Experimental & Clinical Psychopharmacology

A meta-analysis on polymorphic trait of taste perception mediated by TAS2R38 genotype.
The objective of this study is to review the association of TAS2R38 polymorphisms and taste phenotypes to bitter compounds (phenylthiocarbamide [PTC]/propylthiouracil [PROP]), and its association among persons who drink alcohol and individuals with smoking behavior. A literature search was carried out in PubMed, ScienceDirect, Cochrane, and Wiley online library databases using the keyword “(Bitter taste receptor genes OR TAS2R38) AND (PROP OR propylthiouracil) AND (PTC OR phenylthiocarbamide),” “(Bitter taste receptor genes OR TAS2R38) AND (alcohol),” “(Bitter taste receptor genes OR TAS2R38) AND (tobacco OR smoker)” to find articles evaluating the association of taste phenotypes and TAS2R38 polymorphisms, and its association among persons who drink alcohol and individuals with smoking behavior. The analysis show that TAS2R38 taster genotype (proline–alanine–valine [PAV] allele) was significantly (OR, 5.88; CI [3.87, 8.95], p <.001) associated with taster phenotype for bitter compounds (PTC/PROP), and TAS2R38 nontaster genotype (alanine–valine–isoleucine allele) was significantly (OR, 6.73; CI [4.57, 9.90], p <.001) associated with nontaster phenotype for bitter compounds. Further, TAS2R38 taster genotypes (PAV homozygotes and heterozygotes) were significantly associated with higher alcohol intake (OR, 5.15; 95% CI [2.66, 9.98]; p <.001) and among individuals with smoking behavior (OR, 1.73; 95% CI [1.24, 2.42]; p = .001). This suggests that TAS2R38 single nucleotide polymorphisms can be identified by clinically assessing taste phenotype status for bitter compounds and can be used as a potential therapeutic target in the prevention and treatment of harmful higher alcohol intake and smoking behavior. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
Differential effects of repeated fluoxetine and ketamine administration on behavioral and pharmacological stressor-induced depression of digging behavior in mice.
Major depressive disorder is a multifactorial disorder that originates from a complex web of variables and overlaps with similar disorders (e.g., depression and anxiety). As such, animal models should account for the considerable symptom overlap between psychiatric disorders. We sought to extend the findings of behavioral assays that encompass both anxiety and stress/depression components. To do so, we have focused on digging behavior, a compulsive-like behavior displayed in mice, in which we employed behavioral and pharmacological stressors to reduce digging behaviors, producing a depression-like state. Locomotor activity was assessed during each test session. We found that digging behavior remains consistent, but locomotor activity decreased when exposed to multiple test sessions over 4 weeks and no sex differences were observed. A time-course study showed a single swim stress significantly reduced digging behavior for at least 3 days but rebounded to baseline levels by Day 7. Repeated treatment of 10 mg/kg/day fluoxetine, but not ketamine, partially reversed swim stress-induced depression of digging behavior on Days 3 and 7. The pharmacological stressor yohimbine (1.0–5.0 mg/kg) dose-dependently decreased digging behavior. Repeated treatment of 10 mg/kg/day ketamine, but not fluoxetine, reversed yohimbine-induced depression of digging behavior on Days 3 and 7. These data suggest that digging behavior is a stable and consistent behavior displayed by all mice. We were able to depress digging behavior with both behavioral and pharmacological stress. However, the reversal of stress-induced depression of digging behavior was stimulus- (e.g., behavioral vs. pharmacological) and drug-dependent and will require further investigation. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
The subjective value of social context in people who use cannabis.
