator of G protein Signaling 14 (RGS14) suppresses cocaine-induced emotionally motivated behaviors in female mice.

Addictive drugs hijack the neuronal mechanisms of learning and memory in motivation and emotion processing circuits to reinforce their own use. Regulator of G-protein Signaling 14 (RGS14) is a natural suppressor of post-synaptic plasticity underlying learning and memory in the hippocampus. The present study used immunofluorescence and RGS14 knockout mice to assess the role of RGS14 in behavioral plasticity and reward learning induced by chronic cocaine in emotional-motivational circuits. We report that RGS14 is strongly expressed in discrete regions of the ventral striatum and extended amygdala in wild-type mice, and is co-expressed with D1 and D2 dopamine receptors in neurons of the nucleus accumbens (NAc). Of note, we found that RGS14 is upregulated in the NAc in mice with chronic cocaine history following acute cocaine treatment. We found significantly increased cocaine-induced locomotor sensitization, as well as enhanced conditioned place preference and conditioned locomotor activity in RGS14-deficient mice compared to wild-type littermates. Together, these findings suggest that endogenous RGS14 suppresses cocaine-induced plasticity in emotional-motivational circuits, implicating RGS14 as a protective agent against the maladaptive neuroplastic changes that occur during addiction.

Limits and pitfalls in a lethal infant cocaine intoxication

ABSTRACT The case concerns the first Italian report of a fatal cocaine intoxication in an 8-month-old baby girl found dead in the cradle by her parents at 6 am on a summer day. At arrival to the emergency department, the doctors declared the baby dead and the Prosecutor Office ordered an autopsy and toxicological analyses. Despite no history of cocaine use/abuse by both parents, toxicological analyses evidenced a positivity to cocaine in the post-mortem blood, brain and liver. The legal physician concluded for a fatal cocaine intoxication. A crucial aspect to the Court was to discriminate between administration (accidental or voluntary) and intake (almost accidentally), due to different legal consequences for parents (i.e. voluntary homicide or inadequate supervision). In the here presented case discriminating the exact intake was almost impossible in terms of certainty. Such difficulty mainly derived from lacks in the investigation activities in the first hours following the death. Among all possible intake routes, the ‘most probable’ was the accidental one, mostly attributable to a cradle contamination. A lack in the site inspection protocol could strongly affect the case solution making it impossible to offer the Court a definitive ‘scientific’ solution to the case (based on scientifically irrefutable data).

