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The purpose of the present study was to evaluate the efficacy of rapastinel, an allosteric modulator of NMDA receptor function, to accelerate the loss of opioid withdrawal symptoms and blunt or prevent relapse to morphine conditioned place preference (CPP) in rats. Two studies were conducted. In study 1, adult and adolescent male and female rats were treated with increasing doses of morphine (5 mg/kg, bid to 25 mg/kg bid) for 5 days. On day 6 animals were treated with naloxone (1 mg/kg) and withdrawal was assessed. They were then treated with saline or rapastinel (5 mg/kg) on days 6 and 8, and withdrawal was assessed on day 9. Rapastinel treated animals exhibited significantly lower levels of withdrawal signs on day 9. No sex or age differences were observed. In Study 2, CPP for morphine was established in adult rats (males and females) by 4 daily pairings with saline and morphine (am/pm alternation). They were tested for CPP on day 5, and then treated with rapastinel (5 mg/kg) or saline daily on days 6-10 of extinction. On day 11 they received a final dose of rapastinel or saline followed by extinction trial. On day 12, animals received 1 mg/kg of morphine and were tested for relapse. Rapastinel did not affect extinction of CPP, but rapastinel-treated animals spent significantly less time in the previously morphine-paired side than saline-treated animals during the relapse trial. These findings of accelerated loss of withdrawal signs and blunted relapse to CPP suggest that rapastinel could provide an adjunctive therapy for opioid dependence during initiation of pharmacotherapy for opioid dependence., Competing Interests: Declaration of competing interest Drs. Kuhn and Patkar have a patent pending on use of rapastinel in treating drug dependence. The other authors have no interests to declare., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Objective: The genetic background of mood disorders is gradually emerging through the use of large multicenter samples but a detailed phenotyping is complementary in elucidating the role of modulating variants., Methods: In the present paper we focused on the possible modulatory effects of ARC gene variants on two independent mood disorder samples of European (n = 246 bipolar disorder) and Korean (n = 132 bipolar disorder; n = 242 major depressive disorder [MDD]) ancestry., Results: No result survived Bonferroni correction, however we evidenced promising trend toward possible association between ARC gene variants and mood disorder phenotypes. In particular, we evidenced weak correlations of ARC single nucleotide polymorphisms with depressive symptoms severity (evaluated through Hamilton depression rating scale scores) in the MDD Korean (rs7465272) and European (rs11167152) samples. Additionally rs10110456 was found to be related to Family History, while rs7465272 was related to suicide risk in the Korean sample. Finally, rs7465272 was associated with body mass index in the European sample., Conclusion: Overall, ARC gene variants may have a partial role in modulatory effect on treatment efficacy or phenotypes of mood disorders. Further studies, on larger samples may provide a better understanding on the role of ARC gene variants in the symptom severity and treatment outcomes in patients with mood disorders.

Background : SBIRT (Screening, Brief Intervention, and Referral to Treatment) is an effective early intervention approach for individuals with substance misuse. The purpose of this study was to determine if medical learners are more adept at learning a brief substance use intervention compared to non-medical learners (e.g., social work students). The dissemination of SBIRT training among many helping professions can increase service delivery for substance use problems. Methods : A total of 2,488 participants completed SBIRT training, representing 15 different disciplines and over 20 different institutions. General linear models and paired t -tests were used to investigate the effects of SBIRT training on changes in knowledge and attitude of alcohol and drug use and satisfaction. Results : There were no statistical differences in the change of satisfaction, knowledge, and attitude between medical and non-medical discipline participants. Both medical and non-medical participants had greater improvement in attitude and knowledge scores post-training. Similar improvements in attitude, knowledge, and satisfaction were observed in all the health-care discipline participants. Discussion : SBIRT skills may be transferable to disciplines including non-prescribing professionals (e.g., social work, nursing, physical therapy, rehabilitation science, and pharmacy). In an effort to expand treatment, health-care training institutions adopt SBIRT as a core competency for professional practice.

