Patterns of Use and Withdrawal Syndrome in Dual Cannabis and Tobacco Users (DuCATA_GAM-CAT): Protocol for a Mixed Methods Study.

BACKGROUND: Approximately 1 in 6 cannabis users develop a cannabis use disorder (CUD) and the odds increase to 1 in 2 for daily users. OBJECTIVE: The Dual use of Cannabis and Tobacco Monitoreing through a Gamified Web app (DuCATA_GAM-CaT) project aims to identify cannabis-tobacco patterns of use and withdrawal symptoms among individuals with CUD who are attending substance abuse programs. METHODS: The project uses a mixed methods approach consisting of 3 studies. First, a participatory qualitative study involves focus groups comprising individuals with CUD, clinicians, project researchers, and an expert gamification company to co-design a gamified web app. Second, a longitudinal prospective study to follow up individuals over 6 weeks with CUD attending substance abuse programs . Participants report their cannabis-tobacco usage patterns, type and frequency of tobacco use, nicotine dependence, withdrawal symptoms, psychoemotional factors, and motivation to quit both substances. Predictive analysis techniques are used to analyze clinical, demographic, psychological, and environmental data to predict the probability of achieving abstinence. Third, homogeneous focus groups to explore participants' experiences during their CUD treatment. RESULTS: By June 2024, the project had completed the first study, defining eligible cannabis user profiles, developed the initial web app prototype, and initiated recruitment across 10 centers, with 74 participants enrolled, aiming to reach 150 participants in total. CONCLUSIONS: All participants are required to provide informed consent, and their information is kept confidential and anonymized following confidentiality rules. The research team is committed to disseminating the results obtained to professional and patient groups, as well as informing public health agents, to positively influence political and social decision makers and design programmers. Additionally, we aim to prioritize the publication of the results in high-impact journals specialized in drug abuse, public health, and health care services research. TRIAL REGISTRATION: ClinicalTrials.gov NCT05512091; https://clinicaltrials.gov/study/NCT05512091. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/58335.

The lived experience of withdrawal from Selective Serotonin Reuptake Inhibitor (SSRI) antidepressants: A qualitative interview study.

BACKGROUND: Our knowledge of the broader impacts of antidepressant withdrawal, beyond physical side effects, is limited. Further research is needed to investigate the lived experiences of withdrawal, to aid clinicians on how to guide patients through the process. AIM: To explore antidepressant users' experiences and views on the withdrawal process and how it affected their quality of life across multiple life domains. DESIGN AND SETTING: We conducted in-depth qualitative interviews with 20 individuals from the community who had attempted to withdraw from Serotonin Reuptake Inhibitor antidepressants in the past year. METHOD: Semi-structured interviews were conducted online. A topic guide was used to ensure consistency across interviews. The interviews were audio-recorded and transcribed verbatim and analysed using inductive reflexive thematic analysis. RESULTS: Five themes were generated. The first highlighted the challenges of managing the release from emotional blunting and cognitive suppression following antidepressant discontinuation. The second related to the negative impact of withdrawal on close relationships and social interactions. The third showed that concurrent with negative physical symptoms, there was a positive impact on health (exercise was reported by some as a coping mechanism). The fourth theme focused on support from GPs and families, emphasising the importance of mental health literacy in others. The final theme underscored the importance of gradual and flexible tapering in enabling a manageable withdrawal experience, and the consideration of timing. CONCLUSION: The lived experience of withdrawal significantly impacts individuals' well-being. Participants emphasised that withdrawal is not just about physical side effects but also affects their emotional, cognitive, and social functioning. PATIENT AND PUBLIC INVOLVEMENT (PPI): Eight people attended individual online meetings to share their experiences of antidepressant withdrawal to help inform the study design and recruitment strategy. Insights from these meetings informed the development of the topic guide. Questions about GP involvement, family relationships, and mood and thinking changes were included based on this PPI work. This ensured the inclusion of topics important to antidepressant users and facilitated the researcher's questioning during the interviews.

Kappa-opioid receptor antagonism in the nucleus accumbens shell distinguishes escalated alcohol consumption and negative affective-like behavior from physiological withdrawal in alcohol-dependence.