Disordered cannabis use is linked to social problems, which could be explained by a subjective devaluation of nondrug social contexts and/or an overvaluation of cannabis-paired options relative to nondrug alternatives. To examine these hypotheses, measures to assess the subjective value of social- and/or cannabis-paired contexts were collected in people who use cannabis (n = 85) and controls (n = 98) using crowdsourcing methods. Measures included a cued concurrent choice task that presented two images (cannabis, social, social cannabis, and neutral images) paired with monetary options, hypothetical purchase tasks that included access to social parties with and without a cannabis “open bar,” and the Social Anhedonia Scale (SAS). Little evidence was found to suggest that the cannabis group undervalued social contexts. People who used cannabis demonstrated a preference for social- versus neutral-cued options, and no preference for cannabis- versus social cannabis-cued options on the choice task. In addition, social party demand and SAS scores did not differ between groups. In contrast, we observed evidence for an overvaluation of cannabis context in people who use cannabis, including preference for social cannabis- versus social-cued options, and more disadvantageous choices for cannabis-cued options on the choice task, as well as more intense and inelastic demand for the social cannabis party compared to the social party. These results suggest that social problems associated with cannabis use could be at least partially explained by an overvaluation of cannabis-paired options, rather than devaluation of nondrug social-paired options, in the value calculations underlying drug use decisions. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
Prospective associations of behavioral economic demand for cannabis and alcohol with simultaneous cannabis and alcohol use among young adults.
Behavioral economic demand for cannabis and alcohol is robustly associated with cannabis use and alcohol use, respectively. However, few studies have examined the contributions of cannabis and alcohol demand to simultaneous cannabis and alcohol use, which is common among young adults. We examined prospective associations of cannabis demand and alcohol demand with propensity for simultaneous use (broadly defined as using both cannabis and alcohol in the same day) and with cannabis and alcohol consumption during simultaneous use days among young adults. Young adults reporting simultaneous use (N = 107) completed a Marijuana Purchase Task assessing cannabis demand and an Alcohol Purchase Task assessing alcohol demand. They then completed daily smartphone surveys over 21 days assessing cannabis and alcohol use. Multilevel models revealed that higher cannabis demand (i.e., higher Omax, Pmax, and intensity; lower elasticity) was uniquely associated with greater propensity for simultaneous use relative to nonuse. In addition, higher alcohol demand (lower elasticity) was uniquely associated with greater propensity for simultaneous use relative to cannabis-only use, and higher cannabis demand (higher break point and intensity, lower elasticity) was uniquely associated with greater propensity for simultaneous use relative to alcohol-only use. Furthermore, in models limited to simultaneous use days, greater cannabis demand (higher Omax, lower elasticity) and lower alcohol demand (higher elasticity) were uniquely associated with greater overall cannabis flower consumption, and higher alcohol demand (higher Omax, lower elasticity) was uniquely associated with greater overall alcohol consumption. Results suggest that individual differences in cannabis and alcohol demand may contribute to simultaneous cannabis and alcohol use behaviors in a substance-specific pattern. Furthermore, cannabis demand may more strongly drive the tendency to engage in simultaneous use (vs. nonuse) relative to alcohol demand. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
Regression tree applications to studying alcohol-related problems among college students.
Machine learning algorithms hold promise for developing precision medicine approaches to addiction treatment yet have been used sparingly to identify predictors of alcohol-related problems. Recursive partitioning, a machine learning algorithm, can identify salient predictors and clinical cut points that can guide treatment. This study aimed to identify predictors and cut points of alcohol-related problems and to examine result stability in two separate, large data sets of college student drinkers (n = 5,090 and 2,808). Four regression trees were grown using the “rpart” package in R. Seventy-one predictors were classified as demographics (e.g., age), alcohol use indicators (e.g., typical quantity/frequency), or psychosocial indicators (e.g., anxiety). Predictors and cut points were extracted and used to manually recreate the tree in the other data set to test result stability. Outcome variables were alcohol-related problems as measured by the Alcohol Use Disorder Identification Test and Brief Young Adult Alcohol Consequences Questionnaire. Coping with depression, conformity motives, binge drinking frequency, typical/heaviest quantity, drunk frequency, serious harm reduction protective behavioral strategies, substance use, and psychosis symptoms best predicted alcohol-related problems across the four trees; coping with depression (cut point range: 1.83–2.17) and binge drinking frequency (cut point range: 1.5–2.5) were the most common splitting variables. Model fit indices suggest relatively stable results accounting for 17%–30% of the variance. Results suggest the nine salient predictors, particularly coping with depression motives scores around 2 and binge drinking frequency around two to three times per month, are important targets to consider when treating alcohol-related problems for college students. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
Measurement of the self-determination continuum of motivation for engaging in alcohol-related harm reduction behaviors: Improved content coverage of the Treatment Self-Regulation Questionnaire.
