Contingency management interventions for abstinence from cigarette smoking in pregnancy and postpartum: A systematic review and meta-analysis.

Contingency management is one of the most effective treatments for substance use disorders in not-pregnant people. The most recent quantitative review of its efficacy among pregnant and postpartum women who smoke cigarettes concluded with moderate certainty that those receiving contingent financial incentives were twice as likely to be abstinent compared with controls. We aimed to update and extend previous reviews. Five databases were systematically searched for randomized controlled trials (RCTs) published before December 2022 that assessed the effectiveness of incentives for abstinence from substance use. Data from trials of smoking abstinence were pooled using a random-effects meta-analysis model (restricted maximum likelihood). Results are reported as risk-ratios (RRs) with 95% confidence intervals (CIs). This study is registered with PROSPERO, CRD42022372291. Twelve RCTs (3136) pregnant women) were included. There was high certainty evidence that women receiving incentives were more likely to be abstinent than controls at the last antepartum assessment (12 RCTs; RR = 2.43, 95% CI 2.04-2.91, n = 2941, I2 = 0.0%) and moderate certainty evidence at the longest postpartum assessment while incentives were still available (five RCTs; RR = 2.72, 1.47-5.02, n = 659, I2 = 44.5%), and at the longest postpartum follow-up after incentives were discontinued (six RCTs; RR = 1.93, 1.08-3.46, n = 1753, I2 = 51.8%). Pregnant women receiving incentives are twice as likely to achieve smoking abstinence during pregnancy suggesting this intervention should be standard care for pregnant women who smoke. The results also demonstrate that abstinence continues into the postpartum period, including after incentives are discontinued, but more trials measuring outcomes in the postpartum period are needed to strengthen this conclusion.

US state laws relevant to incentives for health behavior: A qualitative analysis.

Contingency management (CM) involves provision of incentives for positive health behaviors via a well-defined protocol and is among the most effective treatments for patients with substance use disorders (SUDs). An understanding of laws affecting incentives for health behaviors and outcomes, including contexts in which incentives are already permitted, could inform efforts to disseminate CM. We conducted a systematic NexisUni legal database review of state statutes and regulations effective during 2022 to identify (a) laws that explicitly permit or prohibit delivery of incentives to patients, employees, or insurance beneficiaries for SUD-specific behaviors or outcomes, and (b) laws that explicitly permit delivery of incentives for any health behaviors or outcomes. We identified 27 laws across 17 jurisdictions that explicitly permit delivery of incentives for SUD-related behaviors or outcomes, with most occurring in the context of wellness programs. No state laws were identified that explicitly prohibit SUD-specific incentives. More broadly, we identified 57 laws across 29 jurisdictions permitting incentives for any health outcomes (both SUD- and non-SUD-related). These laws occurred in the contexts of wellness programs, K-12/early childhood education, government public health promotion, and SUD treatment provider licensing. Considering the urgent need to expand evidence-based SUD treatment in rural and underserved areas throughout the US, these findings could inform efforts to develop laws explicitly permitting provision of incentives in SUD care and enhance efforts to disseminate CM more broadly.

The Impact of the Covid-19 Pandemic on Smoking Among Vulnerable Populations.

AIM: While accumulating evidence suggests that people modified their smoking during the ongoing COVID-19 pandemic, it remains unclear whether those most at risk for tobacco-related health disparities did so. The current study examined changes in smoking among several vulnerable smoker populations during the COVID-19 pandemic. METHODS: A web-based survey was distributed in 2020 to 709 adults with socioeconomic disadvantage, affective disorders, or opioid use disorder who participated in a previous study investigating the effects of very low nicotine content (VLNC) cigarettes on smoking. Current smoking status and rate, and adoption of protective health behaviors in response to the pandemic (eg social distancing, mask wearing) were examined. RESULTS: Among 332 survey respondents (46.8% response rate), 84.6% were current smokers. Repeated measures ANOVA showed that current cigarettes/day (CPD) was higher during COVID than pre-COVID (12.9 ± 1.0 versus 11.6 ± 1.0; p < .001). Most respondents had adopted protective health behaviors to prevent infection (>79% for all behaviors). More than half indicated that they were still leaving their homes specifically to buy cigarettes (64.6%) and were buying more packs per visit to the store (54.5%) than pre-COVID. Individuals unemployed at the time of the survey experienced greater increases in CPD (from 11.4 ± 1.4 to 13.3 ± 1.4, p = .024) as did those with higher levels of anxiety (from 11.5 ± 1.1 to 13.6 ± 1.1, p < .001). CONCLUSIONS: Smoking increased during the COVID-19 pandemic in this sample of adults from vulnerable populations, even while most adopted protective health measures to prevent infection. Unemployment and anxiety might identify those at greatest risk for increases in tobacco use. IMPLICATIONS: Individuals from populations especially vulnerable to smoking might be at risk for greater harm from cigarette smoking during times of pandemic-related stress. Public health interventions are warranted to ameliorate increases in smoking among these populations. Special attention should be paid to those experiencing unemployment and high anxiety.

