Cocaine Group Research Articles

Inflammatory mediators and dual depression: Potential biomarkers in plasma of primary and substance-induced major depression in cocaine and alcohol use disorders.

Major depressive disorder (MDD) is the most prevalent comorbid mental disorder among people with substance use disorders. The MDD can be both primary and substance-induced and its accurate diagnosis represents a challenge for clinical practice and treatment response. Recent studies reported alterations in the circulating expression of inflammatory mediators in patients with psychiatric disorders, including those related to substance use. The aim of the study was to explore TNF-α, IL-1β, CXCL12, CCL2, CCL11 (eotaxin-1) and CX3CL1 (fractalkine) as potential biomarkers to identify comorbid MDD and to distinguish primary MDD from substance-induced MDD in patients with substance disorders. Patients diagnosed with cocaine (CUD, n = 64) or alcohol (AUD, n = 65) use disorders with/without MDD were recruited from outpatient treatment programs [CUD/non-MDD (n = 31); CUD/primary MDD (n = 18); CUD/cocaine-induced MDD (N = 15); AUD/non-MDD (n = 27); AUD/primary MDD (n = 16) and AUD/alcohol-induced MDD (n = 22)]. Sixty-two healthy subjects were also recruited as control group. Substance and mental disorders were assessed according to “Diagnostic and Statistical Manual of Mental Disorders, 4th edition, text revision” (DSM-IV-TR) and a blood sample was collected for determinations in the plasma. The cocaine group showed lower TNF-α (p<0.05) and CCL11 (p<0.05), and higher IL-1β (p<0.01) concentrations than the control group. In contrast, the alcohol group showed higher IL-1β (p<0.01) and lower CXCL12 (p<0.01) concentrations than the control group. Regarding MDD, we only observed alterations in the cocaine group. Thus, CUD/MDD patients showed lower IL-1β (p<0.05), CXCL12 (p<0.05) and CCL11 (p<0.05), and higher CXC3CL1 (p<0.05) concentrations than CUD/non-MDD patients. Moreover, while CUD/primary MDD patients showed higher CCL11 (p<0.01) concentrations than both CUD/non-MDD and CUD/cocaine-induced MDD patients, CUD/cocaine-induced MDD patients showed lower CXCL12 (p<0.05) concentrations than CUD/non-MDD patients. Finally, a logistic regression model in the cocaine group identified CXCL12, CCL11 and sex to distinguish primary MDD from cocaine-induced MDD providing a high discriminatory power. The present data suggest an association between changes in inflammatory mediators and the diagnosis of primary and substance-induced MDD, namely in CUD patients.

Intermittent intake of rapid cocaine injections promotes the risk of relapse and increases mesocorticolimbic BDNF levels during abstinence.

Cocaine is thought to be more addictive when it reaches the brain rapidly. We predicted that variation in the speed of cocaine delivery influences the likelihood of addiction in part by determining the risk of relapse after abstinence. Under an intermittent-access schedule, rats pressed a lever for rapid (injected over 5 s) or slower (90 s) intravenous cocaine injections (0.5 mg/kg/injection). Control rats self-administered food pellets. A tone-light cue accompanied each self-administered reward. The 5s- and 90s-rats took a similar average amount of cocaine. Oneor 45 days after withdrawalfrom cocaine/forced abstinence, lever-pressing behaviour was extinguished during a 6-h session. Immediately thereafter, cue- or cocaine (10 mg/kg, i.p.)-induced reinstatement was assessed for 1 h. Oneor 45 days after withdrawal, only 5s-rats showed significant cocaine-induced reinstatement of reward-seeking behaviour. Inboth cocaine groups, cue-induced reinstatement behaviourwas more pronounced after 45daysthan after 1day of withdrawal from cocaine, indicating incubation of conditioned drug craving. However, cue-induced reinstatement after extended abstinence was greatest in the 5s-rats. Brain-derived neurotrophic factor (BDNF) activity in the brain regulates reinstatement behaviour. Thus, 24 h after reinstatement tests, we measured BDNF protein concentrations in mesocorticolimbic regions. Only 5s-rats showed time-dependent increases in BDNF concentrations in the prelimbic cortex, nucleus accumbens core and ventral tegmental area after withdrawalfrom cocaine (day 45 > day 1). Thus, rapidly rising brain cocaine levels might facilitate addiction by evoking changes in the brain that intensify drug craving after abstinence, and these changes persist long after the last bout of cocaine use.

