Cocaine Withdrawal Research Articles

Output-Specific Adaptation of Habenula-Midbrain Excitatory Synapses During Cocaine Withdrawal.

Projections from the lateral habenula (LHb) control ventral tegmental area (VTA) neuronal populations’ activity and both nuclei shape the pathological behaviors emerging during cocaine withdrawal. However, it is unknown whether cocaine withdrawal modulates LHb neurotransmission onto subsets of VTA neurons that are part of distinct neuronal circuits. Here we show that, in mice, cocaine withdrawal, drives discrete and opposing synaptic adaptations at LHb inputs onto VTA neurons defined by their output synaptic connectivity. LHb axons innervate the medial aspect of VTA, release glutamate and synapse on to dopamine and non-dopamine neuronal populations. VTA neurons receiving LHb inputs project their axons to medial prefrontal cortex (mPFC), nucleus accumbens (NAc), and lateral hypothalamus (LH). While cocaine withdrawal increases glutamate release from LHb onto VTA-mPFC projectors, it reduces presynaptic release onto VTA-NAc projectors, leaving LHb synapses onto VTA-to-LH unaffected. Altogether, cocaine withdrawal promotes distinct adaptations at identified LHb-to-VTA circuits, which provide a framework for understanding the circuit basis of the negative states emerging during abstinence of drug intake.

Cocaine potentiates an inflammatory response in C6 astroglia-like cells.

Cocaine is a highly addictive drug that mediates its effect through altering dopamine metabolism in the central nervous system (CNS), resulting in a feeling of euphoria. Owing to its high lipophilicity, cocaine easily crosses the blood brain barrier of the CNS and reaches various domains of the brain, where it can trigger cellular damage. Cocaine-induced CNS damage may arise due to increased levels of free radicals and nitric oxide (NO) in immunecompetent astroglial cells. In the present study, the potential ability of cocaine to exacerbate the production of inflammatory products, primarily superoxide free radicals (O2-), hydrogen peroxide (H2O2) and NO/nitrite (NO2-) was examined in rat C6 astroglia-like cells challenged with lipopolysaccharide (LPS), a bacterial endotoxin, and interferon gamma (IFNγ), a pro-inflammatory cytokine. Furthermore, the role of cocaine in increasing the expression of hypoxia inducible factor-1 (HIF-1α) and vascular endothelial growth factor (VEGF) in cells was also determined. First, the viability of the cells was assessed when treated with cocaine (0.5-7 mM) for 24 and 48 h. The results showed that cocaine toxicity was both time and dose-dependent. In subsequent studies, cells were challenged with or without LPS and IFNγ, followed by co-treatment with cocaine (1-4 mM) for 24 h. Cocaine treatment did not increase O2- or H2O2 production in the challenged or unchallenged cells. Similarly, cocaine treatment did not increase NO/NO2- production in the unchallenged cells; however, NO/NO2- levels in the challenged cells was increased 40-50-fold upon cocaine treatment compared with the corresponding unchallenged group. The HIF-1α and VEGF levels were significantly increased in the challenged cells at higher cocaine doses compared with the unchallenged cells. Since high concentrations of NO are associated with inflammation, the high levels of NO production observed in the present study suggested that cocaine may have potentiated the inflammatory response in the challenged C6 astroglia-like cells.