545 A PRospective, Case-controlled Evaluation of oLIceridine for Moderate or sEVEre Pain After Burn Injury. (RELIEVE)

Abstract Introduction After acute burn injury, injured tissue and adjacent non-burned tissue, upregulate response to painful and non-painful stimulus (hyperalgesia and allodynia, respectively). Currently, high-dose fentanyl, oxycodone, hydromorphone, and morphine are used at profound doses to mitigate pain. Oliceridine (OLI), a biased, selective opioid agonist, has shown a 3-fold preferential activation of the G-protein (i.e., analgesia) over β-arrestin pathway. There is no literature of use in patients with burn injuries. We hypothesized the use of OLI would provide adequate and safe analgesia after acute burn injury. Methods This single-center, prospective, case-controlled trial was dual IRB approved and included patients with burn injuries admitted between April and September 2023. Informed consent was obtained from the 10 patients receiving OLI. OLI was the only allowed analgesic except for acetaminophen. Dosing and assessments were followed per study protocol and safety and efficacy assessed per study team daily at a minimum. The historical control (CTL) group (i.e., fentanyl, oxycodone, hydromorphone, morphine, etc) was matched 2:1 with the prospective OLI group. The CTL were screened in reverse chronology to find comparable groups according to age, % total body surface area burned (TBSA), history of opioid and illicit drug use, and number of operations. SAS 9.4 was used for descriptive statistics and modelling via UNIVARIATE and GLM procedures. Results Two CTL patients were excluded in the final analysis due to missing assessments. The OLI (n = 10) and CTL (n = 18) groups were comparable in age (52.3 ± 12.3 vs 63.1 ± 17.3 years, p = 0.228), TBSA [8 (3.3, 11.2) vs 6 (2.6, 9.3) percent], operations (0.5 per patient for both), and burn mechanism. No patient had a known history of opioid, cocaine, or methamphetamine use. The baseline Numeric Pain Rating Scale (NRS) for OLI and CTL were similar [9 (7.8, 10) vs 9.5 (8.8, 10); p = 0.360); however, the first day’s mean pain score was higher for CTL (4.8 vs. 5.9, p = 0.035). Over the 7-day period, mean daily pain scores significantly declined in patients receiving OLI (-2.65, p = 0.010), but not for CTL (+0.69, p = 0.496). Whereas, opioid usage [i.e., oral morphine milligram equivalents (MME)] was not significantly different across groups (p = 0.689) or days (p = 0.684). Total MME averaged per patient day were 65.2 and 69.6 mg/day in the OLI and control groups, respectively (P = 0.688). There were no unexpected adverse events related to OLI. Conclusions Although this sample of 10 patients limits inferences outside of acute burn injuries less than 20% TBSA, OLI demonstrated significant pain relief, which was maintained over the 7 days study period. Importantly, the control group demonstrated initial relief, but was not maintained, despite similar MME. Applicability of Research to Practice Oliceridine offers an effective solution for analgesia in patients with acute burn injury.

Addiction and pregnancy: case report on gender perspective.

IntroductionIn recent years, interest has grown in understanding the particularities of addiction in women. One of these singularities, with an important impact on public health, is pregnancy. Substance use during pregnancy has increased in recent decades. Given that addiction is mainly a chronic disease of the brain circuits of reward, motivation and memory, an event such as pregnancy does not exempt people who suffer from substance use disorder (SUD) from the difficulties of achieving abstinence. Moreover, as addiction often involves cycles of relapse and remission, pregnant women can also suffer a relapse even if they previously had achieved abstinence. On the other hand, given that addiction is a disease with a significant social component, we can find patients in precarious economic and social situations who suffer unwanted and therefore unplanned pregnancies.ObjectivesTo describe the case of a pregnant woman with SUD for multiple drugs who is admitted to the inpatient ward of the Hospital Clínic of Barcelona for detoxification. Also to reflect, taking in to account gender perspective, on the particularities of substance use in women on childbearing age.MethodsWe present the case of a 25-year-old woman, six weeks pregnant and homeless, who was admitted to the inpatient ward for presumed psychotic symptoms. Even if the patient had a history of intravenous heroin, cocaine, and methamphetamine use, during the admission she only admitted current alcohol consumption (3 UBE/day). During admission, the patient decided to undergo a legal voluntary abortion. Regarding this case, we did a literature review on the consequences of different substances use to pregnancy (to both the fetus and the mother’s health). Likewise, we reflected on interventions that could be carried out in community mental health facilities to detect cases like the one exposed and provide help.Results Poor obstetric outcomes are six times higher in patients who use substances. Newborns can have withdrawal syndrome, spontaneous abortion, pre-term birth, fetal malformations and fetal growth restriction. More than 50% of women of reproductive age use drugs, mainly alcohol. Routine screening and education of women of reproductive age is the best way to reduce substance use during pregnancy.ConclusionsWe consider it essential for a better management of these patients to remember that the evidence suggests that the decisions that addicts make are mainly driven by a pathology, not by a moral failure. However, pregnancy can be a moment of greater motivation to stop using drugs, given that it is a high risk situation for the mother and the fetus.Disclosure of InterestNone Declared

Beyond cocaine and heroin use: a stacking ensemble-based framework for predicting the likelihood of subsequent substance use disorder using demographics and personality traits

