Objective Cannabis policy, public perception, and consumption patterns have undergone enormous shifts, yet the scientific understanding of these changes has lagged. Our objective is to describe how human behavioral pharmacology studies provide a rigorous framework for modelling Cannabis Use Disorder (CUD) and for informing the development of treatment approaches. Methods This narrative review synthesizes insights from over 25 years of human laboratory research, highlighting how behavioral pharmacology, e.g., dose, placebo control, behavioral specificity, inform the development of evidence-based therapies and targeting the behavioral drivers of CUD. Results Key takeaways: (1) Cannabis potency is not Δ9-tetrahydrocannabinol dose. Participants adjust inhalation patterns as a function of cannabis strength. (2) Placebo responding is robust even among experienced cannabis smokers; placebo-controlled studies are limited by regulatory barriers but are essential to distinguish pharmacological effects from expectancy. (3) How medications alter CUD-relevant behaviors (reinforcement, misuse-related ratings) and non-specific behaviors (e.g., sedation) portend clinical efficacy and tolerability and vary as a function of participant phenotype. Conclusions Rigorous, placebo-controlled human laboratory studies of the behavioral effects of cannabis are essential to informing a quickly evolving field complicated by the complexity of cannabis as a plant with a myriad of active constituents, regulatory hurdles, and industry narrative.
OBJECTIVE:To evaluate whether adverse childhood experiences (ACEs) and resilience assessed during routine prenatal care were associated with same-day mental health referral. METHODS:We conducted a retrospective cohort study of 52,527 pregnant individuals aged ≥18 years in Kaiser Permanente Northern California whose pregnancies began between January 1, 2022, and June 1, 2024, lasted ≥20 weeks, and included ACEs screening. All data were accessed via the electronic health record (EHR). ACEs were categorized as zero, one, two-three, or ≥ four; Road to Resilience scores as low (<15) or normal/high (≥15). The primary outcome was same-day EHR-documented referral; sensitivity analyses assessed referral within 14 days. Modified Poisson regression estimated adjusted prevalence ratios (aPRs) and confidence intervals (CIs), controlling for patient, clinician, and facility characteristics. RESULTS:Overall, 1.4% received same-day referral. Same-day referral increased with one ACE (aPR = 1.45, 95% CI:1.14,1.84), two-three ACEs (aPR = 2.08, 95% CI:1.67,2.59), and ≥ four ACEs (aPR = 3.39, 95% CI:2.78,4.13; p-trend<0.0001). Low resilience was also associated with referral (aPR = 2.28, 95% CI:1.93,2.68). CONCLUSIONS:ACE and resilience scores were associated with prenatal mental health referral even after adjusting for existing mental health risk factors.
OBJECTIVE:The current cervix-focused screening paradigm in systemic lupus erythematosus (SLE) may underestimate extra-cervical anogenital cancer risk. This meta-analysis aimed to quantify the risk of human papillomavirus (HPV) infection and HPV-associated cancers in SLE patients. METHODS:A comprehensive search was conducted in PubMed (2010), Embase (2010), and Cochrane Library (2010) to August 8, 2025. Odds Ratios (ORs) and Standardized Incidence Ratios (SIRs) with 95% Confidence Intervals (CIs) were calculated. The study protocol was registered with PROSPERO (CRD420251122192). RESULTS:SLE was associated with significantly increased odds of HPV infection (OR = 4.12, 95% CI 2.03, 8.32). We further assessed the risk of HPV-associated malignancies in SLE patients. SLE patients exhibited substantially elevated risks across multiple HPV-associated cancers (SIR = 1.90, 95% CI 1.51, 2.38). The risk of cervical cancer was more than doubled (SIR = 2.25, 95% CI 1.75, 2.89). Notably, even higher risks were observed for extra-cervical anogenital cancers, namely vulvar/vaginal cancers (SIR = 5.60, 95% CI 3.71, 8.43). CONCLUSIONS:SLE is associated with elevated risks of HPV infection and a broad spectrum of HPV-associated cancers. Subgroup analyses suggested that cyclophosphamide use, multiple sexual partners, and Asian populations may constitute higher-risk subgroups. These findings highlight the need for additional prospective evidence to better characterize HPV-associated cancer risks in SLE patients.