45698 Molecular Signatures of Cocaine Neurotoxicity in Human Brain Models

ABSTRACT IMPACT: This project will use human neuron models and bioinformatics techniques to elucidate mechanisms of cocaine neurotoxicity, which will allow treatments to be developed for minimizing or preventing neurological damage caused by cocaine abuse and overdose. OBJECTIVES/GOALS: The goals of this project are to identify genes and gene networks altered by cocaine exposure in neurons (short term), and to use these pathways to understand mechanisms of cocaine neurotoxicity for the establishment of therapeutic targets (long term). METHODS/STUDY POPULATION: To study the molecular effects of cocaine, we generated preliminary proteomics and next-generation RNA sequencing (RNAseq) data from human postmortem prefrontal cortex (Broadmann area 9 or BA9) of 12 cocaine overdose subjects and 17 controls. Future directions for this project include RNAseq analysis of neuronal nuclei sorted from human postmortem BA9 and a human induced pluripotent stem cell-derived neuron (hiPSN) model of cocaine exposure from the same postmortem subjects from whom we have brain samples. RESULTS/ANTICIPATED RESULTS: We found alterations in neuronal synaptic protein levels and gene expression, including the serotonin transporter SLC6A4, and synaptic proteins SNAP25, SYN2, SYNGR3. Pathway analysis of our results revealed alterations in specific pathways involved with neuronal function including voltage-gated calcium channels, and GABA receptor signaling. In the future, we expect to see an enhancement in neuron-specific gene expression signatures in our sorted neuronal nuclei and our hiPSN model of cocaine exposure. The hiPSN model will help elucidate which effects are due to acute versus chronic exposure of cocaine. DISCUSSION/SIGNIFICANCE OF FINDINGS: Transcriptomic signatures found with this analysis can help us understand mechanisms of cocaine neurotoxicity in human neurons. With this work and future proposed studies, we can discover targetable molecular pathways to develop drugs that can reduce or reverse cocaine-related impairment.

Sustained brain response to repeated drug cues is associated with poor drug-use outcomes.

A threefold increase in fatal cocaine overdoses during the past decade highlights the critical lack of medications for cocaine use disorders. The brain response to drug cues can predict future drug use; however, results have been mixed. We present preliminary evidence that a sustained response to repeated cocaine cues within a single task is a significant predictor of drug-use outcomes. Seventy-three cocaine inpatients were administered a passive-viewing fMRI task, featuring 500ms novel evocative (cocaine, sexual, aversive) and neutral comparator cues in the first half (Half1), which were then repeated in the second half (Half2). After the baseline scan, patients received eight outpatient treatment weeks with twice-weekly drug screens. Drug-use outcome groups were empirically defined based on cocaine-positive or missing urines averaged across the outpatient phase: GOOD (<40%), POOR (>85%), and Intermediate (INT, between 40% and 85%) outcomes. Differences of response to initial (Half1) and repeated (Half2) cues in a priori (cue-reactive) regions were tested between outcome groups (3 [Group]×2 [Halves] ANOVA). An interaction was found in the brain response to drug (but not sex or aversive) cues, with a significant difference between the GOOD and POOR outcome groups in Half2, driven by a significant decrease in brain response by the GOOD outcome group and a sustained brain response by the POOR outcome group, to repeated cocaine cues. The brain response to repeated drug cues may be a useful predictor of future drug use, encouraging future intervention studies to restore a "healthy" (decreasing) response to the repeated presentation of drug cues.

Substance Use Disorders in the Surgical Patient

Large bodies of evidence link alcohol consumption and substance use disorders (SUDs) with motor vehicle collisions, as well as life-threatening intentional injury. According to the substance use and mental health estimates from the 2013 National Survey on Drug Use and Health, 24.6 million individuals age 12 or older were current illicit drug users in 2013, including 2.2 million adolescents age 12 to 17, and 60.1 million individuals age 12 or older were binge drinkers in the past month. Many people with SUDs become patients; therefore, the surgeon must be able to recognize and manage many of the related issues that can ensue. This review details the definition of SUDs, basic principles of toxicology, acute management of the patient with suspected substance use intoxication or withdrawal, managing life-threatening syndromes in patients with SUDs, overdose and withdrawal syndromes of opioids, stimulants, and depressants, surgical complications of SUDs, perioperative and postoperative considerations in patients with SUDs, and consultation and referral to a toxicologist and poison control center. Figures show first- and zero-order kinetics; pupillary examination, laboratory and radiographic findings in SUDs; polymorphic ventricular tachycardia; consciousness as an interplay between arousal and awareness, an algorithm for the management of seizures, sine, mechanism of cocaine’s cardiac toxicity and hemorrhagic stroke in a cocaine abuser, necrotizing soft tissue infection, digit necrosis associated with intra-arterial injection of cocaine, scars from skin popping, nonocclusive thrombus in the left internal jugular vein, needle fracture with soft tissue dislodgment, oral contrast-enhanced computed tomographic scan showing rounded foreign bodies in the stomach, and fecal impaction associated with heroin. Tables list criteria for substance use disorders according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V), frequently misused drugs, causes of death in SUD, cardiac, neurologic, and metabolic signs and symptoms caused by commonly abused substances , anion and osmolar gap equations, life-threatening manifestations of cocaine toxicity, and alcohol-related disorders. This review contains 15 figures, 8 tables, and 85 references.

