Virtual reality cue-exposure therapy in reducing cocaine craving: the Promoting Innovative COgnitive behavioral therapy for Cocaine use disorder (PICOC) study protocol for a randomized controlled trial.

BACKGROUND: Cocaine craving is a central symptom of cocaine use disorders (CUD). Virtual reality cue-exposure therapy for craving (VRCET) allows more immersive, realistic, and controllable exposure than traditional non-VR cue-exposure therapy (CET), whose efficacy is limited in treating substance use disorders. The purpose of this study is to evaluate the efficacy and acceptability of VRCET, as a stand-alone and add-on intervention (i.e., combined with cognitive therapy), compared to a picture-based CET (PCET), in reducing self-reported cocaine craving in inpatients hospitalized for CUD. METHODS: Fifty-four inpatients hospitalized for CUD will be randomized in one of two intensive 3-week treatment arms: 10 meetings/2-week treatment of VRCET plus 5 meetings/1-week treatment of memory-focused cognitive therapy (MFCT; experimental arm), or 15 meetings/3-week treatment of PCET (active control arm). The Craving Experience Questionnaire (CEQ - F & S) will be used to assess the primary outcome, i.e., the post-treatment decrease of self-reported cocaine craving frequency (within the past 2 weeks) and intensity scores (in VR exposure to cocaine cues). Secondary endpoints include urinary, physiological, and self-reported cocaine use-related measures. Assessments are scheduled at pretreatment, after 2 weeks of treatment (i.e., VRCET vs. PCET), post-treatment (3 weeks, i.e., VRCET + MFCT vs. PCET), and at 1-month follow-up. Acceptability will be evaluated via (i) the Spatial Presence for Immersive Environments - Cybersickness along VRCET and (ii) the Client Satisfaction Questionnaires after 2 weeks of treatment and post-treatment. DISCUSSION: This study will be the first to evaluate the acceptability and efficacy of VRCET for CUD, as a psychotherapeutic add-on, to reduce both cocaine craving frequency and intensity. Additionally, this study will provide evidence about the specific interest of VRCET, compared to a non-VR-based CET, as a cue reactivity and exposure paradigm for treating substance use disorders. TRIAL REGISTRATION: NCT05833529 [clinicaltrials.gov]. Prospectively registered on April 17, 2023.

Predictors of cocaine use disorder treatment outcomes: a systematic review.

BACKGROUND: Psychosocial approaches are the first-line treatments for cocaine dependence, although they still present high dropout and relapse rates. Thus, there is a pressing need to understand which variables influence treatment outcomes to improve current treatments and prevent dropout and relapse rates. The aim of this study is to explore predictors of treatment retention and abstinence in CUD. METHODS: This systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). We searched three databases-PubMed, PsychINFO and Web of Science-for randomized clinical trials (RCTs) published in English and Spanish from database inception through April 1, 2023. We selected all studies that met the inclusion criteria (adults aged ≥ 18, outpatient treatment, CUD as main addiction, and no severe mental illness) to obtain data for the narrative synthesis addressing cocaine abstinence and treatment retention as main outcome variables. After data extraction was completed, risk of bias was assessed using the Cochrane risk-of-bias tool for randomized trials (RoB-2). RESULTS: A total of 566 studies were screened, and, of those, 32 RCTs were included in the synthesis. Younger age, more years of cocaine use, and craving levels were significant predictors of relapse and treatment dropout. Fewer withdrawal symptoms, greater baseline abstinence, greater treatment engagement, and more self-efficacy were all predictors of longer duration of abstinence. The role of impulsivity as a predictor of CUD is unclear due to conflicting data, although the evidence generally suggests that higher impulsivity scores can predict more severe addiction and withdrawal symptoms, and earlier discontinuation of treatment. CONCLUSION: Current evidence indicates which variables have a direct influence on treatment outcomes, including well-studied cocaine use-related variables. However, additional variables, such as genetic markers, appear to have a high impact on treatment outcomes and need further study. SYSTEMATIC REVIEW REGISTRATION: This systematic review is registered at PROSPERO (ID: CRD42021271847). This study was funded by the Spanish Ministry of Science, Innovation and Universities, Instituto Carlos III (ISCIII) (FIS PI20/00929) and FEDER funds and Fundació Privada Hospital de la Santa Creu i Sant Pau (Pla d'acció social 2020).

