Semaglutide and Tirzepatide reduce alcohol consumption in individuals with obesity.

Alcohol Use Disorder (AUD) contributes significantly to global mortality. GLP-1 (Glucagon-like peptide-1) and GLP-1/GIP (Glucose-dependent Insulinotropic Polypeptide) agonists, FDA-approved for managing type 2 diabetes and obesity, where the former has shown to effectively reduce the consumption of alcohol in animal models but no reports exist on the latter. In this report, we conducted two studies. In the first study, we conducted an analysis of abundant social media texts. Specifically, a machine-learning based attribution mapping of ~ 68,250 posts related to GLP-1 or GLP-1/GIP agonists on the Reddit platform. Secondly, we recruited participants (n = 153; current alcohol drinkers; BMI ≥ 30) who self-reported either taking Semaglutide (GLP-1 agonist), Tirzepatide (the GLP-1/GIP combination) for ≥ 30 days or, as a control group; no medication to manage diabetes or weight loss for a within and between subject remote study. In the social media study, we report 8 major themes including effects of medications (30%); diabetes (21%); and Weight loss and obesity (19%). Among the alcohol-related posts (n = 1580), 71% were identified as craving reduction, decreased desire to drink, and other negative effects. In the remote study, we observe a significantly lower self-reported intake of alcohol, drinks per drinking episode, binge drinking odds, Alcohol Use Disorders Identification Test (AUDIT) scores, and stimulating, and sedative effects in the Semaglutide or Tirzepatide group when compared to prior to starting medication timepoint (within-subjects) and the control group (between-subjects). In summary, we provide initial real-world evidence of reduced alcohol consumption in people with obesity taking Semaglutide or Tirzepatide medications, suggesting potential efficacy for treatment in AUD comorbid with obesity.

Effects of 6-month episodic future thinking training on delay discounting, weight loss and HbA1c changes in individuals with prediabetes.

People with prediabetes are at risk for type 2 diabetes. They may discount the future delay discounting (DD), and not engage in preventive health behaviors. Episodic future thinking (EFT) can reduce DD when future scenarios are cued, but research is needed to assess long-term effects of EFT and when EFT is not cued. This study tested EFT training compared to control for people with prediabetes enrolled in a 6-month weight loss program on DD, weight, HbA1c, and physical activity. Results showed a reliable EFT effect on reducing DD in cued (p = 0.0035), and uncued DD tasks (p = 0.048), and significant overall changes in weight (p < 0.001), HbA1c (p, 0.001) and physical activity (p = 0.003), but no significant differences in these outcomes by group (p's > 0.05). Sixty-eight percent of the sample ended below the prediabetes HbA1c range. These results suggest that DD can be modified over extended periods, and the effects of EFT can be observed without EFT cues. However, these data do not suggest that changes in weight, HbA1c or physical activity were due to EFT training. The study was initiated before the COVID-19 pandemic which provided the opportunity to compare differences for people treated in-person or remotely. Analyses showed no differences in DD, weight, HBA1c or physical activity outcomes were observed between in-person and remote treatment, suggesting telehealth is a scalable approach to treating prediabetes.

Future thinking to decrease real-world drinking in alcohol use disorder: Repairing reinforcer pathology in a randomized proof-of-concept trial.

Reinforcer Pathology theory proposes that expanding the temporal window of reinforcement (i.e., reducing delay discounting) using episodic future thinking (EFT) would decrease alcohol consumption. However, evidence of effectiveness in real-world settings is lacking. Using a randomized proof-of-concept field trial, the current study examined the effect of expanding the temporal window of reinforcement, using remotely delivered EFT, on decreasing real-world alcohol consumption among individuals with alcohol use disorder (AUD). Fifty-two individuals (9 females) aged 18-65 years who met the DSM-5 criteria for moderate or severe AUD and aimed to drink in moderation or abstain from drinking completed the study and were included in analysis. EFT significantly (p = .031) reduced alcohol consumption (mean change of consumption pre-post intervention = -2.18 drinks/day) compared to control episodic recent thinking (ERT; mean change of -0.52 drinks/day). Changes in discounting rates pre-post intervention significantly predicted changes in alcohol consumption (coef. = .424, 95% CI [.043-.813], p = .030) even after controlling for age, gender, race, income, education, marital status, and family history of addiction. Overall satisfaction across groups was rated as 3.92 on a 1 to 5-point scale, suggesting that the current remote approach is feasible and acceptable. The current findings were congruent with the theory, Reinforcer Pathology, that EFT expands the temporal window and decreases alcohol consumption, and the remote approach was considered feasible and acceptable. We believe the present study contributes new knowledge with tangible benefits for scientifically understanding and better defining novel interventions that may be clinically deployed to improve treatment outcomes. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Setting a goal could help you control: Comparing the effect of health goal versus general episodic future thinking on health behaviors among cigarette smokers and obese individuals.

Episodic Future Thinking (EFT) reduces delay discounting (DD; preference for smaller, immediate rewards) and various maladaptive behaviors. Exploring potential personalization of EFT to optimize its ability to alter DD and demand for unhealthy reinforcers is important for the development of interventions targeting long-term improvement and maintenance of health. In this investigation, using 2 separate studies, we examined the effects of EFT with and without a health goal on rates of discounting, demand, and craving for cigarettes and fast food among cigarette smokers and obese individuals, respectively. Using data collected from Amazon Mechanical Turk (mTurk), Study 1 (N = 189) examined the effect of EFT on DD and measures of cigarette demand and craving in cigarette smokers who were randomly assigned to 1 of 3 conditions: EFT-health goal, EFT-general, or Episodic Recent Thinking (ERT)-general. Study 2 (N = 255), using a 2x2 factorial design, examined the effects of health goals and general EFT on DD and measures of fast food demand and craving in obese individuals who were randomly assigned to 1 of 4 conditions: EFT-health goal, EFT-general, ERT-health goal or ERT-general. Health goal EFT was not more effective than general EFT in reducing monetary discounting. However, the addition of a health goal to general EFT was significantly associated with higher effect on intensity and elasticity of demand for cigarettes and fast food compared to EFT without a health goal. These findings suggest that the amplification of future thinking through the inclusion of a health goal may promote healthy decisions and result in positive behavior changes. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

Bleak present, bright future: II. Combined effects of episodic future thinking and scarcity on delay discounting in adults at risk for type 2 diabetes.