Cocaine Paired Environment Increases SATB2 Levels in the Rat Paraventricular Thalamus.

SATB2 is a DNA binding protein that specifically binds the nuclear matrix attachment region and functions as a regulator of the transcription of large chromatin domains. Unlike its well addressed role during brain development, the role of SATB2 in adult brain is under-investigated. It has been shown that deletion of SATB2 from the forebrain of adult mice significantly impaired long-term memory for contextual fear and object recognition memory. The aim of the present study was to investigate the effects of appetitive stimuli such as cocaine and social interaction (SI) on SATB2 expression in the adult rat brain. For that, we performed conditioned place preference (CPP) to cocaine (15 mg/kg) and to SI, then assessed SATB2 expression in the brain 1 h (24 h after the last conditioning) and 24 h (48 h after the last conditioning) after the CPP test. We found that SATB2 expression in the paraventricular thalamus of rats was increased 1 h after the cocaine CPP test. This increase was selective for the cocaine-paired environment since the SI-paired environment did not increase SATB2 expression in the paraventricular thalamus. Also, the cocaine paired environment-induced increase of SATB2 levels in the paraventricular thalamus was due to cocaine conditioning as the unpaired cocaine group did not show an increase of SATB2 in the paraventricular thalamus. These results suggest that SATB2 in the paraventricular thalamus appears to be involved in the association between cocaine effects and environmental context. Further studies are needed to address the functional role of SATB2 in cocaine conditioning.

"Evaluating autonomy, beneficence, and justice with substance-using populations: Implications for clinical research participation": Correction to Strickland and Stoops (2018).

Reports an error in "Evaluating autonomy, beneficence, and justice with substance-using populations: Implications for clinical research participation" by Justin C. Strickland and William W. Stoops (Psychology of Addictive Behaviors, 2018[Aug], Vol 32[5], 552-563). In the article, an incorrect Online First date appears in the article. The correct Online First publication date is July 12, 2018. The online version of this article has been corrected. (The following abstract of the original article appeared in record 2018-31276-001.) Narrow inclusion criteria regarding substance use are commonplace in clinical research. This is due, in part, to assumptions about capacity to make "rational" decisions regarding participation by these populations. This study evaluated decision-making and perceptions surrounding each of the Belmont principles among individuals with cocaine use histories, cigarette smokers without illicit substance use histories, and controls without cigarette or illicit substance use histories. Cocaine (n = 124), cigarette (n = 128), and control (n = 145) groups were recruited using Amazon's Mechanical Turk. Participants completed measures evaluating research participation after reading two hypothetical study vignettes varying in risk. Assays assessed capacity to consent, perceived research burden, and endorsement of research participation by various populations. Individuals reporting cocaine use showed a reduced capacity to consent compared to controls, but this effect was small and largely explained by sociodemographic differences (e.g., race) rather than substance use history. Perceived research burden in the cigarette group was lower than in the cocaine group, but this difference was of a small to medium effect size. All groups reported substantively lower endorsement of research participation by individuals with illicit substance use histories relative to healthy adults, with less support indicated by control and cigarette groups compared to the cocaine group. Few differences were observed by substance use history regarding perceptions of and decision-making surrounding research participation. These data highlight the need for the continued study of evidence-based ethics and support more widespread acceptance of research participation by individuals with substance use histories in clinical research. (PsycINFO Database Record

Evaluating autonomy, beneficence, and justice with substance-using populations: Implications for clinical research participation.

Narrow inclusion criteria regarding substance use are commonplace in clinical research. This is due, in part, to assumptions about capacity to make "rational" decisions regarding participation by these populations. This study evaluated decision-making and perceptions surrounding each of the Belmont principles among individuals with cocaine use histories, cigarette smokers without illicit substance use histories, and controls without cigarette or illicit substance use histories. Cocaine (n = 124), cigarette (n = 128), and control (n = 145) groups were recruited using Amazon's Mechanical Turk. Participants completed measures evaluating research participation after reading two hypothetical study vignettes varying in risk. Assays assessed capacity to consent, perceived research burden, and endorsement of research participation by various populations. Individuals reporting cocaine use showed a reduced capacity to consent compared to controls, but this effect was small and largely explained by sociodemographic differences (e.g., race) rather than substance use history. Perceived research burden in the cigarette group was lower than in the cocaine group, but this difference was of a small to medium effect size. All groups reported substantively lower endorsement of research participation by individuals with illicit substance use histories relative to healthy adults, with less support indicated by control and cigarette groups compared to the cocaine group. Few differences were observed by substance use history regarding perceptions of and decision-making surrounding research participation. These data highlight the need for the continued study of evidence-based ethics and support more widespread acceptance of research participation by individuals with substance use histories in clinical research. (PsycINFO Database Record