Background: The national mandate for health systems to transition from ICD-9-CM to ICD-10-CM in October 2015 has an impact on research activities. Clinical phenotypes defined by ICD-9-CM codes need to be converted to ICD-10-CM, which has nearly four times more codes and a very different structure than ICD-9-CM., Methods: We used the Centers for Medicare & Medicaid Services (CMS) General Equivalent Maps (GEMs) to translate, using four different methods, condition-specific ICD-9-CM code sets used for pragmatic trials (n=32) into ICD-10-CM. We calculated the recall, precision, and F score of each method. We also used the ICD-9-CM and ICD-10-CM value sets defined for electronic quality measure as an additional evaluation of the mapping methods., Results: The forward-backward mapping (FBM) method had higher precision, recall and F-score metrics than simple forward mapping (SFM). The more aggressive secondary (SM) and tertiary mapping (TM) methods resulted in higher recall but lower precision. For clinical phenotype definition, FBM was the best (F=0.67), but was close to SM (F=0.62) and TM (F=0.60), judging on the F-scores alone. The overall difference between the four methods was statistically significant (one-way ANOVA, F=5.749, p=0.001). However, pairwise comparisons between FBM, SM, and TM did not reach statistical significance. A similar trend was found for the quality measure value sets., Discussion: The optimal method for using the GEMs depends on the relative importance of recall versus precision for a given use case. It appears that for clinically distinct and homogenous conditions, the recall of FBM is sufficient. The performance of all mapping methods was lower for heterogeneous conditions. Since code sets used for phenotype definition and quality measurement can be very similar, there is a possibility of cross-fertilization between the two activities., Conclusion: Different mapping approaches yield different collections of ICD-10-CM codes. All methods require some level of human validation.

Aims: To evaluate the safety and efficacy of buprenorphine implants (BI) versus placebo implants (PI) for the treatment of opioid dependence. A secondary aim compared BI to open-label sublingual buprenorphine/naloxone tablets (BNX)., Design: Randomized, double-blind, placebo-controlled trial. Subjects received either four buprenorphine implants (80 mg/implant) (n = 114), four placebo implants (n = 54) or open-label BNX (12-16 mg/day) (n = 119)., Setting: Twenty addiction treatment centers., Participants: Adult out-patients (ages 18-65) with DSM-IV-TR opioid dependence., Measurements: The primary efficacy end-point was the percentage of urine samples negative for opioids collected from weeks 1 to 24, examined as a cumulative distribution function (CDF)., Findings: The BI CDF was significantly different from placebo (P < 0.0001). Mean [95% confidence interval (CI)] proportions of urines negative for opioids were: BI = 31.2% (25.3, 37.1) and PI = 13.4% (8.3, 18.6). BI subjects had a higher study completion rate relative to placebo (64 versus 26%, P < 0.0001), lower clinician-rated (P < 0.0001) and patient-rated (P < 0.0001) withdrawal, lower patient-ratings of craving (P < 0.0001) and better subjects' (P = 0.031) and clinicians' (P = 0.022) global ratings of improvement. BI also resulted in significantly lower cocaine use (P = 0.0016). Minor implant-site reactions were comparable in the buprenorphine [27.2% (31 of 114)] and placebo groups [25.9% (14 of 54)]. BI were non-inferior to BNX on percentage of urines negative for opioids [mean (95% CI) = 33.5 (27.3, 39.6); 95% CI for the difference of proportions = (-10.7, 6.2)]., Conclusions: Compared with placebo, buprenorphine implants result in significantly less frequent opioid use and are non-inferior to sublingual buprenorphine/naloxone tablets., (© 2013 Society for the Study of Addiction.)

Background: In opioid dependent youth there is substantial attrition from medication-assisted treatment. If youth at risk for attrition can be identified at treatment entry or early in treatment, they can be targeted for interventions to help retain them in treatment., Methods: Opioid dependent adolescents and young adults (n=152), aged 15-21, were randomized to 12 weeks (BUP, n=74) or 2 weeks of detoxification (DETOX, n=78) with buprenorphine/naloxone (Bup/Nal), both in combination with 12 weeks of psychosocial treatment. Baseline and early treatment related predictors of treatment attrition were identified in each group using bivariate and multivariate logistic regression., Results: In the DETOX group 36% left between weeks 2 and 4, at the end of the dose taper, while in the BUP group only 8% left by week 4. In the BUP group, early adherence to Bup/Nal, early opioid negative urines, use of any medications in the month prior to treatment entry, and lifetime non-heroin opioid use were associated with retention while prior 30-day hallucinogen use was associated with attrition. In the DETOX group, only use of sleep medications was associated with retention although not an independent predictor. A broad range of other pre-treatment characteristics was unrelated to attrition., Conclusions: Prompt attention to those with early non-adherence to medication or an early opioid positive urine, markers available in the first 2 weeks of treatment, may improve treatment retention. Extended Bup/Nal treatment appeared effective in improving treatment retention for youth with opioid dependence across a wide range of demographics, and pre-treatment clinical characteristics., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