Alcohol use disorder (AUD) is a chronic relapsing disease that is deleterious at individual, familial, and societal levels. Although AUD is one of the highest preventable causes of death in the USA, therapies for the treatment of AUD are not sufficient given the heterogeneity of the disorder and the limited number of approved medications. To provide better pharmacological strategies, it is important to understand the neurological underpinnings of AUD. Evidence implicates the endogenous dynorphin (DYN)/κ-opioid receptor (KOR) system recruitment in dysphoric and negative emotional states in AUD to promote maladaptive behavioral regulation. The nucleus accumbens shell (AcbSh), mediating motivational and emotional processes that is a component of the mesolimbic dopamine system and the extended amygdala, is an important site related to alcohol's reinforcing actions (both positive and negative) and neuroadaptations in the AcbSh DYN/KOR system have been documented to induce maladaptive symptoms in AUD. We have previously shown that in other nodes of the extended amygdala, site-specific KOR antagonism can distinguish different symptoms of alcohol dependence and withdrawal. In the current study, we examined the role of the KOR signaling in the AcbSh of male Wistar rats in operant alcohol self-administration, measures of negative affective-like behavior, and physiological symptoms during acute alcohol withdrawal in alcohol-dependence. To induce alcohol dependence, rats were exposed to chronic intermittent ethanol vapor for 14 h/day for three months, during which stable escalation of alcohol self-administration was achieved and pharmacological AcbSh KOR antagonism ensued. The results showed that AcbSh KOR antagonism significantly reduced escalated alcohol intake and negative affective-like states but did not alter somatic symptoms of withdrawal. Understanding the relative contribution of these different drivers is important to understand and inform therapeutic efficacy approaches in alcohol dependence and further emphasis the importance of the KOR/DYN system as a target for AUD therapeutics.

Resveratrol by elevating the SIRT1 BDNF, GDNF and PSD95 levels reduce heroin addiction related behaviors.

OBJECTIVE: To study the effects of resveratrol on heroin addiction-related behaviors and to preliminarily explore the possible intervention mechanism of resveratrol in heroin dependence. METHODS: The effects of resveratrol on heroin withdrawal symptoms were observed by naloxone; The effect of resveratrol on heroin reward memory acquisition was detected by CPP paradigm; The effect of resveratrol on the mental excitability of heroin was tested by open field experiment; The effect of resveratrol on heroin spatial learning and memory was tested by water maze test. Western blot was used to detect Sirtuin 1 (SIRT1) Expression of brain-derived neurotrophic factor (BDNF), glial cell derived neurotrophic factor (GDNF), and postsynaptic density protein (PSD95). RESULTS: The behavioral results showed that the withdrawal behavior of the resveratrol intervention group was reduced compared with the heroin chronic dependence group (P<0.05), and the shift score of the conditioned place preference test of the resveratrol intervention group was reduced compared with the heroin chronic dependence group (P<0.05) The spatial learning and memory ability of the water maze in the resveratrol intervention group was improved compared with the heroin chronic dependence group (P<0.05), and the mental excitability of the resveratrol intervention group was lower than that of the heroin chronic dependence group (P<0.05), but higher than that of the saline group (P<0.05); SIRT1 The expression levels of BDNF, GDNF and PSD95 protein were significantly increased (P<0.05). CONCLUSION: The behavioral results of this study suggest that resveratrol can be used as a potential drug to treat heroin dependence. At the same time, SIRT1 The expression of BDNF, GDNF, and PSD95 increased; SIRT1, BDNF, GDNF, and PSD95 play an essential role in heroin addiction.

N-palmitoylethanolamide attenuates negative emotions induced by morphine withdrawal in mice.

Depression and anxiety are prominent symptoms of withdrawal syndrome, often caused by the abuse of addictive drugs like morphine. N-palmitoylethanolamide (PEA), a biologically active lipid, is utilized as an anti-inflammatory and analgesic medication. Recent studies have highlighted PEA's role in mitigating cognitive decline and easing depression resulting from chronic pain. However, it remains unknown whether PEA can influence negative emotions triggered by morphine withdrawal. This study seeks to explore the impact of PEA on such emotions and investigate the underlying mechanisms. Mice subjected to morphine treatment underwent a 10-day withdrawal period, followed by assessments of the effect of PEA on anxiety- and depression-like behaviors using various tests. Enzyme-linked immunosorbent assay was conducted to measure levels of monoamine neurotransmitters in specific brain regions. The findings indicate that PEA mitigated anxiety and depression symptoms and reduced 5-hydroxytryptamine, noradrenaline, and dopamine levels in the hippocampus and prefrontal cortex. In summary, PEA demonstrates a significant positive effect on negative emotions associated with morphine withdrawal, accompanied with the reduction in levels of monoamine neurotransmitters in key brain regions. These insights could be valuable for managing negative emotions arising from morphine withdrawal.