Psychological Functioning of Women Taking Illicit Drugs during Pregnancy and the Growth and Development of Their Offspring in Early Childhood

Objective: The aim of this research was to assess psychosocial history and psychological functioning in women who use drugs during pregnancy and determine how drug exposure affects child development. Methods: Pregnant women using marijuana (n = 38) and cocaine (n = 35) and receiving methadone maintenance (n = 24), along with a control (n = 49) group of pregnant women, were enrolled and followed every six months through 18–24 months postnatally. Results: There was a significantly higher incidence of mental illness among mothers in the drug-using groups. Prenatal stress and late-term drug severity scores were significantly higher in the mothers who used cocaine and methadone, who were also more likely to have abuse and incarceration histories. At 12 months, there were significantly higher rates of drug use in the marijuana group. Anxiety scores were highest in the methadone group. At 18 to 24 months, the methadone group reported significantly more stress, and methadone and marijuana groups had significantly higher anxiety and depression scores. At birth, neonates from the methadone and marijuana groups had significantly smaller head circumferences, with the smallest values in the methadone group. At one year, children in the cocaine group had significantly lower Bayley Scales of Infant Development–Third Edition (Bayley-III) cognitive and motor scores. At 18 to 24 months, children in the methadone group had significantly smaller head circumferences and Bayley-III cognitive scores. Children in the methadone and cocaine groups had a significantly higher incidence of atypical neurological examinations at 6 to 9 and 18 to 24 months. Conclusions: Mothers in the methadone and cocaine groups presented with more severe prenatal drug use and psychosocial risk factors relative to women who used primarily marijuana. Children in the cocaine and methadone groups were neurologically atypical relative to others at study end. Mothers in the marijuana group reported chronic drug use as well as anxiety and depression at follow-up. At birth, children in the marijuana group were smaller, but this resolved with time. Similarly, children in the cocaine group had motor and cognitive delays that resolved by age two. Children in the methadone group had persistent growth and cognitive deficits. Their mothers demonstrated more anxiety, depression, and stress, the combination of which left these women and children liable to face ongoing psychosocial struggle and psychological distress. Dual interventions for mother and child should be considered in attempting to optimize outcome.

Impairment of spatial working memory and oxidative stress induced by repeated crack cocaine inhalation in rats

Crack cocaine is a highly toxic drug with great potential to induce addiction. It produces more intense effects than cocaine powder, with its use having grown worldwide. However, few studies have focused on the cognitive and biochemical consequences that result from crack cocaine inhalation. This study examined the effects of direct crack cocaine inhalation on spatial working memory and brain oxidative stress parameters in rats. Male adult Wistar rats, well-trained in an eight-arm radial maze (8-RM), underwent five sessions of crack cocaine inhalation (crack cocaine group) once a day or inhalation simulation (sham group), being tested in 1-h delayed tasks 24 h after the last inhalation. An additional inhalation session was carried out the following day, with the prefrontal cortex, hippocampus and striatum being removed five minutes afterwards in order to assess oxidative damage such as lipid peroxidation, thiobarbituric acid-reactive species (TBARS) levels, and advanced oxidation protein products (AOPP), as well as the activity of antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Animals from the crack cocaine group showed more errors (p < 0.01) in the 1-h post-delay performance in the 8-RM when compared to the sham group. The crack cocaine group showed decreased (p < 0.05) lipid peroxidation in the hippocampus and increased (p < 0.001) levels of AOPP and SOD activity (p < 0.05) in the striatum when compared to the sham group. Therefore, the repeated inhalation of crack cocaine impaired long-term spatial working memory and elicited oxidative stress in the hippocampus and striatum of rats.