Psychostimulant abuse continues to present legal, socioeconomic and medical challenges as a primary psychiatric disorder, and represents a significant comorbid factor in major psychiatric and medical illnesses. To date, monotherapeutic drug treatments have not proven effective in promoting long-term abstinence in psychostimulant abusers. In contrast to clinical trials utilizing monotherapies, combinations of dopamine (DA) agonists and selective 5-HT(3), 5HT(2A/2C), or NK(1) antagonists have shown robust efficacy in reversing behavioral and neurobiological alterations in animal models of psychostimulant abuse. One important temporal requirement for these treatments is that the 5-HT or NK(1) receptor antagonist be given at a critical time window after DA agonist administration. This requirement may reflect a necessary dosing regimen towards normalizing underlying dysfunctional neural circuits and "addiction memory" states. Indeed, chronic psychostimulant abuse can be conceptualized as a consolidated form of dysfunctional memory maintained by repeated drug- or cue-induced reactivation of neural circuit and subsequent reconsolidation. According to this concept, the DA agonist given first may reactivate this memory circuit, thereby rendering it transiently labile. The subsequent antagonist is hypothesized to disrupt reconsolidation necessary for restabilization, thus leading progressively to a therapeutically-mediated abolishment of dysfunctional synaptic plasticity. We propose that long-term abstinence in psychostimulant abusers may be achieved not only by targeting putative mechanistic pathways, but also by optimizing drug treatment regimens designed to disrupt the neural processes underlying the addicted state., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Background: Mixed depression reflects the occurrence of a major depressive episode with subsyndromal manic symptoms. Not recognized in DSM-IV, it is included in the proposed changes for DSM-5. Observational and cross-sectional studies have suggested that mixed depression is present in up to one-half of major depressive episodes, whether in MDD or bipolar disorder. Based on observational studies, antidepressants appear to be less effective, and neuroleptics more effective, in mixed than pure depression (major depressive episodes with no manic symptoms). In this report, we examine the specific manic symptoms that are most present in mixed depression, especially as they correlate with prospectively assessed treatment response., Methods: In 72 patients treated in a randomized clinical trial (ziprasidone versus placebo), we assessed the phenomenology of manic symptom type at study entry and their influence as predictors of treatment response., Results: The most common symptom presentation was a clinical triad of flight of ideas (60%), distractibility (58%), and irritable mood (55%). Irritable mood was the major predictor of treatment response. DSM-based diagnostic distinctions between MDD and bipolar disorder (type II) did not predict treatment response., Conclusion: In this prospective study, mixed depression seems to be most commonly associated with irritable mood, flight of ideas, and distractibility, with irritability being an important predictor of treatment outcome with neuroleptic agents. If these data are correct, in the presence of mixed depression, the DSM-based dichotomy between MDD and bipolar disorder does not appear to influence treatment response., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Objective: To examine the efficacy of ziprasidone vs. placebo for the depressive mixed state in patients with bipolar disorder type II or major depressive disorder (MDD)., Methods: 73 patients were randomized in a double-blinded, placebo-controlled study to ziprasidone (40-160 mg/d) or placebo for 6 weeks. They met DSM-IV criteria for a major depressive episode (MDE), while also meeting 2 or 3 (but not more nor less) DSM-IV manic criteria. They did not meet DSM-IV criteria for a mixed or manic episode. Baseline psychotropic drugs were continued unchanged. The primary endpoint measured was Montgomery-Åsberg Depression Rating Scale (MADRS) scores over time. The mean dose of ziprasidone was 129.7±45.3 mg/day and 126.1±47.1 mg/day for placebo., Results: The primary outcome analysis indicated efficacy of ziprasidone versus placebo (p = 0.0038). Efficacy was more pronounced in type II bipolar disorder than in MDD (p = 0.036). Overall ziprasidone was well tolerated, without notable worsening of weight or extrapyramidal symptoms., Conclusions: There was a statistically significant benefit with ziprasidone versus placebo in this first RCT of any medication for the provisional diagnostic concept of the depressive mixed state., Trial Registration: Clinicaltrials.gov NCT00490542.

