Days Of Abstinence Research Articles

The impact of voluntary wheel-running exercise on hippocampal neurogenesis and behaviours in response to nicotine cessation in rats.

The literature indicates that nicotine exposure or its discontinuation impair adult hippocampal neurogenesis in rats, though the impact of exercise on this process remains unclear. We have previously shown that disturbances in the number of doublecortin (DCX, a marker of immature neurons)-positive (DCX+) cells in the dentate gyrus (DG) of the hippocampus during nicotine deprivation may contribute to a depression-like state in rats. This study aimed to investigate the effect of running on hippocampal neurogenesis, depression-like symptoms, and drug-seeking behaviour during nicotine deprivation. The rats were subjected to nicotine (0.03mg/kg/inf) self-administration via an increasing schedule of reinforcement. After 21 sessions, the animals entered a 14-day abstinence phase during which they were housed in either standard home cages without wheels, cages equipped with running wheels, or cages with locked wheels. Wheel running increased the number of Ki-67+ and DCX+ cells in the DG of both nicotine-deprived and nicotine-naive rats. Wheel-running exercise evoked an antidepressant effect on abstinence Day 14 but had no effect on nicotine-seeking behaviour on abstinence Day 15 compared to rats with locked-wheel access. In summary, long-term wheel running positively affected the number of immature neurons in the hippocampus, which corresponded with an antidepressant response in nicotine-weaned rats. One possible mechanism underlying the positive effect of running on the affective state during nicotine cessation may be the reduction in deficits in DCX+ cells in the hippocampus.

Prize-based Incentives for Smoking Cessation Among People with HIV: A Sequential Multiple Assignment Randomized Trial (SMART).

Contingency management (CM) is an incentive-based approach that has demonstrated efficacy for smoking cessation in various populations. There is an unmet need for feasible and effective smoking cessation interventions in people with HIV (PWH). The study purpose is to assess efficacy of prize-based CM for smoking cessation in PWH using a Sequential Multiple Assignment Randomization Trial (SMART) design selected to tailor intervention intensity based on early treatment response. During phase 1, 129 participants were randomly assigned to high-magnitude prize CM (HM-CM) or standard of care (SoC) for 4 weeks. Participants who did not reduce smoking were randomized in Phase 2 to continued counseling with HM-CM plus monitoring support or only continued monitoring support for 8 weeks. Participants who reduced smoking were randomized to booster monitoring with low-magnitude CM or no additional care. Outcomes were biochemically-verified smoking reduction and 7-day abstinence prevalence at post-treatment, 6-month and 12-month follow-up. Phase 1 responders (based on biochemical indicators of smoking reduction) were significantly less likely to return to smoking (during treatment and at 6- and 12-months) if they received low-magnitude incentives. Notably, initial exposure to CM vs. SoC did not increase rate of phase 1 response, and high-magnitude incentives later in treatment did not lead to greater smoking cessation for early treatment non-responders. Weekly CM sessions in the first four weeks of smoking cessation intervention did not perform significantly better than SoC. However, brief booster CM sessions aimed at maintaining early smoking cessation hold clinical promise and warrant further investigation. This represents the first trial to examine the use of contingency management for smoking cessation among people with HIV within the context of a Sequential Multiple Assignment, Randomized Trial (SMART) design.

Pulmonary and Cardiac Smoking-Related History Improves Abstinence Rates in an Urban, Socioeconomically Disadvantaged Patient Population.

Tobacco use continues to take the lives of many, and targeted interventions can counter this health burden. One possible target population is patients who have had a smoking-related diagnosis, as they may have a greater drive to quit. To assess whether patients with previous cardiac or pulmonary conditions directly attributable to smoking have greater rates of abstinence post-discharge from hospitalization in the CHART-NY trial. CHART-NY was a randomized comparative effectiveness trial comparing a more intensive versus a less intensive smoking cessation intervention after hospital discharge. We divided the 1618 CHART-NY participants into a smoking-related history group of 597 and a nonsmoking-related history group of 1021 based on cardiac or pulmonary conditions in a retrospective chart review. We conducted chi-squared analyses on baseline characteristics. Using follow-up survey data, we conducted chi-squared analyses on abstinence outcomes and made logistic regression models for the predictive value of smoking-related conditions on abstinence. A total of 1059 and 1084 participants in CHART-NY who completed both 2- and 6-month follow-up surveys respectively. Self-reported 30-day abstinence at 2- and 6-month follow-up and survey data for baseline characteristics. Those abstinent at 6-month follow-up were more likely to have a smoking-attributable history (OR = 1.40, 95% CI 1.09-1.81). When stratified based on intervention, only the intensive counseling group was significant (OR = 1.53, 95% CI 1.08-2.17). The regression model using a smoking-related comorbidity score was significant at 6months (OR = 1.29, p = 0.03), and the multivariate logistic regression model analyzing each smoking-related condition separately demonstrated significance for myocardial infarction at 6months (OR = 1.66, p = 0.03). People who smoke who have experienced smoking-related conditions may be more likely to benefit from smoking cessation interventions, especially intensive telephone-based counseling. Multiple conditions had an additive effect in predicting long-term abstinence after intervention, and myocardial infarction had the greatest predictive value.