The Independent Contribution of Positive and Negative Metacognitions About Smoking to Urge to Smoke, Withdrawal Symptoms and Dependence in Smoking-Dependent Men.

Previous research has indicated that various factors, such as psychological distress, distress intolerance, anhedonia, impulsivity and smoking metacognitions, have been individually linked to the urge to smoke, withdrawal symptoms and dependence. However, these factors have not been collectively examined to determine whether smoking metacognitions independently and significantly contribute to these outcomes. Therefore, the aim of this study was to investigate the impact of distress intolerance, anhedonia, impulsivity and smoking metacognitions on the urge to smoke, withdrawal symptoms and dependency in men who are dependent on smoking. A total of 300 smoking-dependent men completed psychological scales and smoking-related measures. The findings of the study indicated that positive metacognitions about emotion regulation significantly predicted the urge to smoke, even when accounting for other significant predictors such as the number of daily cigarettes smoked, psychological distress, anhedonia and impulsivity. Furthermore, positive metacognitions about cognitive regulation were found to be a significant predictor of withdrawal symptoms, independent of other significant predictors such as psychological distress and the urge to smoke. Smoking dependence was predicted by negative metacognitions about uncontrollability beyond other significant predictors, including the number of daily cigarettes smoked and distress intolerance. These results highlight the role of metacognitions about smoking in both short- and long-term clinical outcomes related to smoking. Consequently, addressing such beliefs during treatment for smoking dependence should be an important therapeutic goal.

Differential effects of acute and prolonged morphine withdrawal on motivational and goal-directed control over reward-seeking behaviour.

Opioid addiction is a relapsing disorder marked by uncontrolled drug use and reduced interest in normally rewarding activities. The current study investigated the impact of spontaneous withdrawal from chronic morphine exposure on emotional, motivational and cognitive processes involved in regulating the pursuit and consumption of food rewards in male rats. In Experiment 1, rats experiencing acute morphine withdrawal lost weight and displayed somatic signs of drug dependence. However, hedonically driven sucrose consumption was significantly elevated, suggesting intact and potentially heightened reward processing. In Experiment 2, rats undergoing acute morphine withdrawal displayed reduced motivation when performing an effortful response for palatable food reward. Subsequent reward devaluation testing revealed that acute withdrawal disrupted their ability to exert flexible goal-directed control over reward seeking. Specifically, morphine-withdrawn rats were impaired in using current reward value to select actions both when relying on prior action-outcome learning and when given direct feedback about the consequences of their actions. In Experiment 3, rats tested after prolonged morphine withdrawal displayed heightened rather than diminished motivation for food rewards and retained their ability to engage in flexible goal-directed action selection. However, brief re-exposure to morphine was sufficient to impair motivation and disrupt goal-directed action selection, though in this case, rats were only impaired in using reward value to select actions in the presence of morphine-paired context cues and in the absence of response-contingent feedback. We suggest that these opioid-withdrawal induced deficits in motivation and goal-directed control may contribute to addiction by interfering with the pursuit of adaptive alternatives to drug use.

Agmatine alleviates ethanol withdrawal-associated cognitive impairment and neurochemical imbalance in rats.