Context: Limitations of existing pharmacological treatments for opioid dependence include low adherence, medication diversion, and emergence of withdrawal symptoms., Objective: To determine the efficacy of buprenorphine implants that provide a low, steady level of buprenorphine over 6 months for the treatment of opioid dependence., Design, Setting, and Participants: A randomized, placebo-controlled, 6-month trial conducted at 18 sites in the United States between April 2007 and June 2008. One hundred sixty-three adults, aged 18 to 65 years, diagnosed with opioid dependence. One hundred eight were randomized to receive buprenorphine implants and 55 to receive placebo implants., Intervention: After induction with sublingual buprenorphine-naloxone tablets, patients received either 4 buprenorphine implants (80 mg per implant) or 4 placebo implants. A fifth implant was available if a threshold for rescue use of sublingual buprenorphine-naloxone treatment was exceeded. Standardized individual drug counseling was provided to all patients., Main Outcome Measure: The percentage of urine samples negative for illicit opioids for weeks 1 through 16 and for weeks 17 through 24., Results: The buprenorphine implant group had significantly more urine samples negative for illicit opioids during weeks 1 through 16 (P = .04). Patients with buprenorphine implants had a mean percentage of urine samples that tested negative for illicit opioids across weeks 1 through 16 of 40.4% (95% confidence interval [CI], 34.2%-46.7%) and a median of 40.7%; whereas those in the placebo group had a mean of 28.3% (95% CI, 20.3%-36.3%) and a median of 20.8%. A total of 71 of 108 patients (65.7%) who received buprenorphine implants completed the study vs 17 of 55 (30.9%) who received placebo implants (P < .001). Those who received buprenorphine implants also had fewer clinician-rated (P <.001) and patient-rated (P = .004) withdrawal symptoms, had lower patient ratings of craving (P <.001), and experienced a greater change on clinician global ratings of severity of opioid dependence (P<.001) and on the clinician global ratings of improvement (P < .001) than those who received placebo implants. Minor implant site reactions were the most common adverse events: 61 patients (56.5%) in the buprenorphine group and 29 (52.7%) in the placebo group., Conclusion: Among persons with opioid dependence, the use of buprenorphine implants compared with placebo resulted in less opioid use over 16 weeks as assessed by urine samples., Trial Registration: clinicaltrials.gov Identifier: NCT00447564.

Objective: More must be learned about metabolic and biochemical alterations that contribute to the development and expression of drug dependence. Experimental opioid administration influences mechanisms and indices of oxidative stress, such as antioxidant compounds and purine metabolism. We examined perturbations of neurotransmitter-related pathways in opioid dependence (OD)., Methods: In this preliminary study, we used a targeted metabolomics platform to explore whether biochemical changes were associated with OD by comparing OD individuals (n = 14) and non-drug users (n = 10)., Results: OD patients undergoing short-term methadone detoxification showed altered oxidation-reduction activity, as confirmed by higher plasma levels of alpha- and gamma-tocopherol and increased GSH/GSSG ratio. OD individuals had also altered purine metabolism, showing increased concentration of guanine and xanthosine, with decreased guanosine, hypoxanthine and hypoxanthine/xanthine and xanthine/xanthosine ratios. Other drug use in addition to opioids was associated with partly different biochemical changes., Conclusions: This is a preliminary investigation using metabolomics and showing multiple peripheral alterations of metabolic pathways in OD. Further studies should explore the metabolic profile of conditions of opioid abuse, withdrawal and long-term abstinence in relation to agonist and antagonist treatment and investigate biochemical signatures of opioid substances and medications., (Copyright (c) 2009 John Wiley & Sons, Ltd.)