Heroin and cocaine addiction is a global health issue that can result in death. These substances have the ability to change cognitive functions and impulsive behavior control. This study explores the relationship between heroin and cocaine use and the development of additional psychoactive substance addictions, such as cannabis and nicotine. It also investigates whether lighter drug use, like cannabis, leads to heavier drug use. Using subsets of heroin, cocaine, and cannabis data for neural network model training, stacking ensemble learning is employed to uncover these connections. These models predict the risk of subsequent substance abuse based on the history of heroin, cocaine, or cannabis abuse, incorporating demographic factors and personality traits. Results reveal significant impacts: Heroin abuse substantially increases the risk of cannabis and nicotine use (F-scores of 0.95 and 0.94, respectively). Cocaine abuse shows an even stronger association (Accuracy: 0.88) and can lead to heroin and cannabis use. Additionally, cannabis use is linked to subsequent cocaine use. These results have important implications for precision medicine, emphasizing the importance of personalized medications in preventing subsequent addiction development.

Episodic Cocaine Use as a Cause of Venous Thromboembolism and Acute Liver Injury.

BACKGROUND Pulmonary embolism secondary to deep vein thrombosis (DVT) with cor pulmonale is commonly associated with risk factors including surgery, cancer, and prolonged immobility. Cocaine is known to cause vasoconstriction and has a prothrombotic effect. Prolonged and heavy use of cocaine can also cause inflammation and liver damage. However, data on its potential role in causing pulmonary embolism and direct hepatotoxicity in cases of episodic use are scarce. CASE REPORT A 34-year-old man with no significant medical history except for episodic cocaine use presented in respiratory distress. Workup revealed submassive pulmonary embolism with pulmonary infarctions complicated by pneumonia, hypoxemic respiratory failure, and anemia. He was treated with anticoagulation and intensive care. On day 5 of hospitalization, the patient had an acute hepatic injury. His alanine aminotransferase level peaked at over 2000 IU/L on day 7, until finally tapering. Liver failure was found to be secondary to cocaine use. Liver enzyme levels improved with supportive care. He was discharged with apixaban and continued liver enzyme monitoring. CONCLUSIONS When investigating the cause of venous thromboembolism and transaminitis, evaluating cocaine use via patient history or laboratory analysis of cocaine and its metabolites should be considered. Cocaine is known to cause vasoconstriction and has a prothrombotic effect, although data on its potential role in causing pulmonary embolism and direct hepatotoxicity in cases of episodic use are scarce. Further investigation, such as cohort studies, could help strengthen our understanding of the relationship between cocaine use, acute hepatic injury, and pulmonary embolism.

Cocaine history and impulsiveness in professional boxers and mixed martial arts fighters.

Impulsiveness is linked to cocaine history (CH) in the general population and greater fight exposure in professional fighters. Among fighters, no previous studies have quantified CH or investigated its relationship with impulsiveness. Adjusted multivariable regressions were utilized to examine the relationship between CH and impulsiveness in 335 fighters from the Professional Fighters Brain Health Study. Twenty percent of fighters reported CH. CH was significantly associated with impulsiveness overall and on three subscales. Cocaine's prevalence and significant association with impulsiveness in fighters merit further study. We quantify CH and demonstrate its significant association with impulsiveness in professional fighters for the first time.

The Relationship between Substance Use Stigma and COVID-19 Vaccine Hesitancy.