The present study aimed to investigate the role of agmatine in the neurobiology underlying memory impairment during ethanol withdrawal in rats. Sprague-Dawley rats were subjected to a 21-day chronic ethanol exposure regimen (2.4 % w/v ethanol for 3 days, 4.8 % w/v for the next 4 days, and 7.2 % w/v for the following 14 days), followed by a withdrawal period. Memory impairment was assessed using the passive avoidance test (PAT) at 24, 48, and 72 h post-withdrawal. The ethanol-withdrawn rats displayed a significant decrease in step-through latency in the PAT, indicative of memory impairment at 72 h post-withdrawal. However, administration of agmatine (40 µg/rat) and its modulators (L-arginine, arcaine, and amino-guanidine) significantly increases the latency time in the ethanol-withdrawn rats, demonstrating the attenuation of memory impairment. Further, pretreatment with imidazoline receptor agonists enhances agmatine's effects, while antagonists block them, implicating imidazoline receptors in agmatine's actions. Neurochemical analysis in ethanol-withdrawn rats reveals dysregulated glutamate and GABA levels, which was attenuated by agmatine and its modulators. By examining the effects of agmatine administration and modulators of endogenous agmatine, the study aimed to shed light on the potential therapeutic implications of agmatinergic signaling in alcohol addiction and related cognitive deficits. Thus, the present findings suggest that agmatine administration and modulation of endogenous agmatine levels hold potential as therapeutic strategies for managing alcohol addiction and associated cognitive deficits. Understanding the neurobiology underlying these effects paves the way for the development of novel interventions targeting agmatinergic signaling in addiction treatment.

ANK3 rs10994336 and ZNF804A rs7597593 polymorphisms: genetic interaction for emotional and behavioral symptoms of alcohol withdrawal syndrome.

OBJECTIVE: Alcohol withdrawal syndrome (AWS) is a complex condition associated with alcohol use disorder (AUD), characterized by significant variations in symptom severity among patients. The psychological and emotional symptoms accompanying AWS significantly contribute to withdrawal distress and relapse risk. Despite the importance of neural adaptation processes in AWS, limited genetic investigations have been conducted. This study primarily focuses on exploring the single and interaction effects of single-nucleotide polymorphisms in the ANK3 and ZNF804A genes on anxiety and aggression severity manifested in AWS. By examining genetic associations with withdrawal-related psychopathology, we ultimately aim to advance understanding the genetic underpinnings that modulate AWS severity. METHODS: The study involved 449 male patients diagnosed with alcohol use disorder. The Self-Rating Anxiety Scale (SAS) and Buss-Perry Aggression Questionnaire (BPAQ) were used to assess emotional and behavioral symptoms related to AWS. Genomic DNA was extracted from peripheral blood, and genotyping was performed using PCR. RESULTS: Single-gene analysis revealed that naturally occurring allelic variants in ANK3 rs10994336 (CC homozygous vs. T allele carriers) were associated with mood and behavioral symptoms related to AWS. Furthermore, the interaction between ANK3 and ZNF804A was significantly associated with the severity of psychiatric symptoms related to AWS, as indicated by MANOVA. Two-way ANOVA further demonstrated a significant interaction effect between ANK3 rs10994336 and ZNF804A rs7597593 on anxiety, physical aggression, verbal aggression, anger, and hostility. Hierarchical regression analyses confirmed these findings. Additionally, simple effects analysis and multiple comparisons revealed that carriers of the ANK3 rs10994336 T allele experienced more severe AWS, while the ZNF804A rs7597593 T allele appeared to provide protection against the risk associated with the ANK3 rs10994336 mutation. CONCLUSION: This study highlights the gene-gene interaction between ANK3 and ZNF804A, which plays a crucial role in modulating emotional and behavioral symptoms related to AWS. The ANK3 rs10994336 T allele is identified as a risk allele, while the ZNF804A rs7597593 T allele offers protection against the risk associated with the ANK3 rs10994336 mutation. These findings provide initial support for gene-gene interactions as an explanation for psychiatric risk, offering valuable insights into the pathophysiological mechanisms involved in AWS.

Sex Differences in Withdrawal-Induced Anxiety in Rats After Exposure to Tobacco Smoke.