Orbitofrontal cortex to dorsal striatum circuit is critical for incubation of oxycodone craving after forced abstinence.

Relapse is a major challenge in treating opioid addiction, including oxycodone. During abstinence, oxycodone seeking progressively increases, a phenomenon termed incubation of oxycodone craving. We previously demonstrated a causal role of orbitofrontal cortex (OFC) in this incubation. Here, we studied the interaction between glutamatergic projections from OFC and dopamine 1-family receptor (D1R) signaling in dorsal striatum (DS) in this incubation in male rats. We first examined the causal role of D1R signalling in DS in incubated oxycodone seeking. Next, we combined fluorescence-conjugated cholera toxin subunit B (CTb-555, a retrograde tracer) with Fos (a neuronal activity marker) to assess whether the activation of OFC→DS projections was associated with incubated oxycodone seeking. We then used a pharmacological asymmetrical disconnection procedure to examine the role of the interaction between projections from OFC and D1R signalling in DS in incubated oxycodone seeking. We also tested the effect of unilateral pharmacological inactivation of OFC or unilateral D1R blockade of DS on incubated oxycodone seeking. Finally, we assessed whether contralateral disconnection of OFC→DS projections impacted non-incubated oxycodone seeking on abstinence day 1. We found that D1R blockade in DS decreased incubated oxycodone seeking and OFC→DS projections were activated during incubated oxycodone seeking. Moreover, anatomical disconnection of OFC→DS projections, but not unilateral inactivation of OFC or unilateral D1R blockade in DS, decreased incubated oxycodone seeking. Lastly, contralateral disconnection of OFC→DS projections had no effect on oxycodone seeking on abstinence day 1. Together, these results demonstrated a causal role of OFC→DS projections in incubation of oxycodone craving.

Role of dorsal striatum circuits in relapse to opioid seeking after voluntary abstinence

AbstractHigh relapse rate during abstinence is a defining characteristic of drug addiction. We previously found that opioid seeking progressively increases after voluntary abstinence induced by adverse consequences of oxycodone seeking (crossing an electric barrier). Functional MRI revealed that this effect is associated with changes in functional connectivity within medial orbitofrontal cortex (mOFC)- and dorsomedial striatum (DMS)-related circuits. Here, we used a pharmacological manipulation and fMRI to determine the causal role of mOFC and DMS in oxycodone seeking after electric barrier-induced abstinence. We trained rats to self-administer oxycodone (6 h/day, 14 days). Next, we induced voluntary abstinence by exposing them to an electric barrier for 2 weeks. We inactivated the mOFC and DMS with muscimol+baclofen (GABAa and GABAb receptor agonists) and then tested them for relapse to oxycodone seeking on abstinence days 1 or 15 without the electric barrier or oxycodone. Inactivation of DMS (p < 0.001) but not mOFC decreased oxycodone seeking before or after electric barrier-induced abstinence. Functional MRI data revealed that DMS inactivation decreased cerebral blood volume levels in DMS and several distant cortical and subcortical regions (corrected p < 0.05). Furthermore, functional connectivity of DMS with several frontal, sensorimotor, and auditory regions significantly increased after DMS inactivation (corrected p < 0.05). Finally, an exploratory analysis of an existing functional MRI dataset showed that DMS inactivation restored voluntary abstinence-induced longitudinal changes in DMS functional connectivity with these brain regions (p < 0.05). Results indicate a role of DMS and related brain circuits in oxycodone seeking after voluntary abstinence, suggesting potential targets for intervention.

Outcomes of a Comprehensive Mobile Vaping Cessation Program in Adults Who Vape Daily: Cohort Study.