Two parallel public health epidemics affecting the United States include the COVID-19 pandemic and a rise in substance use disorders (SUDs). Limited research has examined the potential relationship between these two epidemics. Our objective was therefore to perform an exploratory study in order to examine the association between public stigma toward people with a past history of opioid, methamphetamine, cocaine, and alcohol use disorder and COVID-19 vaccine hesitancy. A national sample of U.S. adults (N = 6515) completed a survey which assessed the degree of negative perceptions toward individuals with a past history of substance use disorders (referred to as substance use stigma) and COVID-19 vaccine hesitancy, along with variables such as racial prejudice, source of health news, and other demographics. We evaluated four multivariable logistic regression models to predict COVID-19 vaccine hesitancy, utilizing substance use stigma toward opioids, methamphetamine, cocaine, and alcohol use as independent variables. We found that COVID-19 vaccine hesitancy was positively associated with substance use stigma toward opioid (AOR = 1.34, p < 0.05), methamphetamine (AOR = 1.40, p < 0.01), and cocaine (AOR = 1.28, p < 0.05) use, but not alcohol use (AOR = 1.06, n.s.). Predictive models that incorporate substance use stigma may therefore improve our ability to identify individuals that may benefit from vaccine hesitancy interventions. Future research to understand the underlying reasons behind the association between substance use stigma and COVID-19 vaccine hesitancy may help us to construct combined interventions which address belief systems that promote both substance use stigma and vaccine hesitancy.

Disseminated Necrotic Suppurative Ulcers as a Manifestation of Cocaine Abuse.

Pyoderma gangrenosum is an immune-mediated illness that can be caused by several affections, such as inflammatory bowel disease, rheumatoid arthritis, and drug use. We present a rare case of pyoderma gangrenosum induced by levamisole-adulterated cocaine. There have been few cases of this disease reported in the world. Levamisole is an anthelmintic drug used to adulterate cocaine to boost its effect. It also has immune-modulating effects causing, among others, vasculitis and dermatological problems. Clinical case of a 46-year-old man admitted to the hospital University Marqués de Valdecilla in Santander, Spain, in August 2022. We diagnosed pyoderma gangrenosum based on clinical, analytical, and histological parameters. We report a case of pyoderma gangrenosum induced by consumption of levamisole-adulterated cocaine. This patient suffered from a rare and extensive immune-mediated affection with characteristic primary lesions in the form of suppurative ulcers that responded to immunosuppressive treatment. Behind pyoderma gangrenosum there may be underlying conditions such as inflammatory bowel disease, or pyoderma gangrenosum may be secondary to identifiable causes such as cocaine use as in this patient. Pyoderma gangrenosum induced by levamisole-adulterated cocaine has the following features:History of cocaine use.Exaggerated skin injury occurring after minor trauma (pathergy).Characteristic histopathologic findings.

To treat or not to treat? High-potency benzodiazepine use in a case of comorbid hallucinogen persisting perception disorder and alcohol use disorder.

Hallucinogen persisting perception disorder (HPPD) is characterized by visual disturbances that resemble psychedelic intoxication and linger after use has ceased. The most common substances precipitating HPPD, lysergic acid diethylamide (LSD) and psilocybin, are posited to do so via damage to serotonergic neurons involved in vision. Mr. N is a 37-year-old with a history of alcohol, cannabis, LSD, cocaine, and nicotine use disorders who described visual distortions that resolved when he drank heavily or received benzodiazepines for withdrawal. He did not appear psychotic. Over 20 years after his last LSD use, he continued to experience illusions of halos around objects, moving walls, and figures appearing cartoonish. He understood that his perceptual disturbances were not reality based. During hospitalization for suicidal ideation, laboratory tests, head computed tomography (CT), and electroencephalogram (EEG) studies offered no explanation for his visual disturbances other than HPPD. The visual distortions remitted with scheduled clonazepam treatment, although chemical dependency treatment programs were hesitant to accept him while on a benzodiazepine. This case emphasizes the importance of diagnostic clarification when patients present with perceptual disturbances that do not fit typical psychotic presentations. Our discussion will distinguish misperceptions from hallucinations and review the pathophysiology of HPPD. Last, we will discuss management strategies for patients with co-occurring HPPD and substance use disorders. It is necessary to discern the correct cause of visual disturbances in order to provide proper treatment. The risks and benefits of long-term benzodiazepine use must be weighed when deciding whether to prescribe them for patients with comorbid HPPD and alcohol use disorder. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Varenicline induced auditory hallucinations in a young female with bipolar disorder: a case report

