Trends in Self-Reported Fentanyl and Other Illicit Substance Use in South Carolina Emergency Department Patients, 2020-2022.

BACKGROUND: Opioid-involved deaths are continuing to increase across the United States, exceeding 100,000 for the first time in 2021. Contamination with, and intentional use of, synthetic opioids such as fentanyl are a major driver of this increase. Utilizing self-report substance use data of patients being treated in the emergency department (ED) can be useful to determine which substances patients are intentionally seeking. OBJECTIVES: 1) Examine changes in self-reported illicit substance use (including fentanyl) over time; 2) Examine changes in the co-occurrence of self-reported fentanyl with other illicit substance use over time. METHODS: All patients presenting to the study EDs that answered anything other than "never" on the National Institute on Drug Abuse Quick Screen and were seen by a peer recovery specialist in the ED between July 1, 2020 and December 31, 2022 were included for analysis. The substance of use as reported by each patient was recorded by the peer recovery specialist. Differences in substance use by type over time were examined using chi-squared tests of proportions. RESULTS: There were 7568 patients that met inclusion criteria. Self-reported fentanyl (1760%; p < 0.0001) and cocaine (82%; p = 0.034) use increased, whereas heroin use (16%; p < 0.0001) decreased. CONCLUSIONS: Self-reported fentanyl and cocaine use has increased significantly in South Carolina ED patients between 2020 and 2022. Given the high morbidity and mortality associated with fentanyl and fentanyl analog use, further measures to identify these patients and provide harm reduction and treatment from the ED setting are warranted.

Retention in Treatment after Emergency Department-Initiated Buprenorphine.

BACKGROUND: Emergency department-initiated buprenorphine (EDIB) has been shown to be effective in connecting patients with opioid use disorder (OUD) to outpatient treatment. Five diverse emergency departments (EDs) have successfully implemented EDIB programs. OBJECTIVES: 1) To measure attendance at the first referral appointment and 30-day retention in treatment rates for patients receiving EDIB; 2) To describe demographic and opioid use characteristics of patients receiving EDIB; and 3) To determine average length of time in treatment after EDIB at the five participating EDs. METHODS: All patients receiving EDIB at the participating EDs (n = 522) were seen by a peer recovery specialist in the ED and demographic and opioid use characteristics were recorded. Patients were followed prospectively. The referral site was contacted and information regarding attendance at the first referral appointment and 30-day retention in treatment was obtained. All patients still in treatment at 30 days were continually followed at subsequent 30-day intervals until the referral site indicated the patient had ended treatment at their facility. RESULTS: The rate of attendance at the first referral appointment was 77.0% for patients receiving EDIB. At 30-day follow-up, 43.1% of patients were retained in treatment. The mean age of patient enrollment was 36.7 years, 58% of enrollees were male, 90.5% were white, and 73.4% had no medical insurance. Seventy-seven percent reported no substance use other than opioids. The mean time in treatment was 158 days. CONCLUSIONS: EDIB programs across diverse ED settings are effective at promoting attendance at the first referral appointment for OUD treatment; however, additional work is warranted to increase 30-day treatment retention rates, particularly among patients with nonprescription-only use profiles.

Rates of substance use disorder treatment seeking visits after emergency department-initiated buprenorphine.

BACKGROUND: Emergency department-initiated buprenorphine (EDIB) programs have been shown to improve treatment outcomes for patients with opioid use disorders (OUD); however, little is known about how EDIB implementation impacts the patient census at participating hospitals. OBJECTIVES: To determine if implementation of an EDIB program was associated with changes in the number of patients presenting to the ED seeking treatment for substance use disorder (SUD). METHODS: We conducted a retrospective evaluation at a single academic ED that began offering EDIB in December 2017. Data span the period of December 2016 to April 2019, All ED visits with a chief complaint of addiction problem, detoxification, drug/alcohol assessment, drug problem, or withdrawal charted by nursing at the time of triage were eligible for inclusion. Charts were reviewed to determine: (1) treatment status and (2) substance(s) for which the patient was seeking treatment. An interrupted time series analysis was used to compare the pre- and post-EDIB rates for all-substance, as well as opioid-specific, treatment-seeking visits. RESULTS: For all-substance visits, the predicted level change in the treatment-seeking rate after EDIB was implemented was positive but not significant (0.000497, p = 0.53); the trend change after EDIB was also not significant (-0.00004, p = 0.73). For visits involving opioids, the predicted level change was (0.000638, p = 0.21); and the trend change was (0.000047, p = 0.49). CONCLUSION: Implementation of an EDIB program was not associated with increased rates of presentation by patients requesting treatment for a substance use disorder in the participating ED setting.