Self-determination theory (SDT) proposes that people are more likely to engage in behaviors that reduce the harms associated with alcohol use if they do so for more self-determined reasons. There is growing support for this proposal, but the Treatment Self-Regulation Questionnaire (TSRQ), which assesses the self-determination continuum of motivation for engaging in alcohol-related harm reduction behaviors, lacks content coverage. We generated additional items to improve the content coverage of the TSRQ and evaluated its psychometric properties. We also compared two randomly assigned instruction sets that referenced “responsible drinking” or “protective behavioral strategies” (PBS). Participants (n = 2,236) were college students from psychology departments at 10 universities in eight U.S. states who reported past-month alcohol use and completed the revised TSRQ; the online survey was completed for partial course credit. Exploratory factor analysis supported a three-factor structure representing autonomous motivation, controlled motivation, and amotivation for the PBS version. This factor structure was confirmed using exploratory structural equation modeling for both the PBS and responsible drinking versions. Scalar invariance was achieved across instruction sets. Latent mean differences showed that those who received the PBS version had lower autonomous and controlled motivation scores, but higher amotivation scores. Associations of the three TSRQ factors with alcohol-related outcomes were consistent with SDT, and the magnitude of these associations did not differ across instruction sets. More accurate assessment of the self-determination continuum of motivation for alcohol-related harm reduction behaviors will improve research on this topic which has promising implications for alcohol interventions. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
Hippocampal gray matter volume in young adulthood varies with adolescent alcohol use.
Adolescent substance use is linked with negative future outcomes (e.g., depression, anxiety, substance use disorder). Given that the brain undergoes significant maturation during adolescence, this developmental period may represent a time of particular vulnerability to substance use. Neuroimaging research has largely focused on heavy or binge patterns of substance use; thus, relatively less is known about the neural impact of a broader range of adolescent substance use. Characterizing the neural impact of a broader range of adolescent substance use may inform prevention and treatment efforts. The present study investigated relationships between adolescent substance use trajectories (i.e., alcohol, tobacco, and cannabis) and gray matter volume in young adulthood. Substance use was assessed in 1,594 participants at ages 11, 13, 16, and 19. Following the last assessment, 320 participants completed a single magnetic resonance imaging session to assess brain gray matter volume. Latent growth curve models were used to estimate growth parameters characterizing alcohol, tobacco, and cannabis use trajectories for each participant. These growth parameters (i.e., intercept, linear slope, and quadratic slope) were then used as predictors of gray matter volume. The gray matter volume of the hippocampus was positively associated with age 14 alcohol use (i.e., intercept) but not other trajectories (i.e., progression or acceleration) or substances (tobacco or cannabis). These results provide new insight into the neural impact of distinct adolescent alcohol, tobacco, and cannabis use trajectories, which may help to refine prevention and treatment efforts. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
Are alcohol-related attentional biases and holistic perception independent processes?
Excessive alcohol consumption is associated with the development of attentional biases for alcohol-related cues and their prioritization in heavy drinkers. Recently, it has been hypothesized that holistic processing may also play a role in this prioritization, with higher alcohol consumers exhibiting stronger holistic perception for alcohol cues. However, it is unclear how processing stimuli holistically may be related to attentional biases. We explored potential relationships between attentional biases, holistic processing, and alcohol consumption in a sample of drinkers using two tasks. In the first, a visual probe task replicated previous findings by showing an increased attentional bias for alcohol-related stimuli in individuals with higher alcohol consumption. Surprisingly, using an inversion paradigm to measure holistic perception in our second task, we showed reduced holistic processing for both alcohol and nonalcohol cues in higher alcohol consumers compared to light alcohol consumers. Although alcohol consumption was positively associated with attentional biases and negatively associated with holistic processing, these cognitive processes were not associated with each other. This study supports a model of visual perception in which attentional biases and holistic processing are independently linked with alcohol use. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
Assessment of human abuse potential of an unflavored, sucralose-sweetened electronic cigarette in combustible cigarette smokers.
