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Background Several evidence-based tobacco cessation treatment strategies exist, though significant barriers to cessation remain which must be addressed to improve abstinence rates for sub-populations of those smoking cigarettes. Cannabis co-use among those who use tobacco is common and appears to be increasing among adults in the United States (US). The literature evaluating the impact of cannabis use on tobacco cessation has been mixed and has several important limitations, which precludes development of treatment recommendations specific to individuals who use tobacco and co-use cannabis. To date, no prospective studies have evaluated the impact of cannabis use and severity on tobacco cessation or quantified cannabis use changes during tobacco treatment to assess for concurrent reductions, abstinence, or compensatory (i.e., increased) cannabis use. This study’s aims are to: (1) evaluate tobacco cessation outcomes among participants who co-use cannabis compared to participants only using tobacco, (2) using daily diaries and biochemical verification, assess changes in cannabis use during tobacco treatment, and (3) assess for a dose-dependent impact of cannabis use on tobacco cessation. Method A multi-site, prospective, quasi-experimental 12-week tobacco treatment trial enrolling treatment-seeking adults (ages 18–40; N = 208) from three sites across South Carolina (US) who use tobacco daily and oversampling (2:1) those who co-use cannabis. Participants receive tobacco cessation pharmacotherapy (varenicline) paired with behavioral support, while cannabis use is not addressed as part of treatment. The primary outcome is 7-day point prevalence tobacco abstinence at the week 12 end of treatment visit, measured via biochemical verification and self-report. Secondary outcome measures include changes in cannabis use (via biochemical verification and self-report) during tobacco cessation treatment. Discussion Results from this trial have the potential to inform tobacco treatment among those co-using cannabis, which may require a tailored approach to address the role of cannabis in quitting tobacco. Trial registration The trial is registered with ClinicalTrials.gov: NCT04228965. January 14th, 2020.

Abnormalities of sphingolipid metabolism play an important role in diabetes. We compared sphingolipid levels in plasma and in isolated lipoproteins between healthy control subjects and two groups of patients, one with chronic kidney disease without diabetes (ND-CKD), and the other with type 2 diabetes and macroalbuminuria (D-MA). Ceramides, sphingomyelins, and sphingoid bases and their phosphates in LDL were higher in ND-CKD and in D-MA patients compared to controls. However, ceramides and sphingoid bases in HDL2 and HDL3 were lower in ND-CKD and in D-MA patients than in controls. Sphingomyelins in HDL2 and HDL3 were lower in D-MA patients than in controls but were normal in ND-CKD patients. Compared to controls, lactosylceramides in LDL and VLDL were higher in ND-CKD patients but not in D-MA patients. However, lactosylceramides in HDL2 and HDL3 were lower in both ND-CKD and D-MA patients than in controls. Plasma hexosylceramides in ND-CKD patients were increased and sphingoid bases decreased in both ND-CKD and D-MA patients. However, hexosylceramides in LDL, HDL2, and HDL3 were higher in ND-CKD patients than in controls. In D-MA patients, only C16:0 hexosylceramide in LDL was higher than in controls. The data suggest that sphingolipid measurement in lipoproteins, rather than in whole plasma, is crucial to decipher the role of sphingolipids in kidney disease.

