The influences of stomatal size and density on rice abiotic stress resilience.

A warming climate coupled with reductions in water availability and rising salinity are increasingly affecting rice (Oryza sativa) yields. Elevated temperatures combined with vapour pressure deficit (VPD) rises are causing stomatal closure, further reducing plant productivity and cooling. It is unclear what stomatal size (SS) and stomatal density (SD) will best suit all these environmental extremes. To understand how stomatal differences contribute to rice abiotic stress resilience, we screened the stomatal characteristics of 72 traditionally bred varieties. We found significant variation in SS, SD and calculated anatomical maximal stomatal conductance (gsmax ) but did not identify any varieties with SD and gsmax as low as transgenic OsEPF1oe plants. Traditionally bred varieties with high SD and small SS (resulting in higher gsmax ) typically had lower biomasses, and these plants were more resilient to drought than low SD and large SS plants, which were physically larger. None of the varieties assessed were as resilient to drought or salinity as low SD OsEPF1oe transgenic plants. High SD and small SS rice displayed faster stomatal closure during increasing temperature and VPD, but photosynthesis and plant cooling were reduced. Compromises will be required when choosing rice SS and SD to tackle multiple future environmental stresses.

Induced Genetic Variations in Stomatal Density and Size of Rice Strongly Affects Water Use Efficiency and Responses to Drought Stresses.

Rice (Oryza sativa L.) is an important food crop relied upon by billions of people worldwide. However, with increasing pressure from climate change and rapid population growth, cultivation is very water-intensive. Therefore, it is critical to produce rice that is high-yielding and genetically more water-use efficient. Here, using the stabilized fast-neutron mutagenized population of Jao Hom Nin (JHN) - a popular purple rice cultivar - we microscopically examined hundreds of flag leaves to identify four stomatal model mutants with either high density (HD) or low density (LD) stomata, and small-sized (SS) or large-sized (LS) stomata. With similar genetic background and uniformity, the stomatal model mutants were used to understand the role of stomatal variants on physiological responses to abiotic stress. Our results show that SS and HD respond better to increasing CO2 concentration and HD has higher stomatal conductance (gs) compared to the other stomatal model mutants, although the effects on gas exchange or overall plant performance were small under greenhouse conditions. In addition, the results of our drought experiments suggest that LD and SS can better adapt to restricted water conditions, and LD showed higher water use efficiency (WUE) and biomass/plant than other stomatal model mutants under long-term restricted water treatment. Finally, our study suggests that reducing stomata density and size may play a promising role for further work on developing a climate-ready rice variety to adapt to drought and heat stress. We propose that low stomata density and small size have high potential as genetic donors for improving WUE in climate-ready rice.

Rice Stomatal Mega-Papillae Restrict Water Loss and Pathogen Entry.

Rice (Oryza sativa) is a water-intensive crop, and like other plants uses stomata to balance CO2 uptake with water-loss. To identify agronomic traits related to rice stomatal complexes, an anatomical screen of 64 Thai and 100 global rice cultivars was undertaken. Epidermal outgrowths called papillae were identified on the stomatal subsidiary cells of all cultivars. These were also detected on eight other species of the Oryza genus but not on the stomata of any other plant species we surveyed. Our rice screen identified two cultivars that had "mega-papillae" that were so large or abundant that their stomatal pores were partially occluded; Kalubala Vee had extra-large papillae, and Dharia had approximately twice the normal number of papillae. These were most accentuated on the flag leaves, but mega-papillae were also detectable on earlier forming leaves. Energy dispersive X-Ray spectrometry revealed that silicon is the major component of stomatal papillae. We studied the potential function(s) of mega-papillae by assessing gas exchange and pathogen infection rates. Under saturating light conditions, mega-papillae bearing cultivars had reduced stomatal conductance and their stomata were slower to close and re-open, but photosynthetic assimilation was not significantly affected. Assessment of an F3 hybrid population treated with Xanthomonas oryzae pv. oryzicola indicated that subsidiary cell mega-papillae may aid in preventing bacterial leaf streak infection. Our results highlight stomatal mega-papillae as a novel rice trait that influences gas exchange, stomatal dynamics, and defense against stomatal pathogens which we propose could benefit the performance of future rice crops.

