Cocaine Abuse Research Articles

Mapping the Neural Substrates of Cocaine Craving: A Systematic Review.

Craving is one of the most important symptoms of cocaine use disorder (CUD) since it contributes to the relapse and persistence of such disorder. This systematic review aimed to investigate which brain regions are modulated during cocaine craving. The articles were obtained through searches in the Google Scholar, Regional BVS Portal, PubMed, and Scielo databases. Overall, there was a selection of 36 studies with 1574 individuals, the majority being participants with CUD, whereby about 61.56% were individuals with CUD and 38.44% were controls (mean age = 40.4 years). Besides the methodological points, the neurobiological investigations comprised fMRI (58.34%) and PET (38.89%). The induction of cocaine craving was studied using different methods: exposure to cocaine cues (69.45%), stressful stimuli, food cues, and methylphenidate. Brain activations demonstrated widespread activity across the frontal, parietal, temporal, and occipital lobes, basal ganglia, diencephalon, brainstem, and the limbic system. In addition to abnormalities in prefrontal cortex activity, abnormalities in various other brain regions' activity contribute to the elucidation of the neurobiology of cocaine craving. Abnormalities in brain activity are justified not only by the dysfunction of dopaminergic pathways but also of the glutamatergic and noradrenergic pathways, and distinct ways of inducing craving demonstrated the involvement of distinct brain circuits and regions.

1Comprehensive multi-omics analysis reveals the mechanism of loganin from Corni Fructus in improving insulin resistance in mice

Corni Fructus (CF) has great potential as a food product in the treatment of T2DM (thirst-quenching). As the main active ingredient of CF, loganin (LOG) possesses multiple pharmacological propertiesincluding hypoglycemic, hypolipidemic, anti-inflammatory and antibacterial. In this study, we firstly verified the efficacy of LOG in improving the disordered glycolipid metabolism and liver damages in a murine insulin resistance (IR) model, and then determined the ameliorative effect of LOG on IR-HepG2 cell model. To clarify the mechanism of LOG on IR, a series of differentially expressed metabolites (DEM) and genes (DEG) were screened out through non-targeted metabolomics and transcriptomics techniques. In addition, integrative metabolomics and transcriptomics analyses revealed a few key pathways (foxO signaling pathway, glycine serine and threonine metabolism, glutamatergic synapse, cocaine addiction, amphetamine addiction, and valine leucine and isoleucine biosynthesis), important DEM (l-Glutamate), and DEGs (Sgk2, Grin3b, Acadsb, Grik1) were reversely regulated by LOG as compared with the IR model. It is hypothesized that LOG may exert the anti-IR effect via finely tuning amino acid metabolism. Taken together, our data may shine light on the screening of new intervention targets and developing of new LOG-related agents for IR treatment.

Lycium barbarum polysaccharide mitigated methamphetamine addiction and altered methamphetamine-induced gut microbiota dysbiosis.

Methamphetamine (MA) is a highly addictive mental stimulant, and MA abuse remains a significant public health problem worldwide, while effective treatment options are limited. Lycium barbarum polysaccharide (LBP), a major effective component extracted from Lycium barbarum, has potential health-promoting effects on the nervous system; however, its role in MA dependence remains unclear. In this study, the conditioned place preference (CPP) of MA addiction in adult male mice was established to detect changes in gut microbiota profiles after LBP treatment through 16S rRNA gene sequencing. Our results found that LBP administration could alleviate MA-induced CPP and hyperactivity. Interestingly, LBP improved MA-induced gut microbiota dysbiosis by increasing some beneficial autochthonous genus abundances, such as Allobaculum, Gordonibacter, and Ileibacterium. MA exposure induced the co-occurrence network of intestinal microbiota to become weaker and more unstable when compared with the control group, while LBP changed the above effects when compared with the MA group. Bacterial gene function prediction showed that amphetamine addiction, cocaine addiction, and short-chain fatty acid metabolism were enriched. These findings reveal that LBP might regulate MA-induced gut microbiota and behavior changes, which showed potential therapeutic applicability in treating MA addiction by regulating the gut microbiota.