Network Analysis of Intrinsic Functional Brain Connectivity in Male and Female Adult Smokers: A Preliminary Study.

Background: The goal of this study was to conduct a preliminary network analysis (using graph-theory measures) of intrinsic functional connectivity in adult smokers, with an exploration of sex differences in smokers. Methods: Twenty-seven adult smokers (13 males; mean age = 35) and 17 sex and age-matched controls (11 males; mean age = 35) completed a blood oxygen level-dependent resting state functional magnetic resonance imaging experiment. Data analysis involved preprocessing, creation of connectivity matrices using partial correlation, and computation of graph-theory measures using the Brain Connectivity Toolbox. Connector hubs and additional graph-theory measures were examined for differences between smokers and controls and correlations with nicotine dependence. Sex differences were examined in a priori regions of interest based on prior literature. Results: Compared to nonsmokers, connector hubs in smokers emerged primarily in limbic (parahippocampus) and salience network (cingulate cortex) regions. In addition, global influence of the right insula and left nucleus accumbens was associated with higher nicotine dependence. These trends were present in male but not female smokers. Conclusions: Network communication was altered in smokers, primarily in limbic and salience network regions. Network topology was associated with nicotine dependence in male but not female smokers in regions associated with reinforcement (nucleus accumbens) and craving (insula), consistent with the idea that male smokers are more sensitive to the reinforcing aspects of nicotine than female smokers. Implications: Identifying alterations in brain network communication in male and female smokers can help tailor future behavioral and pharmacological smoking interventions. Male smokers showed alterations in brain networks associated with the reinforcing effects of nicotine more so than females, suggesting that pharmacotherapies targeting reinforcement and craving may be more efficacious in male smokers.

Transcranial magnetic stimulation of the dorsal lateral prefrontal cortex inhibits medial orbitofrontal activity in smokers.

BACKGROUND AND OBJECTIVE: Several studies have shown that repetitive transcranial magnetic stimulation (rTMS), applied to the dorsolateral prefrontal cortex (DLPFC), can reduce cue-elicited craving in smokers. Currently, the mechanism of this effect is unknown. We used functional magnetic resonance imaging (fMRI) to explore the effect of a single treatment of rTMS on cortical and sub-cortical neural activity in non-treatment seeking nicotine-dependent participants. METHODS: We conducted a randomized, counterbalanced, crossover trial in which participants attended two experimental visits separated by at least 1 week. On the first visit, participants received either active, or sham rTMS (10 Hz, 5 s-on, 10 s-off, 100% motor threshold, 3,000 pulses) over the left DLPFC, and on the second visit they received the opposite condition (active or sham). Cue craving fMRI scans were completed before and after each rTMS session. RESULTS: A total of 11 non-treatment seeking nicotine-dependent cigarette smokers were enrolled in the study [six female, average age 39.7 ± 13.2, average cigarettes per day 17.3 ± 5.9]. Active rTMS decreased activity in the contralateral medial orbitofrontal cortex (mOFC) and ipsilateral nucleus accumbens (NAc) compared to sham rTMS. CONCLUSIONS: This preliminary data suggests that one session of rTMS applied to the DLPFC decreases brain activity in the NAc and mOFC in smokers. SCIENTIFIC SIGNIFICANCE: rTMS may exert its anti-craving effect by decreasing activity in the NAc and mOFC in smokers. Despite a small sample size, these findings warrant future rTMS/fMRI studies in addictions. (Am J Addict 2017;26:788-794).

Individualized real-time fMRI neurofeedback to attenuate craving in nicotine-dependent smokers.