OBJECTIVE:Electronic cigarettes (e-cigarettes) have risen in popularity in the U.S. While e-cigarettes have shown promise as a viable smoking cessation aid, e-cigarette use is also associated with negative health consequences. Withdrawal from e-cigarettes may provide a barrier to quitting use; however, there is limited empirical research on the timecourse and experience of e-cigarette withdrawal. METHODS:Sixteen regular e-cigarette users completed a seven day, monitored abstinence period in Baltimore, MD (January 2024-May 2025). During this time, measures of withdrawal-induced desire to use and anticipated relief, craving for e-cigarettes, and behavioral economic demand for e-cigarettes were taken at four daily timepoints. These measures were compared to each participants' baseline when they were using e-cigarettes as normal. RESULTS:Desire to use and anticipated relief on the Questionnaire of Smoking Urges showed a significant reduction beginning on Study Day 4, craving measures showed significant changes (consistent with reduced craving) beginning on Study Day 3, and reduced demand for e-cigarettes began on Study Day 2. All changes remained significantly different from baseline through discharge after one week. CONCLUSIONS:These findings indicate that e-cigarette withdrawal symptoms follow a relatively rapid trajectory and has implications for understanding barriers to e-cigarette cessation.
The Maternal Opioid Treatment: Human Experimental Research (MOTHER) study was a rigorous randomized controlled trial that compared methadone and buprenorphine for the treatment of pregnant women with opioid use disorder. Since the primary outcomes were published in 2010, this study has served as a cornerstone of the evidence base guiding both clinical practice and national and international health policy. This commentary examines MOTHER's contributions to the global policy landscape and also traces the scholarly advances it catalyzed, including advances in neonatal abstinence syndrome research, landmark pharmacoepidemiological studies, and innovations in medication delivery, among others. As such, MOTHER is among the most influential clinical trials in addiction medicine and perinatal research and an excellent example of the contributions of behavioral pharmacology, the field concerned with the physiological and behavioral mechanisms by which drugs operate, encompassing not only the effects of drugs on behavior but also how behavioral factors contribute to the actions of drugs and the ways in which they are used, to advancing addiction science.
OBJECTIVE:Alcohol and smoking are established carcinogens; however, evidence on adolescent exposure during mammary development on breast cancer risk remains inconsistent. This study assessed the associations between adolescent alcohol intake, smoking, and adult breast cancer risk. METHODS:A systematic search of PubMed/MEDLINE (1966), Web of Science (1900), and Scopus (1970) from inception to September 2025 identified 31 eligible studies (eleven on alcohol, twenty on smoking). Pooled relative risks (RRs) with 95% confidence intervals (CIs) were estimated using random-effects models. RESULTS:No overall association was observed between adolescent alcohol consumption and breast cancer risk (RR = 1.11, 95% CI: 0.93, 1.33). Although alcohol initiation at ≤15 years was associated with higher risk in subgroup analyses, evidence was inconsistent. Adolescent smoking was associated with increased breast cancer risk (RR = 1.12, 95% CI: 1.05, 1.19). The certainty of evidence was very low for both exposures. CONCLUSIONS:Adolescent smoking was associated with a modest increase in breast cancer risk, whereas no clear association was observed for adolescent alcohol consumption. These findings highlight the potential value of smoking prevention during adolescence. However, the very low certainty of evidence warrants cautious interpretation, and future prospective studies are needed to disentangle adolescent behaviours from lifetime exposures.
OBJECTIVE:Public support for nutrition policies depends on beliefs about responsibility for dietary behaviour. We explored how perceptions of responsibility for healthy and sustainable eating relate to policy acceptability in a representative German sample. METHODS:Cross-sectional survey data were collected online (December 2023-January 2024). Participants rated the responsibility of the state, individuals, cafeterias, food industry, and parents for healthy and sustainable eating among adults and children, and the acceptability of nutrition policies. K-means cluster analyses identified patterns of responsibility attribution across four domains: adult health, adult sustainability, child health, and child sustainability. Differences in demographics and acceptability were assessed using χ2 tests, t-tests, and linear regression. RESULTS:Among 2001 participants, individuals were perceived as most and the state as least responsible for dietary behaviour. Two clusters emerged: a "Shared Responsibility" cluster assigning responsibility to all actors and a "Directed Responsibility" cluster assigning responsibility to industry (adult sustainability) or individuals/parents (other domains). Compared with the Directed Responsibility cluster, participants in the Shared Responsibility cluster reported greater policy acceptability (b = 0.45-0.56, all p < .001). Directed Responsibility participants were older, reported poorer health, and differed politically. CONCLUSION:Emphasising shared responsibility for dietary behaviour may increase policy acceptability.