Sex-Dependent Differences in the Neural Correlates of Cocaine and Emotional Cue-Reactivity in Regular Cocaine Users and Non-Drug-Using Controls: Understanding the Role of Duration and Severity of Use.

INTRODUCTION: The development of cocaine use disorder in females is suggested to be more strongly related to neural mechanisms underlying stress-reactivity, whereas in males it is suggested to be more strongly related to neural mechanisms underlying drug cue-reactivity. Existing evidence, however, is based on neuroimaging studies that either lack a control group and/or have very small sample sizes that do not allow to investigate sex differences. METHODS: The main objective of the current study was to investigate sex differences in the neural correlates of cocaine and negative emotional cue-reactivity within high-risk intranasal cocaine users (CUs: 31 males and 26 females) and non-cocaine-using controls (non-CUs: 28 males and 26 females). A region of interest (ROI) analysis was applied to test for the main and interaction effects of group, sex, and stimulus type (cocaine cues vs. neutral cocaine cues and negative emotional cues vs. neutral emotional cues) on activity in the dorsal striatum, ventral striatum (VS), amygdala, and dorsal anterior cingulate cortex (dACC). RESULTS: There were no significant sex or group differences in cocaine cue-reactivity in any of the ROIs. Results did reveal significant emotional cue-reactivity in the amygdala and VS, but these effects were not moderated by group or sex. Exploratory analyses demonstrated that emotional cue-induced activation of the dACC and VS was negatively associated with years of regular cocaine use in female CUs, while this relationship was absent in male CUs. CONCLUSIONS: While speculative, the sex-specific associations between years of regular use and emotional cue-reactivity in the dACC and VS suggest that, with longer years of use, female CUs become less sensitive to aversive stimuli, including the negative consequences of cocaine use, which could account for the observed "telescoping effect" in female CUs.

Treatment with dextroamphetamine decreases the reacquisition of cocaine self-administration: Consistency across social contexts.

RATIONALE: A return to cocaine use following abstinence frequently occurs in a social context, and the presence of other individuals using cocaine may contribute to the likelihood of use. Previous studies have reported that chronic d-amphetamine treatment decreases cocaine self-administration in laboratory animals and reduces a return to cocaine use following abstinence in humans. OBJECTIVE: The purpose of this study was to examine the effects of chronic d-amphetamine treatment on the reacquisition of cocaine use in rats self-administering cocaine in different social contexts. METHODS: Male and female rats were implanted with intravenous catheters and trained to self-administer cocaine during daily 6-hr sessions. After 14 days, cocaine self-administration was extinguished by substituting saline for the cocaine stimulus. At this time, rats were randomized to receive chronic treatment with either d-amphetamine or saline. After 9 days of extinction, cocaine was again made available during daily 6-hr sessions. At this time, rats were further randomized into three social conditions: (1) rats continued self-administering cocaine in isolation, (2) rats self-administered cocaine in the presence of a same-sex partner that also self-administered cocaine, or (3) rats self-administered cocaine in the presence of a same-sex partner that did not have access to cocaine. Daily treatment with d-amphetamine or saline continued for the duration of reacquisition testing. RESULTS: Chronic treatment with d-amphetamine decreased cocaine intake during reacquisition, but these effects were not influenced by the social context. No sex differences were observed. CONCLUSION: These data support previous studies reporting that d-amphetamine decreases cocaine intake and demonstrate its efficacy across social contexts.

Examining the social and behavioral dynamics of substance use in a longitudinal network study in rural Appalachia.