Leveraging the cigarette purchase task to understand relationships between cumulative vulnerabilities, the relative reinforcing effects of smoking, and response to reduced nicotine content cigarettes.

We examined if the relative-reinforcing effects of smoking increase with greater cumulative vulnerability and whether cumulative vulnerability moderates response to reduced nicotine content cigarettes. Participants were 775 adults from randomized clinical trials evaluating research cigarettes differing in nicotine content (0.4, 2.4, 15.8 mg/g). Participants were categorized as having low (0-1), moderate (2-3), or high (≥4) cumulative vulnerability. Vulnerabilities included rural residence, opioid use disorder, affective disorder, low educational attainment, poverty, unemployment, and physical disability. We used the cigarette purchase task (CPT) to assess the relative-reinforcing effects of participants' usual-brand cigarettes at baseline and study cigarettes during the 12-week trial. The CPT is a behavioral-economic task wherein participants estimate likely smoking (demand) over 24 h under escalating cigarette price. Demand is characterized by two factors: Amplitude (demand volume at zero/minimal price) and Persistence (demand sensitivity to price). Greater cumulative vulnerability was associated with greater demand Amplitude (F[2709] = 16.04,p < .0001) and Persistence (F[2709] = 8.35,p = .0003) for usual-brand cigarettes. Demand Amplitude for study cigarettes increased with increasing cumulative vulnerability (F[2619] = 19.59, p < .001) and decreased with decreasing nicotine content ([4879] = 5.45, p < .001). The only evidence of moderation was on demand Persistence (F[8867] = 2.00,p = .04), with larger reductions at the 0.4 mg/g compared to 15.8 mg/g doses among participants with low compared to moderate or high cumulative vulnerability. The relative-reinforcing effects of smoking clearly increase with greater cumulative vulnerability. Reducing nicotine content would likely reduce demand Amplitude across cumulative-vulnerability levels but reductions in demand Persistence may be more limited among those with greater cumulative vulnerability.

Potential effects of nicotine content in cigarettes on use of other substances.

A national nicotine reduction policy has the potential to reduce cigarette smoking and associated adverse health impacts among vulnerable populations. However, possible unanticipated adverse effects of reducing nicotine content in cigarettes, such as increasing the use of alcohol or other abused substances, must be examined. The purpose of this study was to evaluate the effects of exposure to varying doses of nicotine in cigarettes on use of other substances. This was a secondary analysis (n = 753) of three simultaneous, multisite, double-blind, randomized-controlled trials examining 12 weeks of exposure to study cigarettes varying in nicotine content (0.4, 2.4, 15.8 mg nicotine/g tobacco) among daily smokers from three vulnerable populations: individuals with affective disorders (n = 251), individuals with opioid use disorder (n = 256), and socioeconomically-disadvantaged women of reproductive age (n = 246). Effect of study cigarette assignment on urine toxicology screens (performed weekly) and responses to drug and alcohol use questionnaires (completed at study weeks 6 and 12) were examined using negative binomial regression, logistic regression, or repeated measures analysis of variance, controlling for sex, age, and menthol status. The most common substances identified using urine toxicology included tetrahydrocannabinol (THC; 44.8%), cocaine (9.2%), benzodiazepine (8.6%), and amphetamines (8.0%), with 57.2% of participants testing positive at least once for substance use (27.3% if excluding THC). No significant main effects of nicotine dose were found on any of the examined outcomes. These results suggest that reducing nicotine content does not systematically increase use of other substances, even among individuals at increased risk of substance use. ClinicalTrials.gov Identifiers: NCT02232737, NCT2250664, NCT2250534.

Relating individual differences in the reinforcing value of smoking and dependence severity to nicotine exposure levels in vulnerable populations.