IntroductionCreating appropriate and sustainable treatment plans for patients with concurrent disorders presents a challenge to psychiatrists and addiction medicine specialists alike. Although varenicline has been found to be one of the most effective medications for smoking cessation and abstinence, caution is needed when starting patients on this medication. In this case, a young female provisionally diagnosed with bipolar I disorder was hospitalized for a manic episode in the context of substance abuse and medical noncompliance. She also endorsed a long history of smoking, alcohol, cocaine, cannabis and ketamine use. In addition to being stabilized for bipolar disorder, the patient was started on varenicline for smoking cessation on Day 14 of admission.ObjectivesThis case report highlights the potential risk of de-stabilization in a vulnerable youth with newly diagnosed bipolar I disorder and precarious social circumstances, in attempts to further concurrent approaches to psychiatric care.MethodsIn addition to qualitative observations, the main objective exam used to track patient progress through the duration of her hospitalization was the mental status exam (MSE). This is standard practice for psychiatric care and qualitatively assessed factors related to a patient’s behavioral and cognitive functioning. Important factors assessed for this patient include appearance and behavior, speech, affect and mood, thought form, thought content, perceptual abnormalities, insight and cognition.ResultsPerceptual abnormalities, including auditory hallucinations, were not recorded at admission and the patient’s symptoms of mania were resolving clinically on Day 18. Two days after starting varenicline, the patient developed auditory hallucinations, paranoia and referential beliefs. However, her insight was intact, and she had minimal thought-form disorganization. The patient also reported hearing auditory hallucinations of a derogatory nature, with her mood appearing more distressed during varenicline use. Symptoms were found to be resolved shortly after the discontinuation of varenicline on Day 18 and the patient appeared to be less distressed on following days. In this case, these symptoms were not in keeping with her bipolar diagnosis and thought to be secondary to varenicline after the consideration of potential alternative contributors.ConclusionsThe occurrence of side effects as a result of varenicline use in patients with diagnosed mental health conditions is rare and underlying psychiatric illness is not labeled as an absolute contraindication in the prescription of varenicline. However, it is important to advocate for increased guidance and research on the treatment of substance use disorders in patients with bipolar I disorder.Disclosure of InterestNone Declared

HIV gp120 impairs nucleus accumbens neuroimmune function and dopamine D3 receptor-mediated inhibition of cocaine seeking in male rats

Cocaine Use Disorders (CUDs) are associated with an increased risk of human immunodeficiency virus (HIV) infection. Cocaine and the HIV envelope protein gp120 each induce distinct deficits to mesocorticolimbic circuit function and motivated behavior; however, little is known regarding how they interact to dysregulate these functions or how such interactions impact pharmacotherapeutic efficacy. We have previously shown that the selective, weak partial agonist of the dopamine D3 receptor (D3R), MC-25-41, attenuates cocaine-seeking behavior in male rats. Here, we sought to characterize changes in striatal neuroimmune function in gp120-exposed rats across abstinence from operant access to cocaine (0.75 mg/kg, i.v.) or sucrose (45 mg/pellet), and to examine the impact of gp120 exposure on MC-25-41-reduced cocaine seeking. After establishing a history of cocaine or sucrose self-administration, rats received intracerebroventricular gp120 infusions daily the first 5 days of abstinence and were sacrificed either on day 6 or after 21 days of forced abstinence and a cue-induced cocaine seeking test. We demonstrated that MC-25-41 treatment attenuated cue-induced cocaine seeking among control rats but not gp120-exposed rats. Moreover, postmortem analysis of nucleus accumbens (NAc) core neuroimmune function indicated cocaine abstinence- and gp120-induced impairments, and the expression of several immune factors within the NAc core significantly correlated with cocaine-seeking behavior. We conclude that cocaine abstinence dysregulates striatal neuroimmune function and interacts with gp120 to inhibit the effectiveness of a D3R partial agonist in reducing cocaine seeking. These findings highlight the need to consider comorbidities, such as immune status, when evaluating the efficacy of novel pharmacotherapeutics.