The influence of stomatal morphology and distribution on photosynthetic gas exchange.

The intricate and interconnecting reactions of C3 photosynthesis are often limited by one of two fundamental processes: the conversion of solar energy into chemical energy, or the diffusion of CO2 from the atmosphere through the stomata, and ultimately into the chloroplast. In this review, we explore how the contributions of stomatal morphology and distribution can affect photosynthesis, through changes in gaseous exchange. The factors driving this relationship are considered, and recent results from studies investigating the effects of stomatal shape, size, density and patterning on photosynthesis are discussed. We suggest that the interplay between stomatal gaseous exchange and photosynthesis is complex, and that a disconnect often exists between the rates of CO2 diffusion and photosynthetic carbon fixation. The mechanisms that allow for substantial reductions in maximum stomatal conductance without affecting photosynthesis are highly dependent on environmental factors, such as light intensity, and could be exploited to improve crop performance.

Rice with reduced stomatal density conserves water and has improved drought tolerance under future climate conditions.

Much of humanity relies on rice (Oryza sativa) as a food source, but cultivation is water intensive and the crop is vulnerable to drought and high temperatures. Under climate change, periods of reduced water availability and high temperature are expected to become more frequent, leading to detrimental effects on rice yields. We engineered the high-yielding rice cultivar 'IR64' to produce fewer stomata by manipulating the level of a developmental signal. We overexpressed the rice epidermal patterning factor OsEPF1, creating plants with substantially reduced stomatal density and correspondingly low stomatal conductance. Low stomatal density rice lines were more able to conserve water, using c. 60% of the normal amount between weeks 4 and 5 post germination. When grown at elevated atmospheric CO2 , rice plants with low stomatal density were able to maintain their stomatal conductance and survive drought and high temperature (40°C) for longer than control plants. Low stomatal density rice gave equivalent or even improved yields, despite a reduced rate of photosynthesis in some conditions. Rice plants with fewer stomata are drought tolerant and more conservative in their water use, and they should perform better in the future when climate change is expected to threaten food security.

Molecular control of stomatal development.

Plants have evolved developmental plasticity which allows the up- or down-regulation of photosynthetic and water loss capacities as new leaves emerge. This developmental plasticity enables plants to maximise fitness and to survive under differing environments. Stomata play a pivotal role in this adaptive process. These microscopic pores in the epidermis of leaves control gas exchange between the plant and its surrounding environment. Stomatal development involves regulated cell fate decisions that ensure optimal stomatal density and spacing, enabling efficient gas exchange. The cellular patterning process is regulated by a complex signalling pathway involving extracellular ligand-receptor interactions, which, in turn, modulate the activity of three master transcription factors essential for the formation of stomata. Here, we review the current understanding of the biochemical interactions between the epidermal patterning factor ligands and the ERECTA family of leucine-rich repeat receptor kinases. We discuss how this leads to activation of a kinase cascade, regulation of the bHLH transcription factor SPEECHLESS and its relatives, and ultimately alters stomatal production.

Stomatal development: focusing on the grasses.

The development and patterning of stomata in the plant epidermis has emerged as an ideal system for studying fundamental plant developmental processes. Over the past twenty years most studies of stomata have used the model dicotyledonous plant Arabidopsis thaliana. However, cultivated monocotyledonous grass (or Gramineae) varieties provide the majority of human nutrition, and future research into grass stomata could be of critical importance for improving food security. Recent studies using Brachypodium distachyon, Hordeum vulgare (barley) and Oryza sativa (rice) have led to the identification of the core transcriptional regulators essential for stomatal initiation and progression in grasses, and begun to unravel the role of secretory signaling peptides in controlling stomatal developmental. This review revisits how stomatal developmental unfolds in grasses, and identifies key ontogenetic steps for which knowledge of the underpinning molecular mechanisms remains outstanding.