BACKGROUND: Cue-induced craving plays an important role in relapse, and the neural correlates of cue-induced craving have been elucidated using fMRI. This study examined the utility of real-time fMRI (rtfMRI) neurofeedback to strengthen self-regulation of craving-related neural activation and cue-reactivity in cigarette smokers. METHODS: Nicotine-dependent smokers were randomized to rtfMRI neurofeedback or to a no-feedback control group. Participants completed 3 neuroimaging visits. Within each visit, an initial run during which smoking-related cues were used to provoke craving, an individualized craving-related region of interest (ROI) in the prefrontal cortex or anterior cingulate cortex was identified. In the rtfMRI group, activity from the ROI was fed back via a visual display during 3 subsequent runs while participants were instructed to reduce craving during cue exposure. The control group had an identical experience with no feedback provided. RESULTS: Forty-four nicotine-dependent smokers were recruited to participate in our study; data from the 33 participants who completed a 1-week follow-up visit were included in the analysis. Subjective craving ratings and cue-induced brain activation were lower in the rtfMRI group than in the control group. LIMITATIONS: As participants were not seeking treatment, clinical outcomes are lacking. CONCLUSION: Nicotine-dependent smokers receiving rtfMRI feedback from an individualized ROI attenuated smoking cue-elicited neural activation and craving, relative to a control group. Further studies are needed in treatment-seeking smokers to determine if this intervention can translate into a clinically meaningful treatment modality.

DSM-5-defined attenuated psychosis syndrome and conversion to full-scale schizophrenia spectrum disorders: An institution-wide retrospective review.

BACKGROUND: The objective of the study was to determine if DSM-5-defined attenuated psychosis syndrome (APS) could identify individuals with prodromal psychosis and predict conversion to schizophrenia spectrum disorders at a rate similar to that observed in previous studies that utilized structured interviews and specialized rating scales. METHODS: A retrospective review of patients' medical records was used to identify individuals meeting diagnostic criteria for the APS, followed by further evaluation 2 to 3 years after the initial diagnosis, to determine if they converted to schizophrenia spectrum disorders. Results then were compared with previous studies. RESULTS: Of our study population, 43.4% converted to schizophrenia or schizoaffective disorder 2 to 3 years after initial diagnosis of APS. Comparison at the 3-year mark indicated that there was no significant difference between our observed rates and previously published conversion rates (P = .066). Three covariates were found to increase significantly the rates of conversion when added to the APS criteria: Cannabis use (P = .048), lack of previous Axis I diagnosis (P = .005), and lack of previous treatment with psychotropic medications (P = .009). CONCLUSIONS: APS accurately predicts conversion to full-scale schizophrenia spectrum disorders at a rate similar to that observed in previous studies using structured interviews and specialized rating scales.

Lower subcortical gray matter volume in both younger smokers and established smokers relative to non-smokers.

Although established adult smokers with long histories of nicotine dependence have lower neural tissue volume than non-smokers, it is not clear if lower regional brain volume is also observed in younger, less established smokers. The primary goal of this study was to investigate neural tissue volume in a large group of smokers and non-smokers, with a secondary goal of measuring the impact of age on these effects. We used voxel-based morphometry to compare regional gray matter volume in 118 individuals (59 smokers, 59 age- and gender-matched non-smokers). Younger smokers had significantly lower gray matter volume in the left thalamus and the left amygdala than their non-smoking peers (family-wise error-corrected clusters, P < 0.05). There was no correlation between smoking use variables and tissue volume among younger smokers. Established smokers had significantly lower gray matter volume than age-matched non-smokers in the insula, parahippocampal gyrus and pallidum. Medial prefrontal cortex gray matter volume was negatively correlated with pack-years of smoking among the established smokers, but not the younger smokers. These data reveal that regional tissue volume differences are not limited exclusively to established smokers. Deficits in young adults indicate that cigarette smoking may either be deleterious to the thalamus and amygdala at an earlier age than previously reported, or that pre-existing differences in these areas may predispose individuals to the development of nicotine dependence.

Vilazodone for cannabis dependence: A randomized, controlled pilot trial.

BACKGROUND AND OBJECTIVES: The purpose of this study was to evaluate the efficacy of vilazodone, a selective serotonin receptor inhibitor and partial 5-HT1A agonist, for treatment of cannabis dependence. METHODS: Seventy-six cannabis-dependent adults were randomized to receive either up to 40 mg/day of vilazodone (n = 41) or placebo (n = 35) for 8 weeks combined with a brief motivational enhancement therapy intervention and contingency management to encourage study retention. Cannabis use outcomes were assessed via weekly urine cannabinoid tests; secondary outcomes included cannabis use self-report and cannabis craving. RESULTS: Participants in both groups reported reduced self-reported cannabis use over the course of the study; however, vilazodone provided no advantage over placebo in reducing cannabis use. Men had significantly lower creatinine-adjusted cannabinoid levels and a trend for increased negative urine cannabinoid tests than women. DISCUSSION AND CONCLUSIONS: Vilazodone was not more efficacious than placebo in reducing cannabis use. Important gender differences were noted, with women having worse cannabis use outcomes than men. SCIENTIFIC SIGNIFICANCE: Further medication development efforts for cannabis use disorders are needed, and gender should be considered as an important variable in future trials.