Varenicline induced auditory hallucinations in a young female with bipolar disorder: a case report

BackgroundCreating appropriate and sustainable treatment plans for patients with concurrent disorders presents a challenge to psychiatrists and addiction medicine specialists alike. Although varenicline has been found to be the most effective medication for smoking cessation and abstinence when compared to results from placebo medications, nicotine patches and bupropion, caution is needed when starting patients on this medication. With the high prevalence of concurrent mental health and substance use disorders in vulnerably-housed populations in Canada, it becomes increasingly important to advocate for increased guidance and research into treating concurrent disorders.Case presentationIn this case, a young female patient provisionally diagnosed with bipolar I disorder was hospitalized for a manic episode in the context of substance use and medication noncompliance. She also endorsed a long history of tobacco, alcohol, cocaine, cannabis and ketamine use. Perceptual abnormalities, including auditory hallucinations, were not recorded at admission. In addition to being stabilized for bipolar diagnosis, the patient was started on nicotine replacement therapy on Day 7 of admission followed by initiation of varenicline for smoking cessation on Day 14 of admission. Soon after the varenicline treatment was started, the patient developed auditory hallucinations, paranoia and referential beliefs. However, her insight was intact, and she had minimal thought form disorganization. In this case, these symptoms were thought to be secondary to varenicline after the consideration of potential alternative contributors.ConclusionThe occurrence of side effects as a result of varenicline use in patients with diagnosed mental health conditions is rare and underlying psychiatric illness is not labeled as an absolute contraindication in the prescription of varenicline. However, it is important to advocate for increased guidance and research on the treatment of substance use disorders in patients with bipolar I disorder. Patients may also benefit from increased collaboration between psychiatric and addiction services as that may allow for earlier recognition and intervention of symptoms to minimize distress.

Acute choreiform movements in the feet: A case report

Abstract A 48-year-old man presented to a tertiary care center with a 1.5-year history of sudden-onset choreiform movements in both feet. The movements were greater in the left foot, with a preceding 1-month history of cocaine and amphetamine/dextroamphetamine use. His symptoms persisted even after discontinuing the use of these substances; the movements were present while awake and absent while asleep and caused extreme discomfort while wearing shoes. Numerous trials of medications did not alleviate his symptoms, except for transient improvement with risperidone. His examination was notable for writhing movements of the toes, which was worse in the left foot than the right foot. The movements occasionally spread to the left knee, and he had length-dependent decreased temperature and vibration sensation in the lower extremities and an unsteady gait. Brain magnetic resonance imaging without contrast obtained 1 year after symptom onset demonstrated T2/fluid-attenuated inversion recovery hyperintense signal with a rim of hypointensity in the bilateral globus pallidi. Magnetic resonance imaging 1 year later displayed stable findings of bilaterally symmetric diffuse hypointensities in the globus pallidi. The patient was diagnosed with chorea, presumed secondary to his cocaine use. He was started on multiagent treatment with clonazepam, tetrabenazine, and onabotulinum toxin A. A thorough history and analysis of his risk factors was essential to determine the underlying cause of his symptoms to guide effective treatment; however, to the best of our knowledge, no effective long-term treatments for chorea in patients such as that in our study have been documented to date. This case of cocaine-induced chorea adds to the growing documentation of scenarios, in which cocaine use can lead to chronic movement disorders.

Prelimbic Cortex Activity during a Distress Tolerance Task Predicts Cocaine-Seeking Behavior in Male, But Not Female Rats.