Context: The usual treatment for opioid-addicted youth is detoxification and counseling. Extended medication-assisted therapy may be more helpful., Objective: To evaluate the efficacy of continuing buprenorphine-naloxone for 12 weeks vs detoxification for opioid-addicted youth., Design, Setting, and Patients: Clinical trial at 6 community programs from July 2003 to December 2006 including 152 patients aged 15 to 21 years who were randomized to 12 weeks of buprenorphine-naloxone or a 14-day taper (detox)., Interventions: Patients in the 12-week buprenorphine-naloxone group were prescribed up to 24 mg per day for 9 weeks and then tapered to week 12; patients in the detox group were prescribed up to 14 mg per day and then tapered to day 14. All were offered weekly individual and group counseling., Main Outcome Measure: Opioid-positive urine test result at weeks 4, 8, and 12., Results: The number of patients younger than 18 years was too small to analyze separately, but overall, patients in the detox group had higher proportions of opioid-positive urine test results at weeks 4 and 8 but not at week 12 (chi(2)(2) = 4.93, P = .09). At week 4, 59 detox patients had positive results (61%; 95% confidence interval [CI] = 47%-75%) vs 58 12-week buprenorphine-naloxone patients (26%; 95% CI = 14%-38%). At week 8, 53 detox patients had positive results (54%; 95% CI = 38%-70%) vs 52 12-week buprenorphine-naloxone patients (23%; 95% CI = 11%-35%). At week 12, 53 detox patients had positive results (51%; 95% CI = 35%-67%) vs 49 12-week buprenorphine-naloxone patients (43%; 95% CI = 29%-57%). By week 12, 16 of 78 detox patients (20.5%) remained in treatment vs 52 of 74 12-week buprenorphine-naloxone patients (70%; chi(2)(1) = 32.90, P < .001). During weeks 1 through 12, patients in the 12-week buprenorphine-naloxone group reported less opioid use (chi(2)(1) = 18.45, P < .001), less injecting (chi(2)(1) = 6.00, P = .01), and less nonstudy addiction treatment (chi(2)(1) = 25.82, P < .001). High levels of opioid use occurred in both groups at follow-up. Four of 83 patients who tested negative for hepatitis C at baseline were positive for hepatitis C at week 12., Conclusions: Continuing treatment with buprenorphine-naloxone improved outcome compared with short-term detoxification. Further research is necessary to assess the efficacy and safety of longer-term treatment with buprenorphine for young individuals with opioid dependence., Trial Registration: clinicaltrials.gov Identifier: NCT00078130.

Objective: There is increasing concern about the use of multiple medications in populations with psychiatric illnesses. One large study reported that 99% of pregnant women had received a prescription for at least one medication during pregnancy, with a mean of 13.6 medications per woman. The present descriptive study examined patterns of medication use across pregnancy in a low socioeconomic status population of women who had a psychiatric illness as a primary diagnosis., Method: Data on 115 pregnant women were extracted from a Medicaid Database of 5,000 women who received prenatal and other medical care over a 2-year period (2002-2004). Subjects included women with bipolar disorder, schizoaffective disorder, and schizophrenia. Information on age, diagnoses, dates prescriptions were filled, and type, dose, and quantity of medications was recorded in the database., Results: Data were collected on 115 pregnancies; complete data throughout pregnancy were available for 75 women, while data on certain gestational months were available for the other 40 women. A majority of the 115 women were diagnosed with bipolar or schizoaffective disorder. Their mean age was 26 years. The mean number of medications taken during pregnancy was three (range 0-10; mode = 3); 26.8% of the pregnant women filled prescriptions for 6-10 medications during their pregnancy. No dose changes were made for the prescribed medications to accommodate changing metabolism across pregnancy. The most frequently prescribed medications for these psychiatrically ill women were from the opiate family., Conclusions: Multiple medications are frequently prescribed to pregnant women with psychiatric disorders because of comorbid diagnoses. However, the effects of taking multiple psychotropic or other medications during pregnancy on pregnancy outcome and fetal development are unknown. Therefore, more research is needed concerning the effects on the developing fetus of taking multiple medications with central nervous system effects during pregnancy.

Depression is the most common psychiatric complication after stroke. Its prevalence varies from 20% to 80%, and it is underdiagnosed and undertreated. It has significant impact on rehabilitation, motor recovery, activities of daily living, social and interpersonal life, and mortality. Several studies have shown that biological and psychosocial factors play significant roles in the development of this disabling disease. Recent research shows that neurochemical processes also may play some role in the pathophysiology of this condition. Several trials have shown evidence that the older, as well as newer antidepressants and psychostimulants may reduce/prevent depressive symptoms after stroke. At this point there are no clear guidelines available to choose safe and effective treatments. Drugs are selected based on their efficacy and side effect profile in these patients. More research is needed to understand the pathophysiology of depression after stroke. There also is a need for more randomized clinical trials to better treat patients with this condition.

This study evaluated the overall effectiveness and tolerability of atypical antipsychotics (risperidone vs. olanzapine vs. quetiapine) used in the treatment of bipolar inpatients. After screening 463 patients, the medical records of 158 inpatients with bipolar I disorder, who were given olanzapine, risperidone or quetiapine as adjuncts to mood stabilizers for at least 1 month and not administered with any other antipsychotics, were examined. Details of the tolerability and effectiveness were reviewed according to the treatment records during their hospital stay. The results showed equivalent effectiveness based on the Clinical Global Impression (CGI) and Global Assessment Functioning (GAF) score between the three atypical antipsychotics. The frequency of the extrapyramidal symptom-related side effects were higher in the risperidone-treated group than in the olanzapine and quetiapine-treated group. This suggests that risperidone, olanzapine and quetiapine have a comparable effectiveness in inpatients with bipolar I disorder in a naturalistic setting. However, there were some differences in tolerability between these results as reported from previous Western studies.

