Recent Published Research
Question 1: Why do some individuals become addicted to drugs and alcohol but other do not?
Differential Reward Valuation as an Endophenotype for Alcohol Addiction
A number of theoretical models of addiction propose that drug cue-reactivity is especially likely to be indicative of problematic drug involvement among people who show blunted responses to natural rewards, such as food, social interaction, and sexual intimacy. Few studies have directly tested this idea, however. The incentive-sensitization theory of addiction (Robinson & Berridge, 1993), posits that cues signaling drug availability take on incentive value of the drugs themselves, transforming cues into “motivational magnets” that elicit craving and compel consumption. Reward-deficit models posit that risk for drug use is conferred by a blunting of the incentive-motivational value of natural (i.e., nondrug) reinforcers. For example, the allostatic model of addiction (Koob & Moal, 2001) posits that, with repeated use, the incentive-motivational value of nondrug rewards is attenuated. The reward deficiency hypothesis (Blum et al., 1996) posits that blunted sensitivity to nondrug-related rewards represents a liability factor for substance use. Recent research using behavioral economic and value-based decision-making models (Bickel et al., 2014, Field et al., 2021) asserts that the ratio of substance-free and substance reward is critical to addiction etiology. Yet, researchers have failed to integrate these theories to try to explain the susceptibility to drug addiction. Our recent work has integrated these theoretical perspectives to evaluate the degree to which neurobiological mechanisms of alcohol and natural reward valuation operate to promote problematic drinking.
We have examined this question by measuring P3 event-related brain potential (ERPs) responses–a neurophysiological indicator of incentive salience or motivational significance of a stimulus (e.g., Begleiter et al., 1983,Franken et al., 2011)–to alcohol-related cues (pictures of alcohol) and cues signaling natural reinforcement (e.g., sex; thrill-seeking), and investigated associations between these P3 neural responses, heavy drinking, and alcohol-related problems in a large sample of nondependent, young adult drinkers. This work showed that, when tested individually, neural reactivity elicited by alcohol-related cues (ACR-P3) and natural reward cues (Reward-P3) showed few associations with heavy drinking and alcohol-related problems. However, differential reactivity to both types of cues (i.e., ACR-P3 minus Reward-P3, or reward dysregulation P3 phenotype) showed consistent and robust associations with multiple indicators of alcohol involvement and alcohol-related problems. In addition, ROC curve analyses showed that reward dysregulation P3 brain reactivity scores differentiated high-risk from lower-risk drinkers of developing alcohol use disorder (Martins et al., 2021).
Alcohol Sensivity and Enhanced Neural Responses to Alcohol Cues
In a different but related line of work, we recently completed a study that suggests that the relationship between alcohol sensitivity and reactivity to alcohol cues is primarily driven by blunted sensitivity to the higher-dose/sedation-like effects, an association that emerges in alcohol cues presented without people, but not when the cues depict people drinking (Martins et al., 2019). It is well known that exaggerated neural P3 responses to alcohol-related cues is associated with alcohol use and problematic drinking (Bartholow et al., 2007; Bartholow et al., 2010). Other work has shown that a low level of response to alcohol’s effects (i.e., low sensitivity) is a strong predictor of heavy drinking (Morean & Corbin, 2010; Newlin & Thomson, 1990; Quinn & Fromme, 2011).
We extended prior evidence linking low alcohol sensitivity to neural P3 responses to alcohol cues by examining associations with two alcohol sensitivity phenotypes, and by varying the naturalistic drinking contexts in which alcohol cues were presented (Martins et al., 2019). Our findings suggest that (1) the relationship between alcohol sensitivity and reactivity to alcohol cues is primarily driven by blunted sensitivity to the higher- dose/sedation-like effects, and (2) this association emerges for alcohol cues presented without people, but not when the cues depict people drinking. In sum, we showed that low sensitivity to alcohol effects typically associated with relatively high doses of alcohol (e.g., blacking out) is associated with enhanced neural responses to alcohol cues, suggesting a potential mechanism linking low sensitivity with increased AUD risk.
Reward Dysregulation and Cognitive Control Deficits in Addiction
Traditional dual-process models of addiction (see Wiers et al., 2007; Lindgren et al., 2019) propose that affective/motivational and cognitive processes interact in predicting problematic addictive behaviors. These theoretical perspectives share the core assumption that motivational factors compel addictive behaviors while factors related to cognitive control regulate those behaviors. These perspectives also hold that strong motivation to use drugs, coupled with weak or compromised cognitive control, is a disastrous combination setting the stage for entering the cycle of addiction (Lindgren et al., 2019; Wiers & Gladwin, 2016). These interaction effects, however, have not always borne out in empirical research. We recently reviewed existent evidence for the interplay between motivational and cognitive processes on addiction, focusing on alcohol use and heavy drinking as a prototypical exemplar of a broad class of addictive behaviors (Martins et al., 2018). We question evidence for the interplay between motivational and cognitive processes in addiction, proposing theoretical and methodological reasons for why the interaction between motivational and cognitive factors are not always borne out, and also discussing its practical implications for understanding drug and alcohol addiction.
Question 2: Why is it so difficult to stop or change addictive behaviors and recover from addiction?
Alcohol Craving and Withdrawal as Prognostic Indicators of AUD Treatment
In a separate line of work, we investigated the role of alcohol withdrawal and craving as clinical prognostic indicators of treatment response in treatment-seeking individuals with alcohol use disorder (AUD). Chronic alcohol use increases risk of alcohol withdrawal and abstinence symptoms, including craving, upon alcohol cessation in those entering AUD treatment. Although there are efficacious treatments for AUD, treatment failure and relapse rates remain a significant issue in AUD treatment (Sinha, 2011). We examined whether alcohol withdrawal (AW), craving, and symptoms of depression, anxiety, and sleep difficulties at treatment entry play a role in alcohol use outcomes in patients with AUD entering outpatient treatment (Martins et al., 2022). These are commonly reported symptoms but are not formally considered in assessment and treatment of AUD.
Our findings show that AW and craving place treatment-entering individuals at increased risk for treatment failure, thus jeopardizing their efforts for alcohol recovery. Findings also suggest the need for both assessment of AW and craving at treatment entry, and that targeted treatment specific to this alcohol-related pathophysiology may improve AUD treatment outcomes. We believe that these findings not only support the need to assess important clinical features at treatment entry, but also the consideration of recent evidence on medications (Anton et al., 2020; Sinha et al., 2021), such as gabapentin and prazosin to treat this abstinence-related stress pathophysiology in AUD.