Effects of varenicline on alcohol cue reactivity in heavy drinkers.

RATIONALE: Clinical trials and human laboratory studies have established that varenicline can reduce rates of alcohol use among heavy drinkers. Less is known about the mechanisms by which varenicline has this effect on drinking behavior. Reactivity to alcohol cues is often cited as the primary cause of relapse among those being treated for alcohol use disorder, and several front-line treatments for alcohol use disorder work, at least in part, by minimizing cue-induced alcohol craving. OBJECTIVE: The current double-blind, placebo-controlled human laboratory study tested the effects of varenicline on alcohol cue reactivity in a group of heavy-drinking adult smokers and nonsmokers. METHODS: As part of a larger series of sequential human laboratory experiments testing the effects of varenicline on drinking outcomes, participants were assigned (between-participant) to receive either active varenicline (2 mg/day) or placebo. Following a titration period, participants (n = 77) attended a laboratory session during which they were exposed to alcohol and neutral cues using a standard cue reactivity paradigm. RESULTS: Alcohol cue exposure increased craving for alcohol in both medication groups. However, participants receiving varenicline showed a smaller increase in alcohol craving compared to participants receiving placebo. The medication effect did not differ between smokers and nonsmokers. Among smokers, alcohol cue exposure also increased tobacco craving. Varenicline did not attenuate this effect. CONCLUSIONS: Results support the use of varenicline for reducing alcohol use in heavy drinkers and identify a potential mechanism by which varenicline reduces drinking. Varenicline continues to show promise as a pharmacological treatment for alcohol use disorder.

A preliminary study on the effect of combined nicotine replacement therapy on alcohol responses and alcohol self-administration.

BACKGROUND AND OBJECTIVES: Limiting alcohol consumption may help prevent alcohol-mediated smoking relapse in heavy drinking smokers. This pilot study examined whether combining a nicotine patch with nicotine nasal spray has stronger attenuating effects on alcohol response and consumption than a nicotine patch alone. METHODS: Twenty-two non-alcohol dependent heavy drinking smokers completed the double-blind cross-over, placebo-controlled study (21 mg nicotine patch + nicotine or placebo nasal spray). Six hours after 21 mg nicotine patch application, subjective and physiological responses to a priming drink (0.3 g/kg) were assessed, followed by two 1-hr alcohol self-administration periods, with possible consumption of up to 4 drinks per period (each 0.15 g/kg). Nasal spray (1 mg [active] or 0 mg [placebo] per dose) was administered 10 min prior to the priming dose and each self-administration period. RESULTS: Active nasal spray did not increase serum nicotine levels, compared with placebo administration. The number of drinks consumed did not differ by the nasal spray conditions. However, positive subjective responses to the priming drink were lower in the active nasal spray condition than the placebo nasal spray condition. During the self-administration period, urge to drink was also lower in the active spray condition than the placebo condition. CONCLUSIONS AND SCIENTIFIC SIGNIFICANCE: Augmenting the nicotine patch with nicotine nasal spray attenuated positive subjective alcohol response and craving and suggests that future studies should investigate whether these findings translate to a clinical setting.

Longitudinal associations between smoking cessation medications and alcohol consumption among smokers in the International Tobacco Control Four Country survey.