This analytic essay reviews the transition from unidimensional relative reinforcing efficacy to multidimensional behavioral economic demand analysis in drug reinforcement, focusing on tobacco science. It synthesizes operant laboratory studies in human smokers that use operant demand curve analysis. Reviewed studies used single- and concurrent-commodity sessions in which participants performed operant responses to earn the self-administration of controlled cigarettes puffs, and other commodities included money, and self-administration of denicotinized cigarette puffs, reduced-nicotine cigarette puffs, and nicotine gum. Unlike traditional measures purporting to assess relative reinforcing efficacy, demand curves showed multidimensional reinforcement. Operant demand studies resulted in findings relevant to tobacco science, therapeutics, and regulation. Despite greater demand for money at lower prices, cigarette puffs showed greater resistance to increasing prices. Denicotinized cigarette puffs were more effective substitutes (than nicotine gum) for nicotine-containing cigarettes. Reduced-nicotine and full-nicotine experimental cigarette exposure yielded modest, non-dose-dependent demand reductions. Greenwashing tactics increased demand intensity at low prices, enhancing unconstrained preference. Behavioral economic demand analysis offers a superior framework for understanding and assessing reinforcement over the concept of relative reinforcing efficacy. These findings underscore demand analysis as a versatile tool for investigating abuse liability, therapeutics, and tobacco regulatory science.
OBJECTIVE:Diabetic ketoacidosis (DKA) is a life-threatening complication of type 1 diabetes (T1D) and a marker of delayed diagnosis, associated with significant morbidity, mortality, and healthcare costs. Global estimates of DKA at T1D onset remain inconsistent. METHODS:We conducted a systematic review and meta-analysis, searching PubMed (1996), Web of Science (1966), Embase (1947), and Scopus (1980), each from its inception to October 2025, without restrictions. Studies reporting DKA prevalence at diagnosis in individuals <19 years with newly diagnosed T1D were included. Pooled prevalence was calculated using random-effects meta-analysis. Subgroup analyses explored variations by country, region, World Bank income level, and pre- versus post-COVID-19 period; meta-regression examined continuous moderators. RESULTS:A total of 233 studies from 58 countries (380,191 participants) were included. The pooled global prevalence was 41.9% (CI = 39.7, 44.0; I2 = 99.3%; prediction interval: 12.9, 74.3), ranging from 15.6% (Sweden) to 78.5% (Thailand). Rates were lower in high-income (38.6%) countries (p < 0.001). Younger age and higher female proportion were independently associated with higher prevalence. CONCLUSIONS:Approximately two in five children with new-onset T1D present in DKA. The rising trend is indicative of ongoing challenges in achieving timely diagnosis, demanding urgent public health strategies encompassing clinical vigilance and innovative early detection approaches.
OBJECTIVE:Adverse childhood experiences (ACEs) are important determinants of long-term health and behavior, but limited research has examined their association with household firearm ownership. METHODS:We analyzed data from the 2023 Behavioral Risk Factor Surveillance System in Nevada, New Jersey, Oregon, and Virginia. ACEs and household firearm ownership were self-reported. Weighted multivariable logistic regression was performed to examine the associations. RESULTS:This study included 15,771 participants, of whom 4739 (30.1%, unweighted) self-reported household firearm ownership. Compared with individuals reporting no ACEs, those with 1-2 types of ACEs (adjusted odds ratio [aOR]: 1.21, 95% CI: 1.06, 1.39), 3-5 types of ACEs (aOR: 1.24, 95% CI: 1.06, 1.46), and 6 or more types of ACEs (aOR: 1.30, 95% CI: 1.02, 1.65) had higher odds of household firearm ownership. Among specific types of ACEs, household illegal drug use (aOR: 1.37, 95% CI: 1.13, 1.66), household incarceration (aOR: 1.28, 95% CI: 1.02, 1.59), and verbal abuse (aOR: 1.20, 95% CI: 1.06, 1.36) were each associated with increased likelihood of household firearm ownership. CONCLUSIONS:In these four states, ACEs were positively associated with household firearm ownership, suggesting early-life adversity may shape firearm-related behaviors and highlight its relevance for public health interventions.