Despite the popularity of electronic cigarettes (ECIGs), limited research has examined the role of sweeteners, independent of other flavors, in shaping ECIG human abuse potential (HAP). This study examined the effects of sucralose and nicotine in unflavored ECIG liquid solutions to provide a basic understanding of the effects of sweeteners on ECIG HAP compared to combustible cigarettes. Individuals who smoked cigarettes daily (N = 14) completed five within-subject, Latin-square ordered study sessions that differed by product used: (a) own-brand combustible cigarettes (OB), (b) 0 mg/mL nicotine, unsweetened liquid, (c) 0 mg/mL nicotine, sucralose-sweetened liquid, (d) 15 mg/mL nicotine, unsweetened liquid, and (e) 15 mg/mL nicotine, sucralose-sweetened liquid. Participants completed subjective questionnaires and behavioral tasks following a 10-puff directed use bout during which puff topography was measured, and blood was sampled for later measurement of plasma nicotine concentration. On average, the OB condition had a greater increase in plasma nicotine concentration and produced more pronounced subjective effects compared to the ECIG conditions. The 15 mg/mL nicotine ECIGs delivered significantly more nicotine and produced greater drug effects and reductions in tobacco abstinence symptoms than the 0 mg/mL nicotine ECIGs. Sucralose-containing solutions increased ECIG product appeal, puff duration, and puff volume during the 10-puff directed bout. Findings revealed greater HAP for OB cigarettes relative to all ECIGs tested and suggest that adding sucralose and nicotine elevates ECIG HAP via different mechanisms; sucralose appears to influence HAP through product appeal, while nicotine influences HAP through drug effects and tobacco/nicotine abstinence symptom suppression. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
Constraining electronic nicotine delivery systems (ENDS) nicotine dose by controlling nicotine flux at a limited puff duration.
Nicotine flux, the rate of electronic nicotine delivery system (ENDS) nicotine emission, is important in determining ENDS abuse liability. However, flux does not account for user behavior, including puff duration. Along with nicotine flux, puff duration limits the dose of nicotine that can be inhaled. Controlling both flux and puff duration allows regulators to constrain nicotine dose effectively. This study examined the effects of differing ENDS nicotine fluxes (by manipulating liquid nicotine concentration and holding device power constant), with user puff duration limited to 2 s. Participants (N = 32) completed four sessions, each session differing by nicotine flux (no flux, low flux, cigarettelike flux, and high flux conditions). Participants completed two ENDS use bouts in each session while puff duration was limited to 2 s. Plasma nicotine concentration, heart rate, and subjective effects were measured. At higher flux, higher plasma nicotine concentration and higher heart rate were observed. Moreover, higher fluxes decreased ratings of craving and urge to use nicotine and increased positive subjective effects, such as calmness. This study demonstrates that by manipulating nicotine flux and limiting puff duration, nicotine dose can be controlled. Subsequent research should demonstrate the effects of manipulating puff duration systematically. Results underscore the importance of targeting both flux and puff duration for ENDS regulation, intended to reduce abuse liability while maintaining the potential to facilitate transitions from cigarettes to ENDS. (PsycInfo Database Record (c) 2024 APA, all rights reserved)
Lower motivation for rewarded mental effort in tobacco dependence.
Tobacco dependence is characterized by decision-making impairments, which may increase the risk of smoking relapse by lowering the capacity to resist the immediate gratification of nicotine consumption. Because controlling one’s desires for immediate rewards is experienced as effortful, aversion to effortful control processes may also influence the prospects of successful smoking cessation. We therefore tested whether persons who smoke, compared with persons who do not smoke, show a lower willingness to engage in goal-directed mental effort. Thirty-seven persons who smoke and 38 persons who do not smoke performed a decision task requiring choices on whether to exert a demanding attention task for monetary rewards. Using state-of-the-art drift–diffusion modeling, we found that persons who smoke showed a stronger starting bias toward effort-free rewards. Taken together, our process model approach allowed us to identify the subcomponents of the decision process underlying the stronger aversion against mental effort in tobacco dependence, which may contribute to altered decision making by lowering the motivation to engage in effortful control processes when trying to suppress the desire for nicotine consumption. (PsycInfo Database Record (c) 2024 APA, all rights reserved)

Experimental and Clinical Psychopharmacology - Vol 32, Iss 5