Search

Subtropical gyre (STG) depth and strength are controlled by wind stress curl and surface buoyancy forcing1,2. Modern hydrographic data reveal that the STG extends to a depth of about 1 km in the Northwest Atlantic, with its maximum depth defined by the base of the subtropical thermocline. Despite the likelihood of greater wind stress curl and surface buoyancy loss during the Last Glacial Maximum (LGM)3, previous work suggests minimal change in the depth of the glacial STG4. Here we show a sharp glacial water mass boundary between 33° N and 36° N extending down to between 2.0 and 2.5 km—approximately 1 km deeper than today. Our findings arise from benthic foraminiferal δ18O profiles from sediment cores in two depth transects at Cape Hatteras (36–39° N) and Blake Outer Ridge (29–34° N) in the Northwest Atlantic. This result suggests that the STG, including the Gulf Stream, was deeper and stronger during the LGM than at present, which we attribute to increased glacial wind stress curl, as supported by climate model simulations, as well as greater glacial production of denser subtropical mode waters (STMWs). Our data suggest (1) that subtropical waters probably contributed to the geochemical signature of what is conventionally identified as Glacial North Atlantic Intermediate Water (GNAIW)5–7and (2) the STG helped sustain continued buoyancy loss, water mass conversion and northwards meridional heat transport (MHT) in the glacial North Atlantic.

Ketamine is a glutamate receptor antagonist that was developed over 50 years ago as an anesthetic agent. At subanesthetic doses, ketamine and some metabolites are analgesics and fast-acting antidepressants, presumably through targets other than glutamate receptors. We tested ketamine and its metabolites for activity as allosteric modulators of opioid receptors expressed as recombinant receptors in heterologous systems and with native receptors in rodent brain; signaling was examined by measuring GTP binding, β-arrestin recruitment, MAPK activation, and neurotransmitter release. Although micromolar concentrations of ketamine alone had weak agonist activity at μopioid receptors, the combination of submicromolar concentrations of ketamine with endogenous opioid peptides produced robust synergistic responses with statistically significant increases in efficacies. All three opioid receptors (μ, δ, and κ) showed synergism with submicromolar concentrations of ketamine and either methionine-enkephalin (Met-enk), leucine-enkephalin (Leu-enk), and/or dynorphin A17 (Dyn A17), albeit the extent of synergy was variable between receptors and peptides. S-ketamine exhibited higher modulatory effects compared with R-ketamine or racemic ketamine, with ∼100% increase in efficacy. Importantly, the ketamine metabolite 6-hydroxynorketamine showed robust allosteric modulatory activity at μopioid receptors; this metabolite is known to have analgesic and antidepressant activity but does not bind to glutamate receptors. Ketamine enhanced potency and efficacy of Met-enkephalin signaling both in mouse midbrain membranes and in rat ventral tegmental area neurons as determined by electrophysiology recordings in brain slices. Taken together, these findings support the hypothesis that some of the therapeutic effects of ketamine and its metabolites are mediated by directly engaging the endogenous opioid system.SIGNIFICANCE STATEMENTThis study found that ketamine and its major biologically active metabolites function as potent allosteric modulators of μ, δ, and κopioid receptors, with submicromolar concentrations of these compounds synergizing with endogenous opioid peptides, such as enkephalin and dynorphin. This allosteric activity may contribute to ketamine’s therapeutic effectiveness for treating acute and chronic pain and as a fast-acting antidepressant drug.