In the United States, e-cigarettes, or vapes, are the second most-commonly used tobacco product. Despite abundant smartphone app-based cigarette cessation programs, there are few such programs for vaping and even less supporting data. This exploratory, prospective open-label, single-arm, remote, initial cohort study of the Pivot vaping cessation program assessed enrollment and questionnaire completion rates, participant engagement and retention, changes in attitudes toward quitting vaping, changes in vaping behavior, and participant feedback. The aim was to establish early data in each of these areas to inform program improvements and future study design. U.S. adults aged ≥ 21 years who vape daily, report ≥ 5 vape sessions per day, and plan to quit vaping in the next 6 months were recruited online. Participants completed an online screening form, screening call, electronic informed consent, registration, and onboarding before beginning Pivot. Data were self-reported via app and web-based questionnaires. Outcomes focused on engagement and retention (i.e., weeks in the program, number of Pivot app openings, number of messages sent to coach); vaping attitudes (i.e., success to quit, difficulty to stay quit); vaping behavior (i.e., quit attempts, Penn State Electronic Cigarette Dependence Index, 7- and 30-day point prevalence abstinence [PPA], continuous abstinence [defined as ≥ 7-day PPA at 12 weeks + 30-day PPA at 26 weeks + 0 vaping sessions since 12 weeks]); and participant feedback. Seventy-three participants completed onboarding (intention-to-treat [ITT] sample); 68/73 (93%) completed the 12- and 26-week questionnaires (completer samples). On average, participants were active in Pivot for 13.8 (SD 7.3) weeks, had 87.3 (SD 99.9) app sessions, and sent 37.6 (SD 42.3) messages to their coach over 26 weeks. Success to quit and difficulty to stay quit (scale 1-10) improved from baseline to 12 weeks: 4.9 (SD 2.9) to 7.0 (SD 3.0) and 4.0 (SD 2.8) to 6.2 (SD 3.1), respectively; both P < .001. Most participants (64/73, 88%) made ≥ 1 quit attempt. At 26 weeks, ITT 7-day PPA, 30-day PPA and continuous abstinence rates were: 35/73 (48%), 33/73 (45%), and 22/73 (30%), respectively. Thirty-three participants did not achieve 7-day PPA at 26 weeks; their mean Penn State Electronic Cigarette Dependence Index score decreased from baseline (13.9, SD 3.1) to 26 weeks (10.8, SD 4.5) (mean change -3.2, SD 3.9, P < .001); almost half (16/33, 48%) had improvement in e-cigarette dependence category. At 2 weeks, 51/71 (72%) reported using Pivot increased their motivation to quit vaping; at 4 weeks, 55/70 (79%) reported using Pivot decreased the amount they vape per day. In this first evaluation of Pivot in adult daily vapers, questionnaire completion rates were >90%, average program engagement duration was approximately 14 weeks and most participants reported increased motivation to quit vaping. These and early cessation outcomes herein suggest a role for Pivot in vaping cessation and will inform associated future study and program improvements. ClinicalTrials.gov NCT05642598; https://clinicaltrials.gov/study/NCT05642598.

Changes in nucleus accumbens core translatome accompanying incubation of cocaine craving.

In the 'incubation of cocaine craving' model of relapse, rats exhibit progressive intensification (incubation) of cue-induced craving over several weeks of forced abstinence from cocaine self-administration. The expression of incubated craving depends on plasticity of excitatory synaptic transmission in nucleus accumbens core (NAcC) medium spiny neurons (MSN). Previously, we found that the maintenance of this plasticity and the expression of incubation depends on ongoing protein translation, and the regulation of translation is altered after incubation of cocaine craving. Here we used male and female rats that express Cre recombinase in either dopamine D1 receptor- or adenosine 2a (A2a) receptor-expressing MSN to express a GFP-tagged ribosomal protein in a cell-type specific manner, enabling us to use Translating Ribosome Affinity Purification (TRAP) to isolate actively translating mRNAs from both MSN subtypes for analysis by RNA-seq. We compared rats that self-administered saline or cocaine. Saline rats were assessed on abstinence day (AD) 1, while cocaine rats were assessed on AD1 or AD40-50. For both D1-MSN and A2a-MSN, there were few differentially translated genes between saline and cocaine AD1 groups. In contrast, pronounced differences in the translatome were observed between cocaine rats on AD1 and AD40-50, and this was far more robust in D1-MSN. Notably, all comparisons revealed sex differences in translating mRNAs. Sequencing results were validated by qRT-PCR for several genes of interest. This study, the first to combine TRAP-seq, transgenic rats, and a cocaine self-administration paradigm, identifies translating mRNAs linked to incubation of cocaine craving in D1-MSN and A2a-MSN of the NAcC.

Peer navigation for smoking cessation in people with HIV who smoke: a pilot randomized controlled trial.

