Analogs of Marinopyrrole A Show Enhancement to Observed In Vitro Potency against Acute Toxoplasma gondii Infection.

The apicomplexan parasite Toxoplasma gondii is the causative agent of toxoplasmosis, a globally distributed infection with severe clinical consequences for immunocompromised individuals and developing fetuses. There are few available treatments, and these are associated with potentially severe adverse effects. Marinopyrrole A, a compound discovered in a marine Streptomyces species, has previously been found to exhibit potent antimicrobial activity, prompting our interest in exploring efficacy against Toxoplasma gondii. We found that marinopyrrole A was a highly potent anti-Toxoplasma molecule, with an in vitro 50% maximal inhibitory concentration (IC50) of 0.31 µM, corresponding to a higher potency than that of the current standard of care (pyrimethamine); however, addition of 20% serum led to abrogation of potency, and toxicity to human cell lines was observed. Yet, application of marinopyrrole A to an in vivo lethal acute infection model facilitated significantly enhanced survival at doses of 5, 10, and 20 mg/kg. We then tested a series of marinopyrrole A analogs (RL002, RL003, and RL125) and demonstrated significantly increased potency in vitro, with IC50 values ranging from 0.09 to 0.17 µM (3.6- to 6.8-fold increase relative to pyrimethamine). No detectable cytotoxicity was observed up to 50 µM in human foreskin fibroblasts, with cytotoxicity in HepG2 cells ranging from ∼28 to 50 µM, corresponding to >200-fold selectivity for parasites over host cells. All analogs additionally showed reduced sensitivity to serum. Further, RL003 potently inhibited in vitro-generated bradyzoites at 0.245 µM. Taken together, these data support further development of marinopyrrole A analogs as promising anti-Toxoplasma molecules to further combat this prevalent infection.

Differential impact of doxorubicin dose on cell death and autophagy pathways during acute cardiotoxicity.

Doxorubicin (DOX) is an effective anthracycline used in chemotherapeutic regimens for a variety of haematological and solid tumors. However, its utility remains limited by its well-described, but poorly understood cardiotoxicity. Despite numerous studies describing various forms of regulated cell death and their involvement in DOX-mediated cardiotoxicity, the predominate form of cell death remains unclear. Part of this inconsistency lies in a lack of standardization of in vivo and in vitro model design. To this end, the objective of this study was to characterize acute low- and high-dose DOX exposure on cardiac structure and function in C57BL/6 N mice, and evaluate regulated cell death pathways and autophagy both in vivo and in cardiomyocyte culture models. Acute low-dose DOX had no significant impact on cardiac structure or function; however, acute high-dose DOX elicited substantial cardiac necrosis resulting in diminished cardiac mass and volume, with a corresponding reduced cardiac output, and without impacting ejection fraction or fibrosis. Low-dose DOX consistently activated caspase-signaling with evidence of mitochondrial permeability transition. However, acute high-dose DOX had only modest impact on common necrotic signaling pathways, but instead led to an inhibition in autophagic flux. Intriguingly, when autophagy was inhibited in cultured cardiomyoblasts, DOX-induced necrosis was enhanced. Collectively, these observations implicate inhibition of autophagy flux as an important component of the acute necrotic response to DOX, but also suggest that acute high-dose DOX exposure does not recapitulate the disease phenotype observed in human cardiotoxicity.

Change in alcohol demand following a brief intervention predicts change in alcohol use: A latent growth curve analysis.

BACKGROUND: The association between behavioral economic demand and various alcohol use outcomes is well established. However, few studies have examined whether changes in demand occur following a brief alcohol intervention (BAI), and whether this change predicts alcohol outcomes over the long term. METHODS: Parallel process piecewise latent growth curve models were examined in a sample of 393 heavy drinking emerging adults (60.8% women; 85.2% white; Mage  = 18.77). In these models, two linear slopes represented rates of change in alcohol use, heavy drinking episodes, alcohol-related problems, and demand (intensity and highest expenditure across all price points or Omax ) from baseline to 1 month (slope 1) and 1 month to 16 months (slope 2). Mediation analyses were conducted to estimate the effect of a BAI on 16-month alcohol outcomes through slope 1 demand. RESULTS: A two-session BAI predicted significant reductions in all five outcomes from baseline to 1-month follow-up. Although no further reduction was observed from the 1-month to the 16-month follow-up, there was no regression to baseline levels. Slope 1 demand intensity, but not Omax , significantly mediated the association between BAI and both outcomes-heavy drinking episodes (Est. = -0.23, SE = 0.08, p < 0.01) and alcohol-related problems (Est. = -0.15, SE = 0.07, p < 0.05)-at the 16-month follow-up. CONCLUSIONS: Reducing high valuation of alcohol among heavy drinking emerging adults within the first month following BAI is critical for the long-term efficacy of the intervention. A two-session BAI was associated with enduring reductions in alcohol demand, and the change in demand intensity, but not Omax , was associated with sustained reductions in heavy drinking and alcohol-related problems.