ObjectiveIn light of the current U.S. Food and Drug Administration (FDA) proposal to ban menthol cigarettes, this study updates trends in menthol cigarette use among adolescents age 13–18 years up to the year 2020. The study considers a potential role for the ban to reduce black/non-black disparities in menthol cigarette use, as well as a counterargument that a ban is not necessary because menthol use is already diminishing.MethodsData are from annual, cross-sectional, nationally representative Monitoring the Future (MTF) surveys of 85 547 8th, 10th and 12th grade students surveyed between 2012 and 2020. Analyses include trends in past 30-day menthol and non-menthol cigarette smoking among the total adolescent population, as well as stratified by race/ethnicity.ResultsDeclines in adolescent menthol and non-menthol cigarette smoking continued through 2020 so that in 2018–2020 past 30-day prevalence for each was less than 1% for non-Hispanic black adolescents and less than 2.2% for non-black adolescents. For non-Hispanic black adolescents no smoking declines in mentholated or non-mentholated cigarette use from 2015–2017 to 2018–2020 were statistically significant, in part because prevalence levels approached a floor effect and had little room to fall further. Menthol levels were lower for non-Hispanic black versus all other adolescents in all study years.ConclusionsContinuing declines in adolescent menthol prevalence indicate that both menthol prevalence and also black/non-black disparities in its use are steadily decreasing. However, these decreases in adolescence will take decades to reach later ages through generational replacement. Efforts to accelerate menthol decreases will require new initiatives to increase cessation among adult menthol users.

Acute environmental perturbations are reported to induce deterministic microbial community assembly, while it is hypothesized that chronic perturbations promote development of alternative stable states. Such acute or chronic perturbations strongly impact on the pre-adaptation capacity to the perturbation. To determine the importance of the level of microbial pre-adaptation and the community assembly processes following acute or chronic perturbations in the context of hydrocarbon contamination, a model system of pristine and polluted (hydrocarbon-contaminated) sediments was incubated in the absence or presence (discrete or repeated) of hydrocarbon amendment. The community structure of the pristine sediments changed significantly following acute perturbation, with selection of different phylotypes not initially detectable. Conversely, historically polluted sediments maintained the initial community structure, and the historical legacy effect of chronic pollution likely facilitated community stability. An alternative stable state was also reached in the pristine sediments following chronic perturbation, further demonstrating the existence of a legacy effect. Finally, ecosystem functional resilience was demonstrated through occurrence of hydrocarbon degradation by different communities in the tested sites, but the legacy effect of perturbation also strongly influenced the biotic response. This study therefore demonstrates the importance of perturbation chronicity on microbial community assembly processes and reveals ecosystem functional resilience following environmental perturbation.

Given the promise of the web push plus e-mail survey design for providing cost-effective and high-quality data (Patrick et al. 2018, 2019) as an alternative to a paper-and-pencil mailed survey design for the longitudinal Monitoring the Future (MTF) study, the current study sought to further enhance the web push condition. The MTF sample is based on US nationally representative samples of 12th grade students surveyed annually. The MTF control group for the current study included participants who completed the in-school baseline survey in the 12th grade and were selected to participate in their first follow-up survey in 2017 via mailed surveys (N= 1,222). A supplementary sample (N= ∼2,450) was assigned to one of the two sequential mixed-mode conditions. Those in condition 1 (N = 1,198), or mail push, were invited to complete mailed surveys and later given a web survey option. Those in condition 2 (N= 1,173), or enhanced web push, were invited to complete a web survey (the same as in the 2014 study, but with the addition of text messages and quick response (QR) codes and the web survey was optimized for mobile devices) and then later given a mailed survey option. Research aims were to examine response rates across conditions, as well as how responses were distributed across mode (paper, web), devices (computer, smartphone, table), and method of accessing the web survey (hand-entered URL, QR code, e-mail link, SMS link). Response rates differed significantly: the MTF control group was 34.2 percent, mail push was 35.4 percent, and enhanced web push was 42.05 percent. The higher response rate in the enhanced web push condition suggests that the additional strategies were effective at bringing in more respondents. Key estimates produced by the enhanced web push condition did not differ from those of the MTF control group.