Cigarette smoking is overrepresented in populations with psychiatric conditions and socioeconomic disadvantage. Greater understanding of the role of reinforcement and nicotine dependence in smoking among vulnerable populations may facilitate development of better targeted interventions to reduce smoking. Prior research demonstrated that individual differences in the reinforcing value of smoking and nicotine-dependence severity predicted total nicotine-exposure in vulnerable populations. The present study uses multivariate regression to address two aims: (1) Quantify the degree to which the reinforcing value of smoking, assessed using the Cigarette Purchase Task (CPT), and dependence severity assessed using the Fagerström Test of Nicotine Dependence and Brief Wisconsin Inventory of Smoking Dependence Motives (B-WISDM) each account for individual differences in cotinine-plus-3'-hydroxycotinine (COT+3HC) levels. (2) Explore whether there is overlap in the variance accounted for by the CTP, FTND, and B-WISDM. Participants were 628 adults with co-morbid psychiatric conditions or socioeconomic disadvantage who smoked daily. The CPT, FTND, and B-WISDM models accounted for 23.76%, 32.45%, and 29.61% of the variance in COT+3HC levels, respectively. Adding CPT to the FTND model failed to increase the variance accounted for and adding it to the B-WISDM model did so by only 1.2% demonstrating considerable overlap in the variance in nicotine exposure levels accounted for by these three instruments. These results provide new knowledge on the relationship between individual differences in the reinforcing value of smoking and nicotine-exposure levels and suggest differences in reinforcing value may underpin a considerable portion of the variance in nicotine exposure accounted for by dependence severity.

Randomized Controlled Trial Examining the Efficacy of Adding Financial Incentives to Best practices for Smoking Cessation Among pregnant and Newly postpartum Women.

We report results from a single-blinded randomized controlled trial examining financial incentives for smoking cessation among 249 pregnant and newly postpartum women. Participants included 169 women assigned to best practices (BP) or BP plus financial incentives (BP + FI) for smoking cessation available through 12-weeks postpartum. A third condition included 80 never-smokers (NS) sociodemographically-matched to women who smoked. Trial setting was Burlington, Vermont, USA, January, 2014 through January, 2020. Outcomes included 7-day point-prevalence abstinence antepartum and postpartum, and birth and other infant outcomes during 1st year of life. Reliability and external validity of results were assessed using pooled results from the current and four prior controlled trials coupled with data on maternal-smoking status and birth outcomes for all 2019 singleton live births in Vermont. Compared to BP, BP + FI significantly increased abstinence early- (AOR = 9.97; 95%CI, 3.32-29.93) and late-pregnancy (primary outcome, AOR = 5.61; 95%CI, 2.37-13.28) and through 12-weeks postpartum (AOR = 2.46; CI,1.05-5.75) although not 24- (AOR = 1.31; CI,0.54-3.17) or 48-weeks postpartum (AOR = 1.33; CI,0.55-3.25). There was a significant effect of trial condition on small-for-gestational-age (SGA) deliveries (χ2 [2] = 9.01, P = .01), with percent SGA deliveries (+SEM) greatest in BP, intermediate in BP + FI, and lowest in NS (17.65 + 4.13, 10.81 + 3.61, and 2.53 + 1.77, respectively). Reliability analyses supported the efficacy of financial incentives for increasing abstinence antepartum and postpartum and decreasing SGA deliveries; external-validity analyses supported relationships between antepartum cessation and SGA risk. Adding financial incentives to Best Practice increases smoking cessation among antepartum and postpartum women and improves other maternal-infant outcomes. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02210832.

Effects of Reduced Nicotine Content Cigarettes on Fractional Exhaled Nitric Oxide and Self-Reported Respiratory Health Outcomes Among Smokers With Psychiatric Conditions or Socioeconomic Disadvantage.