Impact of group motivational interviewing on enhancing treatment engagement for homeless Veterans with nicotine dependence and other substance use disorders: A pilot investigation.

BACKGROUND: Prior studies have shown that Group Motivational Interviewing (GMI) for dually diagnosed patients holds promise for increasing treatment engagement. OBJECTIVES: The current study evaluated the impact of a novel GMI protocol that included tobacco-specific components (referred to as "Tobacco GMI or T-GMI") targeting enhanced engagement in smoking cessation treatment. METHODS: Thirty-seven primary alcohol and nicotine-dependent cigarette smoking homeless Veterans with co-morbid psychiatric conditions were recruited to receive four GMI sessions over 4 consecutive days. The first 16 participants received standard GMI, aimed at enhancing engagement in substance abuse treatment and for reducing substance use, while the remaining 21 participants received a modified "tobacco-specific" GMI protocol (T-GMI) that included additional content specific to cessation of tobacco use and enhancing smoking cessation treatment, in addition to the standard substance abuse content of GMI. RESULTS: Participants in T-GMI were more likely to attend tobacco cessation programming (p = .05), as well as to attend combined tobacco cessation programming with prescribed nicotine replacement therapy (p = .03), compared to those in standard GMI. Differences between treatment conditions with respect to alcohol and illicit drug use outcomes were not significant, although overall substance use declined over time in both groups. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Results suggest that inclusion of tobacco-specific components in the context of GMI for substance abuse may enhance treatment engagement for tobacco cessation behaviors among dually diagnosed nicotine dependent homeless patients, a highly vulnerable population for which interventional resources targeting engagement in smoking cessation treatment has historically been lacking. (Am J Addict 2016;25:533-541).

Increasing progesterone levels are associated with smoking abstinence among free-cycling women smokers who receive brief pharmacotherapy.

INTRODUCTION: Preclinical and human laboratory research suggests that (a) progesterone may decrease drug reward, craving, and smoking behavior, and (b) estradiol may enhance drug reward and smoking behavior. A modest majority of treatment research examining the relationship between menstrual cycle phase and outcomes suggests that the luteal menstrual phase, with its uniquely higher progesterone levels, is associated with better cessation outcomes. However, no studies to date have examined the effects of naturally occurring variation in progesterone and estradiol levels on medication-assisted smoking cessation. The present study sought to fill this notable gap in the treatment literature. METHODS: Weekly plasma progesterone and estradiol levels were obtained from nicotine-dependent female smokers enrolled in a 4-week cessation trial. Participants (N = 108) were randomized to receive a 4-week course of either varenicline (VAR) tablets and placebo patches or placebo tablets and nicotine patches. Plasma samples were obtained 1 week before their cessation attempt and weekly during medication administration. Abstinence was assessed weekly. RESULTS: Weekly hormone data replicated commonly observed menstrual cycle patterns of progesterone and estradiol levels. Importantly, increases in progesterone level were associated with a 23% increase in the odds for being abstinent within each week of treatment. This effect was driven primarily by nicotine patch-treated versus VAR-treated females. CONCLUSIONS: This study was the first to identify an association between progesterone level (increasing) and abstinence outcomes in free-cycling women smokers who participated in a medication-based treatment. Furthermore, the potential benefits of progesterone may vary across different pharmacotherapies. Implications of these findings for smoking cessation intervention are discussed.

Gender differences in medication use and cigarette smoking cessation: results from the International Tobacco Control Four Country Survey.