This study examined the relationship between a MnSOD gene (MnSOD) polymorphism (Ala-9Val) and mood disorders such as major depressive disorder (MDD) and bipolar I disorder (BD). Eighty patients with BD, 61 patients with MDD and 106 healthy controls were enrolled in this study and genotyped using a polymerase chain reaction-based method. The patients with MDD and BD, and the controls had a similar distribution of the genotypes and alleles in the Ala-9Val MnSOD polymorphism. The combined analysis (MDD plus BD) also failed to find any association between the Ala-9Val MnSOD polymorphism and mood disorders. Subgroup analyses according to the clinical variables such as the family history, age at onset, psychotic features and suicide history failed to identify any association with the Ala-9Val MnSOD polymorphism. This preliminary data suggests that at least in the Korean population, the Ala-9Val MnSOD polymorphism is not associated with the development of mood disorders or their clinical parameters. However, more study with a larger population sample will be needed.

We compared outcomes during and after treatment for mixed substance dependent patients (N=143) randomly assigned to a high-structure, behaviorally-oriented (HSB) or a low-structure, facilitative (LSF) individual counseling style. We hypothesized that patients with different coping characteristics would respond differently to the two styles of counseling. Patients were treated in once-weekly individual HSB or LSF counseling for up to 12 weeks. Outcome measures included patient and counselor ratings of benefit, retention, symptom reduction, and negative urines; follow-up assessments included control of substance use and psychosocial adjustment. While no differences in outcomes during or after treatment were found for the HSB and LSF patients, both groups did improve equally. Contrary to our hypothesis, our coping measures did not predict different outcomes for patients treated in the LSF and HSB styles. Post-hoc analyses, however, revealed that outcomes could be predicted in each style from patterns of pretreatment characteristics, which included measures of coping strategies, psychological characteristics, and treatment readiness. Moreover, the patterns associated with positive outcomes were different for the HSB and LSF patients: high treatment readiness was most important for success in HSB counseling, while low psychiatric severity and positive coping styles were important for the LSF clients. The finding of no HSB-LSF outcome differences calls into question the exclusive emphasis on behavioral treatment approaches by the present-day managed care industry. Also, the traditional approach to matching studies, ie, employing one patient characteristic at a time to predict differential outcomes for particular treatments, may be simplistic. An alternative approach employing multivariate statistical procedures to predict outcomes from several patient characteristics may hold more promise.

Background: Tobacco use remains the most preventable cause of death and disability in the United States. Public opinion regarding tobacco use is not only an important barometer of the likelihood of effective tobacco-control legislation, but also identifies ongoing public health educational needs. Because > 63,000 children become new smokers annually in Pennsylvania, we chose to evaluate the statewide public health tobacco perspective in order to help tailor future public policy interventions., Study Design and Setting: Registered voters were randomly contacted in a statewide telephone survey. To reduce response bias, an independent polling firm conducted the 643 structured interviews., Results: Most respondents were >or= 45 years old (55%), female (54%), and had at least some college education (62%). Twenty-eight percent (95% confidence interval [CI], 25 to 32%) were current tobacco users, and 38% (95% CI, 34 to 42%) had lost family members or friends to smoking-related disease. Ninety-two percent (95% CI, 90 to 94%) expressed "concern" about adolescent tobacco use, but only 46% (95% CI, 42 to 50%) believed that government needed to do more. Of respondents opposed to government involvement, 65% (95% CI, 61 to 68%) believed it was an improper role for government, or that there are more important non-health government priorities. When framed more personally, 80% (95% CI, 77 to 83%) indicated that elected officials have a responsibility to "dedicate a significant portion of tobacco settlement" to prevention. Still, 28% (95% CI, 25 to 32%) would oppose laws restricting smoking in establishments frequented by youth., Conclusions: Prior public health education initiatives have been effective in shaping the tobacco-related health concerns of Pennsylvania voters. As expected, the overwhelming majority of respondents are concerned about youth tobacco use and agree that money should be spent on tobacco-control initiatives. In contrast, many are reluctant to support "government" involvement in what is still seen as a personal issue. Future public health initiatives should focus on this dichotomy and should highlight the utility of an integrated policy approach to tobacco control.