People with HIV (PWH) cite smoking within their social networks as a barrier to quitting. We examined the feasibility, acceptability, and preliminary efficacy of a tailored intervention, Peer Navigation Social Support for Smoking cessation (PNSS-S), designed specifically for PWH who smoke. We randomized 64 PWH who smoked (mean age 54.5 years; 41% female) to PNSS-S or standard care (SC). After meeting with a clinic nurse to discuss quitting strategies and pharmacotherapy, the PNSS-S group received 12 weekly phone calls from a trained HIV peer navigator (PN), who provided smoking cessation counseling and social support for quitting. Outcomes were assessed at 12- and 24-weeks. Sixty-two percent of participants indicated interest in quitting at baseline. PN utilization was high with a mean number of weekly calls completed of 8.9 (SD 3.1), demonstrating excellent feasibility. Higher treatment satisfaction scores (29.1 [SD 3.0]) were reported in PNSS-S, compared to control (25.8 [SD 4.1], t = -3.39, d = 0.89, p = .001). Notably, positive social support for quitting increased significantly from baseline to week 12 in PNSS-S (17.4 [SD 11.4] to 25.1 [SD 12.2], p = .01), whereas SC showed no significant change (t = 1.11, df 29, p = .24). At week 24, 5 (16.6%) participants in PNSS-S and 3 (8.8%) in SC endorsed 7-day point prevalence smoking abstinence: OR=2.05 95% CI=[0.45-10.88]. Peer-based smoking cessation counseling increased the odds of abstinence and significantly increased social support for quitting. Further study is warranted. Cross training HIV peer navigators to address smoking cessation may be a cost-effective approach, as it utilizes existing HIV clinic-based resources. By strengthening social support and providing a peer-based approach, this intervention may help reduce the burden of tobacco-related health issues in this population, ultimately contributing to better overall health and longevity for PWH. Further research is needed to refine and expand upon these findings.

Residual and enduring effects of cannabis use on cognitive and psychomotor function: A study of adults during unrestricted cannabis use, short-term abstinence, and protracted abstinence.

The impact of cannabis on cognitive and psychomotor function is important to understand, given the role of the endocannabinoid system in these critical processes. The literature has shown robust acute negative effects of cannabis on cognition and psychomotor skills during intoxication, and to a lesser degree, persisting effects following short-term abstinence up to 4 weeks. However, whether these decrements resolve after long-term cessation of use remains unclear. We evaluated cognitive and psychomotor function in 31 adults with current cannabis use during unrestricted use (UNR) and after a 3-day abstinence (RES), 23 adults with former cannabis use (> 90 days abstinent; FU), and 58 nonusing controls (CON) using the cognition and motor batteries of the National Institutes of Health Toolbox. Linear mixed models showed no significant differences in cognitive and motor performance between UNR, RES, and FU groups. Group effects emerged such that CON outperformed UNR on the Oral Reading Recognition Test, and CON outperformed both UNR and RES on the Picture Vocabulary Test. In terms of psychomotor function, FU, RES, and UNR performed better than CON on the Grip Strength Test. In this comprehensive examination of cognitive and psychomotor performance in adults with cannabis use with 3 days to > 90 days of abstinence, our results indicated that the cognitive impacts of chronic, heavy cannabis use are observable during short-term abstinence but remit after > 90 days of abstinence. This highlights widespread impacts of cannabis use abstinence across cognitive and psychomotor domains. Future studies are needed to evaluate whether these effects are also observable with use reduction, as opposed to abstinence. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Cannabis Use and Subsequent CIGARETTE Discontinuation among U.S. Adults in the Population Assessment of Tobacco and Health (PATH) Study, Waves 1-5.

This study examined the association between current co-use of cannabis and cigarettes in the past 30 days, and subsequent cigarette discontinuation (past 30-day point prevalence abstinence) among U.S. adults with established cigarette use in the Population Assessment of Tobacco and Health (PATH) Study. Additionally, we investigated the impact of co-use on the subsequent discontinuation of all combustible tobacco products. A total of 26,381 observations contributed by 8,218 adults with established cigarette use (i.e., smoked ≥ 100 cigarettes in their lifetime, and currently smoking cigarettes every day or some days) from Waves 1-5 of the PATH Study were included in the analysis. Weighted Generalized Estimating Equations (GEE) models were used to evaluate the association between current co-use at baseline (Waves 1-4) with the outcomes assessed at the subsequent wave (cigarette and combustible tobacco discontinuation at Waves 2-5). Final models included: demographic characteristics (age, sex, race and ethnicity, educational attainment), behavior characteristics (intention to quit, internalizing symptoms, externalizing symptoms, substance use problems), and wave-pair. Over one-third (35.91%) of cigarette users self-reported co-use during the study period. Cannabis use among adults with established cigarette use increased over time. Co-use was associated with a decreased odds of cigarette smoking discontinuation at follow-up, after adjusting for covariates (aOR: 0.81; 95% CI: 0.72, 0.93; p=0.0018). Similar effect sizes were observed for discontinuation of all combustible tobacco products (aOR: 0.75; 95% CI: 0.65, 0.86; p<.0001). Cannabis use among adults who smoke cigarettes was inversely related to subsequent cigarette discontinuation, suggesting that co-use may reduce likelihood of successful tobacco cessation. Findings demonstrate that cannabis use may lead to lower odds of discontinuation among adults with established cigarette use; therefore, individuals that co-use cigarettes and cannabis may need additional tobacco cessation support. Notably, this study observed an increase in co-use of cigarettes and cannabis, emphasizing the need for researchers and public health programs to shift their focus towards understanding and addressing concurrent substance use among adults who smoke cigarettes.