Distress tolerance (DT) is defined as the ability to persist in challenging goal-directed behavior in the face of stress, and individuals with low DT exhibit heightened drug-seeking behavior. However, no preclinical studies have examined the neurobiology underlying this phenomenon. To assess this, in vivo electrophysiology was used in Long Evans male and female rats during a DT task to record neural activity in the prelimbic cortex (PrL), a brain region implicated in drug-seeking. Rats were first assessed for DT, defined as the amount of time elapsed before rats quit seeking reward in an increasingly difficult operant task. Subsequently, rats underwent 2 weeks of self-administration for either water/saline or cocaine for 6 h/day. Animals then began a 1 month period of experimenter-imposed abstinence to induce heightened drug-seeking behavior. On day 28 of abstinence, DT and neural activity were reassessed; and on day 30, cocaine-seeking behavior was examined under extinction. Males had significantly higher DT than females and exhibited significantly more phasic PrL activity during the DT task. Furthermore, in male rats with a history of cocaine, PrL activity shifted to track DT; and this change in activity significantly correlated with the change in DT. Additionally, male (but not female) rats with low DT after 28 d of abstinence had significantly heightened drug-seeking behavior. Finally, PrL activity during the DT task predicted cocaine-seeking behavior. Collectively, these data demonstrate an important role for the PrL in DT in males, and link this neural activity and behavior to drug-seeking, particularly in males.SIGNIFICANCE STATEMENT Distress tolerance (DT) is defined as the ability to persist in challenging goal-directed behavior in the face of stress, and individuals with low DT exhibit heightened drug-seeking. Here, we investigated the role of the prelimbic cortex (PrL) in DT and its relationship to cocaine-seeking in male and female rats. We found that males had significantly higher DT than females and exhibited significantly more PrL activity during the DT task. Furthermore, male (but not female) rats with low DT after 28 d of abstinence had significantly heightened drug-seeking behavior. Finally, PrL activity during the DT task predicted cocaine-seeking. These data demonstrate an important role for the PrL in DT and link this neural activity and behavior to drug-seeking in males.

INTERSTITIAL LUNG DISEASE EXACERBATED BY NON-NOVEL SARS-COV-2

INTERSTITIAL LUNG DISEASE EXACERBATED BY NON-NOVEL SARS-COV-2

S1980 Cocaine-Induced Pseudomembranous Colitis With Negative Clostridium difficile Infection

Introduction: Pseudomembranous colitis (PMC) is most commonly caused by Clostridium difficle (C.Diff). The incidence of C.Diff related PMC is 3-8% and increasing. Other than Clostridium difficile, ischemia, infections, medications, and inflammatory conditions can cause PMC. We report a case of pseudomembranous colitis-tested negative PCR for C. difficile. Case Description/Methods: A 52-year-old female with a past medical history of hypothyroidism, asthma, and polysubstance abuse (history of chronic heroin, cocaine, benzodiazepine, alcohol, and cigarette use) with Hx of chronic intermittent diarrhea due to opioid withdrawal presented to the emergency department with bloody watery diarrhea of 3-4 times in a day for 5 days. On initial evaluation, the patient's vital signs are stable. The abdomen is diffusely tender on physical examination with increased tenderness in the left lower quadrant. Labs showed WBC count of 15,900/μL, 90.2% neutrophils, AST of 80 U/L, ALT of 41 U/L, ALP of 97 U/L, total bilirubin of 0.5 mg/dL, lactic acid of 0.9 mmol/L and c-reactive protein of 11.9 mg/dL. The urine drug screen was positive for benzodiazepine, cocaine, opiate, and methadone. CT scan of the abdomen showed mild diffuse concentric colonic wall thickening representing colitis. The patient was empirically treated with IV ceftriaxone, IV metronidazole, and PO vancomycin. Stool for C. difficile PCR was negative 3 times on 3 different days. Stool culture was negative for Salmonella, Shigella, Campylobacter, or E. coli O157:H7. Fecal lactoferrin quantification was 320.72 μg/mL. The patient underwent sigmoidoscopy, which showed discontinuous areas of ulcerated mucosa covered with yellowish punctate membrane with stigmata of recent bleeding in the entire examined colon. Biopsy of the colon showed focal active colitis with superficial crypt erosion and focal adherent mucopurulent material negative for crypt abscesses and granulomas, consistent with pseudomembranous colitis. The patient was continually treated with supportive care including IV fluids and bowel rest. Her diet was advanced, and her diarrhea improved (Figure). Discussion: Other than C. difficile, we propose keeping other differentials of pseudomembranous colitis is essential. Other infections from S. aureus, E. coli, Shigella and Strongyloides may also cause PMC. Non-infectious causes of PMC include chemical endoscope cleaning agents, intestinal ischemia, drug abuse from cocaine, inflammatory bowel disease, and microscopic colitis to avoid over-usage of antibiotics and focus on targeted therapy.Figure 1.: Discontinuous areas of ulcerated mucosa covered with yellowish punctate membrane with stigmata of recent bleeding in the entire examined colon.