BACKGROUND: Available evidence suggests that quitting smoking does not alter alcohol consumption. However, smoking cessation medications may have a direct impact on alcohol consumption independent of any effects on smoking cessation. Using an international longitudinal epidemiological sample of smokers, we evaluated whether smoking cessation medications altered alcohol consumption independent of quitting smoking. METHODS: Longitudinal data were analyzed from the International Tobacco Control Four Country (ITC-4) Survey between 2007 and 2008, a telephone survey of nationally representative samples of smokers from the United Kingdom, Australia, Canada, and the United States (n = 4,995). Quantity and frequency of alcohol consumption, use of smoking cessation medications (varenicline, nicotine replacement [NRT], and no medications), and smoking behavior were assessed across 2 yearly waves. Controlling for baseline drinking and changes in smoking status, we evaluated whether smoking cessation medications were associated with reduced alcohol consumption. RESULTS: Varenicline was associated with a reduced likelihood of any drinking compared with nicotine replacement (OR = 0.56; 95% CI = 0.34 to 0.94), and consuming alcohol once a month or more compared to nicotine replacement (OR = 0.43; 95% CI = 0.27 to 0.69) or no medication (OR = 0.63; 95% CI = 0.41 to 0.99). Nicotine replacement was associated with an increased likelihood of consuming alcohol once a month or more compared to no medication (OR = 1.14; 95% CI = 1.03 to 1.25). Smoking cessation medications were not associated with more frequent drinking (once a week or more) or typical quantity consumed per episode. Medication effects on drinking frequency were independent of smoking cessation. CONCLUSIONS: This epidemiological investigation demonstrated that varenicline was associated with a reduced frequency of alcohol consumption. Continued work should clarify under what conditions nicotine replacement therapies may increase or decrease patterns of alcohol consumption.

Does co-morbid depression alter the inverse relationship between obesity and substance use disorders?

BACKGROUND: Substance use disorders and obesity are often inversely related to one another, hypothetically due to competition over shared neurobiological reward circuitry. However, obesity and substance use disorders share common risk factors, such as other psychiatric disorders. It is unknown whether the inverse relationship between obesity and substance use disorders continues to exist in the presence of shared risk factors. METHODS: For the current study, we examined the associations between major depression, alcohol and drug use disorders, and overweight/obesity status in a nationally representative sample of U.S. adults (n=40,715). RESULTS: Our findings demonstrated that adults with major depression were more likely to be obese, whereas adults with alcohol or drug use disorders were less likely to be obese. However, the inverse relationship between substance use and obesity continued to exist in adults with co-morbid depression. Adults with depression disorders co-morbid with alcohol (Relative Risk [RR]=0.63, 95% CI=0.47-0.84) or drug (RR=0.54, 95% CI=0.36-0.81) use disorders were less likely to be obese vs normal weight. CONCLUSIONS: Our findings provide support for the proposal that excess food consumption and excess drug use appear to compete over shared neurobiology even when the motivation to self-medicate with either food or substances might be elevated.

Non-daily smoking predicts hazardous drinking and alcohol use disorders in young adults in a longitudinal U.S. sample.

BACKGROUND: It is known that daily smoking is associated with the development of alcohol use disorders. However, non-daily smoking is prevalent in young adults and is associated with increased rates of problematic alcohol use in cross-sectional data. It is unknown whether non-daily smoking is predictive of hazardous drinking and alcohol use disorders using longitudinal data. The primary aim of the present investigation was to explore the temporal relationship between non-daily smoking and drinking in young adults, and secondarily, whether college status modified this relationship. METHODS: Using Waves 1 (2001-2002) and 2 (2004-2005) of the National Epidemiological Survey on Alcohol and Related Conditions (NESARC), we examined the predictive relationship of smoking status at Wave 1 and change in college status between Waves on alcohol drinking, hazardous drinking, and alcohol abuse and dependence disorders at Wave 2. The sample was restricted to individuals aged 18-25 years at Wave 1. FINDINGS: Daily and non-daily smokers at Wave 1, compared to nonsmokers, were at a greater risk for hazardous drinking and alcohol use disorders at Wave 2, after controlling for Wave 1 drinking. College status did not modify smoking and drinking interactions. CONCLUSIONS: The findings indicate non-daily smoking is predictive of increased, problematic alcohol use among young adults longitudinally and they support increasing evidence that non-daily smokers represent an important population. Future research should be conducted to continue developing targeted interventions. Early treatments for smoking behavior might have a beneficial effect on reducing the development of problematic patterns of alcohol use and alcohol use disorders.

Alcohol and distraction interact to impair driving performance.