Insights from the Twittersphere: a cross-sectional study of public perceptions, usage patterns, and geographical differences of tweets discussing cocaine.

Cocaine abuse represents a major public health concern. The social perception of cocaine has been changing over the decades, a phenomenon closely tied to its patterns of use and abuse. Twitter is a valuable tool to understand the status of drug use and abuse globally. However, no specific studies discussing cocaine have been conducted on this platform. 111,508 English and Spanish tweets containing "cocaine" from 2018 to 2022 were analyzed. 550 were manually studied, and the largest subset underwent automated classification. Then, tweets related to cocaine were analyzed to examine their content, types of Twitter users, usage patterns, health effects, and personal experiences. Geolocation data was also considered to understand regional differences. A total of 71,844 classifiable tweets were obtained. Among these, 15.95% of users discussed the harm of cocaine consumption to health. Media outlets had the highest number of tweets (35.11%) and the most frequent theme was social/political denunciation (67.88%). Regarding the experience related to consumption, there are more tweets with a negative sentiment. The 9.03% of tweets explicitly mention frequent use of the drug. The continent with the highest number of tweets was America (55.44% of the total). The findings underscore the significance of cocaine as a current social and political issue, with a predominant focus on political and social denunciation in the majority of tweets. Notably, the study reveals a concentration of tweets from the United States and South American countries, reflecting the high prevalence of cocaine-related disorders and overdose cases in these regions. Alarmingly, the study highlights the trivialization of cocaine consumption on Twitter, accompanied by a misleading promotion of its health benefits, emphasizing the urgent need for targeted interventions and antidrug content on social media platforms. Finally, the unexpected advocacy for cocaine by healthcare professionals raises concerns about potential drug abuse within this demographic, warranting further investigation.

β2* nAChR sensitivity modulates acquisition of cocaine self-administration in male rats

Signaling through nicotinic acetylcholine receptors (nAChRs) plays a role in cocaine reward and reinforcement, suggesting that the cholinergic system could be manipulated with therapeutics to modulate aspects of cocaine use disorder (CUD). We examined the interaction between nAChRs and cocaine reinforcement by expressing a hypersensitive β2 nAChR subunit (β2Leu9′Ser) in the ventral tegmental area of male Sprague Dawley rats. Compared to control rats, β2Leu9′Ser rats acquired (fixed ratio) intravenous cocaine self-administration faster and with greater likelihood. By contrast, β2Leu9′Ser rats were approximately equivalent to controls in their intake of cocaine on a progressive ratio schedule of reinforcement, suggesting differential effects of cholinergic signaling depending on experimental parameters. Like progressive ratio cocaine SA, β2Leu9′Ser rats and controls did not differ significantly in food SA assays, including acquisition on a fixed ratio schedule or in progressive ratio sessions. These results highlight the specific role of high-affinity, heteropentameric β2* (β2-containing) nAChRs in acquisition of cocaine SA, suggesting that mesolimbic acetylcholine signaling is active during this process.

Further proof on the role of accumbal nNOS in cocaine-seeking behavior in rats.

Cocaine use disorder (CUD) remains a severe health problem with no effective pharmacological therapy. One of the potential pharmacological strategies for CUD pharmacotherapy includes manipulations of the brain glutamatergic (Glu) system which is particularly involved in drug withdrawal and relapse. Previous research indicated a pivotal role of ionotropic N-methyl-D-aspartate (NMDA) receptors or metabotropic receptors' type 5 (mGlu5) receptors in controlling the reinstatement of cocaine. Stimulation of the above molecules results in the activation of the downstream signaling targets such as neuronal nitric oxide synthase (nNOS) and the release of nitric oxide. In this paper, we investigated the molecular changes in nNOS in the prefrontal cortex and nucleus accumbens following 3 and 10days of cocaine abstinence as well as the effectiveness of nNOS blockade with the selective enzyme inhibitor N-ω-propyl-L-arginine hydrochloride (L-NPA) on cocaine seeking in male rats. The effect of L-NPA on locomotor activity in drug-naïve animals was investigated. Ten-day (but not 3-day) cocaine abstinence from cocaine self-administration increased nNOS gene and protein expression in the nucleus accumbens, but not in the prefrontal cortex. L-NPA (0.5-5mg/kg) administered peripherally did not change locomotor activity but attenuated the reinstatement induced with cocaine priming or the drug-associated conditioned cue. Our findings support accumbal nNOS as an important molecular player for cocaine seeking while its inhibitors could be considered as anti-cocaine pharmacological tools in male rats.