In Vitro Selection Implicates ROP1 as a Resistance Gene for an Experimental Therapeutic Benzoquinone Acyl Hydrazone in Toxoplasma gondii.

Toxoplasma gondii is a globally distributed apicomplexan parasite and the causative agent of toxoplasmosis in humans. While pharmaceuticals exist to combat acute infection, they can produce serious adverse reactions, demonstrating a need for enhanced therapies. KG8 is a benzoquinone acyl hydrazone chemotype identified from a previous chemical screen for which we previously showed in vitro and in vivo efficacy against T. gondii However, the genetic target and mechanism of action of KG8 remain unknown. To investigate potential targets, we generated resistant T. gondii lines by chemical mutagenesis followed by in vitro selection. Whole-genome sequencing of resistant clones revealed a P207S mutation in the gene encoding rhoptry organelle protein 1 (ROP1) in addition to two lesser resistance-conferring mutations in the genes for rhoptry organelle protein 8 (ROP8) and a putative ADP/ATP carrier protein (TGGT1_237700). Expressing ROP1P207S in parental parasites was sufficient to confer significant (10.3-fold increased half-maximal effective concentration [EC50]) KG8 resistance. After generating a library of mutants carrying hypermutated rop1 alleles followed by KG8 pressure, we sequenced the most resistant clonal isolate (>16.9-fold increased EC50) and found independent recapitulation of the P207S mutation, along with three additional mutations in the same region. We also demonstrate that a rop1 knockout strain is insensitive to KG8. These data implicate ROP1 as a putative resistance gene of KG8. This work further identifies a compound that can be used in future studies to better understand ROP1 function and highlights this novel chemotype as a potential scaffold for the development of improved T. gondii therapeutics.

A new trick for an old dog? Myocardial-specific roles for prostaglandins as mediators of ischemic injury and repair.

The small lipid-derived paracrine signaling molecules known as prostaglandins have been recognized for their ability to modulate many facets of cardiovascular physiology since their initial discovery more than 85 years ago. Although the role of prostaglandins in the vasculature has gained significant attention across time, a handful of historical studies have also directly implicated the cardiomyocyte in both prostaglandin synthesis and release. Recently, our understanding of how prostaglandin receptor modulation impacts and contributes to myocardial structure and function has gained attention while leaving most other components of myocardial prostaglandin metabolism and signaling unexplored. This mini-review highlights both the key historical studies that underpin modern prostaglandin research in the heart, while concurrently presenting the latest findings related to how prostaglandin metabolism and signaling impact myocardial injury and repair.

Trajectories of reward availability moderate the impact of brief alcohol interventions on alcohol severity in heavy-drinking young adults.

BACKGROUND: Behavioral economic theory predicts that low access to environmental reward is a risk factor for alcohol use disorder (AUD). The Substance-Free Activity Session (SFAS) is a behavioral economic supplement to standard brief alcohol interventions that attempts to increase environmental reward and may therefore have beneficial effects, particularly for individuals with low levels of environmental reward. METHODS: Participants were 393 college students who reported at least 2 heavy-drinking episodes in the past month. Participants were randomly assigned to 1 of 3 conditions following a baseline assessment: a standard alcohol-focused brief motivational intervention plus relaxation training session (BMI + RT), BMI plus Substance-Free Activity Session (BMI + SFAS), or an assessment-only control condition (AO). In a secondary analysis of the data from this study, we used person-centered statistical techniques to describe trajectories of alcohol severity and environmental reward over a 16-month follow-up and examined whether environmental reward levels moderated the effectiveness of the interventions. RESULTS: Piecewise growth mixture modeling identified 2 trajectories of reward availability: low increasing (LR; n = 120) and high stable (HR; n = 273). Depressive symptoms, cannabis use, sensation seeking, and low life satisfaction were associated with a greater probability of classification in the LR trajectory. Alcohol severity was greater in the LR trajectory than the HR trajectory. For students in the LR trajectory, at 1, 6, and 12 months, BMI + SFAS led to greater increases in reward availability and reduced levels of alcohol severity compared with the BMI + RT and AO conditions and at 16 months compared with AO. CONCLUSIONS: Young adults with low levels of environmental reward are at heightened risk for greater alcohol severity and may show greater benefit from brief alcohol interventions that focus on increasing substance-free reward than individuals who are not deficient in reward availability.