AbstractFibromyalgia syndrome (FMS) is defined by chronic widespread pain persisting for more than 3 months without an apparent physical cause. The prevalence of FMS peaks between 50 and 70 years old, and it can be difficult to diagnose and treat due to other comorbid conditions. Recent work has suggested that neurodegenerative conditions can be complicated by chronic pain. This case study presents four patients with FMS residing in nursing homes. In all four cases, with the progression of Alzheimer’s disease, patients saw improvements in pain syndromes, albeit to different degrees, and marked improvements in mobility. All four patients also developed challenging behavioral and psychological symptoms of dementia requiring psychotropic prescriptions.

The influence of organic compounds on iodine (I2) emissions from the O3+ I–reaction at the sea surface was investigated in laboratory and modeling studies using artificial solutions, natural subsurface seawater (SSW), and, for the first time, samples of the surface microlayer (SML). Gas-phase I2was measured directly above the surface of liquid samples using broadband cavity enhanced absorption spectroscopy. I2emissions were consistently lower for artificial seawater (AS) than buffered potassium iodide (KI) solutions. Natural seawater samples showed the strongest reduction of I2emissions compared to artificial solutions with equivalent [I–], and the reduction was more pronounced over SML than SSW. Emissions of volatile organic iodine (VOI) were highest from SML samples but remained a negligible fraction (<1%) of the total iodine flux. Therefore, reduced iodine emissions from natural seawater cannot be explained by chemical losses of I2or hypoiodous acid (HOI), leading to VOI. An interfacial model explains this reduction by increased solubility of the I2product in the organic-rich interfacial layer of seawater. Our results highlight the importance of using environmentally representative concentrations in studies of the O3+ I–reaction and demonstrate the influence the SML exerts on emissions of iodine and potentially other volatile species.

ObjectiveAdolescent cigarette smoking declined steadily and substantially from 2000 to 2018. This paper considers the potential consequences of this ‘great decline’ for the prevalence of other drug use among adolescents.MethodsData are annual, cross-sectional, nationally representative Monitoring the Future surveys of more than 1.2 million US students in 12th, 10th and 8th grades from 2000 to 2018. Analyses include trends in the past 12 months’ non-medical amphetamine, tranquillisers and opioid use overall, among ever and never cigarette smokers, and projected if adolescent cigarette smoking levels had remained at 2000 levels.ResultsWithin groups of ever and never cigarette smokers, the prevalence for each of the three substances has either changed little or overall increased in 2018 as compared with 2000. When the two groups were combined into one pool, the overall prevalence for each of the drugs declined by about half. The decline resulted from the growing group of never smokers, whose levels of non-medical drug use over the study period were at least four times lower than the levels of ever smokers.ConclusionsThe results support the ‘gateway’ prediction that declines in cigarette smoking among adolescents pull downward their non-medical use of amphetamines, tranquillisers and opioids. Continuing to reduce adolescent smoking through policy and programmatic prevention efforts should have further positive spillover effects on adolescent drug use.

In the mid-1970s, an intense race to identify endogenous substances that activated the same receptors as opiates resulted in the identification of the first endogenous opioid peptides. Since then, >20 peptides with opioid receptor activity have been discovered, all of which are generated from three precursors, proenkephalin, prodynorphin, and proopiomelanocortin, by sequential proteolytic processing by prohormone convertases and carboxypeptidase E. Each of these peptides binds to all three of the opioid receptor types (μ, δ, or κ), albeit with differing affinities. Peptides derived from proenkephalin and prodynorphin are broadly distributed in the brain, and mRNA encoding all three precursors are highly expressed in some peripheral tissues. Various approaches have been used to explore the functions of the opioid peptides in specific behaviors and brain circuits. These methods include directly administering the peptides ex vivo (i.e., to excised tissue) or in vivo (in animals), using antagonists of opioid receptors to infer endogenous peptide activity, and genetic knockout of opioid peptide precursors. Collectively, these studies add to our current understanding of the function of endogenous opioids, especially when similar results are found using different approaches. We briefly review the history of identification of opioid peptides, highlight the major findings, address several myths that are widely accepted but not supported by recent data, and discuss unanswered questions and future directions for research.SIGNIFICANCE STATEMENTActivation of the opioid receptors by opiates and synthetic drugs leads to central and peripheral biological effects, including analgesia and respiratory depression, but these may not be the primary functions of the endogenous opioid peptides. Instead, the opioid peptides play complex and overlapping roles in a variety of systems, including reward pathways, and an important direction for research is the delineation of the role of individual peptides.