Simultaneous determination of ethyl glucuronide, cocaine, cocaethylene, and benzoylecgonine in hair by using LC–MS/MS

Alcohol and cocaine (COC) are commonly co-used drugs that cause addiction and have harmful effects. Their abuse may threaten the health of the abuser and public safety by causing serious accidents or crimes. The recidivism rate of drug-related crimes closely correlates with alcoholism. Several incidences of alcohol consumption in combination with drug abuse have been reported. Here, liquid chromatography tandem mass spectrometric method was developed to simultaneously analyze ethyl glucuronide (EtG), a metabolite of ethanol; COC; cocaethylene (CE), an alcohol-derived metabolite of COC; and benzoylecgonine (BZE), a major metabolite of COC, to determine the concurrent use of alcohol with COC. For pre-treatment, ultracentrifugation (5 min, 50,000 g) and mixed-mode anion exchange solid-phase extraction were used to increase the recovery of target compounds and minimize the matrix effect of hair. The lower limits of quantification were: 7 pg/mg (EtG), 2 pg/mg (COC), 10 pg/mg (CE), and 1 pg/mg (BZE). The correlation coefficient (r) of the calibration curve within the quantified range of target compounds was ≥ 0.9978. The intra- and inter-day accuracies were − 6.1–9.7% and − 9.3–8.3%, and intra- and inter-day precisions were 0.5–10.3% and 0.6–14.4%, respectively. The recovery, matrix effect, process efficiency, and autosampler stability were 89.2–104.8%, 81.6–105.4%, 81.5–107.1%, and 96.6–109.7%, respectively. The novel analytical method was validated with hair samples from individuals suspected of alcohol and COC use, and the method could distinguish between independent and concurrent use. Based on the findings, the analytical approach developed in this study is anticipated to be valuable in drug and alcohol dependence tests that require the simultaneous detection of alcohol and COC abuse.

The HMGB1-RAGE axis in nucleus accumbens facilitates cocaine-induced conditioned place preference via modulating microglial activation.

Repeated exposure to cocaine induces microglial activation. Cocaine exposure also induces a release of high mobility group box-1 (HMGB1) from neurons into the extracellular space in the nucleus accumbens (NAc). HMGB1 is an important late inflammatory mediator of microglial activation. However, whether the secretion of HMGB1 acts on microglia or contributes to cocaine addiction is largely unknown. Rats were trained by intraperitoneal cocaine administration and cocaine-induced conditioned place preference (CPP). Expression of HMGB1 was regulated by viral vectors. Activation of microglia was inhibited by minocycline. Interaction of HMGB1 and the receptor for advanced glycation end products (RAGE) was disrupted by peptide. Cocaine injection facilitated HMGB1 signaling, together with the delayed activation of microglia concurrently in the NAc. Furthermore, the inhibition of HMGB1 or microglia activation attenuated cocaine-induced CPP. Box A, a specific antagonist to interrupt the interaction of HMGB1 and RAGE, abolished the expression of cocaine reward memory. Meanwhile, the inhibition of HMGB1-RAGE interaction suppressed cocaine-induced microglial activation, as well as the consolidation of cocaine-induced memory. All above results suggest that the neural HMGB1 induces activation of microglia through RAGE, which contributes to the consolidation of cocaine reward memory. These findings offer HMGB1-RAGE axis as a new target for the treatment of drug addiction.