Nicotine, a component of cigarettes, possesses strong reinforcing properties and improves cognitive function, which can lead to dependence. Upon cigarette smoking cessation, withdrawal symptoms occur and may cause an individual to relapse. Affective withdrawal symptoms, such as anxiety, is of great concern as studies have shown its ability to cause relapse in men and women. In this in vivo study, anxiety resulting from smoking cessation after 2-day smoke-free intervals per week for the duration of 4 weeks was investigated in 8 male and 8 female rats after their exposure to cigarette smoke compared to unexposed control rats (8 males and 8 female rats). The anxiety in rats during smoke-free intervals was investigated using an elevated plus-maze (EPM), open-field (OF), and light/dark test (LD). In all tests male rats exhibited significantly higher anxiety symptoms compared to female rats during nicotine withdrawal, despite control rats showing no differences. In the EPM, male rats spent less time in open arm as well having as lower number of crossings than female rats. As for the OFT, the amount of time spent in the center of the open field was also lower in male rats than female rats. In the LD test, the time spent in the light chamber and the latency (delay) to enter the dark chamber was lower in male rats compared to female rats. Our study showed that male rats show greater nicotine withdrawal effects, in terms of anxiety-like behavior than female rats.

Bidirectional relationship between attentional deficits and escalation of nicotine intake in male rats.

RATIONALE: People with tobacco addiction have deficits in cognition, in particular deficits in attention. It is not clear however, whether deficits are a cause or a consequence, or both, of chronic nicotine use. Here we set out a series of experiments in rats to address this question and, more specifically, to assess the effects of exposure to and withdrawal from chronic nicotine self-administration on attentional performance. METHODS: Animals were trained in a 5-choice serial reaction time task to probe individual attentional performance and, then, were given access to a fixed versus increasing dose of intravenous nicotine for self-administration, a differential dose procedure known to induce two between-session patterns of nicotine intake: a stable versus escalation pattern. Attentional performance was measured daily before, during and also 24-h after chronic access to the differential dose procedure of nicotine self-administration. CONCLUSIONS: We found that pre-existing individual variation in attentional performance predicts individual vulnerability to develop escalation of nicotine intake. Moreover, while chronic nicotine self-administration increases attention, withdrawal from nicotine intake escalation induces attentional deficits, a withdrawal effect that is dose-dependently reversed by acute nicotine. Together, these results suggest that pre-existing individual variation in attentional performance predicts individual vulnerability to develop escalation of nicotine intake, and that part of the motivation for using nicotine during escalation might be to alleviate withdrawal-induced attentional deficits.

Pain and withdrawal are common among patients receiving medications for opioid use disorder and associated with pain catastrophizing, negative affect, and poor sleep.

Substantial percentages of persons receiving medications for opioid use disorder (MOUD) continue to experience clinically significant levels of pain and opioid withdrawal, which may pose barriers to reducing opioid use. Continued pain, in particular, may increase the risk for psychiatric problems and poorer treatment retention, especially with a lack of adequate care for pain. The goals of these analyses were to characterize the prevalence of, and patient-level variables associated with, pain and opioid withdrawal, as well as utilization of related coping strategies and treatments. Participants were 18 years of age or older and received methadone or buprenorphine for opioid use disorder (n = 179). Participants completed this survey in person, within their MOUD clinic. Participants completed patient-level and demographic questions as well as measures of pain, withdrawal, utilization of related coping strategies, and pain treatment. Numerous participants endorsed chronic pain (41.9%) or opioid withdrawal (89.4%) and indicated reliance upon over-the-counter medications and prayer for pain management. Multiple linear regression models showed greater pain catastrophizing and negative affect accounted for variability in pain severity and pain interference, as well as opioid withdrawal. Persons who slept less and endorsed chronic pain also reported greater pain severity and interference, and pain interference was higher with increased age. These and previous findings combine to further highlight the detrimental role that pain catastrophizing and negative affect can play in pain perception and withdrawal, but also represent promising treatment targets to facilitate pain and withdrawal management and improved quality of life. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Hush, little baby: The role of C-tactile afferents in babywearing infants with neonatal opioid withdrawal.