Misoprostol attenuates neonatal cardiomyocyte proliferation through Bnip3, perinuclear calcium signaling, and inhibition of glycolysis.

Systemic hypoxia resulting from preterm birth, altered lung development, and cyanotic congenital heart disease is known to impede the regulatory and developmental pathways in the neonatal heart. While the molecular mechanisms are still unknown, hypoxia induces aberrant cardiomyocyte proliferation, which may be initially adaptive, but can ultimately program the heart to fail in early life. Recent evidence suggests that the prostaglandin E1 analogue, misoprostol, is cytoprotective in the hypoxia-exposed neonatal heart by impacting alternative splicing of the Bcl-2 family member Bnip3, resulting in the generation of a variant lacking the third exon (Bnip3ΔExon3 or small Nip; sNip). Using a rodent model of neonatal hypoxia, in combination with rat primary neonatal cardiomyocytes (PVNCs) and H9c2 cells, we sought to determine if misoprostol can prevent cardiomyocyte proliferation and what the key molecular mechanisms might be in this pathway. In PVNCs, exposure to 10% oxygen induced myocyte proliferation concurrent with molecular markers of cell-cycle progression, such as Cyclin-D1, which were prevented by misoprostol treatment. Furthermore, we describe a critical role for sNip in opposing cardiomyocyte proliferation through several mechanisms, including reduced expression of the proliferative MEF2C-myocardin-BMP10 pathway, accumulation of nuclear calcium leading to NFATc3 activation, and increased expression of the cardiac maturation factor BMP2. Intriguingly, misoprostol and sNip inhibited hypoxia-induced glycolytic flux, which directly influenced myocyte proliferation. These observations were further supported by knockdown studies, where hypoxia-induced cardiomyocyte proliferation is restored in misoprostol-treated cells by an siRNA targeting sNip. Finally, in postnatal day (PND)-10 rat pups exposed to hypoxia, we observed histological evidence of increased nuclei number and increased PPH3 staining, which were completely attenuated by misoprostol treatment. Collectively, this data demonstrates how neonatal cardiomyocyte proliferation can be pharmacologically modulated by misoprostol treatment, which may have important implications for both neonatal and regenerative medicine.

High Opportunity Cost Demand as an Indicator of Weekday Drinking and Distinctly Severe Alcohol Problems: A Behavioral Economic Analysis.

INTRODUCTION: Behavioral economic theory views addiction as a reinforcer pathology characterized by excessive demand for drugs relative to alternatives. Complementary to this theory, Lamb and Ginsburg (Pharmacology Biochemistry and Behavior, 164, 2018, 62) describe addiction as a behavioral allocation disorder and predict that decisions to drink under increasingly stringent constraints are a central indicator of addiction. This study used a modified demand-curve paradigm to examine alcohol demand in the context of a next-day contingency (high opportunity cost demand) as a specific indicator of a severe pattern of alcohol problems. METHODS: Participants were 370 undergraduates (61.1% female, 86.5% white, Mage  = 18.8) reporting multiple past-month heavy drinking episodes (5/4 drinks per occasion for men/women) who completed 2 versions of an alcohol purchase task (APT), along with measures of past-month alcohol use and problems. In 1 APT (low opportunity cost), students imagined they had no next-day responsibilities, and in the other APT (high opportunity cost), they imagined having a 10:00 am test the next day. Item-response theory analyses were used to determine mild and severe alcohol problems from the Young Adult Alcohol Consequences Questionnaire (Journal of Studies on Alcohol, 67, 2006, 169), and the most and least severe binge drinking days throughout the week. RESULTS: Low opportunity cost demand (ß = 0.15, p = 0.02) significantly predicted beyond high opportunity cost demand for the least severe problems, and high opportunity cost demand (ß = 0.17, p = 0.009) significantly predicted beyond low opportunity cost demand for the most severe problems. Similarly, low opportunity cost demand (ß = 0.26, p < 0.001) was more highly associated with weekend drinking, whereas high opportunity cost demand (ß = 0.21, p = 0.001) was more highly associated with weekday drinking. CONCLUSIONS: The current results suggest high opportunity cost alcohol demand is a distinct marker of severe alcohol problems among college student heavy drinkers.