Hospitalized cocaine detoxification patients in Paris, France: Increased patient levels and changing population characteristics since 2011

The past twenty years have seen a rise in cocaine-related statistics in France, including cocaine use in the general population, emergency ward presentations of acute cocaine intoxication, cocaine use disorders related outpatient appointments and cocaine-related deaths. This study's objectives were to describe trends in patients' admission for specific cocaine detoxification as well as changes in patients' characteristics in the Assistance publique-Hôpitaux de Paris (AP-HP) hospitals group located in Paris region, France. We reviewed the international classification of diseases 10th edition (ICD-10) discharge codes of the AP-HP hospitals group between 2011 and 2021. In addition, medical reports of the largest addiction medicine ward were also analysed for changes across the years 2009, 2014, 2019 and 2022. The regional database showed an almost 3-fold increase in cocaine-related disorders discharge codes between 2011 and 2019. This occurred due to a rise in hospital stays for cocaine dependence or cocaine acute intoxication prior to the fall in levels of inpatient stays associated with the coronavirus disease 2019 (COVID-19) pandemic. The in-depth analysis of inpatients' stays in the specialized addiction medicine ward also showed an increase in admissions for cocaine detoxification programs, with a prevalence of 1.19% in 2009 to 15.73% in 2022 (P=1.44×10-20). Inpatient characteristics showed significant changes, especially in 2022, namely: more daily users, less intravenous administration and less comorbid illicit substances use disorders, with heightened levels of cured hepatitis C patients (P<0.05). Inpatient prescriptions were primarily dopaminergic antagonists with sedatives properties (cyamemazine, loxapine and chlorpromazine), dopamine-receptors partial agonist (aripiprazole) and serotonin reuptake inhibitors. The referral to hospital care for cocaine detoxification has increased in Paris region since 2011, coupled with changes in inpatients' characteristics. This trend has significant implications for the management of inpatient hospital services.

Patient perspectives on current and potential therapies and clinical trial approaches for cocaine use disorder.

Cocaine use disorder (CUD) is characterized by the continued use of cocaine despite serious impacts on life. This study focused on understanding the perspective of individuals with current CUD, individuals in CUD remission, and their supporters regarding current therapies, future therapies, and views on clinical trials for CUD. The online bulletin board (OBB) is a qualitative tool where participants engage in an interactive discussion on a virtual forum. Following completion of a screening questionnaire to determine eligibility, individuals in CUD remission and their supporters logged in to the OBB and responded to questions posed by the moderator. Individuals with current CUD participated in a one-time virtual focus group. All individuals with current CUD and 94% of those in CUD remission reported a diagnosis consistent with CUD or substance use disorder during screening. Individuals with current CUD and their supporters were recruited from the United States (US). Individuals in CUD remission were recruited from five countries, including the US. Individuals with current CUD reported hesitation about seeking treatment due to stigma, a lack of privacy, and being labeled as a drug seeker; barriers to therapy included time, cost, and a lack of privacy. Participants wanted a safe therapy to stop cravings and withdrawal symptoms. Seven clinical trial outcomes, including long-term abstinence and craving control, were suggested based on collected insights. This study can help inform the design of clinical trials and emphasize the need for effective, safe, and accessible therapies. Recruiting participants will require significant trust building.