INTRODUCTION: This study examined whether exposure to reduced-nicotine-content cigarettes (RNCCs) for 12 weeks alters respiratory health using Fractional Exhaled Nitric Oxide (FeNO), a validated biomarker of respiratory epithelial health, and the Respiratory Health Questionnaire (RHQ), a subject-rated questionnaire on respiratory symptoms. Participants were 747 adult daily smokers enrolled in three double-blind, randomized clinical trials evaluating effects of cigarette nicotine content (0.4, 2.4, 15.8 mg nicotine/g tobacco) in people with affective disorders, opioid use disorder (OUD), or socioeconomic disadvantage. AIMS AND METHODS: FeNO levels and RHQ ratings were collected at baseline and Weeks 6 and 12 following randomization. Multiple regression was used to assess associations of FeNO and RHQ with smoking characteristics. Mixed-model repeated-measures ANOVA was used to evaluate the effects of nicotine content on FeNO and RHQ outcomes over the 12-week study period. RESULTS: FeNO levels but not RHQ ratings varied inversely with smoking characteristics at baseline (Ps < 0.0001) in smokers with affective disorders and socioeconomic disadvantage but less so in those with OUD. Participants with affective disorders and socioeconomic disadvantage, but not those with OUD, who were assigned to RNCCs had higher FeNO levels at Week 12 than those assigned to the 15.8 mg/g dose [F(2,423) = 4.51, p = .01, Cohen's d = 0.21]. No significant dose-related changes in RHQ scores were identified. CONCLUSIONS: Use of RNCCs across a 12-week period attenuates smoking-related reductions in FeNO levels in smokers with affective disorders and socioeconomic disadvantage although not those with OUD. FeNO changes were not accompanied by changes in respiratory-health ratings. TRIAL REGISTRATION: Inclusion and exclusion criteria for the sample and experimental manipulation of the nicotine content of assigned cigarettes are registered: NCT02232737, NCT02250664, NCT02250534. The FeNO measure reported in this manuscript is an exploratory outcome that was not registered. IMPLICATIONS: Should a reduced nicotine content standard be implemented; these results suggest that reduced nicotine content in cigarettes will not exacerbate and instead may attenuate smoking-related decreases in FeNO. This is significant as NO is an important component in maintaining a healthy respiratory system and necessary to defend against infection. Furthermore, the results of the current study demonstrate that the adoption of the reduced nicotine content standard may result in beneficial impacts on respiratory epithelial health among vulnerable populations that are disproportionally affected by the adverse health outcomes precipitated by combustible tobacco use.

Challenges and opportunities during the COVID-19 pandemic: Treating patients for substance use disorders during the perinatal period.

The coronavirus disease 2019 (COVID-19) pandemic exacerbated the opioid use disorder epidemic and accelerated alcohol and other substance use disorders. Sudden health care service delivery changes during the COVID-19 pandemic created both challenges and opportunities for all patients with substance use disorders including the use of virtual or telemedicine visits, medication access issues and ensuring access to naloxone when supplies cannot be handed out. Unique challenges for pregnant and post-partum patients with substance use disorders includes some evidence of reduced access to medication to treat opioid use disorders and changes in delivery protocols that isolate birthing people from supports. Opportunities for all patients with substance use disorders include virtual platforms presenting positive opportunities for treatment. They are time efficient, eliminate transportation barriers, and potentially reduce childcare barriers. For pregnant and post-partum patients with substance use disorders, hybrid models of telemedicine and in-person visits reduced no-show visit rates and increased flexibility in medication dosing regimens. Thus, there is a unique opportunity to study the success of different virtual care models given the variety of implemented strategies. The COVID-19 pandemic provides an unprecedented opportunity to dramatically transform standard care approaches to help optimize care for all patients, including pregnant and post-partum people.

Opioid use disorder treatment in rural settings: The primary care perspective.

Despite the efficacy of medications for treating opioid use disorder (OUD), they are underutilized, especially in rural areas. Our objectives were to determine the association between primary care practitioners (PCPs) rurality and concerns for patient substance use, and to identify factors associated with PCP comfort treating OUD, focusing on barriers to treatment. We developed a web-based survey completed by 116 adult-serving PCPs located in Vermont's rural and non-rural counties between April-August 2020. The instrument included PCP-identified concerns for substance use among patients, barriers to treating patients with OUD, and current level of comfort treating patients with OUD. On a scale from 0 to 10, rural PCPs reported higher concern for heroin (mean difference; Mdiff = 1.38, 95% CI: 0.13 to 2.63), fentanyl (Mdiff = 1.52, 95% CI: 0.29 to 2.74), and methamphetamine (Mdiff = 1.61, 95% CI: 0.33 to 2.90) use among patients compared to non-rural PCPs, and practitioners in both settings expressed high concern regarding their patients' use of tobacco (7.6 out of 10) and alcohol (7.0 out of 10). There was no difference in reported comfort in treating patients with OUD among rural vs. non-rural PCPs (Mdiff = 0.65, 95%CI: 0.17 to 1.46; P = 0.119), controlling for higher comfort among male PCPs and those waivered to prescribe buprenorphine (Ps < 0.05). Lack of training/experience and medication diversion were PCP-identified barriers associated with less comfort treating OUD patients, while time constraints was associated with more comfort (Ps < 0.05). Taken together, these data highlight important areas for dissemination of evidence-based training, support, and resources to expand OUD treatment capacity in rural communities.

Cumulative vulnerabilities as a potential moderator of response to reduced nicotine content cigarettes.