Revisiting long-access versus short-access cocaine self-administration in rats: intermittent intake promotes addiction symptoms independent of session length.

In rats, continuous cocaine access during long self-administration sessions (6 versus 1-2hours) promotes the development of behavioral symptoms of addiction. This has led to the assumption that taking large amounts of drug during extended daily bouts is necessary to develop an addiction phenotype. Recent work shows that within-session intermittent access (IntA) to cocaine produces much less drug intake than continuous-access procedures (i.e. long-access sessions) but evokes addiction symptoms more effectively. IntA-sessions are also long, typically lasting 6hours. It is not known whether IntA-sessions must be extended to promote addiction-relevant changes in drug use over time. Here, we determined the influence of IntA-session length on patterns of cocaine use relevant to addiction. Two groups of male Wistar rats self-administered cocaine (0.25mg/kg/injection, injected over 5seconds) during 18 daily IntA-sessions. One group had long 6-hour sessions (Long-IntA), the other group had shorter, 2-hour sessions (Short-IntA). Only Long-IntA rats escalated their cocaine intake over sessions, but both groups developed a burst-like pattern of drug use over time and similar levels of psychomotor sensitization. The two groups also showed robust and similar levels of both responding for cocaine under a progressive ratio schedule of reinforcement and cocaine-induced reinstatement of extinguished drug-seeking behavior. In summary, long IntA-sessions lead to greater cocaine intake than shorter IntA-sessions, but the two conditions are equally effective in evoking the patterns of drug-taking and drug-seeking that define addiction. This suggests that chronic intermittent cocaine use, even during short daily bouts, is sufficient to promote addiction symptoms.

Effects of Cocaine Self-Administration and Its Extinction on the Rat Brain Cannabinoid CB1 and CB2 Receptors

The aim of this study was to evaluate changes in the expression of cannabinoid type 1 (CB1) and 2 (CB2) receptor proteins in several brain regions in rats undergoing cocaine self-administration and extinction training. We used a triad-yoked procedure to distinguish between the motivational and pharmacological effects of cocaine. Using immunohistochemistry, we observed a significant decrease in CB1 receptor expression in the prefrontal cortex, dorsal striatum, and the basolateral and basomedial amygdala following cocaine (0.5 mg/kg/infusion) self-administration. Increased CB1 receptor expression in the ventral tegmental area in rats with previous cocaine exposure was also found. Following cocaine abstinence after 10 days of extinction training, we detected increases in the expression of CB1 receptors in the substantia nigra in both cocaine groups and in the subregions of the amygdala for only the yoked cocaine controls, while any method of cocaine exposure resulted in a decrease in CB2 receptor expression in the prefrontal cortex (p < 0.01), nucleus accumbens (p < 0.01), and medial globus pallidus (p < 0.01). Our findings further support the idea that the eCB system and CB1 receptors are involved in cocaine-reinforced behaviors. Moreover, we detected a cocaine-evoked adaptation in CB2 receptors in the amygdala, prefrontal cortex, and globus pallidus.

Comparative hazards of acute myocardial infarction among hospitalized patients with methamphetamine- or cocaine-use disorders: A retrospective cohort study

BackgroundIt is assumed that recreational use of methamphetamine can trigger acute myocardial infarction (AMI) events, but estimates of longitudinal hazards of AMI among methamphetamine users are lacking. MethodsRetrospective cohort study: Competing-risks analysis was used to estimate time-to-AMI patterns in methamphetamine versus matched appendicitis (population-proxy) and matched cocaine (drug-control) groups. Cohorts were propensity-score-matched using demographic and clinical variables. SettingCalifornia, 1990–2005. ParticipantsCohorts of individuals with no prior or concurrent history of AMI hospitalized with methamphetamine- (n = 73,056), cocaine- (n = 47,726), or appendicitis-related conditions (n = 330,109). MeasurementsICD-9/ICD-10 indications of AMI (ICD-9 410.X; ICD-10 I21.X) in death records or inpatient hospital data. ResultsPatients in methamphetamine cohort were more likely to develop subsequent AMI in comparison to those in matched appendicitis cohort [Hazard ratio (HR): 1.41; 95% CI, 1.23–1.62, p < 0.0001], with increased risk most marked in young methamphetamine users (age 15–34 years; HR: 2.04; 95% CI, 1.63–2.57, p = 0. 0001). Risk was slightly increased vs. that in matched cocaine group (HR: 1.19; 95% CI, 1.02–1.39, p = 0. 029). Individuals in cocaine cohort were also more likely to experience AMI outcome vs. appendicitis cohort (HR: 1.25; 95% CI, 1.08–1.45, p = 0. 0023). ConclusionOur longitudinal data support results of earlier epidemiological studies suggesting that persons with methamphetamine- (or cocaine-) use disorders might have increased AMI risk. However, because of potential study limitations and the unexpectedly modest magnitude of the observed increased AMI hazard, these findings must be considered preliminary and require replication.