Ketamine for Adults With Substance Use Disorders

What Is the Issue&#x0D; &#x0D; Accumulating research has demonstrated that subanesthetic doses of ketamine have rapid and sustained antidepressant effects. In 2019, the US FDA approved the S-enantiomer of ketamine (esketamine) for the treatment of patients with treatment-resistant depression.&#x0D; Since then, there has been interest in the development of ketamine for the treatment of a broad range of mental health conditions beyond depression, including substance use disorders (SUDs).&#x0D; Decision-makers want to know if there is any evidence to support the use of ketamine for treating SUDs in adults.&#x0D; &#x0D; What Did We Do?&#x0D; &#x0D; To inform decisions about using ketamine for treating SUDs, we sought to identify and summarize the literature comparing the clinical and cost-effectiveness of ketamine with placebo or no treatment, with alternative interventions, or among ketamine administered via different routes for SUDs. We also searched for evidence-based recommendations for the use of ketamine for SUDs.&#x0D; A research information specialist conducted a literature search of peer-reviewed and grey literature sources published between January 1, 2018, and November 28, 2023. One reviewer screened citations for inclusion based on predefined criteria, critically appraised the included studies, and narratively summarized the findings.&#x0D; &#x0D; What Did We Find?&#x0D; &#x0D; We found 2 systematic reviews (SRs) and 1 randomized controlled trial (RCT) on the use of ketamine for the treatment of patients with alcohol use disorder (AUD), cocaine use disorder (CUD), and opioid use disorder (OUD).&#x0D; Evidence from 2 SR suggests that a combination of ketamine infusion and psychotherapy treatment may be effective in promoting abstinence and reduced consumption of alcohol and cocaine use. There were mixed results regarding the effect of ketamine on withdrawal and craving.&#x0D; The effects of ketamine on OUD were inconclusive as the results were derived from a single study with a small sample size. Similarly, the effects of ketamine on health care utilization (e.g., hospital readmission, emergency department visit) in patients with severe AUD reported in a RCT were also inconclusive due to the small sample size.&#x0D; Adverse events associated with ketamine treatment included the dissociative and psychotomimetic effects and nondissociative effects. The authors of the included SR reported that these events were mild and transient.&#x0D; We did not find any studies on the cost-effectiveness or evidence-based guidelines of ketamine for treating SUDs that met our criteria for this review.&#x0D; &#x0D; What Does It Mean?&#x0D; &#x0D; The conclusions on the positive effects of ketamine for AUD and CUD should be interpreted with caution due to the high risk of bias of the studies included in the SRs.&#x0D; There is a need for more robust clinical trials with larger sample sizes, blinding, and low risk of bias to provide more accurate findings on clinical efficacy, dosing strategies, and safety profile of ketamine for the treatment of AUD, CUD, and OUD.&#x0D; Additional studies on other substances of abuse (e.g., nicotine, amphetamines, and cannabis) may provide important insights into the overall efficacy of ketamine in the treatment of SUDs.&#x0D;

Transcriptomic effects of paternal cocaine-seeking on the reward circuitry of male offspring

It has been previously established that paternal development of a strong incentive motivation for cocaine can predispose offspring to develop high cocaine-seeking behavior, as opposed to sole exposure to the drug that results in drug resistance in offspring. However, the adaptive changes of the reward circuitry have not been fully elucidated. To infer the key nuclei and possible hub genes that determine susceptibility to addiction in offspring, rats were randomly assigned to three groups, cocaine self-administration (CSA), yoked administration (Yoke), and saline self-administration (SSA), and used to generate F1. We conducted a comprehensive transcriptomic analysis of the male F1 offspring across seven relevant brain regions, both under drug-naïve conditions and after cocaine self-administration. Pairwise differentially expressed gene analysis revealed that the orbitofrontal cortex (OFC) exhibited more pronounced transcriptomic changes in response to cocaine exposure, while the dorsal hippocampus (dHip), dorsal striatum (dStr), and ventral tegmental area (VTA) exhibited changes that were more closely associated with the paternal voluntary cocaine-seeking behavior. Consistently, these nuclei showed decreased dopamine levels, elevated neuronal activation, and elevated between-nuclei correlations, indicating dopamine-centered rewiring of the midbrain circuit in the CSA offspring. To determine if possible regulatory cascades exist that drive the expression changes, we constructed co-expression networks induced by paternal drug addiction and identified three key clusters, primarily driven by transcriptional factors such as MYT1L, POU3F4, and NEUROD6, leading to changes of genes regulating axonogenesis, synapse organization, and membrane potential, respectively. Collectively, our data highlight vulnerable neurocircuitry and novel regulatory candidates with therapeutic potential for disrupting the transgenerational inheritance of vulnerability to cocaine addiction.