Social touch through infant holding, skin-to-skin contact, and infant carrying (babywearing) decreases infant distress and promotes secure attachment. Unknown is the extent to which these effects are the result of the activation of C-Tactile afferents (CTs), the constellation of nerve fibers associated with affective touch, primarily located in the head and trunk of the body. The purpose of the present study was to compare dynamic touch (CTs activated) to static touch (CTs less activated) during a babywearing procedure among infants experiencing Neonatal Opioid Withdrawal Syndrome (NOWS). NOWS is a spectrum of clinical symptoms, including elevated heart rate (HR), associated with withdrawal from intrauterine opioid exposure. We hypothesized that stroking an infant's head during babywearing would amplify the pleasurable effect of babywearing as measured by changes in infant HR. Twenty-nine infants in a Neonatal Intensive Care Unit (NICU) in the Southwestern USA were worn in an infant carrier starting at five days old (M = 5.4, SD = 2.6; 46.2 % White, 26.9 % Latinx, 11.5 % Native American) and physiological readings were conducted daily; heart rates of infants and caregivers were taken every 15-seconds for 5-minutes, before, during, and after babywearing (30 min per phase). Each day infants alternated (randomly) in a static touch (hands-free babywearing) or dynamic touch condition (stroking the top of the infants' head at a velocity of 3 cm/s while babywearing). On average, infants completed 3 dynamic and 3 static babywearing sessions. Hospital and research staff participated in babywearing when a parent was not available (31.0 % of infants were exclusively worn by volunteers, 27.6 % were exclusively worn by parents). We analyzed the data using Hierarchical Linear Models due to the 3-level nested design (N = 29 infants, N = 191 readings, N = 11,974 heart rates). Compared to baseline (infant calm/asleep and without contact), infant's HRs significantly declined during and after babywearing, controlling for pharmacological treatment. These effects were significantly stronger during the dynamic touch condition (reduction in HR of 11.17 bpm) compared to the static touch condition (reduction in HR of 3.74 bpm). These effects did not significantly vary by wearer (mother, father, volunteer). However, differences between the dynamic and static conditions were significantly stronger in earlier babywearing sessions, potentially indicating a learning effect. There was evidence for a calming effect among caregivers as well, particularly in the dynamic touch condition, when caregivers were engaged in active touch. Activation of CTs appears to be an important mechanism in the physiological benefits of babywearing and in the symbiotic role of caregiver-infant attachment.

Menthol versus tobacco e-liquid flavor: Impact on acute subjective effects, puff patterns, and intentions for use among Black and White menthol smokers.

BACKGROUND: The proposed FDA product standard to prohibit menthol as a characterizing flavor in combustible cigarettes has the potential to significantly reduce tobacco-related health disparities. Whether a menthol e-liquid product standard would improve or hinder public health is unknown. No known research has directly examined the impact of menthol vs. tobacco flavored e-liquid use on acute e-cigarette use patterns, subjective experience, behavioral intentions, and craving and withdrawal among menthol cigarette smokers. METHODS: Black (n = 47) and White (n = 4) nicotine-deprived menthol smokers with limited e-cigarette experience completed two counterbalanced in-laboratory 30-minute ad libitum vaping sessions with menthol and tobacco nicotine salt-based e-liquid in a randomized crossover pilot trial design. Questionnaires assessed reductions in craving and withdrawal and post-session subjective experience and behavioral intentions. Puff topography was measured continuously throughout each vaping session. RESULTS: Measures of puff topography did not differ significantly by e-liquid flavor (all p > .40). Similarly, menthol and tobacco flavored e-cigarettes were both rated positively in terms of subjective effects and behavioral intentions (all p > .10) and about 40 % of participants reported a preference for the tobacco-flavored e-liquid. Finally, participants showed comparable reductions in craving (p = .210) and withdrawal (p = .671) from pre- and post-session regardless of e-liquid flavor. CONCLUSIONS: Among menthol smokers in a lab-based setting, findings suggest that menthol vs tobacco e-liquid flavor has little impact on acute changes in puff patterns, subjective experience, behavioral intentions, or craving and withdrawal.

Hereditary and cortical morphological biomarker of sensitivity to reward in short-term withdrawal methamphetamine abusers.