IntroductionContinued smoking following a cancer diagnosis has substantial health risks including increased overall and cancer-specific mortality, risk of secondary malignancies, cancer treatment toxicity and risk of surgical complications. These risks can be mitigated by quitting smoking. The preoperative period represents a prime opportunity in which to administer robust smoking cessation treatment to both improve health and support and improve surgical outcomes. We will conduct a randomised clinical trial to evaluate the effectiveness of financial incentives delivered contingent on biochemically verified smoking abstinence (contingency management (CM)) in patients with cancer undergoing surgery.Methods and analysisThe study will take place across two study sites, and participants (N=282) who smoke, are diagnosed with or suspected to have any type of operable cancer and have a surgical procedure scheduled in the next 10 days to 5 weeks will be randomised to receive standard care plus Monitoring Only or CM prior to surgery. All patients will receive breath carbon monoxide (CO) tests three times per week, nicotine replacement therapy and counselling. The CM group will also earn payments for self-reported smoking abstinence confirmed by CO breath test ≤4 ppm on an escalating schedule of reinforcement (with a reset if they smoked). Point prevalence abstinence (PPA) outcomes (self-report of 7-day abstinence confirmed by CO≤4 ppm and/or anabasine ≤2 ng/mL) will be assessed on the day of surgery and 6 months after surgery. The effect of CM on 7-day PPA at the time of surgery and 6-month follow-up will be modelled using generalised linear mixed effects models.Ethics and disseminationThis study has been reviewed and approved by the Medical University of South Carolina Institutional Review Board. We will disseminate our scientific results through traditional research-oriented outlets such as presentations at scientific meetings and publications in peer-reviewed journals.Trial registration numberNCT04605458.

Background With advances in antiretroviral therapy, people with HIV (PWH) are living longer and are less likely to die from AIDS-related complications. Yet, prior research has shown that smoking is often not addressed in the context of HIV care, and few individuals are offered cessation treatment. Optimizing tobacco treatment delivery for PWH may increase engagement with evidence-based treatments and successful quit attempts. Methods The current study is a type 1 hybrid effectiveness-implementation trial to evaluate the impact of a proactive, opt-out tobacco treatment intervention on cessation outcomes and advance understanding of key barriers and facilitators of implementation processes. A total of 230 PWH who smoke will be recruited from an infectious diseases clinic at an academic medical center and will be randomized to receive (1) treatment as usual (TAU) or (2) Pr oactive O utreach with M edication O pt-out for T obacco Treatment E ngagement (PrOMOTE). Primary outcomes include: biochemically verified 7-day point prevalence abstinence (PPA) rates, continuous abstinence (Weeks 9–12), and the number of 24-hour quit attempts at the end of study treatment (Week 12). Secondary outcomes include: participant reach (proportion reached out of contact attempts), implementation fidelity (including number of prescriptions written), participant adherence to prescribed pharmacotherapy, acceptability (participant and provider satisfaction with intervention delivery and content), and perceived barriers. Discussion This study will examine a novel approach to optimizing tobacco treatment delivery for PWH. Integrating effectiveness and implementation results will help define best practices for engaging PWH with evidence-based tobacco treatment interventions. The intervention is low-cost, has the potential to be highly scalable, and could be translatable to other ambulatory HIV clinic settings. Trial Registration ClinicalTrials.gov: NCT05019495 (August 24, 2021).

Cannabis use disorder is particularly prevalent and impairing among young people, and evidence-based treatments are limited. Prior trials of N-acetylcysteine, added to contingency management as a platform behavioral intervention, yielded positive findings in youth but not in adults. This trial sought to rigorously evaluate whether N-acetylcysteine is efficacious in youth when not paired with a robust behavioral treatment platform. Treatment-seeking youth with cannabis use disorder ( N  = 192, ages 14–21) were randomized to receive a double-blind 12-week course of oral N-acetylcysteine 1200 mg or placebo twice daily; all received weekly medical management and brief behavioral counseling. The primary efficacy outcome was the proportion of negative urine cannabinoid tests during treatment, compared between groups. An array of self-report and urine testing measures were examined secondarily to assess cannabis use reduction and cessation outcomes. The N-acetylcysteine and placebo groups did not differ in proportion of negative urine cannabinoid tests (RR = 0.93, 95% CI = 0.53, 1.64; p  = 0.80) or self-reported cannabis abstinence (RR = 1.02, 95% CI = 0.63, 1.65; p  = 0.93) during treatment. The mean percentage of cannabis use days and grams of cannabis used per using day decreased over time during treatment but did not differ between groups. More N-acetylcysteine than placebo treated participants reported gastrointestinal adverse events (63/98 versus 37/94, χ 2 1  = 11.9 p  < 0.001); adverse events were otherwise similar between groups. Findings indicate that N-acetylcysteine is not efficacious for youth cannabis use disorder when not paired with contingency management, highlighting the potentially crucial role of a robust behavioral treatment platform in facilitating prior positive efficacy findings with N-acetylcysteine. Trial Registration: Clinicaltrials.gov identifier NCT03055377