Risk for smoking increases in a summative manner corresponding to the number of co-occurring vulnerabilities present (cumulative vulnerability). We examined whether cumulative vulnerabilities moderate response to reduced nicotine content cigarettes in a secondary analysis of results from 775 participants in three 12-week randomized clinical trials examining research cigarettes varying in nicotine content (0.4, 2.4, 15.8 mg nicotine/g tobacco). Participants were categorized as having 0-1, 2-3, or ≥ 4 cumulative vulnerabilities. Vulnerabilities included: rural residence, current substance use disorder, current affective disorder, low educational attainment, poverty, unemployment, physical disability. The primary outcome was total cigarettes per day (CPD) during Week 12; secondary outcomes included CPD across weeks, toxin exposure, dependence severity, craving/withdrawal (17 dependent measures). Results were analyzed using repeated measures analysis of covariance and growth-curve modeling. Total CPD during Week 12 increased as cumulative-vulnerability increased (P = 0.004), and decreased as nicotine content decreased (P < 0.001), with no significant interaction of cumulative vulnerability and dose (P = 0.67). Effects on other outcomes generally followed that same pattern. The only exception across the other outcomes was on Questionnaire-on-Smoking-Urges Factor-2 ratings for usual-brand cigarettes where cumulative vulnerability, dose, and time interacted (P = 0.007), with craving at the 0.4 and 2.4 mg/g doses decreasing over time, but inconsistently across vulnerability categories. Overall, we saw little evidence that cumulative vulnerabilities moderate response to reduced nicotine content cigarettes suggesting that a policy reducing nicotine content in cigarettes to minimally addictive levels could benefit even highly vulnerable smokers including those residing in rural or other regions with overrepresentation of co-occurring vulnerabilities. Clinicaltrials.gov identifiers: NCT02232737, NCT02250664, NCT02250534.

Abuse liability of cigarettes with very low nicotine content in pregnant cigarette smokers.

The U.S. Food and Drug Administration has proposed reducing the nicotine content of cigarettes to a minimally-addictive level. To our knowledge, this study is the first to examine how pregnant smokers respond to very low nicotine content (VLNC) cigarettes. In Phase 1, participants blindly sampled two VLNC cigarettes (0.4 and 2.4 mg/g of tobacco) and their usual brand (UB) cigarette in separate sessions, then completed a behavioral economic simulation task and measures of subjective effects, craving/withdrawal, and smoking topography. Phase 2 directly compared the relative reinforcing effects of the cigarettes using concurrent choice testing. All possible dose-pair combinations were tested in separate sessions where puffs were earned ad libitum by clicking the code associated with their preferred cigarette 10 times. Phase 3 tested the 0.4 mg/g-UB dose-pair where UB puffs could be earned with a progressively incremented number of clicks (maximum 8400). Ten pregnant smokers in Burlington, VT and Baltimore, MD participated in 2017-2018. Regarding abuse liability, participants chose the 0.4-mg/g dose less than UB (22% vs. 78%) during concurrent choice testing and the 0.4-mg/g dose sustained less demand than the 2.4-mg/g and UB doses on the simulation task. Positive subjective effects were also lower for both VLNC cigarettes vs. UB. Each cigarette reduced nicotine craving/withdrawal and no significant changes indicative of compensatory smoking were noted. Reducing the nicotine content of cigarettes may decrease their abuse liability in pregnant smokers without causing untoward craving/withdrawal or compensatory smoking. Studies of extended exposure to VLNCs in pregnant women are warranted.

Relating individual differences in nicotine dependence severity to underpinning motivational and pharmacological processes among smokers from vulnerable populations.

We examined whether elucidating underpinning smoking motivation and related pharmacological processes enhances understanding of nicotine dependence among smokers from vulnerable populations. Data were obtained between Oct, 2016 and Sept, 2019 from 745 adult smokers with co-morbid psychiatric conditions or socioeconomic disadvantage at University of Vermont, Brown University, Johns Hopkins University. Smoking motivation was assessed using the Cigarette Purchase Task (CPT), a behavioral-economic task that models the relative reinforcing value of smoking under varying monetary constraint. Dependence severity was measured using the Heaviness of Smoking Index (HSI), Fagerström Test for Nicotine Dependence total scores (FTND), and FTND total scores minus items 1 and 4 (FTND2,3,5,6). We also assessed associations between dependence severity and smoking motivation with nicotine levels and metabolism rate. Principal Component Analysis was used to examine the latent structure of the conventional five CPT indices; bivariate and multivariable modeling was used to test associations. Factor analysis resulted in a two-factor solution, Amplitude (demand unconstrained by price) and Persistence (price sensitivity). CPT latent factors were associated with each dependence-severity measure (ps ≤ 0.0001), with associations stronger for Amplitude than Persistence across each, especially HSI which was exclusively associated with Amplitude. Amplitude and each dependence measure were associated with nicotine intake (ps ≤ 0.0002); Persistence was not (p = .19). Demand Amplitude more than Persistence appears key to understanding individual differences in dependence severity. Regarding potential application, the results suggest a need for interventions that more effectively target demand Amplitude to make greater headway in reducing smoking in vulnerable populations. Trial Registration:clinicaltrials.gov identifiers: NCT02232737, NCT02250664, NCT02250534.