Substance Use Disorders in the Surgical Patient

Large bodies of evidence link alcohol consumption and substance use disorders (SUDs) with motor vehicle collisions, as well as life-threatening intentional injury. According to the substance use and mental health estimates from the 2013 National Survey on Drug Use and Health, 24.6 million individuals age 12 or older were current illicit drug users in 2013, including 2.2 million adolescents age 12 to 17, and 60.1 million individuals age 12 or older were binge drinkers in the past month. Many people with SUDs become patients; therefore, the surgeon must be able to recognize and manage many of the related issues that can ensue. This review details the definition of SUDs, basic principles of toxicology, acute management of the patient with suspected substance use intoxication or withdrawal, managing life-threatening syndromes in patients with SUDs, overdose and withdrawal syndromes of opioids, stimulants, and depressants, surgical complications of SUDs, perioperative and postoperative considerations in patients with SUDs, and consultation and referral to a toxicologist and poison control center. Figures show first- and zero-order kinetics; pupillary examination, laboratory and radiographic findings in SUDs; polymorphic ventricular tachycardia; consciousness as an interplay between arousal and awareness, an algorithm for the management of seizures, sine, mechanism of cocaine’s cardiac toxicity and hemorrhagic stroke in a cocaine abuser, necrotizing soft tissue infection, digit necrosis associated with intra-arterial injection of cocaine, scars from skin popping, nonocclusive thrombus in the left internal jugular vein, needle fracture with soft tissue dislodgment, oral contrast-enhanced computed tomographic scan showing rounded foreign bodies in the stomach, and fecal impaction associated with heroin. Tables list criteria for substance use disorders according to the Diagnostic and Statistical Manual of Mental Disorders, fifth edition (DSM-V), frequently misused drugs, causes of death in SUD, cardiac, neurologic, and metabolic signs and symptoms caused by commonly abused substances , anion and osmolar gap equations, life-threatening manifestations of cocaine toxicity, and alcohol-related disorders. This review contains 15 figures, 8 tables, and 85 references.

AMPA and NMDA Receptor Trafficking at Cocaine-Generated Synapses.

Cocaine experience generates AMPA receptor (AMPAR)-silent synapses in the nucleus accumbens (NAc), which are thought to be new synaptic contacts enriched in GluN2B-containing NMDA receptors (NMDARs). After drug withdrawal, some of these synapses mature by recruiting AMPARs, strengthening the newly established synaptic transmission. Silent synapse generation and maturation are two consecutive cellular steps through which NAc circuits are profoundly remodeled to promote cue-induced cocaine seeking after drug withdrawal. However, the basic cellular processes that mediate these two critical steps remains underexplored. Using a combination of electrophysiology, viral-mediated gene transfer, and confocal imaging in male rats as well as knock-in (KI) mice of both sexes, our current study characterized the dynamic roles played by AMPARs and NMDARs in generation and maturation of silent synapses on NAc medium spiny neurons after cocaine self-administration and withdrawal. We report that cocaine-induced generation of silent synapses not only required synaptic insertion of GluN2B-containing NMDARs, but also, counterintuitively, involved insertion of AMPARs, which subsequently internalized, resulting in the AMPAR-silent state on withdrawal day 1. Furthermore, GluN2B NMDARs functioned to maintain these cocaine-generated synapses in the AMPAR-silent state during drug withdrawal, until they were replaced by nonGluN2B NMDARs, a switch that allowed AMPAR recruitment and maturation of silent synapses. These results reveal dynamic interactions between AMPARs and NMDARs during the generation and maturation of silent synapses after cocaine experience and provide a mechanistic basis through which new synaptic contacts and possibly new neural network patterns created by these synapses can be manipulated for therapeutic benefit.SIGNIFICANCE STATEMENT Studies over the past decade reveal a critical role of AMPA receptor-silent, NMDA receptor-containing synapses in forming cocaine-related memories that drive cocaine relapse. However, it remains incompletely understood how AMPA and NMDA receptors traffic at these synapses during their generation and maturation. The current study characterizes a two-step AMPA receptor trafficking cascade that contributes to the generation of silent synapses in response to cocaine experience, and a two-step NMDA receptor trafficking cascade that contributes to the maturation of these synapses after cocaine withdrawal. These results depict a highly regulated cellular procedure through which nascent glutamatergic synapses are generated in the adult brain after drug experience and provide significant insight into the roles of glutamate receptors in synapse formation and maturation.