Environmental enrichment reduces cocaine neurotoxicity during cocaine-conditioned place preference in male rats

Environmental enrichment (EE) has a neuroprotective role and prevents the development of cocaine addiction behavior in rats. Studies showing the role of EE in cocaine toxicity are nonexistent. We hypothesized that rats exposed to EE are protected from cocaine-induced changes in the redox profile and DNA damage after undergoing conditioned place preference (CPP). Ten male Wistar rats were placed in EE cages equipped with toys, a ladder and tunnels, and ten were provided clean, standard laboratory housing (non-EE). EE and non-EE rats were randomly allocated to the classical CPP cocaine vs. saline (COC/Saline) group, where cocaine (15 mg/kg; i.p.) was tested alternately with saline. Afterwards, intracellular reactive species and antioxidant enzymes were evaluated and the comet essay was performed in the prefrontal cortex and hippocampus of rats. As expected, EE rats spent less time in the cocaine-paired chamber, and as a new result, less cocaine-induced DNA damage was observed in the two brain structures. Altogether, our results demonstrate that EE decreases neurotoxicity in brain regions linked to cocaine addiction but does not extinguish it completely.

Regional drug abuse prevalence depending on laboratory based urine illicit drug screening results

Objectives: To determine the laboratory based drug abuse prevalence of persons who have illicit and/or addictive substance test requests instead of alcohol in a city in Middle Anatolia in Turkey. Methods: Laboratory information system’s data of urine samples, submitted to Biochemistry Laboratory from various clinics, between January 2014 and June 2016 were retrospectively investigated. In comprehension of illicit drug use amphetamin, cannabis, opiate, cocaine and benzodiazepin group tests were screened with Cloned Enzyme Donor Immunoassay method. Positivity-negativity rates according to years, age-gender distribution and number of multiple substance usage were investigated. Results: Totally 79873 illicit drugs were screened in 19763 urine samples. 18080 males (% 91.5) and 1683 females (%8.5), with a mean age of 30.7±10.8 years (range: 4-86) and 27.2±10.5 years (range: 1-86) respectively were included. The average positivity rate according to the sample size in last 2.5 years was 23%; 19% in 2014, 23% in 2015, and 27% in 2016. The positivity rates according to number of analyzed tests were 5.9%, 6.7% and 7.5% respectively. In 2014 the maximum positivity rate was in benzodiazepine (12.5%) and secondly in cannabinoids (11.9%). Whereas amphetamine were the most common drug used (16.3%) with a 4.17 fold increase in 2015 compared to 2014. The increase in amphetamine group substance positivity continued in the first half of 2016 compared to previous year. The most common and the second most common multiple substance usage were amphetamine+ cannabis and amphetamine+opiate respectively. Conclusion: According to laboratory information of illicit drug screening results in urine, drug abuse is increasing through years. Amphetamine group is the most common used substance in the last two years in this region. This is the first study contributing to the prevalence of substance use in a city of Middle Anatolia in Turkey with a large sample volume and patient population.

Evaluation of plasma cytokines in patients with cocaine use disorders in abstinence identifies transforming growth factor alpha (TGFα) as a potential biomarker of consumption and dual diagnosis.