INTRODUCTION: There is conflicting evidence for gender differences in smoking cessation, and there has been little research on gender differences in smoking cessation medication (SCM) use and effectiveness. Using longitudinal data from the International Tobacco Control Four Country Surveys (ITC-4) conducted in the United Kingdom, the United States, Canada, and Australia, we examined gender differences in the incidence of quit attempts, reasons for quitting, use of SCMs, reasons for discontinuing use of SCMs, and rates of smoking cessation. METHODS: Data were analyzed from adult smokers participating in the ITC-4, annual waves 2006-2011 (n = 7,825), as well as a subsample of smokers (n = 1,079) who made quit attempts within 2 months of survey. Adjusted modeling utilized generalized estimating equations. RESULTS: There were no gender differences in the likelihood of desire to quit, plans to quit, or quit attempts between survey waves. Among quit attempters, women had 31% lower odds of successfully quitting (OR = 0.69; 95% CI = 0.51, 0.94). Stratified by medication use, quit success was lower among women who did not use any SCMs (OR = 0.59; 95% CI = 0.39, 0.90), and it was no different from men when medications were used (OR = 0.73; 95% CI = 0.46, 1.16). In particular, self-selected use of nicotine patch and varenicline contributed to successful quitting among women. CONCLUSIONS: Women may have more difficulty quitting than men, and SCMs use may help attenuate this difference.

Right anterior insula connectivity is important for cue-induced craving in nicotine-dependent smokers.

The insula has been implicated in cue-induced craving and relapse in nicotine-dependent tobacco cigarette smokers. The aims of the present study were to identify brain regions that exhibit greater functional connectivity with the right anterior insula in response to smoking cues than to neutral cues and the role of functional connectivity between these regions in mediating cue-induced craving in healthy (free of axis I psychiatric disorders) nicotine-dependent tobacco cigarette smokers. Functional magnetic resonance imaging data were collected from 63 healthy nicotine-dependent smokers viewing blocks of smoking and neutral cues. Craving ratings were obtained after each block. A psychophysiologic interaction approach was used to identify regions that exhibited significantly greater functional connectivity with the right anterior insula (seed) during the smoking cues than during the neutral (corrected cluster thresholding, Z > 2.3, P = 0.05). Parameter estimates of the interaction effects from each region were regressed against the mean cue-induced craving scores. Significant task by seed interactions were observed in two clusters centered in the bilateral precuneus and left angular gyrus. The strength of connectivity between the right anterior insula and the precuneus, which is involved interoceptive processing and self-awareness, was positively correlated with the magnitude of the craving response to the smoking cues (r(2) = 0.15; P < 0.01). These data suggest that among smokers, cue-induced craving may be a function of connectivity between two regions involved in interoception and self-awareness. Moreover, treatment strategies that incorporate mindful attention may be effective in attenuating cue-induced craving and relapse in nicotine-dependent smokers.

Reduced executive and reward connectivity is associated with smoking cessation response to repetitive transcranial magnetic stimulation: A double-blind, randomized, sham-controlled trial.

Repetitive transcranial magnetic stimulation (rTMS) can reduce cue-elicited craving, decrease cigarette consumption, and increase the abstinence rate in tobacco use disorders (TUDs). We used functional magnetic resonance imaging (fMRI) to investigate the effect of 10 sessions of rTMS on cortical activity and neural networks in treatment-seeking smokers. Smoking cue exposure fMRI scans were acquired before and after the 10 sessions of active or sham rTMS (10 Hz, 3000 pulses per session) to the left dorsal lateral prefrontal cortex (DLPFC) in 42 treatment-seeking smokers (≥ 10 cigarettes per day). Brain activity and functional connectivity were compared before and after 10 sessions of rTMS. Ten sessions of rTMS significantly reduced the number of cigarettes consumed per day (62.93%) compared to sham treatment (39.43%) at the end of treatment (p = 0.027). fMRI results showed that the rTMS treatment increased brain activity in the dorsal anterior cingulate cortex (dACC) and DLPFC, but decreased brain activity in the bilateral medial orbitofrontal cortex (mOFC). The lower strength of dACC and mOFC connectivity was associated with quitting smoking (Wald score = 5.00, p = 0.025). The reduction of cigarette consumption significantly correlated with the increased brain activation in the dACC (r = 0.76, p = 0.0001). By increasing the brain activity in the dACC and prefrontal cortex and decreasing brain activity in the mOFC, 10 sessions of rTMS significantly reduced cigarette consumption and increased quit rate. Reduced drive-reward and executive control functional connectivity was associated with the smoking cessation effect from rTMS. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02401672.

Sustained reduction of nicotine craving with real-time neurofeedback: exploring the role of severity of dependence.