BACKGROUND: Recognition of the risks associated with alcohol intoxication and driver distraction has led to a wealth of simulated driving research aimed at studying the adverse effects of each of these factors. Research on driving has moved beyond the individual, separate examination of these factors to the examination of potential interactions between alcohol intoxication and driver distraction. In many driving situations, distractions are commonplace and might have little or no disruptive influence on primary driving functions. Yet, such distractions might become disruptive to a driver who is intoxicated. METHODS: The present study examined the interactive impairing effects of alcohol intoxication and driver distraction on simulated driving performance in 40 young adult drivers using a divided attention task as a distracter activity. The interactive influence of alcohol and distraction was tested by having drivers perform the driving task under four different conditions: 0.65 g/kg alcohol; 0.65 g/kg alcohol+divided attention; placebo; and placebo+divided attention. RESULTS: As hypothesized, divided attention had no impairing effect on driving performance in sober drivers. However, under alcohol, divided attention exacerbated the impairing effects of alcohol on driving precision. CONCLUSIONS: Alcohol and distraction continue to be appropriate targets for research into ways to reduce the rates of driving-related fatalities and injuries. Greater consideration of how alcohol and distraction interact to impair aspects of driving performance can further efforts to create prevention and intervention measures to protect drivers, particularly young adults.

Stress decreases the ability to resist smoking and potentiates smoking intensity and reward.

We have developed a novel human laboratory model to examine two primary aspects of stress-precipitated tobacco relapse: (1) Does stress reduce the ability to resist the first cigarette? (2) Once the first cigarette is initiated, does stress facilitate subsequent smoking? Using a within-subject design, daily smokers (n = 37) who were nicotine deprived overnight received a personalized imagery induction (stress or neutral) on two separate days, and then had the option of initiating a tobacco self-administration session or delaying initiation for up to 50 min in exchange for three levels of monetary reinforcement. Subsequently, the tobacco self-administration session entailed a 1-hour period in which subjects could choose to smoke using a smoking topography system. Following the stress induction, subjects were less able to resist smoking, smoked more intensely (increased puffs, shorter inter-puff interval, and greater peak puff velocity), and perceived greater satisfaction and reward from smoking. Stress significantly increased hypothalamus-pituitary-adrenal (HPA) axis reactivity, tobacco craving, negative emotion, and physiologic reactivity relative to the neutral condition. In addition, increased cortisol, ACTH, and tobacco craving were associated with reduced ability to resist smoking following stress. These findings have implications for understanding the impact of stress on smoking relapse and model development to assess smoking lapse behavior.

Alcohol expectancy increases positive responses to cigarettes in young, escalating smokers.

RATIONALE: A large proportion of smokers consolidate their smoking patterns during young adulthood, and it is possible that the high rates of drinking found in this age group may facilitate the transition from nondaily to daily cigarette use. OBJECTIVE: The primary aim of this study was to examine how alcohol alters the subjective effects of smoking in heavy-drinking young adults (age 21-25) who are still at an experimental stage of smoking but show recent increases in their smoking behavior. METHODS: Using a within-subject design, we examined whether alcohol or the expectation of receiving alcohol increased either subjective responses to smoking or the amount smoked. Subjects participated in three sessions, in which they received alcohol (0.08 g/dL targeted blood alcohol level), a taste-masked placebo presented as alcohol, or a mixer beverage not presented as alcohol. Measures included positive and negative subjective reactivity (e.g., satisfaction, nausea, craving relief, and enjoyment of airway sensations) associated with smoking a single cigarette and subsequent ad lib smoking behavior. RESULTS: Both conditions in which the subjects expected to receive alcohol increased positive effects of smoking (satisfaction, calm, and taste), compared to the mixer beverage. Alcohol, compared to the placebo and mixer beverages, decreased negative effects (nausea) associated with smoking a cigarette and increased subsequent smoking. CONCLUSIONS: This initial study has implications for understanding how alcohol and the expectation of alcohol improves the experience of smoking in nondaily smokers who are still at an experimental stage of smoking.