Abstract Introduction The co-use of cannabis and alcohol among tobacco-using youth is common. Alcohol co-use is associated with worse tobacco cessation outcomes, but results are mixed regarding the impact of cannabis on tobacco outcomes and if co-use leads to increased use of non-treated substances. This secondary analysis from a youth smoking cessation trial aimed to (1) evaluate the impact of cannabis or alcohol co-use on smoking cessation, (2) examine changes in co-use during the trial, and (3) explore secondary effects of varenicline on co-use. Methods The parent study was a 12-week, randomized clinical trial of varenicline for smoking cessation among youth (ages 14–21, N = 157; Mage = 19, 40% female; 76% White). Daily cigarette, cannabis, and alcohol use data were collected via daily diaries during treatment and Timeline Follow-back for 14 weeks post-treatment. Results Baseline cannabis co-users (68%) had double the odds of continued cigarette smoking throughout the trial compared with noncannabis users, which was pronounced in males and frequent cannabis users. Continued smoking during treatment was associated with higher probability of concurrent cannabis use. Baseline alcohol co-users (80%) did not have worse smoking outcomes compared with nonalcohol users, but continued smoking was associated with higher probability of concurrent drinking. Varenicline did not affect co-use. Conclusions Inconsistent with prior literature, results showed that alcohol co-users did not differ in smoking cessation, whereas cannabis co-users had poorer cessation outcomes. Youth tobacco treatment would benefit from added focus on substance co-use, particularly cannabis, but may need to be tailored appropriately to promote cessation. Implications Among youth cigarette smokers enrolled in a pharmacotherapy evaluation clinical trial, alcohol and/or cannabis co-use was prevalent. The co-use of cannabis affected smoking cessation outcomes, but more so for males and frequent cannabis users, whereas alcohol co-use did not affect smoking cessation. Reductions in smoking were accompanied by concurrent reductions in alcohol or cannabis use. Substance co-use does not appear to affect all youth smokers in the same manner and treatment strategies may need to be tailored appropriately for those with lower odds of smoking cessation.

Rationale Stress has been shown to be a significant factor in the maintenance of marijuana use. Oxytocin is a hypothalamic neuropeptide that has been shown to moderate behavioral responding to stress as well as play a role in the neuroadaptations that occur as a consequence of long-term drug use. Objectives The current study evaluated the impact of oxytocin pretreatment on craving, stress, and anxiety responses following a psychosocial stress task in marijuana-dependent individuals. Methods In a laboratory setting, baseline measurements of craving (assessed using the Marijuana Craving Questionnaire; MCQ), salivary cortisol and dehydroepiandrosterone (DHEA), stress, and anxiety were collected in 16 participants (age 19–40) meeting DSM-IV criteria for marijuana dependence. Participants were then administered either oxytocin 40 IU ( n  = 8) or placebo ( n  = 8) nasal spray prior to completion of the Trier Social Stress Task (TSST). Measurements were repeated pre-TSST, immediately post-TSST, and 5-, 35-, and 60-min post-TSST. Results Oxytocin reduced both MCQ total score and DHEA levels from before to after the TSST. It also decreased anxiety, but not subjective stress ratings. Conclusions Although preliminary, these results suggest that oxytocin may play a role in the amelioration of stress-induced reactivity and craving in marijuana-dependent individuals.