BACKGROUND: Prior studies have shown that individuals and their peers often have similar substance use behaviors, but the mechanisms driving these similarities - particularly in rural settings, are not well understood. The primary objectives of this analysis are to (1) identify factors that contribute to relationship turnover and maintenance within a rural network of persons who use drugs (PWUD), (2) determine whether assimilation and/or homophily shape participants use of injection drugs, heroin, and stimulants (methamphetamine and cocaine), and (3) assess the extent that these mechanisms influence networks ties and/or behaviors and whether these effects vary across time. METHODS: Sociometric network data were collected from a cohort of PWUD in rural Eastern Kentucky at baseline (2008-2010) and at four follow-up visits conducted approximately semiannually. Stochastic actor-oriented models (SAOMS) were used to model network structure and participant behaviors as jointly dependent variables and to identify characteristics associated with the maintenance, dissolution, and formation of network ties and changes in drug use behaviors. RESULTS: Findings suggest (1) greater network stability over time for reciprocal and transitive relationships, (2) both homophily and assimilation played a greater role in shaping injection drug use (IDU) initiation and cessation than they did in shaping heroin and stimulant use, and (3) the importance of these mechanisms appeared consistent over time. CONCLUSION: Given the stability of particular network structures and evidence of both homophily and assimilation with respect to drug-use behaviors, interventions that leverage social networks could be used to motivate health-promoting behaviors.

Prior cocaine self-administration does not impair the ability to delay gratification in rats during diminishing returns.

Previous exposure to drugs of abuse produces impairments in studies of reversal learning, delay discounting and response inhibition tasks. While these studies contribute to the understanding of normal decision-making and how it is impaired by drugs of abuse, they do not fully capture how decision-making impacts the ability to delay gratification for greater long-term benefit. To address this issue, we used a diminishing returns task to study decision-making in rats that had previously self-administered cocaine. This task was designed to test the ability of the rat to choose to delay gratification in the short-term to obtain more reward over the course of the entire behavioral session. Rats were presented with two choices. One choice had a fixed amount of time delay needed to obtain reward [i.e. fixed delay (FD)], while the other choice had a progressive delay (PD) that started at 0 s and progressively increased by 1 s each time the PD option was selected. During the 'reset' variation of the task, rats could choose the FD option to reset the time delay associated with the PD option. Consistent with previous results, we found that prior cocaine exposure reduced rats' overall preference for the PD option in post-task reversal testing during 'no-reset' sessions, suggesting that cocaine exposure made rats more sensitive to the increasing delay of the PD option. Surprisingly, however, we found that rats that had self-administered cocaine 1-month prior, adapted behavior during 'reset' sessions by delaying gratification to obtain more reward in the long run similar to control rats.

Decoding cocaine-induced proteomic adaptations in the mouse nucleus accumbens.

Cocaine use disorder (CUD) is a chronic neuropsychiatric condition that results from enduring cellular and molecular adaptations. Among substance use disorders, CUD is notable for its rising prevalence and the lack of approved pharmacotherapies. The nucleus accumbens (NAc), a region that is integral to the brain's reward circuitry, plays a crucial role in the initiation and continuation of maladaptive behaviors that are intrinsic to CUD. Leveraging advancements in neuroproteomics, we undertook a proteomic analysis that spanned membrane, cytosolic, nuclear, and chromatin compartments of the NAc in a mouse model. The results unveiled immediate and sustained proteomic modifications after cocaine exposure and during prolonged withdrawal. We identified congruent protein regulatory patterns during initial cocaine exposure and reexposure after withdrawal, which contrasted with distinct patterns during withdrawal. Pronounced proteomic shifts within the membrane compartment indicated adaptive and long-lasting molecular responses prompted by cocaine withdrawal. In addition, we identified potential protein translocation events between soluble-nuclear and chromatin-bound compartments, thus providing insight into intracellular protein dynamics after cocaine exposure. Together, our findings illuminate the intricate proteomic landscape that is altered in the NAc by cocaine use and provide a dataset for future research toward potential therapeutics.

Intrinsic connectivity demonstrates a shared role of the posterior cingulate for cue reactivity in both gambling and cocaine use disorders.

Cue reactivity is relevant across addictive disorders as a process relevant to maintenance, relapse, and craving. Understanding the neurobiological foundations of cue reactivity across substance and behavioral addictions has important implications for intervention development. The present study used intrinsic connectivity distribution methods to examine functional connectivity during a cue-exposure fMRI task involving gambling, cocaine and sad videos in 22 subjects with gambling disorder, 24 with cocaine use disorder, and 40 healthy comparison subjects. Intrinsic connectivity distribution implicated the posterior cingulate cortex (PCC) at a stringent whole-brain threshold. Post-hoc analyses investigating the nature of the findings indicated that individuals with gambling disorder and cocaine use disorder exhibited decreased connectivity in the posterior cingulate during gambling and cocaine cues, respectively, as compared to other cues and compared to other groups. Brain-related cue reactivity in substance and behavioral addictions involve PCC connectivity in a content-to-disorder specific fashion. The findings suggesting that PCC-related circuitry underlies cue reactivity across substance and behavioral addictions suggests a potential biomarker for targeting in intervention development.