Potential Moderating Effects of Sex/Gender on the Acute Relative Reinforcing and Subjective Effects of Reduced Nicotine Content Cigarettes in Vulnerable Populations.

INTRODUCTION: Reports in relatively healthy smokers suggest men are more sensitive than women to the subjective effects of reduced nicotine content cigarettes (RNCCs). We know of no reports examining sex differences in the relative reinforcing effects of RNCCs, an important outcome in assessing smoking's addiction potential. The aim of the present study is to address this gap by examining sex/gender differences on reinforcing effects while examining whether sex differences in subjective effects are discernible in vulnerable populations. METHODS: Secondary analysis of a within-subject, double-blinded experiment examining acute effects of cigarettes varying in nicotine content (0.4, 2.4, 5.2, 15.8 mg/g) among 169 adult smokers with psychiatric conditions or socioeconomic disadvantage. Effects of dose, sex, and their interaction were examined on reinforcing (concurrent-choice and Cigarette Purchase Task [CPT] testing), and subjective effects (Cigarette Evaluation Questionnaire [CEQ] and craving/withdrawal ratings). RESULTS: Reducing nicotine content decreased the relative reinforcing effects of smoking in concurrent-choice and CPT testing (p's < .05) with no significant effects of sex nor dose × sex/gender interactions. Reducing nicotine content decreased CEQ ratings with only a single significant effect of sex (higher Psychological Reward scores among women than men, p = .02) and no significant dose × sex/gender interactions. Results on craving/withdrawal paralleled those on the CEQ. CONCLUSIONS: Reducing nicotine content decreases the addiction potential of smoking independent of sex in populations highly vulnerable to smoking and addiction, with no indication that women are less sensitive to subjective effects of RNCCs or would benefit less from a policy reducing the nicotine content of cigarettes. IMPLICATIONS: A policy reducing the nicotine content of cigarettes has the potential to reduce the addiction potential of smoking across men and women who are especially vulnerable to smoking, addiction, and tobacco-related adverse health impacts.

Contraceptive Knowledge among Females and Males Receiving Medication Treatment for Opioid Use Disorder Compared to Those Seeking Primary Care.

BACKGROUND: Rates of unintended pregnancy among women receiving medication treatment for opioid use disorder (mOUD) are high, likely due in part to low rates of contraceptive use. Lack of knowledge about contraception may be contributing to inadequate contraceptive use. Objectives: To compare contraceptive knowledge among women and men receiving mOUD relative to a comparison group seeking primary care. Methods: We surveyed 332 reproductive-age women and men receiving mOUD or primary care with the recently validated 25-item Contraceptive Knowledge Assessment. We examined overall differences between patient groups and between females and males using two-way analyses of variance; individual item differences were tested using logistic regression. Results: The mean percent of total correct responses was lower among individuals receiving mOUD (n = 167) relative to the comparison group (n = 165), 47.7% vs. 53.8%, respectively (p < .001), and higher among females (n = 169) relative to males (n = 163), 56.1% vs. 45.2%, respectively (p < .001). Individual item analyses revealed patient group and sex differences primarily in the areas of contraceptive efficacy, attributes of contraceptive methods, and fertility awareness. Conclusion: While there were modest differences between patient groups and sexes, the results suggest a deficit in contraceptive knowledge across all groups. Substance use disorder treatment clinics could be an opportunistic setting in which to provide accurate information about contraception to patients with OUD and other substance use disorders.

Innovative approaches to reduce unintended pregnancy and improve access to contraception among women who use opioids.