Brief Motivational Interventions Are Associated with Reductions in Alcohol-Induced Blackouts Among Heavy Drinking College Students.

BACKGROUND: Alcohol-induced blackouts, a form of anterograde amnesia that restricts the encoding of short-term memories into long-term ones, are among the most severe alcohol-related consequences. College students are at high risk of experiencing alcohol-induced blackouts, and there is a need to determine whether alcohol interventions can effectively reduce blackouts in this population. The current study uses data from 3 randomized clinical trials to examine the effect of various intervention approaches on alcohol-induced blackouts. METHODS: Four interventions were compared over 3 studies: (i) a computerized feedback intervention (electronic Check-Up To Go [e-Chug]; Study 1); (ii) a single-session brief motivational intervention (BMI; Study 1); (iii) a BMI plus behavioral economic session focused on increasing substance-free activities (BMI + Substance-Free Activity Session [SFAS]; Studies 2 and 3); and (iv) a BMI plus supplemental Relaxation Training session (BMI + Relaxation Training; Studies 2 and 3). Studies 1 and 3 also included an assessment-only control condition. For each study, participants reported whether they had experienced an alcohol-induced blackout at each time point; binary logistic regressions examined differential likelihood of experiencing an alcohol-induced blackout over time. RESULTS: Neither the single-session BMI nor e-Chug reduced alcohol-induced blackouts over assessment only; however, participants in the BMI + SFAS or BMI + Relaxation Training condition were significantly less likely to experience an alcohol-induced blackout compared to assessment only at 1-month (Wald = 4.77, odds ratio [OR] = 0.53, p = 0.03) and 6-month follow-ups (Wald = 5.72, OR = 0.52, p = 0.02). Study 2 also revealed a larger effect for the BMI + SFAS over the BMI + Relaxation Training condition at 6 months (Wald = 4.11 OR = 0.22, p = 0.043), although this was not replicated in Study 3. The effects for the 2-session BMIs lasted 6 months, at which point maturation effects diminished differences between assessment-only and intervention conditions. CONCLUSIONS: Two sessions of BMI are a substantial enough dose to result in reductions in alcohol-induced blackouts among college student heavy drinkers.

The Efficacy of an Event-Specific, Text Message, Personalized Drinking Feedback Intervention.

Tailgating drinking prior to a football game is a type of event-specific drinking associated with increased alcohol use and related problems. Personalized drinking feedback interventions (PFI) are efficacious in reducing alcohol use and problems. The current study aimed to advance understanding of event-specific interventions by examining: (1) the efficacy of an event-specific, text message PFI on tailgating alcohol outcomes, and (2) the extent to which intervention effects generalize to "typical" alcohol outcomes at 1-month follow-up. College students (N = 130; 71% female; 92% white) who reported tailgating within the past 30 days and binge drinking when tailgating in the past year completed assessments on tailgating and typical alcohol use. They were randomly assigned to one of two text message conditions delivered on the morning of a home football game: event-specific PFI (TXT PFI) or a control condition. Multilevel modeling examined the association of treatment condition on tailgating and 1-month alcohol outcomes. When tailgating, participants in TXT PFI reported lower estimated peak blood alcohol concentration (eBAC) and consumed less drinks than the control condition. At the 1-month "typical" drinking follow-up, participants in TXT PFI reported lower peak eBAC and fewer alcohol-related problems than the control condition. Perceived tailgating drinking norms were found to statistically mediate the relationship between condition and alcohol outcome at tailgating and 1-month follow-ups. Findings provide preliminary support for the efficacy of an event-specific, text message PFI in reducing both tailgating and typical drinking alcohol outcomes. Event-specific TXT PFI can be used for prevention/intervention of alcohol misuse.

Acculturative stress as a moderator for international student drinking behaviors and alcohol use consequences.

Drinking behaviors and alcohol use consequences can have a major effect on well-being in college student populations. Little research has addressed how the unique acculturative stress experiences of international students may affect their alcohol use and consequences. This study examined acculturative stress as a moderator of the relationship between international student drinking behaviors and alcohol use consequences. Data were collected from 175 international students and analyzed using hierarchal regression analysis to assess the moderating effect of acculturative stress. Acculturative stress moderated the relationship between alcohol use and related consequences such that the relationship was stronger among those with higher levels of acculturative stress. Efforts to alleviate acculturative stress experiences of this population may help decrease alcohol use consequences.