Impact of Quitline Services on Tobacco Cessation: An Application of Modern Epidemiological Methods.

This study investigated the effectiveness of quitline service intensity (high vs. low) on past 30-day tobacco abstinence at 7-months follow-up, using observational data from the Oklahoma Tobacco Helpline (OTH) between April 2020 and December 2021. To assess the impact of loss to follow-up and non-random treatment assignment, we fit the parameters of a marginal structural model to estimate inverse probability weights for censoring (IPCW) and treatment (IPTW) and combined (IPCTW). The Risk Ratio (RR) was estimated using modified Poisson regression with robust variance estimator. Of the 4,695 individuals included in the study, 64% received high-intensity cessation services, and 53% were lost to follow-up. Using the conventional complete case analysis (responders only), high-intensity cessation services were associated with abstinence (RR=1.18; 95 CI: 1.04, 1.34). The effect estimate was attenuated after accounting for censoring (RR=1.14; 95% CI: 1.00, 1.30). After adjusting for both baseline confounding and selection bias via IPTCW, high-intensity cessation services were associated with 1.23 times (95% CI: 1.08, 1.41) the probability of abstinence compared to low-intensity services. Despite relatively high loss to follow-up, accounting for selection bias and confounding did not notably impact quit rates or the relationship between intensity of quitline services and tobacco cessation among OTH participants.

Sex-specific effects of chronic stress prior to cocaine exposure on cue- vs drug-induced relapse after prolonged abstinence

The comorbidity between cocaine use disorder (CUD) and trauma/stressor-related disorders suggests a connection between neurophysiological changes induced by stress and those that lead to cocaine use. Due to the unexpected and sometimes uncontrollable nature and timing of stressful life events, their capacity to induce drug use poses a significant challenge for the administration of cocaine relapse therapy. This study aims to investigate the impact of chronic stress applied prior to cocaine acquisition on the development of cocaine-seeking behavior after different periods of drug abstinence in male and female rats. Rats were exposed to five days of inescapable footshocks (chronic stress) before undergoing extended access cocaine self-administration. Different groups then underwent forced abstinence periods of 1, 15, or 30 days before cue- and cocaine-induced seeking tests. Results showed that, after 30 days of abstinence, stressed females exhibited higher cue-induced, but not cocaine-induced seeking, compared to female controls and to males. In contrast, at 30 days, stressed males showed higher cocaine-, but not cue-induced seeking, versus controls. Such sex-dependent alterations in motivation and drug effects following prolonged abstinence highlight the importance of considering sex-specific differences in stress-related addiction research. Ongoing work should evaluate other stressors and self-administration models to elucidate neurophysiological and hormonal mechanisms underlying the incubation of cocaine craving. Identifying shared pathways between chronic stress and addiction could offer novel strategies for treating trauma/stress-related substance use disorders in a sex-specific manner.

Buprenorphine treatment and clinical outcomes under the opioid use disorder cascade of care

BackgroundChallenges to engagement and retention on buprenorphine undermine treatment of individuals with opioid use disorder (OUD). Under the OUD Cascade of Care framework, we sought to identify patient characteristics and treatment response associated with superior clinical outcomes. MethodsA retrospective cohort study of specialty buprenorphine treatment patients entering treatment (n=19,487) based on EHR records from a large multi-state buprenorphine treatment network (2011–2019). Person-level care episodes were evaluated across treatment intake, engagement (i.e. 2+ visits in the month following intake), and retention at 6, 12, and 24 months. Time to achieving 90 days of continuous opioid abstinence was assessed using Cox proportional hazards regressions models and also assessed as a predictor of long-term retention. ResultsMost patients engaged (82.4 %), but retention steadily declined over 6-month (38.7 %), 12-month (26.2 %), and 24-month (17.1 %) timepoints. Opioid-positive baseline tests were associated with lower hazards of achieving continuous abstinence for both buprenorphine-positive (aHR=0.33, p<.001) and buprenorphine-negative (aHR=0.49,p<.001) intakes. Opioid abstinence was associated with buprenorphine-positive baseline testing (aHR=1.59,p<.001), especially for those testing opioid-negative (aHR=1.82,p<.001). Patients who achieved and sustained abstinence at 6 months in care were 4.1 and 5.5 times as likely to achieve 12-month and 24-month retention, respectively, compared to patients with intermittent opioid use. ConclusionTreatment discontinuation was concentrated early in care and buprenorphine and opioid status at intake were prognostic of achieving and sustaining abstinence. Early abstinence was associated with higher likelihood of subsequent stage progression. Implementing interventions to support early clinical stability for high-risk patients is critical to improve clinical outcomes.