Neurovascular effects of cocaine: relevance to addiction.

Cocaine is a highly addictive drug, and its use is associated with adverse medical consequences such as cerebrovascular accidents that result in debilitating neurological complications. Indeed, brain imaging studies have reported severe reductions in cerebral blood flow (CBF) in cocaine misusers when compared to the brains of healthy non-drug using controls. Such CBF deficits are likely to disrupt neuro-vascular interaction and contribute to changes in brain function. This review aims to provide an overview of cocaine-induced CBF changes and its implication to brain function and to cocaine addiction, including its effects on tissue metabolism and neuronal activity. Finally, we discuss implications for future research, including targeted pharmacological interventions and neuromodulation to limit cocaine use and mitigate the negative impacts.

The direct link between adult hippocampal neurogenesis and mouse’s enhanced vulnerability to drug addiction

Drug addiction has long been a problem in human history, causing a series of physiological and mental issues. Among them, cocaine is known for its relatively strong damage to the human body, and many studies have been done on its addictive features. Throughout the past decade, researchers have been perpetually searching for ways to improve the treatment for drug addiction, especially cocaine addiction. By testing the effect of reduced adult hippocampal neurogenesis on mice, researchers in previous studies have found that there exists either a direct or indirect relationship between adult hippocampal neurogenesis (AHN) and cocaine addiction. This article examines previous studies that used cocaine to test the relationship between reduced AHN and the vulnerability to addiction in mice and compares cocaine with other types of strong drugs to analyze whether the same relationship with AHN exists for those drugs as well.

Discriminative functional connectivity signature of cocaine use disorder links to rTMS treatment response.

Cocaine use disorder (CUD) is prevalent, and repetitive transcranial magnetic stimulation (rTMS) shows promise in reducing cravings. However, the association between a consistent CUD-specific functional connectivity signature and treatment response remains unclear. Here we identify a validated functional connectivity signature from functional magnetic resonance imaging to discriminate CUD, with successful independent replication. We found increased connectivity within the visual and dorsal attention networks and between the frontoparietal control and ventral attention networks, alongside reduced connectivity between the default mode and limbic networks in patients with CUD. These connections were associated with drug use history and cognitive impairments. Using data from a randomized clinical trial, we also established the prognostic value of these functional connectivities for rTMS treatment outcomes in CUD, especially involving the frontoparietal control and default mode networks. Our findings reveal insights into the neurobiological mechanisms of CUD and link functional connectivity biomarkers with rTMS treatment response, offering potential targets for future therapeutic development.

Neuroprotective effects of quinpirole on lithium chloride pilocarpine-induced epilepsy in rats and its underlying mechanisms