Effect of drug use in the treatment of acute ischemic stroke: A scoping review.

Background: Drugs of abuse have been associated with ischemic stroke; however, the clinical presentation, outcomes, and treatment data in this population are limited. The overall safety and efficacy of thrombolytic therapy and thrombectomy in these patients remain unclear. This scoping review summarizes published complications and clinical outcomes in patients with recent abuse of cocaine, methamphetamine (MA), cannabis, decongestant, opioids, alcohol, and 3,4-methylenedioxymethamphetamine (MDMA) presenting with acute ischemic stroke.Methods: We conducted a scoping review of the primary literature that assessed outcomes data of thrombolytic therapy or thrombectomy in drug users with acute ischemic stroke. We searched PubMed, Ovid Medline, and Web of Science. Demographic and stroke characteristics, treatment, complications, and clinical outcomes at last follow-up were collected and summarized.Results: We identified 51 studies in this review. Drugs of abuse of interest were cocaine (14 studies), MDMA (one study), MA (eight studies), cannabis (23 studies), alcohol (two studies), decongestants (one study), and opioids (two studies). Clinical presentation and stroke presentation were most commonly described features. Thrombectomy outcomes were reported for four patients total (two studies), all with history of cocaine use. Thrombolysis treatment and outcomes were reported for 8851 patients (five studies) with history of cocaine, alcohol, or cannabis. Both treatments were pursued in three patients (three studies). Treatment complications included intracerebral hemorrhage, vasospasm, and cerebral edema.Conclusion: Evidence for thrombolytic and thrombectomy treatment in drug users remains limited. Controlled studies are needed to examine complication profile and outcomes following thrombolytic and thrombectomy treatment in this population.

Cross-sectional examination of ultra-processed food consumption and adverse mental health symptoms.

To explore whether individuals who consume higher amounts of ultra-processed food (UPF) have more adverse mental health symptoms. Using a cross-sectional design, we measured the consumption of UPF as a percentage of total energy intake in kilo-calories using the NOVA food classification system. We explored whether individuals who consume higher amounts of UPF were more likely to report mild depression, more mentally unhealthy days and more anxious days per month using multivariable analyses adjusting for potential confounding variables. Representative sample from the United States National Health and Nutrition Examination Survey between 2007 and 2012. 10 359 adults aged 18+ without a history of cocaine, methamphetamine or heroin use. After adjusting for covariates, individuals with the highest level of UPF consumption were significantly more likely to report at least mild depression (OR: 1·81; 95 % CI1·09, 3·02), more mentally unhealthy (risk ratio (RR): 1·22; 95 % CI 1·18, 1·25) and more anxious days per month (RR: 1·19; 95 % CI 1·16, 1·23). They were also significantly less likely to report zero mentally unhealthy (OR: 0·60; 95 % CI 0·41, 0·88) or anxious days (OR: 0·65; 95 % CI 0·47, 0·90). Individuals reporting higher intakes of UPF were significantly more likely to report mild depression, more mentally unhealthy and more anxious days and less likely to report zero mentally unhealthy or anxious days. These data add important information to a growing body of evidence concerning the potential adverse effects of UPF consumption on mental health.