BackgroundThe use of e-cigarettes has been increasing, especially since the introduction of ‘pod’ devices to the marketplace since 2018. Most adults who vape report interest in quitting. The present study examined level of interest in e-cigarette cessation between users with varying cigarette smoking histories and device types.MethodsData obtained from wave 5 (2018–2019) of the Population Assessment of Tobacco and Health study (n=34 309). Analyses were conducted on adult current established e-cigarette users, categorised on cigarette smoking history (current, former or never) and device type (disposable, cartridge/pod, tank or mod). Participants reported if they planned to ever quit e-cigarettes, attempted to quit in the past year and attempted to quit by cutting back in the past year.ResultsOf the 2922 established e-cigarette users, 68.21% reported plans to quit vaping; 17.27% reported attempting to quit e-cigarettes in the past year; and 29.28% reported attempting to quit by cutting back in the past year. Cartridge users had higher odds of interest in quitting than tank and mod users. Disposable and cartridge users had higher odds of reporting a past year quit attempt than tank and mod users. Individuals with no smoking history had higher odds of reporting a past year quit attempt or cutting back relative to those reporting dual use (of both e-cigarettes and cigarettes) and former smoking.ConclusionsTobacco control should consider the type of e-cigarette device that is being used, alongside users’ cigarette smoking history, when developing interventions and other resources for vaping cessation.

RationaleWomen with cocaine use disorder have worse treatment outcomes compared with men. Sex differences in cocaine addiction may be driven by differences in neurobiology or stress reactivity. Oxytocin is a potential therapeutic for stress reduction in substance use disorders, but no studies have examined the effect of oxytocin on neural response to drug cues in individuals with cocaine use disorders or potential sex differences in this response.ObjectivesThe goal of this study was to examine the effect of intranasal oxytocin on cocaine cue reactivity in cocaine dependence, modulated by gender and history of childhood trauma.MethodsCocaine-dependent men with (n = 24) or without (n = 19) a history of childhood trauma and cocaine-dependent women with (n = 16) or without (n = 8) a history of childhood trauma completed an fMRI cocaine cue reactivity task under intranasal placebo or oxytocin (40 IU) on two different days. fMRI response was measured in the right amygdala and dorsomedial prefrontal cortex (DMPFC).ResultsIn the DMPFC, oxytocin reduced fMRI response to cocaine cues across all subject groups. However, in the amygdala, only men with a history of childhood trauma showed a significantly reduced fMRI response to cocaine cues on oxytocin versus placebo, while women with a history of childhood trauma showed an enhanced amygdala response to cocaine cues following oxytocin administration. Cocaine-dependent subjects with no history of childhood trauma showed no effect of oxytocin on amygdala response.ConclusionsOxytocin can reduce cue reactivity in cocaine dependence, but its effect is modified by sex and childhood trauma history. Whereas men with cocaine dependence may benefit from oxytocin administration, additional studies are needed to determine whether oxytocin can be an effective therapeutic for cocaine-dependent women.

RationaleThe hypothalamic–pituitary–adrenal (HPA) axis is a critical hormonal system involved in stress response. A number of studies have investigated the HPA axis response of drug-dependent individuals to stressors. Stress-induced vulnerabilities in the HPA axis may differ in response to chronic use of different substances, possibly leading to different target therapies. There has not been a direct comparison of HPA axis and subjective response between individuals with different types of substance use disorders following a laboratory stress intervention.ObjectivesThe primary goal of the current study was to compare subjective and neuroendocrine response to the Trier Social Stress Task (TSST) across multiple primary types of substance use disorders and investigate differential response between males and females.MethodsFour hundred participants were drawn from seven studies completed at the Medical University of South Carolina between 2011 and 2021. The TSST was utilized across studies and subjective and neuroendocrine responses measured following completion. Generalized linear mixed effects models and area under the response curve analysis were used to compare both substance type and sex differences.ResultsThe study groups involving individuals with cocaine use disorder had blunted stress, craving and cortisol response following the TSST as compared to other substance use groups. Females in the cocaine groups reported higher subjective stress but lower cortisol than males.ConclusionsThe study results indicate that there may be differential effects of substances on the HPA axis, with cocaine using individuals exhibiting more blunting of the HPA axis response as compared to users of other substances.