Effects of the nicotinic receptor antagonist mecamylamine on ad-lib smoking behavior, topography, and nicotine levels in smokers with and without schizophrenia: a preliminary study.

Individuals with schizophrenia have higher plasma nicotine levels in comparison to non-psychiatric smokers, even when differences in smoking are equated. This difference may be related to how intensely cigarettes are smoked but this has not been well studied. Mecamylamine (MEC), a non-competitive nicotinic acetylcholine receptor (nAChR) antagonist, which has been shown to increase ad-lib smoking and to affect smoking topography, was used in the current study as a pharmacological probe to increase our understanding of smoking behavior, smoking topography, and resulting nicotine levels in smokers with schizophrenia. This preliminary study used a within-subject, placebo-controlled design in smokers with schizophrenia (n=6) and healthy control smokers (n=8) to examine the effects of MEC (10mg/day) on ad-lib smoking behavior, topography, nicotine levels, and tobacco craving across two smoking deprivation conditions (no deprivation and 12-h deprivation). MEC, compared to placebo, increased the number of cigarettes smoked and plasma nicotine levels. MEC increased smoking intensity and resulted in greater plasma nicotine levels in smokers with schizophrenia compared to controls, although these results were not consistent across deprivation conditions. MEC also increased tobacco craving in smokers with schizophrenia but not in control smokers. Our results suggest that antagonism of high-affinity nAChRs in smokers with schizophrenia may prompt compensatory smoking, increasing the intensity of smoking and nicotine exposure without alleviating craving. Further work is needed to assess whether nicotine levels are directly mediated by how intensely the cigarettes are smoked, and to confirm whether this effect is more pronounced in smokers with schizophrenia.

Nicotine deprivation and trait impulsivity affect smokers' performance on cognitive tasks of inhibition and attention.

Increased nicotine deprivation and impulsivity have been associated with relapse but the degree to which they together influence cognitive processing has not been explored. We examined the effects of increasing levels of nicotine deprivation on cognitive processing, and assessed the relationship of trait impulsivity with these effects in daily smokers (n=30). Using a within-subject design with three deprivation conditions (nondeprived, 5-hr, 17-hr), volunteers completed the Conners' Continuous Performance Task-II and the Cued Go/No-Go Task. Trait impulsivity was assessed at intake with the Barratt Impulsiveness Scale (Patton et al., 1995). Mixed-model regression analyses revealed deprivation slowed reaction time, increased errors, increased variability in responding, and increased failures of inhibitory control. Performance at 17 hours of deprivation was most likely to be affected. Significant deprivation and impulsivity interactions indicated impulsiveness was negatively correlated with deprivation-associated performance decrements. Less impulsive smokers were more affected by deprivation, demonstrating greater impairment. Research is needed to understand mechanisms by which impulsivity confers greater risk for relapse. Our results suggest deprivation may not increase relapse risk among impulsive smokers by increasing impairment of cognitive processing.

Varenicline reduces alcohol self-administration in heavy-drinking smokers.

BACKGROUND: Alcohol and tobacco dependence are highly comorbid disorders, with preclinical evidence suggesting a role for nicotinic acetylcholine receptors (nAChRs) in alcohol consumption. Varenicline, a partial nicotinic agonist with high affinity for the alpha4beta2 nAChR receptor, reduced ethanol intake in rodents. We aimed to test whether varenicline would reduce alcohol consumption and alcohol craving in humans. METHODS: This double-blind, placebo-controlled investigation examined the effect of varenicline (2 mg/day vs. placebo) on alcohol self-administration using an established laboratory paradigm in non-alcohol-dependent heavy drinkers (n = 20) who were daily smokers. Following 7 days of medication pretreatment, participants were first administered a priming dose of alcohol (.3 g/kg) and subjective, and physiologic responses were assessed. A 2-hour alcohol self-administration period followed during which participants could choose to consume up to 8 additional drinks (each .15 g/kg). RESULTS: Varenicline (.5 +/- SE = .40) significantly reduced the number of drinks consumed compared to placebo (2.60 +/- SE = .93) and increased the likelihood of abstaining from any drinking during the self-administration period. Following the priming drink, varenicline attenuated alcohol craving and reduced subjective reinforcing alcohol effects (high, like, rush, feel good, intoxicated). Adverse events associated with varenicline were minimal and, when combined with alcohol, produced no significant effects on physiologic reactivity, mood, or nausea. CONCLUSIONS: This preliminary investigation demonstrated that varenicline significantly reduced alcohol self-administration and was well tolerated, alone and in combination with alcohol in heavy-drinking smokers. Varenicline should be investigated as a potential treatment for alcohol use disorders.