BackgroundCocaine use disorder (CUD) is a complex health condition, especially when it is accompanied by comorbid psychiatric disorders (dual diagnosis). Dual diagnosis is associated with difficulties in the stratification and treatment of patients. One of the major challenges in clinical practice of addiction psychiatry is the lack of objective biological markers that indicate the degree of consumption, severity of addiction, level of toxicity and response to treatment in patients with CUD. These potential biomarkers would be fundamental players in the diagnosis, stratification, prognosis and therapeutic orientation in addiction. Due to growing evidence of the involvement of the immune system in addiction and psychiatric disorders, we tested the hypothesis that patients with CUD in abstinence might have altered circulating levels of signaling proteins related to systemic inflammation.MethodsThe study was designed as a cross-sectional study of CUD treatment-seeking patients. These patients were recruited from outpatient programs in the province of Malaga (Spain). The study was performed with a total of 160 white Caucasian subjects, who were divided into the following groups: patients diagnosed with CUD in abstinence (N = 79, cocaine group) and matched control subjects (N = 81, control group). Participants were clinically evaluated with the diagnostic interview PRISM according to the DSM-IV-TR, and blood samples were collected for the determination of chemokine C-C motif ligand 11 (CCL11, eotaxin-1), interferon gamma (IFNγ), interleukin-4 (IL-4), interleukin-8 (IL-8), interleukin-17α (IL-17α), macrophage inflammatory protein 1α (MIP-1α) and transforming growth factor α (TGFα) levels in the plasma. Clinical and biochemical data were analyzed in order to find relationships between variables.ResultsWhile 57% of patients with CUD were diagnosed with dual diagnosis, approximately 73% of patients had other substance use disorders. Cocaine patients displayed greater cocaine symptom severity when they were diagnosed with psychiatric comorbidity. Regarding inflammatory factors, we observed significantly lower plasma levels of IL-17α (p < 0.001), MIP-1α (p < 0.001) and TGFα (p < 0.05) in the cocaine group compared with the levels in the control group. Finally, there was a significant primary effect of dual diagnosis on the plasma concentrations of TGFα (p < 0.05) in the cocaine group, and these levels were lower in patients with dual diagnosesDiscussionIL-17α, MIP-1α and TGFα levels are different between the cocaine and control groups, and TGFα levels facilitate the identification of patients with dual diagnosis. Because TGFα reduction is associated with enhanced responses to cocaine in preclinical models, we propose TGFα as a potential biomarker of complex CUD in humans.

Impact of Cocaine Use on Acute Ischemic Stroke Patients: Insights from Nationwide Inpatient Sample in the United States.

Cocaine is the third most common substance of abuse after cannabis and alcohol. The use of cocaine as an illicit substance is implicated as a causative factor for multisystem derangements ranging from an acute crisis to chronic complications. Vasospasm is the proposed mechanism behind adverse events resulting from cocaine abuse, acute ischemic strokes (AIS) being one of the few. Our study looked into in-hospital outcomes owing to cocaine use in the large population based study of AIS patients. Using the national inpatient sample (NIS) database from 2014 of United States of America, we identified AIS patients with cocaine use using International Classification of Disease, Ninth Revision (ICD-9) codes. We compared demographics, mortality, in-hospital outcomes and comorbidities between AIS with cocaine use cohort versus AIS without cocaine use cohort. Acute ischemic strokes (AIS) with cocaine group consisted of higher number of older patients (> 85 years) (25.6% versus 18.7%, p <0.001) and females (52.4% versus 51.0%, p <0.001). Cocaine cohort had higher incidence of valvular disorders (13.2% versus 9.7%, p <0.001), venous thromboembolism (3.5% versus 2.6%, p<0.03), vasculitis (0.9% versus 0.4%, p <0.003), sudden cardiac death (0.4% versus 0.2%, p<0.02), epilepsy (10.1% versus 7.4%, p <0.001) and major depression (13.2% versus 10.7%, p<0.007). The multivariate logistic regression analysis found cocaine use to be the major risk factor for hospitalization in AIS cohort. In-hospital mortality (odds ratio (OR)= 1.4, 95% confidence interval= 1.1-1.9, p <0.003) and the disposition to short-term hospitals (odds ratio (OR)= 2.6, 95% confidence interval = 2.1-3.3, p <0.001) were also higher in cocaine cohort. Venous thromboembolism was observed to be linked with cocaine use (OR= 1.5, 95% confidence interval= 1.0-2.1, p < 0.01) but less severely than vasculitis (OR= 3.0, 95% confidence interval= 1.6-5.8, p <0.001). Further prospective research is warranted in this direction to improve the outcomes for AIS and lessen the financial burden on the healthcare system of the United States.