Older adults with frailty are at increased risk of premature death, and numerous negative sequalae including falls, disability, and dementia alongside increased healthcare costs. Most healthcare interactions for older people with frailty take place in primary care, and there is increasing interface working between primary and secondary care to manage this patient group including virtual wards, frailty management programmes and Hospital @ Home. This commentary aims to place proactive frailty into recent policy perspective, alongside highlighting some of the current challenges around the implementation of proactive frailty programmes.

Depression is a frequent diagnosis for people with dementia, with between 25% and 42% of such patients receiving antidepressants. The diagnosis can be challenging to make, and this patient group is more vulnerable to side effects of commonly used medications. This article outlines the diagnostic considerations and therapeutic approaches for managing depression in people with dementia.

Thrombosis is a frequent, life-threatening complication of systemic infection associated with multiple organ damage. We have previously described a novel mechanism of inflammation-driven thrombosis induced by Salmonella Typhimurium infection of mice. Thrombosis in the liver develops 7 days after infection, persisting after the infection resolves, and is monocytic cell dependent. Unexpectedly, thrombosis was not prominent in the spleen at this time, despite carrying a similar bacterial burden as the liver. In this study, we show that thrombosis does occur in the spleen but with strikingly accelerated kinetics compared with the liver, being evident by 24 hours and resolving rapidly thereafter. The distinct kinetics of thrombosis and bacterial burden provides a test of the hypothesis that thrombi form in healthy vessels to trap or remove bacteria from the circulation, often termed immunothrombosis. Remarkably, despite bacteria being detected throughout infected spleens and livers in the early days of infection, immunohistological analysis of tissue sections show that thrombi contain very low numbers of bacteria. In contrast, bacteria are present throughout platelet aggregates induced by Salmonella in vitro. Therefore, we show that thrombosis develops with organ-specific kinetics and challenge the universality of immunothrombosis as a mechanism to capture bacteria in vivo.

Invasions by insects introduced via international trade continue to cause worldwide impacts. Surveillance programs using traps baited with host volatiles and pheromones can detect incursions of nonnative species. We report on two experiments executed to determine if attractants for several insect species can be combined without compromising trap catches and detection ability of target species. In the first experiment, we tested the effect of bark beetle pheromones (plus α-pinene) and trap contact with foliage on trap catches of the brown marmorated stink bug Halyomorpha halysStål (Hemiptera: Pentatomidae) in traps baited with a mixture of bisabolenes and methyl (E,E,Z)-2,4,6-decatrienoate. Trap capture of H. halysadults was greater in traps not in contact with foliage, and the bark beetle pheromones ipsenol and ipsdienol did not affect trap capture of H. halys. In the second experiment, we tested the effects of multi-lure interactions among the primary host attractants α-pinene and ethanol, and the pheromones monochamol, ipsenol, ipsdienol, lanierone, and the H. halyscompounds, on trap captures of various forest and agricultural insect pests. Specifically, we targeted Monochamusspp. (Coleoptera: Cerambycidae), Ipsspp. (Coleoptera: Scolytinae) and H. halys. We found that a combination of all lures did not catch significantly lower numbers of Monochamus carolinensisOlivier, Monochamus scutellatusSay (Coleoptera: Cerambycidae), and Ips piniSay (Coleoptera: Scolytidae) than lure combinations missing components although removal of both lanierone and ipsdienol somewhat increased catches of Ips grandicollisEichhoff (Coleoptera: Curculionidae). Our results support the use of traps baited with a full combination of these attractants in surveillance programs. This should reduce costs and increase detection rates of a wider range of conifer forest pests and H. halys.