Experimenting and daily smokers: episodic patterns of alcohol and cigarette use.

Alcohol use may facilitate the development of nicotine dependence. Alcohol is often paired with cigarette smoking, particularly in those experimenting with smoking. However, little research has examined episodic patterns of alcohol and cigarette use. This study examined patterns of alcohol and cigarette use in a college-aged sample (n=237) designated as experimenters or smokers based on their smoking history. Participants reported their consumption of drinks and cigarettes by hour, for each hour, of a typical drinking and smoking episode. Self-reported pleasure and desire associated with smoking generally and while drinking was assessed. No group difference was observed in total number of drinks. However, experimenters delayed smoking until more drinks were consumed, suggesting they smoked after reaching binge levels of alcohol. By contrast, smokers smoked after fewer drinks. Both groups reported increased smoking while drinking and increased pleasure and desire when smoking while drinking. The increase was greater in experimenters. Concurrent alcohol and cigarette use may facilitate the development of tobacco dependence and interventions interrupting their pairing might impede the transition from experimenter to smoker.

Nondaily smoking and alcohol use, hazardous drinking, and alcohol diagnoses among young adults: findings from the NESARC.

BACKGROUND: Nondaily smoking and heavy alcohol use are prevalent behaviors among young adults, with nondaily smoking occurring primarily in the context of alcohol use. Although the relationship between drinking and daily smoking has been well characterized in young adults, few epidemiological investigations have investigated the association between nondaily smoking and drinking behavior. METHODS: We examined Wave 1 of the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; Grant et al., 2003b; n = 43,093). Young adults (aged 18 to 25 years; n = 5,838) were stratified on current smoking behavior (daily, nondaily, and nonsmokers in the past 12 months) and differences in weekly quantity of alcohol use, frequency of alcohol use, frequency of binge drinking behavior, rates of NIAAA-defined hazardous drinking, and rates of DSM-IV alcohol diagnoses were investigated. College student status was examined. RESULTS: Twenty-five percent were current smokers and 7% were smoking on a nondaily basis. Seventy-one percent were current drinkers, 39% reported binge drinking at least once a month, 41% met criteria for hazardous drinking, and 18% had alcohol use disorders. Across all measures of alcohol use, there was a significant effect of smoking status, with daily smokers having greater alcohol use patterns, compared with nondaily smokers, with nonsmokers consuming the least. Nondaily smokers were more likely to report any binge drinking in the past 12 months. However, daily smokers were more likely to report daily binge drinking. With regard to hazardous drinking and alcohol use disorders, nondaily smoking conferred the greatest risk, followed by daily smoking with nonsmoking as the reference group. Multinomial logistic regression demonstrated that the odds of being a hazardous drinker were 16 times greater (95% CI 9.46-26.48) in a nondaily smoker compared with a nonsmoker, whereas the odds for a daily smoker were increased by 7-fold (95% CI 5.54-9.36). A similar pattern of results was demonstrated for DSM-IV alcohol diagnoses. No differences across college student status were observed. CONCLUSIONS: The increased risk of hazardous drinking and alcohol use disorders conferred by nondaily smoking supports the findings that nondaily smoking and drinking are highly concomitant behaviors. Results such as these suggest that interventions disengaging alcohol and cigarette use patterns (e.g., smoking bans in alcohol venues) might serve to limit the occurrence of hazardous drinking among young adults at heightened risk for this behavior.