IntroductionEpilepsy is a common neurological disorder that presents with challenging mechanisms and treatment strategies. This study investigated the neuroprotective effects of quinpirole on lithium chloride pilocarpine-induced epileptic rats and explored its potential mechanisms.MethodsLithium chloride pilocarpine was used to induce an epileptic model in rats, and the effects of quinpirole on seizure symptoms and cognitive function were evaluated. The Racine scoring method, electroencephalography, and Morris water maze test were used to assess seizure severity and learning and memory functions in rats in the epileptic group. Additionally, immunohistochemistry and Western blot techniques were used to analyze the protein expression levels and morphological changes in glutamate receptor 2 (GluR2; GRIA2), BAX, and BCL2 in the hippocampi of rats in the epileptic group.ResultsFirst, it was confirmed that the symptoms in rats in the epileptic group were consistent with features of epilepsy. Furthermore, these rats demonstrated decreased learning and memory function in the Morris water maze test. Additionally, gene and protein levels of GluR2 in the hippocampi of rats in the epileptic group were significantly reduced.Quinpirole treatment significantly delayed seizure onset and decreased the mortality rate after the induction of a seizure. Furthermore, electroencephalography showed a significant decrease in the frequency of the spike waves. In the Morris water maze test, rats from the quinpirole treatment group demonstrated a shorter latency period to reach the platform and an increased number of crossings through the target quadrant. Network pharmacology analysis revealed a close association between quinpirole and GluR2 as well as its involvement in the cAMP signaling pathway, cocaine addiction, and dopaminergic synapses.Furthermore, immunohistochemistry and Western blot analysis showed that quinpirole treatment resulted in a denser arrangement and a more regular morphology of the granule cells in the hippocampi of rats in the epileptic group. Additionally, quinpirole treatment decreased the protein expression of BAX and increased the protein expression of BCL2.ConclusionThe current study demonstrated that quinpirole exerted neuroprotective effects in the epileptic rat model induced by lithium chloride pilocarpine. Additionally, it was found that the treatment not only alleviated the rats' seizure symptoms, but also improved their learning and memory abilities. This improvement was linked to the modulation of protein expression levels of GLUR2, BAX, and BCL2. These findings provided clues that would be important for further investigation of the therapeutic potential of quinpirole and its underlying mechanisms for epilepsy treatment.

Prenatal incidence of cleft lip/palate and cocaine abuse in parents: a systematic review and meta-analysis.

The study aimed to investigate the association between maternal cocaine abuse during pregnancy and the prevalence of cleft lip/palate (CL/P) in offspring, synthesizing existing evidence through a systematic review and meta-analysis. CL/P is a congenital craniofacial anomaly with complex etiology, and prior research has suggested potential links between maternal cocaine use and CL/P. However, these associations remain inconclusive. A comprehensive literature search was conducted to identify relevant studies published up to the study's cutoff date in September 2021. Several databases were systematically searched using predefined search terms. Inclusion criteria were set to encompass studies reporting on the prevalence of CL/P in infants born to mothers with a history of cocaine use during pregnancy, with a comparison group of non-cocaine-using mothers. Data were extracted, and a meta-analysis was performed using a random-effects model to calculate pooled odds ratios (OR) and relative risks (RR) with their respective 95% confidence intervals (CI). The review included data from 4 studies that met the inclusion criteria. The combined OR from two studies was 0.05 (95% CI: 0.00, 4.41), which does not suggest a statistically significant association between prenatal cocaine exposure and the incidence of CL/P due to the confidence interval crossing the null value. Additionally, the combined RR was 0.17 (95% CI: 0.04, 0.66), indicating a statistically significant decrease in the risk of CL/P associated with prenatal cocaine exposure. These results, with an OR that is not statistically significant and an RR suggesting decreased risk, should be interpreted with caution due to considerable heterogeneity and variability among the included studies' findings. Further research is needed to clarify these associations. The findings from this systematic review and meta-analysis suggest that maternal cocaine use during pregnancy is not a statistically significant independent risk factor for the development of CL/P in offspring. These results underscore the multifactorial nature of CL/P etiology and emphasize the importance of considering other genetic, environmental, and nutritional factors in understanding the condition's origins. While the study provides important insights, limitations such as data heterogeneity and potential confounders should be acknowledged. Future research should adopt rigorous study designs and explore a broader range of potential risk factors to comprehensively elucidate CL/P development.

Heat shock protein (HSP) and its correlation to cocaine-related death: a systematic review.