Higher sensitivity to reward (SR) and weaker sensitivity to punishment (SP) construct the fundamental craving characteristics of methamphetamine abuse. However, few studies have appraised relationships between SR/SP (SR or SP) and cortical morphological alterations in methamphetamine abusers and whether hereditary factors take effects on SR/SP is unclear. Based on surface-based morphometric analysis, cortical discrepancy was investigated between 38 methamphetamine abusers and 37 healthy controls. Within methamphetamine abusers, correlation profiling was performed to discover associations among aberrant neuroimaging substrates, SR, SP, and craving. According to nine single nucleotide polymorphism sites of dopamine-related genes, we conducted univariate general linear model to find different effects of genotypes on cortical alterations and SR/SP/craving (SR, SP, or craving). Ultimately, mediation analyses were conducted among single nucleotide polymorphism sites, SR/SP/craving, and cortical morphological alterations to discover their association pathways. Compared to healthy controls, thinner cortices in inferior temporal gyrus, lateral orbitofrontal cortex, medial orbitofrontal cortex, inferior parietal lobule, and lateral occipital cortex in the left hemisphere were found in methamphetamine abusers (P < 0.05, family-wise error corrected). Cortical thickness in the inferior temporal gyrus was negatively correlated with SR scores. We found that rs1800497 A-containing genotypes had lower cortical thickness in the left inferior parietal lobule than the GG genotype. The rs5751876 had effects on SR scores. This study would provide convincing biomarkers for SR in methamphetamine abusers and offer potential genetic targets for personalizing relapse prevention.

Is impulsivity related to attentional bias in cigarette smokers? An exploration across levels of nicotine dependency and deprivation.

Research has largely focused on how attentional bias to smoking-related cues and impulsivity independently influence the development and maintenance of cigarette smoking, with limited exploration of the relationship between these mechanisms. The current experiments systematically assessed relationships between multiple dimensions of impulsivity and attentional bias, at different stages of attention, in smokers varying in nicotine dependency and deprivation. Nonsmokers (NS; n  = 26), light-satiated smokers (LS; n  = 25), heavy-satiated smokers (HS; n  = 23) and heavy 12-hour nicotine-deprived smokers (HD; n  = 30) completed the Barratt Impulsivity Scale, delayed discounting task, stop-signal task, information sampling task and a visual dot-probe assessing initial orientation (200 ms) and sustained attention (2000 ms) toward smoking-related cues. Sustained attention to smoking-related cues was present in both HS and LS, while initial orientation bias was only evident in HS. HS and LS also had greater levels of trait motor and nonplanning impulsivity and heightened impulsive choice on the delay discounting task compared with NS, while heightened trait attentional impulsivity was only found in HS. In contrast, in HD, nicotine withdrawal was associated with no attentional bias but heightened reflection impulsivity, poorer inhibitory control and significantly lower levels of impulsive choice relative to satiated smokers. Trait and behavioral impulsivity were not related to the extent of attentional bias to smoking-related cues at any stage of attention, level of nicotine dependency or state of deprivation. Findings have both clinical and theoretical implications, highlighting the unique and independent roles impulsivity and attentional bias may play at different stages of the nicotine addiction cycle.

An Interpretive Description of Drug Withdrawal Among Pregnant Women in Jail.

OBJECTIVE: To explore the experience of drug withdrawal among pregnant women in jail. DESIGN: A qualitative interpretive descriptive approach. SETTING/PROBLEM: The care of incarcerated pregnant women constitutes a complex and significant public health problem. Many have substance use disorder (SUD) and cycle in and out of jails in their community, resulting in repeated experiences of drug withdrawal. Most jails do not provide medication-assisted therapy for management of withdrawal, a situation that violates standards of care set by leading health organizations. The experience of drug withdrawal among pregnant women in jail has not been qualitatively explored in the literature. PARTICIPANTS: Five women completed interviews for the study. INTERVENTION: In-depth, qualitative interviews. RESULTS: Five themes with subthemes emerged from the interviews: Framing the Story Through Life History: I Need You to Know Where I Come From, Patterns of Thinking About Substance Use, The Manifestations of Withdrawal: Body and Mind, Perceived Punishment for Drug Use During Pregnancy, and Mixed Perceptions of Withdrawal Treatment. CONCLUSION: Participants told a story beyond that of the physical withdrawal symptoms, revealing new insights into their maternal distress and the need for compassionate, nonstigmatized care to address physical and mental symptoms, as well as advocacy for the provision of an evidence-based standard of care. Nurses who care for pregnant women with SUD in the jail setting could benefit from collaborative relationships with other health care professionals in the community to reduce disparate health outcomes for this vulnerable population.

A pilot study of virtual reality for inpatients with opioid use disorder.