Drug-Seeking Behavior Is Significantly Attenuated in Nutritionally Supplemented Cocaine Withdrawn Sprague-Dawley Rats

Aim: The effect of patented nutritional supplementation on drug-seeking behavior in cocaine addicted rats during acute drug withdrawal was investigated using a biased Conditioned Place Preference (CPP) paradigm. Method: Twenty-four (24) male Sprague-Dawley rats with pre-conditioned preference for the black chamber of the CPP box were randomly divided into Cocaine (COC) or Saline (SAL) treated groups. Rats (n = 12) treated with cocaine hydrochloride 20 mg/kg/ml, i.p. (COC group) were confined individually to the white chamber on days 1, 3, 5 and 7. On alternate days, they were given 1 ml saline vehicle, i.p. and confined to the black chamber. Control rats (SAL group, n = 12) received only vehicle on all 8 days and were confined on alternate days to the white or black chamber. Positive place preference was confirmed for COC rats, which subsequently received 6 increasing daily doses of cocaine. CPP performances of both COC and SAL rats were recorded following an acute 3-day withdrawal period. All animals were then randomly assigned to rats fed either chow reconstituted with the nutritional supplement (COC-S and SAL-S) or standard rat chow (COC-N and SAL-N) for 8 weeks, followed by final CPP performances. Results: Following supplementation, COC-S rats made significantly less entries and time spent in the white chamber (p Conclusion: Drug-seeking behavior that persisted during cocaine withdrawal was significantly diminished in the nutritionally supplemented.

Opioid, Cocaine and Methamphetamine Overdose Crisis and Deaths in 2021

Opioid, Cocaine and Methamphetamine Overdose Crisis and Deaths in 2021

Resting state hypothalamic and dorsomedial prefrontal cortical connectivity of the periaqueductal gray in cocaine addiction.

Cocaine-dependent (CD) individuals demonstrate significant anxiety and dysphoria during withdrawal, a negative emotional state that may perpetuate drug seeking and consumption. An extensive body of work has focused on characterizing reward circuit dysfunction, but relatively little is known about the pain circuit during cocaine withdrawal. In an earlier study, we highlighted how cue-elicited functional connectivity between the periaqueductal gray (PAG), a subcortical hub of the pain circuit, and ventromedial prefrontal cortex supports tonic craving in recently abstinent CD. The functional organization of the brain can be characterized by intrinsic connectivities, and it is highly likely that the resting state functional connectivity (rsFC) of the PAG may also be altered in association with cocaine use variables. Here, we examined this issue in 52 CD and 52 healthy control (HC) participants. Imaging data were processed with published routines, and the findings were evaluated with a corrected threshold. In a covariance analysis, CD as compared with HC showed higher PAG rsFC with the hypothalamus, dorsomedial prefrontal, and inferior parietal cortices. Further, these connectivities were correlated negatively with tonic cocaine craving and recent cocaine use, respectively. Higher hypothalamic and frontoparietal rsFC with the PAG may reflect a compensatory process to regulate craving and compulsive drug use. The findings provide additional evidence in humans implicating the PAG circuit and may help research of the role of negative reinforcement in sustaining habitual drug use in cocaine addiction.

Cannabidiol Modulates Behavioural and Gene Expression Alterations Induced by Spontaneous Cocaine Withdrawal.