BACKGROUND: Neurofeedback delivered via real-time functional magnetic resonance imaging (rtfMRI) is a promising therapeutic technique being explored to facilitate self-regulation of craving in nicotine-dependent cigarette smokers. The current study examined the role of nicotine-dependence severity and the efficacy of multiple visits of neurofeedback from a single region of interest (ROI) in the anterior cingulate cortex (ACC) on craving reduction. METHODS: Nine nicotine-dependent cigarette smokers participated in three rtfMRI visits that examined cue-induced craving and brain activation. Severity of nicotine dependence was assessed with the Fagerström Test for Nicotine Dependence. When viewing smoking-related images with instructions to "crave," patient-tailored ROIs were generated in the vicinity of the ACC. Activity levels from the ROI were fed back while participants viewed smoking cues with the instruction to reduce craving. RESULTS: Neurofeedback from a single ROI in the ACC led to consistent decreases in self-reported craving and activation in the ACC across the three visits. Dependence severity predicted response to neurofeedback at Visit 3. CONCLUSIONS: This study builds upon previous rtfMRI studies on the regulation of nicotine craving in demonstrating that feedback from the ACC can reduce activation to smoking cues across three separate visits. Individuals with lower nicotine-dependence severity were more successful in reducing ACC activation over time. These data highlight the need to consider dependence severity in developing more individualized neurofeedback methods.

Volitional reduction of anterior cingulate cortex activity produces decreased cue craving in smoking cessation: a preliminary real-time fMRI study.

Numerous research groups are now using analysis of blood oxygen level-dependent (BOLD) functional magnetic resonance imaging (fMRI) results and relaying back information about regional activity in their brains to participants in the scanner in 'real time'. In this study, we explored the feasibility of self-regulation of frontal cortical activation using real-time fMRI (rtfMRI) neurofeedback in nicotine-dependent cigarette smokers during exposure to smoking cues. Ten cigarette smokers were shown smoking-related visual cues in a 3 Tesla MRI scanner to induce their nicotine craving. Participants were instructed to modify their craving using rtfMRI feedback with two different approaches. In a 'reduce craving' paradigm, participants were instructed to 'reduce' their craving, and decrease the anterior cingulate cortex (ACC) activity. In a separate 'increase resistance' paradigm, participants were asked to increase their resistance to craving and to increase middle prefrontal cortex (mPFC) activity. We found that participants were able to significantly reduce the BOLD signal in the ACC during the 'reduce craving' task (P=0.028). There was a significant correlation between decreased ACC activation and reduced craving ratings during the 'reduce craving' session (P=0.011). In contrast, there was no modulation of the BOLD signal in mPFC during the 'increase resistance' session. These preliminary results suggest that some smokers may be able to use neurofeedback via rtfMRI to voluntarily regulate ACC activation and temporarily reduce smoking cue-induced craving. Further research is needed to determine the optimal parameters of neurofeedback rtfMRI, and whether it might eventually become a therapeutic tool for nicotine dependence.

A comparison of trauma profiles among individuals with prescription opioid, nicotine, or cocaine dependence.

BACKGROUND AND OBJECTIVES: Exposure to traumatic events is common among individuals with substance use disorders. Little is known, however, about the trauma histories among individuals with various types of addiction. METHODS: The present study compared the trauma histories (general, sexual, physical and emotional) of non-treatment seeking outpatients dependent on prescription opioids (n = 41), nicotine (n = 87) or cocaine (n = 73). The Life Stressor Checklist-Revised (LSC-R) was completed by participants to assess childhood and adult trauma. RESULTS: The findings revealed that all three groups endorsed high levels of trauma exposure, with 96.5% of the entire sample experiencing at least one traumatic event in their lifetime. The prescription opiate group experienced a greater number of general and total traumas than the nicotine group. However, no group differences in the number of emotional, physical, or sexual traumas were revealed. The prescription opiate group reported a younger age of first traumatic event than the cocaine group, and was significantly more likely to report childhood traumatic events than both the cocaine and nicotine groups. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: The findings provide clinically relevant information that may help improve screening, interventions, and preventative efforts.

Resisting the urge to smoke and craving during a smoking quit attempt on varenicline: results from a pilot fMRI study.