Dramatic increases in the rate of opioid use disorder (OUD) during pregnancy have been paralleled by substantial increases in the number of neonates diagnosed with neonatal abstinence syndrome (NAS). Women with OUD have reliably reported high rates of unintended pregnancy and a number of studies also indicate they desire easier access to contraception. Recent statements from the Centers for Disease Control and Prevention and the American Academy of Pediatrics/American College of Obstetricians and Gynecologists have drawn increased attention to efforts to prevent unintended pregnancy and improve access to contraception among women with OUD. We briefly review a number of innovative clinical approaches in these areas, including efforts to integrate family planning services into substance use disorder (SUD) treatment and other settings that serve people with OUD and interventions that aim to make family planning a higher priority among women with OUD. Results suggest many of these approaches have led to increases in contraceptive use and may aid in efforts to reduce unintended pregnancy and improve access to contraception among women with OUD now and in the future.

Examining effects of unit price on preference for reduced nicotine content cigarettes and smoking rate.

Cigarette preference increases as a function of greater nicotine content, but manipulating cost can shift preference. The aims of the present study are to model whether (1) the behavioral-economic metric unit price (cost/reinforcer magnitude) accounts for preference shifts and (2) whether preference shifts toward reduced nicotine content are associated with smoking reductions. In a multisite study between 2015 and 2016, 169 daily smokers from vulnerable populations completed two concurrent-choice conditions examining preference for smoking normal (15.8 mg/g) and reduced (0.4 mg/g) nicotine content cigarettes. In Condition 1, both products were available at 10 responses/choice. In Condition 2, availability of the 0.4 mg/g dose remained at 10 responses/choice while the 15.8 mg/g dose was available on a progressive-ratio (PR) schedule wherein response cost increased following each choice. Unit prices were calculated by dividing dose by response requirement. Results were analyzed using ANOVA and binomial tests (p < .05). Participants preferred the 15.8 over 0.4 mg/g dose in Condition 1, but shifted preference to the 0.4 mg/g dose in Condition 2 (p < .001) immediately before the point in the PR progression where unit price for 15.8 dose exceeded unit price for the 0.4 dose (p < .001). This shift was associated with a reduction in smoking (p < .001). The unit price of nicotine appears to underpin cigarette product preference and may provide a metric for predicting preference and potentially impacting it through tobacco regulations. These results also demonstrate that reduced compared to normal nicotine content cigarettes sustain lower smoking rates discernible even under acute laboratory conditions and in vulnerable populations.

Pregnancy-Induced Increases in the Nicotine Metabolite Ratio: Examining Changes During Antepartum and Postpartum.

INTRODUCTION: Pregnancy-induced increases in nicotine metabolism may contribute to difficulties in quitting smoking during pregnancy. However, the time course of changes in nicotine metabolism during early and late pregnancy is unclear. This study investigated how pregnancy alters the nicotine metabolite ratio (NMR), a common biomarker of nicotine metabolism among nonpregnant smokers. METHODS: Urinary NMR (trans-3'-hydroxycotinine [3HC]/cotinine [COT]) was assessed using total (free + glucuronide) and free compounds among women (N = 47) from a randomized controlled trial for smoking cessation who self-reported smoking and provided a urine sample during early pregnancy (M ± SD = 12.5 ± 4.5 weeks' gestation), late pregnancy (28.9 ± 2.0 weeks' gestation), and 6 months postpartum (24.7 ± 1.2 weeks since childbirth). Urine samples were analyzed using liquid chromatography-tandem mass spectrometry and NMR were calculated as Total 3HC/Free COT, Free 3HC/Free COT, and Total 3HC/Total COT. RESULTS: NMR was significantly higher during early and late pregnancy compared to postpartum and significantly increased from early to late pregnancy as measured by Total 3HC/Free COT (0.76, 0.89, 0.60; all p's < .05) and Free 3HC/Free COT (0.68, 0.80, 0.51; all p's < .05). Total 3HC/Total COT did not vary over time (p = .81). CONCLUSIONS: Total 3HC/Free COT and Free 3HC/Free COT increased in the first trimester and continued to increase throughout pregnancy, suggesting a considerable increase in nicotine metabolism over gestation. Future analyses are needed to interpret the changes in NMR in the context of nicotine pharmacokinetics, as well as its impact on changes in smoking behavior and cessation outcomes. IMPLICATIONS: We observed that the NMR was significantly higher as early as 12 weeks' gestation and increased further as a function of gestational age. Among nonpregnant smokers, elevated NMR is associated with smoking phenotypes such as smoking more cigarettes per day and poorer response to nicotine patch; therefore, pregnancy-induced increases in the NMR may contribute to smoking during the first trimester of pregnancy and reducing or quitting smoking may become more challenging as the rate of nicotine metabolism accelerates over the course of pregnancy.