The aim of this study was to evaluate the effects of cannabidiol (CBD) on the behavioural and gene expression changes in a new animal model of spontaneous cocaine withdrawal. For this purpose, male CD-1 mice were exposed to progressive increasing doses of cocaine for 12days (15 to 60mg/kg/day, i.p.), evaluating spontaneous cocaine withdrawal 6h after the last cocaine administration. The effects of CBD (10, 20, and 40mg/kg, i.p.) were evaluated on cocaine withdrawal-induced alterations in motor activity, somatic signs, and anxiety-like behaviour. Furthermore, gene expression changes in dopamine transporter (DAT) and tyrosine hydroxylase (TH) in the ventral tegmental area, and in cannabinoid receptors 1 (CNR1) and 2 (CNR2) in the nucleus accumbens, were analysed by real-time PCR. The results obtained in the study showed that mice exposed to the spontaneous cocaine withdrawal model presented increased motor activity, somatic withdrawal signs, and high anxiety-like behaviour. Interestingly, the administration of CBD normalized motor and somatic signs disturbances and induced an anxiolytic effect. Moreover, the administration of CBD blocked the increase of DAT and TH gene expression in mice exposed to the cocaine withdrawal, regulated the decrease of CNR1 and induced an additional upregulation of CNR2 gene expression. Thus, this model of spontaneous cocaine withdrawal induces clear behavioural and gene expression changes in mice. Interestingly, CBD alleviates these behavioural and gene expression alterations suggesting its potential for the management of cocaine withdrawal.

P.032 Cannabidiol-mediated effects on behavioural and gene expression changes induced by a new animal model of spontaneous cocaine withdrawal

Trabajo presentado al 33rd ECNP Congress Virtual, celebrado del 12 al 15 de septiembre de 2020.

Cocaine-induced neural adaptations in the lateral hypothalamic melanin-concentrating hormone neurons and the role in regulating rapid eye movement sleep after withdrawal.

Sleep abnormalities are often a prominent contributor to withdrawal symptoms following chronic drug use. Notably, rapid eye movement (REM) sleep regulates emotional memory, and persistent REM sleep impairment after cocaine withdrawal negatively impacts relapse-like behaviors in rats. However, it is not understood how cocaine experience may alter REM sleep regulatory machinery, and what may serve to improve REM sleep after withdrawal. Here, we focus on the melanin-concentrating hormone (MCH) neurons in the lateral hypothalamus (LH), which regulate REM sleep initiation and maintenance. Using adult male Sprague Dawley rats trained to self-administer intravenous cocaine, we did transcriptome profiling of LH MCH neurons after long-term withdrawal using RNA-sequencing, and performed functional assessment using slice electrophysiology. We found that three weeks after withdrawal from cocaine, LH MCH neurons exhibit a wide range of gene expression changes tapping into cell membrane signaling, intracellular signaling, and transcriptional regulations. Functionally, they show reduced membrane excitability and decreased glutamatergic receptor activity, consistent with increased expression of voltage-gated potassium channel gene Kcna1 and decreased expression of metabotropic glutamate receptor gene Grm5. Finally, chemogenetic or optogenetic stimulations of LH MCH neural activity increase REM sleep after long-term withdrawal with important differences. Whereas chemogenetic stimulation promotes both wakefulness and REM sleep, optogenetic stimulation of these neurons in sleep selectively promotes REM sleep. In summary, cocaine exposure persistently alters gene expression profiles and electrophysiological properties of LH MCH neurons. Counteracting cocaine-induced hypoactivity of these neurons selectively in sleep enhances REM sleep quality and quantity after long-term withdrawal.