Sex-specific behavioral and thalamo-accumbal circuit adaptations after oxycodone abstinence.

Opioid use disorder is marked by a progressive change in the motivation to administer the drug even in the presence of negative consequences. After long periods of abstinence, the urge to return to taking the drug intensifies over time, known as incubation of craving. Conditioned responses to drug-related stimuli, can acquire motivational properties and exert control over motivated behaviors leading to relapse. Although, preclinical data suggest that the behavioral expression of opioid use is similar between male and female rodents, we do not have conclusive results on sex differences on craving and relapse across abstinence periods. Here, we investigated the effects of abstinence from oxycodone self-administration on neurotransmission in the paraventricular thalamus (PVT) to nucleus accumbens shell (NAcSh) pathway in male and female rats. Using optogenetics and ex vivo electrophysiology, we assessed synaptic strength and glutamate release probability in this pathway, as well as NAcSh medium spiny neurons (MSN) intrinsic excitability, in slices from rats which were subjected to either 1 (acute) or 14 (prolonged) days of forced abstinence after self-administration. Our results revealed no sex differences in oxycodone self-administration or somatic withdrawal symptoms following acute abstinence. However, we found a sex-specific enhancement in cue-induced relapse after prolonged, but not acute, abstinence from oxycodone self-administration, with females exhibiting higher relapse rates. Notably, prolonged abstinence led to similar increases in synaptic strength at PVT-NAcSh inputs compared to saline controls in both sexes, which was not observed after acute abstinence. Thus, prolonged abstinence results in a time-dependent increase in PVT-NAcSh synaptic strength and sex-specific effects on cue-induced relapse rates. These findings suggest that prolonged abstinence leads to significant synaptic changes, contributing to heightened relapse vulnerability, highlighting the need for targeted therapeutic strategies in opioid use disorder.

A Vaping Cessation Text Message Program for Adolescent E-Cigarette Users

E-cigarettes are the most commonly used tobacco product among adolescents. Despite known harms of nicotine exposure among teens, there are no empirically tested vaping cessation interventions. To compare the effectiveness of a text message program for nicotine vaping cessation among adolescents with assessment-only control. A parallel, 2-group, double-blind, individually randomized clinical trial with follow-ups at 1 and 7 months after randomization was conducted from October 1, 2021, to October 18, 2023. Participants were recruited via social media ads; the intervention was delivered via text message; and assessments were completed online or by telephone. Eligible individuals were US residents aged 13 to 17 years who reported past 30-day e-cigarette use, were interested in quitting within 30 days, and owned a mobile phone with an active text message plan. To optimize study retention, all participants received monthly assessments via text message about e-cigarette use. Assessment-only controls (n = 744) received only study retention text messages. Intervention participants (n = 759) also received an automated, interactive text message program for vaping cessation that delivers cognitive and behavioral coping skills training and social support. The primary outcome was self-reported 30-day point-prevalence abstinence from vaping at 7 months analyzed as intention-to-treat, with missingness coded as vaping. Among n = 1503 adolescents randomized, average age was 16.4 (SD, 0.8) years. The sample was 50.6% female, 42.1% male, and 7.4% nonbinary/other; 10.2% Black/African American, 62.6% White, 18.5% multiracial, and 8.7% another race; 16.2% Hispanic; 42.5% sexual minority; and 76.2% vaped within 30 minutes of waking. The 7-month follow-up rate was 70.8%. Point-prevalence abstinence rates were 37.8% (95% CI, 34.4%-41.3%) among intervention participants and 28.0% (95% CI, 24.9%-31.3%) among control participants (relative risk, 1.35 [95% CI, 1.17-1.57]; P < .001). No baseline variables moderated the treatment-outcome relationship. There was no evidence that adolescents who quit vaping transitioned to combustible tobacco products. A tailored, interactive text message intervention increased self-reported vaping cessation rates among adolescents recruited via social media channels. ClinicalTrials.gov Identifier: NCT04919590.

Decídetexto: Mobile cessation support for Latino adults who smoke. A randomized clinical trial.