Potential Moderating Effects of Psychiatric Diagnosis and Symptom Severity on Subjective and Behavioral Responses to Reduced Nicotine Content Cigarettes.

INTRODUCTION: Given FDA's authority to implement a cigarette nicotine reduction policy, possible outcomes of this regulation must be examined, especially among those who may be most affected, such as those with comorbid psychiatric disorders. METHODS: In this secondary analysis of a multisite, randomized, clinical laboratory study, we used analyses of variance to examine the effects of nicotine dose (0.4, 2.4, 5.2, and 15.8 mg/g of tobacco), depressive and anxiety diagnoses (depression only, anxiety only, both, or neither), and depressive and anxiety symptom severity on cigarette choice, smoke exposure, craving, and withdrawal across three vulnerable populations: socioeconomically disadvantaged women of reproductive age, opioid-dependent individuals, and those with affective disorders (n = 169). RESULTS: Diagnosis and symptom severity largely had no effects on smoking choice, total puff volume, or CO boost. Significant main effects on craving and withdrawal were observed, with higher scores in those with both anxiety and depression diagnoses compared with depression alone or no diagnosis, and in those with more severe depressive symptoms (p's < .001). These factors did not interact with nicotine dose. Cigarettes with <15.8 mg/g nicotine were less reinforcing, decreased total puff volume, and produced significant but lower magnitude and shorter duration reductions in craving and withdrawal than higher doses (p's < .01). CONCLUSIONS: Reducing nicotine dose reduced measures of cigarette addiction potential, with little evidence of moderation by either psychiatric diagnosis or symptom severity, providing evidence that those with comorbid psychiatric disorders would respond to a nicotine reduction policy similarly to other smokers. IMPLICATIONS: Thus far, controlled studies in healthy populations of smokers have demonstrated that use of very low nicotine content cigarettes reduces cigarette use and dependence without resulting in compensatory smoking. These analyses extend those findings to a vulnerable population of interest, those with comorbid psychiatric disorders. Cigarettes with very low nicotine content were less reinforcing, decreased total puff volume, and produced significant but lower magnitude and shorter duration reductions in craving and withdrawal than higher doses. These nicotine dose effects did not interact with psychiatric diagnosis or mood symptom severity suggesting that smokers in this vulnerable population would respond to a nicotine reduction strategy similarly to other smokers.

Examining Age as a Potential Moderator of Response to Reduced Nicotine Content Cigarettes in Vulnerable Populations.

INTRODUCTION: Young adults (aged 18-24 years) have a higher smoking prevalence than younger and older age groups and young adulthood is an important developmental period during which long-term behavior patterns like cigarette smoking are established. The aim of the current study was to examine how young adult smokers with additional vulnerabilities to smoking respond to reduced nicotine content cigarettes. METHODS: This is a secondary analysis of a double-blind, within-subject experiment conducted with 169 cigarette smokers recruited from populations with comorbid psychiatric conditions or socioeconomic disadvantage assessing acute effects of research cigarettes varying in nicotine content (0.4, 2.4, 5.2, 15.8 mg/g). Participants were dichotomized by chronological age (18-24 vs. ≥25 years). Across 14 laboratory sessions effects of nicotine content were examined on measures of relative reinforcing efficacy (Cigarette Purchase Task [CPT] and Concurrent Choice testing), subjective effects, craving/withdrawal, and smoking topography. Repeated measures analysis of variances were used to examine potential moderating effects of age. RESULTS: Young adults exhibited lower demand for reduced nicotine content cigarettes than older adults across three of five CPT indices (ps < .05). No differences by age were observed on other measures of reinforcing efficacy, subjective effects, craving/withdrawal, or smoking topography where effects generally decreased as an orderly function of decreasing nicotine content (ps <.05). CONCLUSION: Overall, these findings suggest that reducing the nicotine content of cigarettes would decrease the addiction potential of cigarette smoking in young adult smokers as much or perhaps more than older adult smokers from populations at increased vulnerability to smoking, addiction, and smoking-related health consequences. IMPLICATIONS: Reducing the nicotine content in cigarettes to lower addiction potential of smoking has been proposed as a means to improve overall population health. It is imperative to examine how young adults may respond to a nicotine reduction policy. We saw minimal evidence that age moderates acute response and where there was evidence it was in the direction of reduced nicotine content cigarettes having less addictive potential among young versus older adults (eg, steeper decreases in demand for very low nicotine content cigarettes among young versus older adults). Overall, a nicotine reduction policy has the potential to reduce smoking across age groups.