Comparative study of psychiatric comorbidity differences in patients with ADHD and cocaine substance use disorders and patients ADHD and cannabis use disorders

Substance Use Disorders (SUD) and Attention Deficit Hyperactive Disorder (ADHD) are frequent conditions in out drug treatment centers. There are evidences about the high prevalence of ADHD in SUD patients (20%) compared with just ADHD in general population (1–7.3%). Both disorders and psychiatric comorbidity are important in the diagnosis proceeding. The objective of this study is search the difference in psychiatric comorbidity conditions between patients with ADHD and Cocaine SUD and ADHD and Cannabis SUD. ADHD was present in 158 patients of a total sample in which 46,8% used cocaine, 17.1% cannabis and 36.1% used both. Mood disorders were 26.8% in cocaine users, 21.7% in cannabis and 18.9% in both. Anxiety disorders were 20.3% in cocaine users, 37.5 in cannabis and 13% in both users. Primary psychotic disorders were 2.9% in cocaine users, none in cannabis and 11,1% in both drug users. Personality disorders by cluster were, Cluster A: 11.3% in cocaine group, 36% in cannabis group and 24.5 in cannabis and cocaine group. Cluster B: 33.8% in cocaine group, 44% in cannabis group and 51.9% in cannabis and cocaine group. Cluster C: 9.9% in cocaine group, 28% in cannabis group and 19.2% in cannabis and cocaine group. There could be common pathways of neuronal damage related to psychiatric comorbidity depending of used drug, the differences in comorbidity found in this study could explain a little part of it. It is important to manage SUD-ADHD and other psychiatric comorbidity in order to improve the outcomes of these patients.Disclosure of interestThe authors have not supplied their declaration of competing interest.

Cannabis and cue-induced craving in cocaine-dependent individuals: A pilot study

BackgroundCannabis consumption is common among cocaine users; however, little is known about its effect on cocaine craving. The objective of this study was to assess whether cannabis co-use is associated with lower cue-induced cocaine craving in non-treatment-seeking cocaine-dependent individuals. MethodsData from twenty-eight cocaine-dependent men were analyzed in this pilot study. Cocaine-dependent subjects (n=12) were compared with cocaine-dependent subjects who also abused or were dependent on cannabis (n=16). After at least 72h of cocaine abstinence, verified using the Timeline Followback and a drug screening test, subjects participated in a functional magnetic resonance imaging session during which neutral and drug cue video sequences were presented. Each sequence comprised four video blocks alternating with resting blocks. We report here subjective craving measures that were collected using the Visual Analog Scale, administered before and after each video block as per standard craving measurement paradigms. ResultsCocaine craving was successfully induced, with no significant difference in cue-induced craving between the two groups. However, post-hoc analyses revealed a significant increase in pre-video cocaine craving scores over time among individuals with cannabis use disorders. ConclusionWe could not highlight significant differences in cocaine craving induction between groups, but we observed a possible deficit in craving decay in the cocaine and cannabis group. In light of this finding, methodology of craving assessment in non-treatment-seeking users, particularly when different substances are combined, should possibly include outcomes linked to craving decay. Studies examining the association between cocaine craving decay and other outcome measures, such as relapse, are also warranted.

Role of perineuronal nets in the anterior dorsal lateral hypothalamic area in the acquisition of cocaine-induced conditioned place preference and self-administration

Addiction involves drug-induced neuroplasticity in the circuitry of motivated behavior, which includes the medial forebrain bundle and the lateral hypothalamic area. Emerging at the forefront of neuroplasticity regulation are specialized extracellular matrix (ECM) structures that form perineuronal nets (PNNs) around certain neurons, mainly parvalbumin positive (PV+), fast-spiking interneurons (FSINs), making them a promising target for the regulation of drug-induced neuroplasticity. Despite the emerging significance of PNNs in drug-induced neuroplasticity and the well-established role of the lateral hypothalamic area (LHA) in reward, reinforcement, and motivation, very little is known about how PNN-expressing neurons control drug-seeking behavior. We found that a discrete region of the anterior dorsal LHA (LHAad) exhibited robust PNN and dense ECM expression. Approximately 87% of parvalbumin positive (PV+) neurons co-expressed the PNN marker Wisteria floribunda agglutinin (WFA), while 62% of WFA positive (WFA+) neurons co-expressed PV in the LHAad of drug naïve rats. Removal of PNNs within this brain region via chrondroitinase ABC (Ch-ABC) administration abolished acquisition of cocaine-induced CPP and significantly attenuated the acquisition of cocaine self-administration (SA). Removal of LHAad PNNs did not affect locomotor activity, sucrose intake, sucrose-induced CPP, or acquisition of sucrose SA in separate groups of cocaine naïve animals. These data suggest that PNN-dependent neuroplasticity within the LHAad is critical for the acquisition of both cocaine-induced CPP and SA but is not general to all rewards, and that PNN degradation may have utility for the management of drug-associated behavioral plasticity and memory in cocaine addicts.