There are no licensed vaccines against Plasmodium vivax. We conducted two phase 1/2a clinical trials to assess two vaccines targeting P. vivaxDuffy-binding protein region II (PvDBPII). Recombinant viral vaccines using chimpanzee adenovirus 63 (ChAd63) and modified vaccinia virus Ankara (MVA) vectors as well as a protein and adjuvant formulation (PvDBPII/Matrix-M) were tested in both a standard and a delayed dosing regimen. Volunteers underwent controlled human malaria infection (CHMI) after their last vaccination, alongside unvaccinated controls. Efficacy was assessed by comparisons of parasite multiplication rates in the blood. PvDBPII/Matrix-M, given in a delayed dosing regimen, elicited the highest antibody responses and reduced the mean parasite multiplication rate after CHMI by 51% (n= 6) compared with unvaccinated controls (n= 13), whereas no other vaccine or regimen affected parasite growth. Both viral-vectored and protein vaccines were well tolerated and elicited expected, short-lived adverse events. Together, these results support further clinical evaluation of the PvDBPII/Matrix-M P. vivaxvaccine.

This study examined changes during the past decade, from 2005 to 2015, in binge and high‐intensity drinking in 7 separate age groups of U.S. 12th graders and young adults. National longitudinal data (N= 6,711) from Monitoring the Future were used to examine trends in consuming 5+, 10+, and 15+ drinks on the same occasion in the past 2 weeks from ages 18 to 29/30 overall and by gender. Results were compared with trends in past 12‐month and 30‐day alcohol use for the same age groups. Between 2005 and 2015, binge (5+) and high‐intensity drinking (10+, 15+) generally decreased for individuals in their early 20s, remained somewhat stable for individuals in their mid‐20s, and increased for individuals at the end of young adulthood (age 29/30). The observed historical trends in binge and high‐intensity drinking were similar to those for past 12‐month and past 30‐day alcohol use for those aged 18 to 20, but diverged for most other age groups in young adulthood. Trends were generally similar for men and women, except that the increase in prevalence began earlier in young adulthood for women than for men. Binge and high‐intensity drinking among U.S. 12th graders and young adults are dynamic phenomena. Prevention and intervention efforts aimed at reducing the harms resulting from 5+, 10+, and 15+ drinking should acknowledge and focus on differences in trends in these behaviors by age and gender. Between 2005 and 2015 among US young adults, participation in binge (5+ drinks per occasion) and high‐intensity (10+, 15+ drinks per occasion) drinking was highest for individuals aged 21/22 to 25/26. Binge and high‐intensity drinking generally decreased for individuals in their early 20s, remained somewhat stable during their mid‐20s, and increased at the end of young adulthood (ages 29/30). Trends were generally similar for men and women, but increases were observed at earlier ages for women than men.

Recent research suggests that memantine may have a beneficial role in treating chronic pain in patients with fibromyalgia syndrome (FMS). This study wished to assess whether patients with Alzheimer's disease (AD) and FMS prescribed memantine have improved pain control to those patients not receiving memantine. Nursing home patients with a diagnosis of AD and FMS were identified from one GP practice list in Arbroath, Scotland. Patients with another diagnosis that cause pain were excluded. Cognition was quantified and pain was assessed on a fortnightly basis for 4 months. Baseline cognitive and pain scores prior to treatment were also recorded. Ten patients with AD and FMS were identified. Four patients were excluded as they had other conditions causing pain. Three patients were prescribed memantine and three patients were prescribed donepezil. Baseline cognition and pain were similar between groups (prior to therapy), with lower pain scores and reduction for patients receiving memantine over the study period. This small research project, albeit with caveats, extends the findings to date that memantine may improve pain in patients with FMS, to those residing in nursing homes with diagnosis of AD.