Attentional ERPs in consumers of smoked and insufflated cocaine associated with neuropsychological performance.

BACKGROUND: Cocaine consumption is associated with reduced attentional event-related potentials (ERPs), namely P3a and P3b, indicating bottom-up and top-down deficits respectively. At cognitive level, these impairments are larger for faster routes of administration (e.g., smoked cocaine [SC]) than slower routes (e.g., insufflated cocaine [IC]). Here we assess these ERPs considering the route of cocaine administration. We hypothesized that SC dependent (SCD) would exhibit reduced amplitude of the P3a, while both SCD and IC dependent (ICD) would show reduced amplitude of the P3b. METHODS: We examined 25 SCD, 22 ICD matched by poly-consumption profiles, and 25 controls matched by demographic variables. We combined EEG data from the Global-Local task with behavioral data from attentional cognitive tasks. RESULTS: At the behavioral level, SCD exhibited attentional deficits in both bottom-up and top-down processes, while ICD only showed a tendency for top-down deficits. The amplitude of P3a and P3b was lower in Users groups. We observed subtle route-based differences, with larger differences in the P3a for SCD and in the P3b for ICD. Neurophysiological and behavioral data converged, with the P3a associated to bottom-up performance and P3b to top-down. CONCLUSIONS: Different routes of administration lead to distinct attentional neurocognitive profiles. Specifically, SCD showed greater attentional impairment, mainly at bottom-up/P3a, while ICD showed a trend of top-down/P3b deficits. These findings emphasize the crucial role of considering the route of administration in both clinical and research settings and support the use of attentional ERPs as valid measures for assessing attentional deficits in substance Dependence.

Serotonin Signaling in Hippocampus during Initial Cocaine Abstinence Drives Persistent Drug Seeking.

The initiation of abstinence after chronic drug self-administration is stressful. Cocaine-seeking behavior on the first day of the absence of the expected drug (Extinction Day 1, ED1) is reduced by blocking 5-HT signaling in dorsal hippocampal cornu ammonis 1 (CA1) in both male and female rats. We hypothesized that the experience of ED1 can substantially influence later relapse behavior and that dorsal raphe (DR) serotonin (5-HT) input to CA1 may be involved. We inhibited 5-HT1A/1B receptors (WAY-100635 plus GR-127935), or DR input (chemogenetics), in CA1 on ED1 to test the role of this pathway on cocaine-seeking persistence 2 weeks later. We also inhibited 5-HT1A or 5-HT1B receptors in CA1 during conditioned place preference (CPP) for cocaine, to examine mechanisms involved in the persistent effects of ED1 manipulations. Inhibition of DR inputs, or 5-HT1A/1B signaling, in CA1 decreased drug seeking on ED1 and decreased cocaine seeking 2 weeks later revealing that 5-HT signaling in CA1 during ED1 contributes to persistent drug seeking during abstinence. In addition, 5-HT1B antagonism alone transiently decreased drug-associated memory performance when given prior to a CPP test, whereas similar antagonism of 5-HT1A alone had no such effect but blocked CPP retrieval on a test 24 h later. These CPP findings are consistent with prior work showing that DR inputs to CA1 augment recall of the drug-associated context and drug seeking via 5-HT1B receptors and prevent consolidation of the updated nondrug context via 5-HT1A receptors. Thus, treatments that modulate 5-HT-dependent memory mechanisms in CA1 during initial abstinence may facilitate later maintenance of abstinence.

Contingency management plus acceptance and commitment therapy for initial cocaine abstinence: Results of a sequential multiple assignment randomized trial (SMART).