OBJECTIVE:This study aimed to examine whether employment transitions are associated with within-person variation in binge drinking and whether unemployment insurance may buffer this risk. METHODS:Using 19 waves of data from the Understanding America Study (May 2020-March 2021; N = 1710) in the United States, mixed-effects models examined within-person associations between employment transitions and binge drinking days. Postestimation contrasts evaluated restorative changes associated with upward employment transitions. RESULTS:Shifts from secure employment to underemployment (β = 0.033, p < .10) or unemployment without benefits (β = 0.055, p < .10) were associated with more binge drinking. Loss of benefits while unemployed (β = 0.130, p < .05) and remaining unemployed without benefits (β = 0.083, p < .01) were also associated with more binge drinking. Patterns consistent with restorative changes were observed only for shifts to secure employment and not for those involving underemployment. Gaining unemployment benefits while unemployed was also associated with less binge drinking, compared to remaining unemployed without benefits (β = -0.116, p < .05). CONCLUSIONS:Employment transitions are differentially associated with binge drinking. Underemployment may represent a distinct state for alcohol-related risk, and unemployment insurance may mitigate binge drinking during employment insecurity.
E-cigarettes are an effective way to stop smoking but there is disagreement regarding their use as treatment. One concern is that recommending e-cigarettes for adults who smoke (AWS) could result in sustained dual use of both products among those who fail to quit smoking. Given most quit attempts end in failure, it is important to understand the likelihood of developing dual use and its consequences when considering e-cigarettes for AWS. We describe variability in dual use within a behavioral economics framework, including literature which addresses the likelihood that trying to quit smoking with e-cigarettes will lead to established dual use as well as the impact that dual use has on smoking heaviness and smoking cessation. Limited evidence suggests that a meaningful minority of AWS who initiate e-cigarettes with support to quit smoking establish dual use. Compared to exclusive smoking, dual use appears to be associated with an overall reduction in smoking and an increase in the likelihood of cessation. However, outcomes appear to vary based on substitutive versus complementary use patterns, with the potential for dual use to lead to sustained or increased smoking for a small proportion of AWS who initiate e-cigarettes. Compared to exclusive smoking, developing dual use is likely associated with reduced smoking for the majority of AWS, providing further support for including e-cigarettes as a smoking cessation treatment option. Future prospective and controlled research is needed to explore predictors of developing substitutive versus complementary patterns of dual use and subsequent smoking cessation.
OBJECTIVE:To estimate the association between maternal exposure to Head Start and offspring mental health. METHODS:In this retrospective cohort study using a difference-in-differences approach, we leveraged the quasi-random rollout of Head Start in the United States in the 1960's and the timing of birth cohorts in the National Longitudinal Survey of Youth 1979 to estimate associations between maternal Head Start exposure and offspring depression (among those aged 15+ in years 1994-2020) and suicidal ideation (among those aged 15+ in years 2012-2020). We examined heterogeneity by offspring race, ethnicity, and sex. RESULTS:Maternal Head Start exposure was associated with 0.79 (95% CI = 0.62, 0.99) times the risk of depression among female Hispanic/Latina offspring and 0.66 (95% CI = 0.50, 0.87) times the risk of depression among female White offspring. We found null associations for other races, ethnicities, and males, and for the outcome of suicidal ideation. CONCLUSIONS:Maternal Head Start exposure may meaningfully reduce risk of depression among Hispanic/Latina and White female offspring-groups who tend to report higher risk of depression. POLICY IMPLICATIONS:Findings suggest social policies that invest in the social, economic, and human capital of vulnerable children can improve mental health outcomes across generations.
OBJECTIVE:To examine whether objective audiometric hearing loss and subjective hearing difficulty show differential associations with depressive symptoms in a nationally representative Korean population. METHODS:Data were obtained from 6589 participants aged ≥40 years in the Korea National Health and Nutrition Examination Survey (2020 and 2022). Hearing status was classified into four groups based on pure-tone audiometry (≥26 dB HL at 0.5-4 kHz in the better ear) and self-reported hearing difficulty. Depressive symptoms were defined as a Patient Health Questionnaire-9 (PHQ-9) score ≥ 10, with symptom-level analyses conducted for each PHQ-9 item. Survey-weighted logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS:Overall, 4.3% of participants had depressive symptoms. Compared with normal hearing, participants with subjective hearing difficulty but no audiometric hearing loss had higher odds of depressive symptoms (OR = 1.74, 95% CI = 1.01, 3.00). Symptom-level analyses showed significant associations between subjective hearing difficulty without audiometric loss and psychomotor changes, suicidal ideation, concentration difficulties, low self-esteem, and appetite changes. CONCLUSIONS:Subjective hearing difficulty, even without audiometric loss, was associated with depressive symptoms. As an easily ascertainable measure, it may represent a marker of vulnerability to depressive symptoms and may warrant consideration in mental health screening.