Deficits in Access to Reward Are Associated with College Student Alcohol Use Disorder.

BACKGROUND: Reward deprivation has been implicated in major depressive disorder and severe substance abuse, but its potential relation to alcohol use disorder (AUD) symptoms in non-treatment-seeking young adult drinkers is less clear. Depression is often comorbid with alcohol misuse, so relations of AUD with reward deprivation might be due in part to the presence of depressive symptoms in young adults. Behavioral economic theory views addiction as a state that is related in part to deficits in drug-free rewards, and therefore requires an investigation into whether reward deprivation has a direct relation to alcohol misuse that is, at least partially, independent of mood. METHODS: This study evaluates the contribution of 2 facets of reward deprivation (reward availability and experience) to alcohol use, AUD symptoms, and depression in a sample of young adult heavy episodic drinkers. Data were collected from 392 undergraduates (60.4% female, 85.1% Caucasian) who reported recent heavy drinking (83.7% with at least 1 AUD symptom). RESULTS: Low reward availability (environmental suppression) was significantly associated with both DSM-5 AUD symptoms and alcohol-related problems after controlling for age, gender, depressive symptomatology, and drinking level. CONCLUSIONS: This study provides support for behavioral economic models that emphasize reward deprivation as a unique risk factor for AUD that is independent of mood and drinking level. Limited access to natural rewards may be a risk and/or maintaining factor for AUD symptoms in college student drinkers.

Depressive Symptoms and Gambling Behavior: Mediating Role of Coping Motivation and Gambling Refusal Self-Efficacy.

Understanding the variables that contribute to the comorbidity of depression and gambling behaviors is important in developing effective intervention strategies for those who experience gambling-related problems. The purpose of this study was to implement core concepts from Jacob's general theory of addiction and the social cognitive theory in a multiple mediation model. Specifically, we tested two models to examine whether coping motivation and refusal self-efficacy mediated the relationship between depressive symptoms, gambling related problems, and days gambled. Data was collected from 333 undergraduate students at a large public Midwest university, participating in a larger clinical trial. Analyses indicated a direct effect between depressive symptoms and gambling related problems. Depressive symptoms were found to have a significant indirect effect through coping motivation and gambling refusal self-efficacy on gambling related problems and days gambled. These results provide further support regarding the mechanisms through which depressive symptoms may increase risk for problematic gambling behavior.

Elevated alcohol demand is associated with driving after drinking among college student binge drinkers.

BACKGROUND: Alcohol-impaired driving among college students represents a significant public health concern, yet little is known about specific theoretical and individual difference risk factors for driving after drinking among heavy drinking college students. This study evaluated the hypothesis that heavy drinkers with elevated alcohol demand would be more likely to report drinking and driving. METHOD: Participants were 207 college students who reported at least 1 heavy drinking episode (4/5 or more drinks in 1 occasion for a woman/man) in the past month. Participants completed an alcohol purchase task that assessed hypothetical alcohol consumption across 17 drink prices and an item from the Young Adult Alcohol Consequences Questionnaire that assessed driving after drinking. RESULTS: In binary logistic regression models that controlled for drinking level, gender, ethnicity, age, and sensation seeking, participants who reported higher demand were more likely to report driving after drinking. CONCLUSIONS: These results provide support for behavioral economics models of substance abuse that view elevated/inelastic demand as a key etiological feature of substance misuse.

Application of Generalizability Theory to the Big Five Inventory.

The purpose of the present study was to examine the Big Five Personality Inventory score reliability (BFI: John, Donahue, & Kentle, 1991) utilizing Generalizability Theory analyses. Participants were recruited from a large public Midwestern university and provided complete data for the BFI on three measurement occasions (n = 264). Results suggested score reliability for scales with 7-10 items were adequate. However, score reliability for two item scales did not reach a .80 threshold. These findings have indicated BFI score reliability was, in general, acceptable and demonstrated the advantages of using Generalizability Theory analyses to examine score reliability.

Protective Behavioral Strategies, Social Norms, and Alcohol-Related Outcomes.