BACKGROUND: This study tested an adaptive intervention for optimizing abstinence outcomes over phases of treatment for cocaine use disorder using a SMART design. Phase 1 assessed whether 4 weeks of contingency management (CM) improved response with the addition of Acceptance and Commitment Therapy (ACT). Phase 2 assessed pharmacological augmentation with modafinil (MOD) vs. placebo (PLA) for individuals not achieving abstinence during Phase 1. METHOD: For Phase 1 of treatment, participants (N=118) were randomly allocated to ACT+CM or Drug Counseling (DC+CM), the comparison condition. At week 4, treatment response was defined as the submission of six consecutive cocaine-negative urine drug screens (UDS). Phase 1 non-responders were re-randomized to MOD or PLA as adjunct to their initial treatment. Phase 1 responders continued receiving their initial treatment. Primary outcomes included response rate and proportion of cocaine-negative UDS for Phase 1 and 2. Analyses used Bayesian inference with 80% pre-specified as the posterior probability (PP) threshold constituting moderate evidence that an effect exists. RESULTS: Phase 1 response was higher in the ACT+CM group (24.5%) compared to the DC+CM group (17.5%; PP = 84.5%). In Phase 2, the proportion of cocaine-negative UDS among Phase 1 responders did not differ by initial treatment (PP = 61.8%) but remained higher overall compared to Phase 1 non-responders (PPs > 99%). No evidence of an effect favoring augmentation with MOD was observed. DISCUSSION: Adding ACT to CM increased abstinence initiation. Initial responders were more likely to remain abstinent compared to initial non-responders, for whom modafinil was not an effective pharmacotherapy augmentation strategy.

Percentage of negative urine drug screens as a clinically meaningful endpoint for RCTs evaluating treatment for cocaine use.

BACKGROUND: This study examined a threshold based on the percentage of cocaine-negative (CN) urine drug screens (UDS) collected during treatment as a potential meaningful endpoint for clinical trials. We hypothesized that individuals providing at least 75% CN UDS would have better long-term outcomes than those providing less than 75% CN UDS. METHODS: Two separate pooled datasets of randomized clinical trials conducted at different institutions were used for analyses: one composed of eight trials (N = 760) and the other composed of three trials (N = 416), all evaluating behavioral and/or pharmacological treatments for cocaine use. UDS were collected at least once per week (up to three times per week) during the 8- or 12-week treatment period across all trials, with substance use and psychosocial functioning measured up to 12 months following treatment. Chi-squares and ANOVAs compared within-treatment and follow-up outcomes between the groups. RESULTS: Compared to those who did not achieve the threshold, participants who achieved the 75%-CN threshold were retained in treatment longer and had a longer period of continuous abstinence, and were more likely to report problem-free functioning. Additionally, participants who achieved the 75%-CN threshold were more likely to report sustained abstinence and better psychosocial functioning throughout a follow-up period up to 12 months than those who did not achieve the threshold. CONCLUSIONS: A threshold of 75%-CN UDS is associated with short- and long-term clinical benefits. Future clinical trials may consider this a meaningful threshold for defining treatment responders.

Transgenerational Cycle of Traumatization and HIV Risk Exposure among Crack Users.

The aim of this manuscript is to understand the impact of childhood sexual abuse on the development of Post-Traumatic Stress Disorder (PTSD), Human Immunodeficiency Virus (HIV) exposure. and parental neglect in crack cocaine users, considering the role of gender. This study is a secondary database analysis of a sample from a multicenter cross-sectional study with 715 crack cocaine users receiving outpatient treatment in public mental health networks in six Brazilian capitals. Prevalence ratios were estimated by Poisson regression. In crack cocaine users with childhood sexual abuse, traumatic experiences seem to remain fixed through the development of Post Traumatic Stress Disorder (PTSD) in adulthood. Crack cocaine users with childhood abuse and PTSD in adulthood showed more sexual risk behaviors, including outcomes such as HIV (PR = 3.6 p < 0.001 for childhood abuse and PR = 3.7 p < 0.001 for PTSD). Furthermore, this traumatic trajectory affects the functional ability of crack cocaine users, especially women, to work thus impacting their inclusion and sense of social belonging. Such a chain seems to be reflected in the establishment of a circle of transgenerational transmission, to the extent that subjects with a history of abuse and PTSD reported more parental neglect towards their children. This study reinforces the importance of preventive public policies regarding early socio-emotional vulnerabilities and the need to support families, especially women, to avoid HIV and self-destructive outcomes such as crack cocaine use.

Impulsivity and Treatment Outcomes in Individuals with Cocaine Use Disorder: Examining the Gap between Interest and Adherence.