Multi-domain unfolding of the Fab fragment of a humanized anti-cocaine mAb characterized by non-reducing SDS-PAGE

Monoclonal antibodies and their fragments are widely used for research and therapy. Fab fragments are useful since they retain antigen binding specificity, but being smaller proteins, are better able to penetrate biological compartments and tumors, and do not induce Fc-dependent immunological system activation. Our laboratory developed an anti-cocaine mAb (named h2E2) for the treatment of cocaine use disorders, which is currently in advanced pre-clinical development. We are also interested in the Fab fragment of this mAb for potential therapy of acute cocaine overdose. Previously, we showed that this mAb and its F(ab’)2 and Fab fragments undergo discrete domain unfolding, as detected by non-reducing SDS-PAGE, and that ligand-induced protein thermal stabilization can be quantitated utilizing differential scanning fluorimetry in the absence of SDS. Here, we demonstrate that multiple Fab protein gel bands observed using non-reducing SDS-PAGE in the presence and absence of cocaine and its metabolites can be explained and interpreted based on the differential stabilization of two unfolding domains in the Fab fragment. The variable domain is stabilized by ligands against SDS unfolding, while the constant domain is not. This data and its interpretation are also supported by differential scanning fluorimetry data for the Fab fragment in SDS. It is likely that these non-reducing SDS-PAGE results and the gel band domain unfolding model will be applicable to other small molecule binding antibodies. Thus, non-reducing SDS-PAGE is a widely available and simple method for assessing domain stability and multi-step unfolding of Fab fragments.

A brief overview on the importance of analyzing drug adulterants in the treatment of non-fatal overdose and substance use disorder of street cocaine

A brief overview on the importance of analyzing drug adulterants in the treatment of non-fatal overdose and substance use disorder of street cocaine

Cue-elicited functional connectivity of the periaqueductal gray and tonic cocaine craving

BackgroundWithdrawal from chronic cocaine use leads to anxiety and dysphoria that may perpetuate habitual drug use. The pain circuit is widely implicated in the processing and manifestations of negative emotions. Numerous studies have focused on characterizing reward circuit dysfunction but relatively little is known about the pain circuit response during cocaine withdrawal. MethodsHere we examined the activity and connectivity of the periaqueductal gray (PAG), a hub of the pain circuit, during cocaine cue exposure in 52 recently abstinent cocaine dependent participants (CD, 42 men). Imaging data were processed with published routines, and the results were evaluated at a corrected threshold. ResultsCD showed higher activation of the PAG and connectivity of the PAG with the ventromedial prefrontal cortex (vmPFC) during cocaine as compared to neutral cue exposure. PAG-vmPFC connectivity was positively and negatively correlated with tonic cocaine craving, as assessed by the Cocaine Craving Questionnaire, in male and female CD, respectively, and the sex difference was confirmed by a slope test. Granger causality analyses showed that the PAG Granger caused vmPFC time series in men and the reverse was true in women, substantiating sex differences in the directional interactions of the PAG and vmPFC. ConclusionThe findings provide the first evidence in humans implicating the PAG circuit in cocaine withdrawal and cocaine craving and advance our understanding of the role of the pain circuit and negative reinforcement in sustaining habitual drug use in cocaine addiction.

Cocaine use and overdose mortality in the United States: Evidence from two national data sources, 2002–2018

BackgroundCocaine-involved overdose mortality has recently risen in the United States (US), yet it is unclear to what extent patterns in cocaine-involved overdose mortality parallel patterns in cocaine use. This study: examined time trends (2002–2018) in past-year cocaine use and cocaine-involved overdose mortality in the US; and compared demographics and drug involvement of adults who reported past-year cocaine use versus adults who died of a cocaine-involved overdose. MethodsData from two sources were utilized: (1) the National Survey on Drug Use and Health (n = 1,334 adults self-reporting cocaine use in 2018); and (2) the Multiple Cause of Death dataset of the National Center for Health Statistics (N = 14,630 adults who died of a cocaine-involved overdose in 2018). The study examined prevalence of past-year cocaine use, mortality rates for cocaine-involved overdose, 2002–2018 trends, demographic characteristics, and involvement of other drugs. ResultsResults of Joinpoint Regression indicated that the prevalence of past-year cocaine use increased after 2011, with an annual percent change of 5.13, while age-adjusted cocaine-involved overdose mortality rates escalated after 2012, with an annual percent change of 26.54. In 2018, prevalence of past-year cocaine use did not significantly differ (p = 0.09) by racial/ethnic group, yet Non-Hispanic Blacks had an age-adjusted cocaine-involved overdose mortality rate more than double the rate in Non-Hispanic Whites and significantly higher (p < 0.001) than in any other group. ConclusionsWhile the prevalence of cocaine use has increased modestly, cocaine-involved overdose mortality has risen dramatically. Cocaine-involved overdose mortality is disproportionately affecting individuals who are Black, older, or with lower educational attainment.