Myocardial oxidative damage is induced by cardiac Fas-dependent and mitochondria-dependent apoptotic pathways in human cocaine-related overdose

The aim of this study is to analyse cardiac specimens from human cocaine-related overdose, to verify the hypothesis that cardiac toxicity by acute exposure to high dosage of cocaine could be mediated by unbalanced myocardial oxidative stress, and to evaluate the apoptotic response. To address these issues, biochemical and immunohistological markers of oxidative/nitrosative stress were evaluated. We found that i-NOS, NOX2 and nitrotyrosine expression were significantly higher in the hearts of subjects who had died from high doses of cocaine, compared to the control group. Increase of these markers was associated with a dramatic increase in 8-OHdG, another marker of oxidative stress. A high number of TUNEL-positive apoptotic myocells was observed in the study group compared to the control group. The immunoexpression of TNF-α was significantly higher in the cocaine group compared to the control group. Furthermore, we detected a significantly stronger immunoresponse to anti-SMAC/DIABLO in our study group compared to control cases. Both cardiac Fas-dependent and mitochondria-dependent apoptotic pathways appeared to be activated to a greater extent in the cocaine group than in the control group. Our results highlight the central role of oxidative stress in cocaine toxicity. High levels of NOS can promote the oxidation process and lead to apoptosis.

Intermittent intake of rapid cocaine injections promotes robust psychomotor sensitization, increased incentive motivation for the drug and mGlu2/3 receptor dysregulation

The choice between smoking, injecting or swallowing a drug influences the risk of addiction, as this determines both how much drug gets into the brain and how fast. Most animal studies on addiction focus on how much drug it takes to produce pathological drug use. How fast drugs get to the brain is generally ignored. A few studies have examined the influence of the speed of drug onset, but speed varied along with cumulative intake. Here we held average cumulative intake constant and determined whether variation in the speed of cocaine onset alone predicts outcome. Two groups of rats self-administered intravenous cocaine (0.25 mg/kg/injection) during daily sessions. Cocaine was available intermittently during each session. This produces the spikes and troughs in brain levels of cocaine thought to model how addicts take the drug. To vary the speed of cocaine onset, each injection was delivered over 5 s to one group, and over 90 s to the other. Average cumulative cocaine intake was the same in the two groups. However, rapid injections promoted robust psychomotor sensitization and potentiated incentive motivation for cocaine (0.063–0.25 mg/kg/injection). This addiction-relevant phenotype was accompanied by enhanced functional activity of metabotropic glutamate group II receptors (mGluR2/3s) in the prelimbic cortex and nucleus accumbens. Pharmacological activation of mGluR2/3s with LY379268 also preferentially decreased the motivation to take cocaine in rats previously exposed to rapid drug injections. Thus, varying the speed of drug onset can be used to parse the neurobiology of addiction from that of mere drug taking.

Drug Trafficking Through Body Packers

Drug trafficking is a serious global issue leading to law and order problems in the affected countries. A 29 year old, female, Zambian citizen was brought to Guru Nanak Dev Hospital, Amritsar, Punjab by Indian Border Security Force in semi-conscious state from Indo-Pak International Border, Wagah, Amritsar. Initially which was thought to be a case of sexual assault but later on, during her post-mortem examination, 50 large cylindrical hard shelled capsules were recovered from her gastro-intestinal tract and surprisingly it turned out to be a case of drug trafficking by body packer and poisoning of the deliriant cerebral group of drug cocaine, from ruptured capsules was the ultimate cause of death. In this case postmortem examination not only helped in establishing the cause of death, mode and manner of death but also had exposed almost fatal new mode of drug trafficking by body packing, across the international border, without arousing any suspicion to the police or intelligence agencies.