Background: Impulsivity is implicated in the development and maintenance of Cocaine Use Disorder (CUD). Less work has examined impulsivity's role on interest in initiating treatment, treatment adherence, or treatment response. No pharmacotherapies are approved for CUD, so efforts to understand and bolster the effects of psychotherapy are important in guiding and refining treatment. The present study examined the impact of impulsivity on interest in treatment, treatment initiation, treatment adherence, and treatment outcomes in individuals with CUD. Methods: Following the completion of a larger study on impulsivity and CUD participants were offered 14 sessions of (12 weeks) Cognitive Behavioral Relapse Prevention (CBT-RP). Before starting treatment, participants completed seven self-report and four behavioral measures of impulsivity. Sixty-eight healthy adults (36% female) with CUD (aged 49.4 ± 7.9) expressed an interest in treatment. Results: Greater scores on several self-report measures of impulsivity, and fewer difficulties with delayed gratification were associated with increased interest in treatment in both males and females. 55 participants attended at least 1 treatment session, while 13 participants did attend a single session. Individuals who attended at least one treatment session scored lower on measures of lack of perseverance and procrastination. Still, measures of impulsivity did not reliably predict session attendance nor the frequency of cocaine-positive urine samples throughout treatment. Males attended nearly twice as many treatment sessions as females despite nonsignificant associations between impulsivity in males and the number of sessions attended. Conclusions: Greater impulsivity in individuals with CUD was associated with expressing an interest in treatment, but not treatment adherence or response.

Cocaine Use May Moderate the Associations of HIV and Female Sex with Neurocognitive Impairment in a Predominantly African American Population Disproportionately Impacted by HIV and Substance Use.

HIV-associated neurocognitive disorders (HAND) remain a major challenge for people with HIV in the antiretroviral therapy era. Cocaine use may trigger/exacerbate HAND among African American (AA) adults, especially women. Between 2018 and 2019, 922 adults, predominantly AAs, with/without HIV and with/without cocaine use in Baltimore, Maryland, were enrolled in a study investigating the association of HIV and cocaine use with neurocognitive impairment (NCI). Neurocognitive performance was assessed with the NIH Toolbox Cognition Battery (NIHTB-CB). NCI was considered to be present if the fully adjusted standard score for at least two cognitive domains was 1.0 standard deviation below the mean. Although the overall analysis showed HIV and female sex were associated with NCI, the associations were dependent on cocaine use. Neither HIV [adj prevalence ratio (PR): 1.12, confidence interval (95% CI): 0.77-1.64] nor female sex (adj PR: 1.07, 95% CI: 0.71-1.61) was associated with NCI among cocaine nonusers, while both HIV (adj PR: 1.39, 95% CI: 1.06-1.81) and female sex (adj PR: 1.53, 95% CI: 1.18-1.98) were associated with NCI in cocaine users. HIV was associated with two NIHTB-CB measures overall. In addition, HIV was associated with a lower dimensional change card sort score (an executive function measure) in cocaine users and not in nonusers. Cognitive performance was poorer in female than in male cocaine users. The adverse effect of HIV on cognitive performance predominantly affected cocaine users. However, cocaine use may moderate the impact of HIV and female sex on cognitive performance, highlighting the importance of reducing cocaine use in NCI prevention among the AA population.

Cuidado em saúde mental com gestantes usuárias de crack / Mental health care with pregnant crack users / Cuidadode salud mental con mujeres embarazadas que utilizan crack

Neste manuscrito, apresentamos uma pesquisa cujo objetivo foi o de compreender como vem sendo produzidas as práticas de cuidado às gestantes usuárias de crack nos serviços de saúde de um município do interior do Rio Grande do Sul. Este estudo de abordagem qualitativa, foi realizado junto a dois serviços públicos, o Programa de Redução de Danos (PRD) e o Centro de Atenção Psicossocial para Álcool e outras Drogas (CAPSad III), com cinco mulheres voluntárias para a pesquisa. As histórias de vida foram reconstruídas a partir de suas narrativas e também de profissionais da saúde que proveram algum tipo de cuidado às participantes. Após a exposição das histórias, refletimos sobre três pistas importantes para pensarmos as práticas de cuidado às gestantes usuárias de crack: saúde mental, uso de drogas e interseccionalidade; direitos humanos, hierarquias reprodutivas e concepções de maternidade; e as práticas de cuidado em saúde. Observamos que as concepções dos profissionais acerca da maternidade direcionam as práticas de cuidado em saúde, caracterizando-se como um cuidado no espectro da saúde materno-infantil, e não um cuidado direcionado à saúde da mulher. Conhecer as demandas de cuidado dessas mulheres é essencial para que possamos pensar em práticas de saúde pautadas pela clínica ampliada. (AU)