Provider Prescription Drug Monitoring Program Utilization and Self-Auditing-A Pilot Study.

Alabama has the highest prescription rate in the country. The national incidence of overdose deaths from prescription opioids exceeds the combined death rates from heroin and cocaine overdose. Monitoring prescription access should be an essential activity among providers and can be used to protect patient health and well-being. Prescription drug monitoring programs (PDMPs) are tools that assist in diminishing opioid therapy risks such as diversion, abuse, overdose, and death. The purpose of the study was to examine the effects of an educational intervention on opioid prescriptive rates, frequency of self-auditing and days of opioid supply among healthcare providers. The anticipated goal of the project was that rates and days of supply for opioid prescriptions would decrease. A pretest-posttest design was used to assess a sample of 21 DEA licensed providers who attended a PDMP presentation and conducted a self-audit using the PDMP. Analysis showed that 81% of the participants had never conducted a self-audit prior to the intervention. Self-report data indicated that 85.7% of the providers planned to increase their self-auditing use postintervention and 14.3% planned to make no changes to their current use of the PDMP. Among those who prescribed opioids, the range of monthly prescriptions written was 3-142 preintervention (M = 32.28, SD = 41.04) and 3-149 postintervention (M = 32.26, SD = 43.32). Analysis also found the days of opioid supply prescribed were also high. In both cases, these numbers were correlated to patient census. The PDMP is an effective surveillance tool that provides aggregate data to state public health officials. For a PDMP to be effective, it must be used by prescribing providers. While the anticipated goal for this study was not achieved, the PDMP is an effective surveillance tool for monitoring the controlled substance prescription histories of patients. Using the PDMP before prescribing can aid providers in distinguishing those who legitimately have a need from those who may be seeking to misuse the medications. Additionally, use of a PDMP can provide aggregate data to state public health officials so that education programs, for practitioners and patients, can be developed.

Death following cocaine poisoning in body packer: Two cases report and review of the literature

Background: Body packing is the concealment of illicit drugs enclosed in containers inside the body by swallowing or insertion into the rectum or vagina, usually for transportation to escape detection by customs agents. This report seeks to explore ways of establishing general definition of body packer in the Moroccan context and assess it’s possible implications on data collection and future research. Materials and Methods: This is a descriptive and analytical retrospective study of two fatal cases related to Cocaine toxicity of body packers. The deceased underwent an autopsy at Medico-legal institute of Ibn Rochd University Hospital (UHC) of Casablanca, Morocco. Cases presentation: In these index cases, 02 male youths of foreign nationality in their twenties died in Casablanca airport. The young men took ill at the airport. Abdominal CT scan subsequently performed at the hospital revealed intra-abdominal capsules in both cases. Autopsy showed 47 whitish capsules in the stomach and colon in the first case and 67 similar capsules in the small intestine in the second case. Rapid toxicology testing in the forensic laboratory confirmed the powder to be cocaine. The cause of death was secondary to acute intoxication by leakage of cocaine substances from their packaging. Conclusion: Prevention and compliance with the legislation governing drug trafficking activities, are of vital interest in reducing the incidence of youth use as vectors of drugs and mortality consequence.

Utilizing Simulation Technology to Train Doctors in Indian Society of Toxicology Life Support Course at Poison Control Centre

Simulation has been widely adopted as a training and assessment tool in medical education. Conventional teaching methods may be inadequate to properly train healthcare providers for rare but potentially lethal events in Toxicology such as managing associated polytrauma in alcoholic drink and drive cases, Acute Brain stroke due to cocaine toxicity, acute coronary syndrome in Cannabis and cardio-respiratory arrest in Opioid abuse. We have observed that Simulation based training, by enhancing provider skills, can subsequently decrease medical errors and increase patient safety.