Latino adults experience multiple barriers to health care access and treatment that result in tobacco-related disparities. Mobile interventions have the potential to deliver smoking cessation treatment among Latino adults, the highest users of mobile technologies. Is Decídetexto, a culturally accommodated mobile health intervention, more effective for smoking cessation compared with standard care among Latinx adults who smoke? A two-arm parallel group randomized clinical trial (RCT) was conducted in Kansas, New Jersey, and New York between October 2018 and September 2021. Eligible Latino adults who smoke (n= 457) were randomly assigned to Decídetexto or a standard care group. The primary outcome was biochemically verified 7-day smoking abstinence at week 24. Secondary outcomes included self-reported 7-day smoking abstinence at weeks 12 and 24 and uptake and adherence of nicotine replacement therapy (NRT). Participants' mean age was 48.7 (SD, 11.1) years, 45.2%were female, and 50.3%smoked≥10 cigarettes per day. Two hundred twenty-nine participants were assigned to Decídetexto and 228 to standard care. Treating those lost to follow-up as participants who continued smoking, 14.4%of participants in the Decídetexto group were biochemically verified abstinent at week 24 compared with 9.2%in the standard care group (OR, 1.66; 95%CI, 0.93-2.97; P= .09). Treating those lost to follow-up as participants who continued smoking, 34.1%of the participants in the Decídetexto group self-reported smoking abstinence at week 24 compared with 20.6%of participants in the standard care group (OR, 1.99; 95%CI, 1.31-3.03; P< .001). Analyzing only participants who completed the assessment at week 24, 90.6%(174/192) of participants in the Decídetexto group self-reported using NRT for at least 1day compared with 70.2%(139/198) of participants in standard care (OR, 4.10; 95%CI, 2.31-7.28; P< .01). Among Latino adults who smoke, the Decídetexto intervention was not associated with a statistically significant increase in biochemically verified abstinence at week 24. However, the Decídetexto intervention was associated with a statistically significant increase in self-reported 7-day smoking abstinence at weeks 12 and 24 and uptake of NRT. This RCT provides encouragement for the use of Decídetexto for smoking cessation among Latino adults. ClinicalTrials.gov identifier: NCT03586596.

Medications for alcohol-use disorder and follow-up after hospitalization for alcohol withdrawal: A multicenter study.

Alcohol withdrawal is a common reason for admission to acute care hospitals. Prescription of medications for alcohol-use disorder (AUD) and close outpatient follow-up are commonly recommended, but few studies report their effects on postdischarge outcomes. The objective of this study is to evaluate the effects of medications for AUD and follow-up appointments on readmission and abstinence. This retrospective cohort study evaluated veterans admitted for alcohol withdrawal to medical services at 19 Veteran Health Administration hospitals between October 1, 2018 and September 30, 2019. Factors associated with all-cause 30-day readmission and 6-month abstinence were examined using logistic regression. Of the 594 patients included in this study, 296 (50.7%) were prescribed medications for AUD at discharge and 459 (78.5%) were discharged with follow-up appointments, including 251 (42.8%) with a substance-use clinic appointment, 191 (32.9%) with a substance-use program appointment, and 73 (12.5%) discharged to a residential program. All-cause 30-day readmission occurred for 150 patients (25.5%) and 103 (17.8%) remained abstinent at 6 months. Medications for AUD and outpatient discharge appointments were not associated with readmission or abstinence. Discharge to residential treatment program was associated with reduced 30-day readmission (adjusted odds ratio [AOR]: 0.39, 95% confidence interval [95% CI]: 0.18-0.82) and improved abstinence (AOR: 2.50, 95% CI: 1.33-4.73). Readmission and return to heavy drinking are common for patients discharged for alcohol withdrawal. Medications for AUD were not associated with improved outcomes. The only intervention at the time of discharge that improved outcomes was discharge to residential treatment program, which was associated with decreased readmission and improved abstinence.

A preliminary investigation of sex differences in cognitive and fMRI changes following 28 days of cannabis abstinence

BackgroundPrevious studies have investigated the influence of cannabis on cognition among people with MS (pwMS), yet the influence of sex in the context of cannabis use remains unexplored. We aim to fill this gap by investigating cannabis-sex related differences in verbal learning, memory and processing speed in association with fMRI (resting state, and task-based) metrics. MethodOur sample consisted of 19 long-term, frequent cannabis users (8 males, 11 females). Assessments were conducted at baseline and after 28 days of cannabis abstinence. The tests included measures of verbal memory (Selective Reminding Test (SRT)), working memory (n-back), information processing speed (Symbol Digit Modalities Test (SDMT)) and the resting state DMN. To evaluate the effects of cannabis abstinence, we performed a group x time interaction analysis using repeated measures ANCOVA. This analysis controlled for several covariates, including the level of disability (EDSS), baseline cannabis THC metabolite levels, and cannabis withdrawal symptoms. By controlling for these variables, we aimed to isolate the impact of cannabis abstinence on cognitive performance over time. Statistical significance was set at p < 0.05. ResultsThere were no baseline cognitive differences between the sexes. After 28 days of cannabis abstinence, females performed better on the Selective Reminding Test (SRT) (p = 0.04), with a large effect size (η² = 0.286). The mean correct response improved over time for females, but there was no statistically significant group x time interaction on the Symbol Digit Modalities Test (SDMT) and the n-back task. Resting state default mode network data showed overall increased activation in females relative to males at day 28, which meshed with lower brain activation during task-based fMRI paradigms. ConclusionCannabis negated sex-based cognitive differences. Functional MRI task-based paradigms revealed less cerebral activation in females compared to males, which was associated with comparable or better cognitive performance in females, particularly after cannabis abstinence.