In this manuscript, we present a research whose objective was to understand how the practicesof care to the pregnant women users of crack have been being produced in the services of health in a town of Rio Grande do Sul. This study of qualitative approach it was developed jointly to two public services, the Program of Reduction of Harms (PRH) andPsychosocial Care Centers Alcohol and other Drugs (CAPSad), with five voluntary women for the research. The life histories were rebuilt starting from their narratives and also of health's professionals that provided some care to the participants.After exposing the stories, we reflected on three important clues to think about care practices for pregnant women who use crack: mental health, drug use and intersectionality; human rights, reproductive hierarchies and conceptions of motherhood; and health care practices. We observed that the professionals' conceptions about maternity guide health care practices, characterized as care in the spectrum of maternal and child health, and not care directed at women's health.Knowing the care demands of these women is essential for us to think about health practices guided by the expanded clinic. (AU)

En este manuscrito presentamos una investigación cuyoobjetivo fue comprender cómo se ha producidolas prácticas de atención a las embarazadas usuarias de crack en los servicios de salud de una ciudad del interior de Rio Grande do Sul. Este estudio cualitativo se realizó con dos servicios públicos, el Programa de Reducción de Daños (PRD) y el Centro de Atención Psicosocial de Alcohol y Otras Drogas (CAPSad III), con cinco mujeres voluntarias para la investigación. Las historias de vida fueron reconstruidas a partir de sus narrativas y también de profesionalesde la salud que brindaron algún tipo de atención a los participantes. Luego de exponer las historias, reflexionamos sobre tres claves importantes para pensar en las prácticas de cuidado de las embarazadas que consumen crack: salud mental, consumo de drogas y interseccionalidad; derechos humanos, jerarquías reproductivas y concepciones de la maternidad; y prácticas de atención de la salud.Observamos que las concepciones de los profesionales sobre la maternidad orientan las prácticas de atención de la salud, caracterizadas como cuidados en el espectro de la salud maternoinfantil, y no cuidados dirigidos a la salud de la mujer. Conocer las demandas de atención de estas mujeres es fundamental para que pensemos en las prácticas de salud guiadas por la clínica ampliada. (AU)

The complexity of cortical folding is reduced in chronic cocaine users.

Cocaine use is a worldwide health problem with psychiatric, somatic and socioeconomic complications, being the second most widely used illicit drug in the world. Despite several structural neuroimaging studies, the alterations in cortical morphology associated with cocaine use and addiction are still poorly understood. In this study, we compared the complexity of cortical folding (CCF), a measure that aims to summarize the convoluted structure of the cortex between patients with cocaine addiction (n = 52) and controls (n = 36), and correlated it with characteristics of addiction and impulsivity. We found that patients with cocaine addiction had greater impulsivity and showed reduced CCF in a cluster that encompassed the left insula and the supramarginal gyrus (SMG) and in one in the left medial orbitofrontal cortex. Finally, the CCF in the left medial orbitofrontal cortex was correlated with the age of onset of cocaine addiction and with attentional impulsivity. Overall, our findings suggest that chronic cocaine use is associated with changes in the cortical surface in the fronto-parieto-limbic regions that underlie emotional regulation and these changes are associated with earlier cocaine use. Future longitudinal studies are warranted to unravel the association of these changes with the diathesis for the disorder and with the chronic use of this substance.

Cue-induced cocaine craving enhances psychosocial stress and vice versa in chronic cocaine users.