OBJECTIVES:This umbrella review tested the hypothesis that increased sedentary time and behaviours (e.g., television viewing) would be associated with increased risk in all-cause mortality, even when accounting for physical activity and measured using device-based and self-report measures. METHODS:Reviews were included if they conducted a systematic review and/or meta-analysis on the impact of sedentary time/behaviours on all-cause mortality in adults. Sources were searched from inception-March 2025 and included Scopus, EMBASE, MEDLINE, CINAHL, and Academic Search Premier with no date restrictions applied. The Joanna Briggs Institute and Risk of Bias in Systematic Reviews tools assessed study quality and PRISMA reporting were followed. RESULTS:Thirty reviews (n = 83 unique studies, n = 2,778,595 unique participants) were included and investigated total sedentary time (n = 28, meta-analyses n = 17) and television viewing time (n = 7, meta-analyses n = 7). Average study quality was 9.6 ± 1.6/11.0. n = 29/30 observed a positive relationship between sedentary time or television viewing time with all-cause mortality. Results remained significant but were attenuated after accounting for physical activity. Results were consistent across studies using self-report and device-based sedentary measures. CONCLUSION:This umbrella review of high-quality reviews provides evidence that increased sedentary time and television viewing represent a unique risk for all-cause mortality, even when accounting for physical activity.
OBJECTIVE:Human papillomavirus (HPV) causes oropharyngeal, anal, and penile cancers in men. In 2019, HPV vaccination for boys was included in Denmark's free-of-charge childhood vaccination program. This study examines sociodemographic and parental health factors associated with HPV vaccine initiation among Danish boys. METHODS:This nationwide, register-based cohort study included all boys living in Denmark and born July 2007-December 2010 (n = 113,519), representing the first eligible cohorts. Boys were followed up until December 2024, and vaccine initiation within 12 months after their 12th birthday was identified through national registers, which also provided sociodemographic factors and parental medical conditions. Logistic regression estimated odds ratios (ORs) and 95% confidence intervals (CIs) for associations with vaccine initiation. RESULTS:Prevalence of HPV vaccine initiation was 79.5%. Uptake was lower among boys of immigrant origin (OR = 0.85; 95%CI: 0.79, 0.90) and those not living with both legal parents. Uptake was higher among boys from families with higher education (OR = 1.29; 95%CI: 1.23, 1.35), higher income (OR = 1.95; 95%CI: 1.85, 2.05), or a parental history of cancer or HPV-associated precancer (OR = 1.11; 95%CI: 1.06, 1.17). CONCLUSIONS:Most eligible Danish boys initiate HPV vaccination. Social disparities persist despite universal free access, and key predictors of uptake were ethnicity, family structure, and socioeconomic status.
OBJECTIVE:This study aimed to assess vaccination coverage among individuals receiving HIV pre-exposure prophylaxis (PrEP). METHODS:A systematic review and meta-analysis were conducted following PRISMA guidelines. PubMed, Scopus, and Web of Science were searched from January 2011 to March 2026. Studies assessing vaccination coverage among individuals receiving PrEP within routine care were included. Random-effects meta-analyses were performed for each vaccine, and subgroup analyses were conducted when adequate data were available. RESULTS:Twenty-four studies including 13,087 individuals were analysed. Vaccination coverage was highest for HBV (73.00%, 95% CI [59.00, 88.00]), followed by Monkeypox (61.00%, 95% CI [40.00, 83.00]) and HAV (59.00%, 95% CI [48.00, 71.00]), and lowest for HPV (43.00%, 95% CI [34.00, 52.00]). Evidence on other vaccines was limited. High heterogeneity was observed across studies, and vaccination status was frequently self-reported (63.00%). No consistent geographical pattern emerged. CONCLUSIONS:Vaccination coverage among individuals receiving PrEP remains relatively low across most key vaccines, highlighting missed opportunities for prevention. Strengthening the integration of vaccination within PrEP care pathways and enhancing proactive provider engagement are key priorities. Future efforts should focus on high-quality primary studies, standardized methodologies, evaluation of targeted interventions, and economic evidence to better inform policy decisions.