Investigating deaths related to chronic cocaine abuse can be a difficult task, particularly when they occur suddenly and without explanation. Cocaine abuse can trigger biological effects similar to physiological stressors, causing the body to produce heat-shock proteins (HSPs). However, there is still limited information on the specific levels of each HSP type. This systematic review aims to comprehensively collect and analyze all existing literature data regar-ding the relationship between HSPs and cocaine abuse to investigate whether HSPs can be utilized as forensic markers for accurately dia-gnosing cocaine-related deaths. The Authors conducted the literature search using PubMed and Scopus databases, searching for articles published between 1 January 1992 and 1 April 2024 using the text string: "heat shock protein" AND "cocaine". Twenty articles were collected, but only nine were included in the systematic review. The data gathered pertained to both human and murine species. The majority of the analyzed articles revealed an elevation in HSP25, HSP27, HSP60, HSP70, HSP72, and HSP73 levels in the brain, cerebellum, and liver, indicating cocaine-induced stress. The relationship between HSP and cocaine has been unclear over time. However, recent studies have shown that cocaine consumption leads to an increase in HSP levels, particularly in the central nervous system. This correlation can also be observed in certain types of liver cells that are capable of binding cocaine metabolites. In conclusion, HSP brain levels, along with other biomarkers, may be used to diagnose sudden, unexpected death related to cocaine abuse.

Abstract WP277: Stroke Etiology in Young Adults With Substance Abuse

Introduction: Recent public health trends suggest increasing rates of substance abuse among young people. Substance use has been associated with an increased risk of stroke, and specifically, cocaine use is known to more likely cause lacunar and cardioembolic strokes. However, less is known about the stroke etiology with other substances. Methods: We conducted a retrospective review of stroke patients between the ages of 18 to 50 years presenting to our Young Stroke Center between April 2022 through August 2023. For each case, data including basic demographics and medical history were collected, and stroke etiology was determined by a vascular neurologist. Patients with substance use at the time of stroke were compared to all non-substance use related stroke and analyzed with respect to TOAST stroke etiology. Substance use was defined as use of opioids, cocaine, marijuana, or alcohol abuse. Analysis was performed with logistic regression adjusting for age, sex, and race. Results: Of 187 patients in the registry, 25 patients had substance use at time of stroke compared with 162 patients with non-substance use related stroke. There were 10 marijuana, 4 opioid, 0 cocaine, 3 alcohol abuse and 8 polysubstance use (including 3 cocaine) cases. There were no significant differences in age at time of stroke (36.9 ± 7.1 vs. 38.8 ± 8.2 years) and race (50.0% vs. 53.4% Black) between substance use and non-substance use related stroke groups, respectively. There was a significantly higher proportion of males with substance use (62.5% vs. 31.9% male; OR [95% CI]: 4.0 [1.6-10.0]). In the substance use group, a higher proportion had cardioembolic stroke etiology (20.8% vs. 9.2%; OR [95% CI]: 4.1 [1.2-14.0]); however, there was no significant difference with respect to the other TOAST stroke etiologies. In patients with active substance use and cardioembolic stroke etiology, heart failure with reduced ejection fraction and atrial fibrillation were the etiologies found. Conclusion: Our findings indicate that among young individuals with active substance use at the time of their stroke, cardioembolic etiology appears to be more likely than in young stroke patients without substance use. This underscores the need for comprehensive cardiac evaluation in this population.

Attentional biases in abstinent patients with cocaine use disorder: rapid orienting or delayed disengagement?

Addiction-related attentional biases may play a central role in the development and maintenance of drug-seeking and drug-taking behaviors. However, evidence in cocaine dependence is limited and mixed. This study examined the time course and component processes of attentional biases for cocaine-related cues in a sample of 47 outpatients (38 men) with cocaine use disorder (CUD) with varying durations of current abstinence. Reaction times in a visual dot-probe task with two picture exposure durations -500 ms, to assess initial stages of attention, and 2,000 ms, to assess maintained attention- were recorded. We found faster responses to probes replacing cocaine-related vs. matched control pictures in the 500 ms but not in the 2,000 ms condition, indicative of early but not late attentional biases for cocaine cues in abstinent patients with CUD. Further comparisons with a neutral baseline revealed that it was not due to rapid orienting but to delayed disengagement from cocaine-related pictures, being this effect greater the longer the period of current abstinence. Consistent with the incentive-sensitization theory, these data suggest that cocaine-related stimuli maintain the capacity to hold spatial attention in abstinent patients with CUD, even after months of abstinence, highlighting the relevance of carrying out stimulus control to avoid relapses.