ObjectiveTo prospectively examine vaping as a predictor of future cigarette smoking among youth with and without previous cigarette smoking experience. A secondary aim is to investigate whether vaping may desensitise youth to the dangers of smoking.MethodsAnalysis of prospective longitudinal panel data from the nationally representative Monitoring the Future study. The analysis is based on 347 12th grade students who were part of a randomly selected subsample that completed in-school surveys in 2014 and were resurveyed 1-year later.ResultsAmong youth who had never smoked a cigarette by 12th grade, baseline, recent vapers were more than 4 times (relative risk (RR)=4.78) more likely to report past-year cigarette smoking at follow-up, even among youth who reported the highest possible level of perceived risk for cigarette smoking at baseline. Among 12th grade students who had smoked in the past but had not recently smoked at baseline, recent vapers were twice (RR=2.15) as likely to report smoking in the past 12 months at the follow-up. Vaping did not predict cessation of smoking among recent smokers at baseline. Among never-smokers at baseline, recent vapers were more than 4 times (RR=4.73) more likely to move away from the perception of cigarettes as posing a ‘great risk’ of harm, a finding consistent with a desensitisation process.ConclusionsThese results contribute to the growing body of evidence supporting vaping as a one-way bridge to cigarette smoking among youth. Vaping as a risk factor for future smoking is a strong, scientifically-based rationale for restricting youth access to e-cigarettes.

ObjectiveTo examine what substances US youth vape.MethodsData come from Monitoring the Future, an annual, nationally representative survey of USA 12th-grade, 10th-grade and 8th-grade students. Respondents reported what substance they vaped the last time they used a vaporiser such as an e-cigarette.ResultsAmong students who had ever used a vaporiser, 65–66% last used ‘just flavouring’ in 12th, in 10th and in 8th grade, more than all other responses combined. In all three grades, the percentage using ‘just flavouring’ was above 57% for males, females, African-Americans, Hispanics, Whites, and students both with and without a parent with a college degree. Nicotine use came in a distant second, at about 20% in 12th and 10th grade and 13% in 8th grade. Taking into account youth who vaped nicotine at last use increases national estimates of tobacco/nicotine prevalence in the past 30 days by 24–38% above and beyond cigarette smoking, which is substantial but far less than estimates that assume all vaporiser users inhale nicotine.ConclusionsThese results challenge the common assumption that all vaporiser users inhale nicotine. They (a) call into question the designation of vaporisers and e-cigarettes as ENDS (‘Electronic Nicotine Delivery System’), (b) suggest that the recent rise in adolescent vaporiser use does not necessarily indicate a nicotine epidemic, and (c) indicate that vaporiser users can be candidates for primaryprevention programmes. Finally, the results suggest the importance of developing different rationales for the regulation of vaporiser devices as compared to the regulation of substances marketed for vaporiser use.