BACKGROUND: Varenicline has been shown to reduce cigarette craving during a quit attempt. OBJECTIVES: Use BOLD fMRI to explore differences in smoking cue reactivity at baseline and after five weeks of varenicline smoking cessation treatment. METHODS: Treatment-seeking nicotine-dependent adult smokers underwent BOLD fMRI scans with block presentation of visual smoking, neutral, and rest cues under two conditions: craving or resisting the urge to smoke at baseline and following 5 weeks of standard varenicline therapy. Data were analyzed using FMRI Expert Analysis Tool, version 5.98 of Functional Magnetic Imaging of the Brain Software Library focused on the smoking vs. neutral cue contrast at the individual and group level, Z>2.3 with cluster threshold p=0.05. RESULTS: Twenty-one participants were scanned at baseline and 16 completed the study; 10 were abstinent at the 2(nd) session, confirmed with urinary cotinine. In the Crave Condition no significant differences were found between the abstinent and non-abstinent groups at either time point. During the baseline Resist Condition, the abstinent group compared to the non-abstinent group demonstrated activation in a distributed network involved in alertness, learning and memory. Additionally, within the abstinent group, increased activation of the superior frontal gyrus was found at baseline compared to week 5. CONCLUSION: Successful smoking cessation with varenicline is associated with increased activation, prior to a quit attempt, in brain areas related to attentiveness and memory while resisting the urge to smoke Scientific Significance: Varenicline may exert effects by both reducing craving and enhancing resistance to smoking urges during cue-elicited craving.

Disparities in years of potential life lost to Drug-involved overdose deaths in South Carolina.

INTRODUCTION: South Carolina has experienced a surge in fatal overdoses, primarily fueled by opioid-involved overdose deaths. This work aims to quantify the burden of premature mortality due to fatal opioid-involved overdoses in South Carolina while documenting the contribution of synthetic opioids to excess mortality, examining substance specific geographic and demographic patterns of mortality burden, and measuring the effect of fatal opioid and synthetic opioid-involved overdoses on average lifespan. METHODS: We obtained death certificates for fatalities involving opioids, cocaine, benzodiazepines, and psychostimulants (N = 3,726) in South Carolina from 2014 to 2018. Years of Potential Life Lost (YPLL) was used to examine gender, racial, and geographic disparities in mortality burden. We assessed the contribution of synthetic opioid poisoning to the overall opioid mortality burden over time and calculated the effect of fatal opioid and synthetic opioid-involved overdoses on average lifespan. RESULTS: From 2014 to 2018, opioid-involved overdose deaths resulted in 124,451 YPLL. The average age of fatal male and female opioid-involved overdoses decreased 2.8 and 3.9 years, respectively. Synthetic opioids increasingly contributed to opioid YPLL, accounting for 22% in 2014 to 64% in 2018. Mortality burden was not shared equally between races, sexes, or rural/urban counties. The largest change occurred in black male synthetic opioid-involved deaths (2234%). Rural counties comprised 44-48% of the population adjusted YPLL despite containing 34% of the population. CONCLUSION: Opioid-involved overdoses account for a critical cause of mortality in South Carolina, demonstrate significant impact on YPLL and highlight mortality burden disparities in gender, race, and rural/urban settings.

Oxytocin moderates corticolimbic social stress reactivity in cocaine use disorder and healthy controls.

Social stress can contribute to the development of substance use disorders (SUDs) and increase the likelihood of relapse. Oxytocin (OT) is a potential pharmacotherapy that may buffer the effects of social stress on arousal and reward neurocircuitry. However, more research is needed to understand how OT moderates the brain's response to social stress in SUDs. The present study examined the effect of intransasal OT (24 IU) versus placebo (PBO) on corticolimbic functional connectivity associated with acute social stress in individuals with cocaine use disorder (CUD; n = 67) and healthy controls (HC; n = 52). Psychophysiological interaction modeling used the left and right amygdala as seed regions with the left and right orbitofrontal and anterior cingulate cortex as a priori regions of interest. Moderators of the OT response included childhood trauma history and biological sex, which were examined in independent analyses. The main finding was that OT normalized corticolimbic connectivity (left amygdala-orbitofrontal and left amygdala-anterior cingulate) as a function of childhood trauma such that connectivity was different between trauma-present and trauma-absent groups on PBO, but not between trauma groups on OT. Effects of OT on corticolimbic connectivity were not different as a function of diagnosis (CUD vs HC) or sex. However, OT reduced subjective anxiety during social stress for CUD participants who reported childhood trauma compared to PBO and normalized craving response as a function of sex in CUD. The present findings add to some prior findings of normalizing effects of OT on corticolimbic circuitry in individuals with trauma histories and provide some initial support that OT can normalize subjective anxiety and craving in CUD.