BACKGROUND AND OBJECTIVES: While inpatient withdrawal management/acute stabilization can improve outcomes for individuals with opioid use disorder (OUD), patients often leave treatment early due to mood, tension, and cravings associated with opioid withdrawal. The aim of this study was to evaluate the feasibility and preliminary effectiveness of a novel virtual reality (VR) based intervention; 3D Therapy Thrive (3DTT). METHODS: Subjects with OUD (N = 32) were recruited from a community acute stabilization program and received up to two sessions of 3DTT. They completed questionnaires related to their overall satisfaction with the experience and side effects; as well as those related to mood, tension, and cravings. RESULTS: There were no reported side effects and the majority of subjects (94%) reported high satisfaction with the experience. Out of 62 patients approached, 33 patients agreed to participate (53%) 33 patients completed one, and 17 of these patients (52%) completed both sessions of 3DTT, with 19 participants (58%) completing their treatment protocols. Compared to baseline, 3DTT participants reported significant reductions in depression, tension, and cravings (p's < 0.001). DISCUSSION AND CONCLUSIONS: This pilot study supports the feasibility and preliminary effectiveness of 3DTT for improving outcomes for inpatients with OUD. Future randomized controlled trials are necessary to evaluate the efficacy of 3DTT for improving retention, reducing cravings, and improving mood and tension. SCIENTIFIC SIGNIFICANCE: This is the first study to evaluate the feasibility of a psychologically informed VR intervention in inpatients with OUD.

LY2444296, a κ-opioid receptor antagonist, selectively reduces alcohol drinking in male and female Wistar rats with a history of alcohol dependence.

Alcohol use disorder (AUD) remains a major public health concern. The dynorphin (DYN)/κ-opioid receptor (KOP) system is involved in actions of alcohol, particularly its withdrawal-associated negative affective states. This study tested the ability of LY2444296, a selective, short-acting, KOP antagonist, to decrease alcohol self-administration in dependent male and female Wistar rats at 8 h abstinence. Animals were trained to orally self-administer 10% alcohol (30 min/day for 21 sessions) and were made dependent via chronic intermittent alcohol vapor exposure for 6 weeks or exposed to air (nondependent). After 6 weeks, the effect of LY2444296 (0, 3, and 10 mg/kg, p.o.) was tested on alcohol self-administration at 8 h of abstinence. A separate cohort of rats was prepared in parallel, and their somatic withdrawal signs and alcohol self-administration were measured after LY2444296 administration at 8 h, 2 weeks, and 4 weeks abstinence. LY2444296 at 3 and 10 mg/kg significantly reduced physical signs of withdrawal in dependent rats at 8 h abstinence, only. Furthermore, 3 and 10 mg/kg selectively decreased alcohol self-administration in dependent rats at only 8 h abstinence. These results highlight the DYN/KOP system in actions of alcohol during acute abstinence, suggesting KOP antagonism could be beneficial for mitigating acute withdrawal signs and, in turn, significantly reduce excessive alcohol consumption associated with AUD.

The association of pain impact and sleep disruption with opioid withdrawal during opioid-use disorder treatment.

AIMS: Persons with opioid-use disorder (OUD) often experience opioid withdrawal and opioid craving, which can drive continued opioid use and treatment discontinuation. In addition, hyperalgesia is common among persons with OUD, yet few studies have examined the role of pain impact during OUD treatment. The purpose of the present study was to test whether opioid withdrawal and craving were elevated in the context of greater pain impact (i.e. greater pain intensity and interference), and whether these associations changed throughout treatment. METHODS: Participants in residential OUD treatment (n = 24) wore wrist actigraphy to measure sleep and completed daily measures of pain impact, opioid withdrawal and opioid craving for up to 28 days. Mixed effects models were used to examine whether daily elevations in pain impact and sleep continuity were associated with withdrawal severity and opioid craving. RESULTS: Elevations in withdrawal, but not craving, occurred on days when individuals reported higher scores on the pain impact scale. Associations between pain impact and withdrawal were present throughout treatment, but stronger during early treatment. In contrast, both withdrawal and opioid craving were elevated following nights of greater wake after sleep onset and awakenings, but these findings were often more pronounced in early treatment. CONCLUSIONS: Pain impact and sleep disturbance are 2 factors associated with opioid withdrawal and opioid craving. Novel pharmacotherapies and scalable adjunctive interventions targeting sleep and pain impact should be tested in future work to improve OUD treatment outcomes.