Stress and craving, it has been found, contribute to the development and maintenance of and relapse in cocaine use disorder. Chronic cocaine users (CU), previous research has shown, display altered physiological responses to psychosocial stress and increased vegetative responding to substance-related cues. However, how psychosocial stress and cue-induced craving interact in relation to the CU's physiological responses remains largely unknown. We thus investigated the interaction between acute psychosocial stress and cocaine-cue-related reactivity in 47 CU and 38 controls. In a crossed and balanced design, the participants were randomly exposed to a video-based cocaine-cue paradigm and the Trier Social Stress Test (TSST) or vice versa to investigate possible mutually augmenting effects of both stressors on physiological stress responses. Over the course of the experimental procedure, plasma cortisol, ACTH, noradrenaline, subjective stress, and craving were assessed repeatedly. To estimate the responses during the cocaine-cue paradigm and TSST, growth models and discontinuous growth models were used. Overall, though both groups did not differ in their endocrinological responses to the TSST, CU displayed lower ACTH levels at baseline. The TSST did not elevate craving in CU, but when the cocaine-cue video was shown first, CU displayed an enhanced cortisol response to the subsequent TSST. In CU, cocaine-cues robustly evoked craving but no physiological stress response, while cue-induced craving was intensified after the TSST. Taken together, though CU did not show an altered acute stress response during the TSST, stress and craving together seemed to have mutually augmenting effects on their stress response.

Towards a machine-learning assisted diagnosis of psychiatric disorders and their operationalization in preclinical research: Evidence from studies on addiction-like behaviour in individual rats.

Over the last few decades, there has been a progressive transition from a categorical to a dimensional approach to psychiatric disorders. Especially in the case of substance use disorders, interest in the individual vulnerability to transition from controlled to compulsive drug taking warrants the development of novel dimension-based objective stratification tools. Here we drew on a multidimensional preclinical model of addiction, namely the 3-criteria model, previously developed to identify the neurobehavioural basis of the individual's vulnerability to switch from controlled to compulsive drug taking, to test a machine-learning assisted classifier objectively to identify individual subjects as vulnerable/resistant to addiction. Datasets from our previous studies on addiction-like behaviour for cocaine or alcohol were fed into a variety of machine-learning algorithms to develop a classifier that identifies resilient and vulnerable rats with high precision and reproducibility irrespective of the cohort to which they belong. A classifier based on K-median or K-mean-clustering (for cocaine or alcohol, respectively) followed by artificial neural networks emerged as a highly reliable and accurate tool to predict if a single rat is vulnerable/resilient to addiction. Thus, each rat previously characterized as displaying 0-criterion (i.e., resilient) or 3-criteria (i.e., vulnerable) in individual cohorts was correctly labelled by this classifier. The present machine-learning-based classifier objectively labels single individuals as resilient or vulnerable to developing addiction-like behaviour in a multisymptomatic preclinical model of addiction-like behaviour in rats. This novel dimension-based classifier increases the heuristic value of these preclinical models while providing proof of principle to deploy similar tools for the future of diagnosis of psychiatric disorders.

Effects of Human Immunodeficiency Virus Infection and Former Cocaine Dependence on Neuroanatomical Measures and Neurocognitive Performance.

Evidence from animal research, postmortem analyses, and magnetic resonance imaging (MRI) investigations indicate substantial morphological alteration in brain structure as a function of human immunodeficiency virus (HIV) or cocaine dependence (CD). Although previous research on HIV+ active cocaine users suggests the presence of deleterious morphological effects in excess of either condition alone, a yet unexplored question is whether there is a similar deleterious interaction in HIV+ individuals with CD who are currently abstinent. To this end, the combinatorial effects of HIV and CD history on regional brain volume, cortical thickness, and neurocognitive performance was examined across four groups of participants in an exploratory study: healthy controls (n = 34), HIV-negative individuals with a history of CD (n = 21), HIV+ individuals with no history of CD (n = 20), HIV+ individuals with a history of CD (n = 15). Our analyses revealed no statistical evidence of an interaction between both conditions on brain morphometry and neurocognitive performance. While descriptively, individuals with comorbid HIV and a history of CD exhibited the lowest neurocognitive performance scores, using Principle Component Analysis of neurocognitive testing data, HIV was identified as the primary driver of neurocognitive impairment. Higher caudate volume was evident in CD+ participants relative to CD- participants. Findings indicate no evidence of compounded differences in neurocognitive function or structural measures of brain integrity in HIV+ individuals in recovery from CD relative to individuals with only one condition.