A numerical solute transport model was calibrated to a high‐resolution monitoring data set to characterize a multicomponent source of nonaqueous phase liquids (NAPLs) and evaluate the uncertainty of estimated parameters. The dissolution of NAPL mass was simulated using SEAM3D with parameter zones including adjustable NAPL saturations and mass transfer coefficients, representing the heterogenous architecture of the source zone. Source zone parameters were simultaneously estimated using PEST from aqueous‐phase concentrations measured in a multilevel monitoring transect and from mass recovery rates measured at extraction wells during a controlled field experiment. Data‐worth analyses, facilitated by PEST ancillary software, linked maximum aqueous‐phase concentrations of all compounds to reductions in the pre‐calibration uncertainty of mass transfer coefficients. In turn, decreasing concentrations of the most soluble NAPL fraction constrained the source mass estimation. The accurate estimation of model parameters was possible by removing concentrations measured during early NAPL dissolution stages, identified as drivers of model bias using the iterative ensemble smoother PESTPP‐iES. Although uncertainty analyses highlighted model limitations for representing sub‐grid‐scale heterogeneity of NAPL distribution and mass transfer rates, final stages of NAPL dissolution measured at multilevel ports eliminated parameter bias and produced long‐term projections of multi‐stage source zone depletion. Including mass discharge rates for model calibration further improved the accuracy of estimated residual source mass, complementing multilevel monitoring constraints on the saturation distribution and mass transfer coefficients. Predicting the persistence of groundwater contamination by dense non‐aqueous phase liquids (DNAPLs), such as chlorinated solvents, is crucial for effective environmental stewardship. The dissolution behavior of DNAPL source zones depends on the contaminant mass distribution within hydrogeologic systems, referred to as the source zone architecture, which cannot be measured directly at contaminated sites. We investigated the worth of high‐resolution monitoring of aqueous concentrations during a controlled field experiment for indirectly characterizing a multicomponent DNAPL source zone, including its architecture and dissolution behavior. Our methods coupled numerical modeling of groundwater flow and contaminant transport with parameter estimation and uncertainty analysis techniques. Parameter uncertainties were linked to the variability of DNAPL dissolution rates observed at multiple scales of monitoring resolution, including a multilevel transect and groundwater recovery wells. While early aqueous concentration peaks were identified as drivers of model bias, the depletion profile of the most soluble DNAPL component accurately constrained the estimated source architecture and dissolution behavior. Hence, our characterization approach can benefit remedial designs for managing DNAPL source zones undergoing final depletion stages at sites with monitoring histories. Aqueous‐phase concentrations monitored in a field experiment were simulated to quantify nonaqueous phase liquid (NAPL) distribution and dissolution ratesDepletion profiles of the most soluble dense NAPL component accurately constrained the source zone architectureMultiscale heterogeneity of source zone architecture controlled the uncertainty of estimated mass transfer coefficients Aqueous‐phase concentrations monitored in a field experiment were simulated to quantify nonaqueous phase liquid (NAPL) distribution and dissolution rates Depletion profiles of the most soluble dense NAPL component accurately constrained the source zone architecture Multiscale heterogeneity of source zone architecture controlled the uncertainty of estimated mass transfer coefficients

Effective policies that can reduce alcohol use behaviors and impaired driving among young people at a population level are needed. Graduated driver licensing (GDL) laws increase the driving privileges of young novice drivers as they age and gain more driving experience. In this study, we seek to determine the effects of GDLs on risky driving behaviors of youth and to assess if GDLs have an unintended effect on underage drinking behaviors. We utilized 2000 to 2013 data on 12th grade students from the Monitoring the Future (MTF) study, an ongoing, annual national survey (since 1975) that studies the substance use behaviors of adolescents, as well as data on GDLlaws obtained via the Insurance Institute for Highway Safety (IIHS). We conducted a series of regular logistic regression models that included fixed effects for year and state, and adjusted for demographic characteristics, school characteristics, and other state alcohol policies. Total weighted sample size was 129,289 12th graders. Past month alcohol use and binge drinking (i.e., ≥5 drinks on one occasion) in the past 2 weeks were 45 and 26%, respectively. Seventeen percent of respondents reported riding with a driver who drank alcohol. Nearly 12% reported driving in the past 2 weeks after drinking alcohol, and 7% reported driving after binge drinking. Over half of the students lived in a state with a “good” GDLlaw. The logistic regression models suggest a link between restrictive GDLpolicies and a reduction of alcohol use behaviors and risky driving behaviors among youth. Our findings indicate that the effects of GDLs extend beyond driving‐related risks and into other drinking‐related behaviors that pose immediate or delayed health risks for young people. We speculate that GDLs may dictate social norms and expectations for youth risk behaviors, and should be maximized throughout the United States. Graduated driver licensing (GDL) laws increase the driving privileges of young novice drivers as they age and gain more driving experience. In multivariable models, we found relatively consistent associations between restrictive GDLlaws and reduced youth alcohol use behaviors and alcohol‐related risky driving behaviors. The effects of GDLs extend beyond driving‐related risks and into other drinking‐related behaviors that pose immediate or delayed health risks for young people. All states should work toward implementing restrictive GDLs.