The present study examined the unique contributions of protective behavioral strategies and social norms in predicting alcohol-related outcomes. Participants were 363 students from a large public university in the Midwest who reported at least one binge-drinking episode (5+/4+ drinks for men/women in one sitting) in the past 30 days. Data were collected 1/2010-3/2011. We used SEM to test models where protective behavioral strategies (PBS) and social norms were predictors of both alcohol use and alcohol-related problems, after controlling for the effects of gender. Both PBS and descriptive norms had relationships with alcohol use. PBS also had a relationship with alcohol-related problems. Overall, the findings suggest that PBS and social norms have unique associations with distinct alcohol-related outcomes.

A pilot trial of a brief intervention for cannabis use supplemented with a substance-free activity session or relaxation training.

OBJECTIVE: Cannabis use is increasing among college students and commonly co-occurs with anxiety symptoms in this age group. Interventions that reduce anxiety may also reduce cannabis use. Behavioral economic theory suggests that substance use reductions are most likely when there is an increase in substance-free reinforcement. This randomized pilot trial evaluated the efficacy of a brief motivational intervention (BMI) for cannabis supplemented by either a substance-free activity session (SFAS) or a relaxation training (RT) session for reducing cannabis use, problems, craving, and anxiety symptoms. METHOD: One hundred thirty-two college students (Mage = 19.9; 54% female; 67% White, 31% Black) who reported five or more past-month cannabis use days were randomized to: (a) assessment-only (AO); (b) BMI plus SFAS; or (c) BMI plus RT. Participants in the BMI conditions received two individual counselor-administered sessions plus a brief phone booster session. Outcomes were evaluated 1- and 6-months postintervention. RESULTS: Relative to assessment, both BMI + SFAS and BMI + RT were associated with significant reductions in cannabis problems and craving at 1-month follow-up, and significant reductions in anxiety at 6-month follow-up. Relative to AO, BMI + RT was associated with significant reductions in cannabis use at 1-month follow-up. There were no differences between BMI conditions. CONCLUSIONS: This pilot trial was not adequately powered to conclusively evaluate relative efficacy but provides preliminary support for the short-term efficacy of both two-session interventions for reducing anxiety and cannabis-related risk among nontreatment seeking emerging adults. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Predicting the math/science career goals of low-income prospective first-generation college students.

The present study used social cognitive career theory (SCCT; Lent, Brown, & Hackett, 1994) to predict the math/science goal intentions of a sample of low-income prospective first-generation college students (N = 305). Structural equation modeling was used to test a model depicting relationships between contextual (i.e., social class, learning experiences, proximal supports and barriers) and person-cognitive (i.e., self-efficacy, outcome expectations, interests, goals) variables as hypothesized in SCCT and based on previous literature on low-income first-generation college students. Results indicated that the hypothesized model provided the best representation of the data. All paths in the model were statistically significant, with the exceptions of paths from self-efficacy to goals, outcome expectations to interests, and perceived barriers to self-efficacy. Bootstrapping procedures revealed that the relationships between social class, self-efficacy, and outcome expectations were mediated through learning experiences. Furthermore, the relationship between social supports and goals was mediated by self-efficacy and interests and the relationships between self-efficacy, outcome expectations, and goals were mediated by interests. Contrary to hypotheses, the relationship between barriers and goals was not mediated by self-efficacy and interests. The hypothesis that proximal contextual supports and barriers would moderate the relationship between interests and goals was not supported. The final model explained 66% and 55% of the variance in math/science interests and goals, respectively. Implications for future research and practice are discussed.

Examining a curvilinear model of readiness to change and alcohol consumption.

Research examining the relationship between readiness to change and alcohol consumption among college students is inconsistent. The purpose of the present study was to extend these findings, using two different measures of readiness to change. We hypothesized a curvilinear effect would occur such that the relationship between readiness to change and alcohol use would be relatively low for students low and high on readiness to change, whereas the relationship would be relatively high for those with moderate levels of readiness to change. Data were collected from two studies: Study 1 consisted of 263 undergraduate students and Study 2 consisted of 245 undergraduates participating in either intercollegiate or recreational athletics at three US universities. In Study 1, we examined the association between both linear and quadratic scores on a readiness to change measure and alcohol use. In Study 2, we examined the relationship between scores on a stage of change measure that included subscales indicative of different levels of readiness to change and alcohol use. The pattern of relationships supported the existence of an effect where the highest levels of alcohol use occurred among those with scores representing moderate levels of readiness to change.