Poor Sperm Chromatin Condensation Is Associated with Cryopreservation-Induced DNA Fragmentation and Cell Death in Human Spermatozoa.

Background/Objectives: Semen cryopreservation is routinely performed in fertility clinics for a variety of reasons, including fertility preservation and storage of donor sperm, yet the freeze-thaw process leads to cellular damage via ice crystal formation, osmotic shock, and supraphysiological levels of oxidative stress. Sperm resistance to damage during the freeze-thaw process varies widely, yet the intrinsic factors associated with sperm cryotolerance are largely unknown. The study aimed to investigate whether poor chromatin condensation renders sperm vulnerable to DNA fragmentation and cell death induced by the freeze-thaw process. Methods: Participants (n = 51) from the general community who met the inclusion criteria collected a semen sample after 3-8 days of abstinence. Neat semen samples underwent traditional semen analysis, aniline blue (AB)-eosin staining for chromatin condensation, the terminal deoxynucleotidyl transferase dUTP nick end labelling (TUNEL) assay for DNA fragmentation, and the Annexin V assay for apoptosis/necrosis, prior to being cryopreserved using the liquid nitrogen vapour method and stored at -196 °C. Stored samples were later thawed at room temperature and processed using density gradient centrifugation. Motile sperm concentration, DNA fragmentation and apoptosis/necrosis were analysed in post-thaw samples. Results: As indicated by a significant interaction effect in linear mixed models, an increased proportion of AB-positive sperm in the pre-freeze sample exacerbated the adverse effect of freezing on sperm DNA fragmentation (p = 0.004), late apoptosis (p = 0.007), and necrosis (p = 0.007). AB-staining was positively correlated with all three parameters in the post-thaw sample (all rs ≥ 0.424, all p < 0.01) and remained significant after adjusting for neat sperm concentration (all partial rs ≥ 0.493, all p < 0.01). Similarly, AB-staining was significantly correlated with the percentage point change in sperm DNA fragmentation (rs = 0.366, p = 0.014) and necrosis (rs = 0.403, p = 0.009), both of which remained significant after adjusting for neat sperm concentration (both partial rs ≥ 0.404, both p < 0.01), and borderline significantly correlated with percentage point change in late apoptosis (rs = 0.307, p = 0.051). Conclusions: Sperm with poorly condensed chromatin may be more susceptible to cellular damage during the freeze-thaw process, independent of pre-freeze sperm concentration. These findings may help to explain the intrinsic variation in sperm resistance to cryodamage within and between individuals that is poorly understood.

Dynamic alterations in gene co-expression networks and gene-transcript associations characterize co-morbidities in cocaine use disorder.

Individuals with cocaine use disorder (CUD) who attempt abstinence experience craving and relapse, which poses challenges in treatment. Longitudinal studies linking behavioral manifestations in CUD to the blood transcriptome in living individuals are limited. Therefore, we investigated the connection between drug use behaviors during abstinence with blood transcriptomics. We conducted a comprehensive longitudinal study involving 12 subjects (9 males, 3 females) with CUD and RNA sequencing on blood collected at a drug-free baseline, and 3, 6 & 9 months thereafter. We categorized subjects into 2 responder groups (high-low) based on scores of drug use variables, and 3 responder groups (low-intermediate-high) on days of abstinence. We investigated differential expression and gene-transcript associations across responder groups at each time point. Lastly, we examined genes that are both co-expressed and showed dynamic expression with time. Genes with significant transcript associations between high and. intermediate days of abstinence at 9 months were notably enriched for cannabis use disorder, drinks weekly, and coronary artery disease risk genes. Time-specific gene co-expression analysis prioritized transcripts related to immune processes, cell cycle, RNA-protein synthesis, and second messenger signaling for days of abstinence. We demonstrate that abstinence reflects robust changes in drug use behaviors and the blood transcriptome in CUD. We also highlight the importance of longitudinal studies to capture complex biological processes during abstinence in CUD.