The present study sought to determine if episodic future thinking (EFT) can decrease delay discounting (DD) and demand for fast food under simulations of economic scarcity in adults at risk for diabetes (i.e., overweight/obese and with hemoglobin A1c values in, or approaching, the prediabetic range). Across two sessions, participants completed assessments of DD and food demand at baseline and while prompted to: (1) engage in either EFT or control episodic recent thinking, and (2) while reading a brief narrative describing either economic scarcity or neutral income conditions. Results showed that EFT significantly reduced DD, whereas the economic scarcity narrative significantly increased DD; no significant interaction between EFT and scarcity was observed. No significant effect of either EFT or scarcity was observed on food demand. We conclude that EFT decreases DD even when challenged by simulated economic scarcity in adults at risk for diabetes. The absence of a significant interaction between EFT and scarcity suggests that these variables operate independently to influence DD in opposing directions. Effects of EFT and economic scarcity on food demand require further study. The present study was registered on clinicaltrials.gov (NCT03664726).

Safety and efficacy of a prescription digital therapeutic as an adjunct to buprenorphine for treatment of opioid use disorder.

OBJECTIVES: To evaluate the safety and efficacy of a digital therapeutic in treatment-seeking individuals with opioid use disorder (OUD) in an analysis of randomized clinical trial (RCT) data (ClinicalTrials.gov identifier: NCT00929253). METHODS: Secondary analysis of an RCT including 170 adults meeting DSM-IV criteria for OUD. Participants were randomized to 12-weeks of treatment-as-usual (TAU) or TAU plus a digital therapeutic providing 67 digital, interactive educational modules based on the Community Reinforcement Approach. TAU consisted of buprenorphine maintenance therapy, 30 min biweekly clinician interaction, and abstinence-based contingency management. Primary endpoints were treatment retention and abstinence (negative urine drug screen) during weeks 9-12 of treatment. Safety was assessed by evaluating adverse events. RESULTS: Participants randomized to TAU plus a digital therapeutic had significantly greater odds of opioid abstinence during weeks 9-12 compared to TAU: 77.3 versus 62.1%, respectively (p=.02), OR 2.08, 95% CI 1.10-3.95. The risk of patients leaving treatment was significantly lower in the digital therapeutic group (HR 0.49, 95% CI 0.26-0.92). No significant difference was observed in the rate of adverse events between groups (p=.42). CONCLUSIONS: A prescription digital therapeutic (PDT) in combination with buprenorphine therapy improves clinically significant patient outcomes including abstinence from illicit opioids and retention in treatment compared with treatment as usual.

Does Episodic Future Thinking Repair Immediacy Bias at Home and in the Laboratory in Patients With Prediabetes?

OBJECTIVE: This study aimed to determine if episodic future thinking (EFT) can decrease delay discounting (DD) among adults with prediabetes both in and out of the laboratory. DD measures how much the value of a reinforcer decreases as a function of the delay to receive it. METHODS: Adults with prediabetes (n = 67) completed a three-session study. At session 1, baseline measures (including DD) were collected. At sessions 2 and 3, participants were prompted to engage in either EFT or control episodic thinking (CET) while completing DD and other measures. In addition, between the completion of sessions 2 and 3, participants engaged in EFT or CET at home and completed DD tasks remotely via smartphones or other Internet-connected devices. RESULTS: Results showed significant -1.2759 (-20.24%) reductions in DD in the EFT group compared with a + 0.0287 (+0.46%) DD increase in the CET group (p = .0149) in the laboratory; and -0.4095 (-8.85%) reduction in DD in the EFT group compared with a + 0.2619 (+5.64%) increase in the CET group (p = .011) at home. Working memory (measured by Backwards Corsi and Digit Span) was found to moderate the effects of EFT on some measures of DD. EFT did not change measures from the food purchase task or a food ad libitum procedure. CONCLUSIONS: Results show that EFT decreases DD in and out of the laboratory and supports the further exploration of EFT as an intervention for prediabetes and related chronic diseases. CLINICAL TRIAL REGISTRATION: NCT03664726.

The temporal window of valuation is constricted among adolescent smokers.

Healthy decisions are associated with valuation of the future whereas unhealthy decisions are associated with devaluation of the future. Comparisons of future discounting of delayed rewards in adolescent smokers and non-smokers have been equivocal and past discounting of monetary gains has not been reported in adolescents. Here, adolescents completed future and past delay discounting tasks. A mixed-model analysis of covariance using a model with the lowest Bayesian Information Criterion revealed that adolescents discount the past more than the future and smokers discount more than non-smokers. These results suggest that adolescent smokers have a constricted temporal window, which may lead to disadvantageous decisions.

Alcohol-dependent individuals discount sex at higher rates than controls.

BACKGROUND: Research on delay discounting has expanded our understanding of substance dependence in many ways. Recently, orderly discounting of sexual rewards has been demonstrated in both substance-dependent individuals, and healthy controls. Less clear, however, is if rates of sexual discounting are higher than controls in alcohol-dependent-individuals. METHODS: 20 alcohol-dependent individuals and 21 healthy control participants completed two delay-discounting tasks. One task involved monetary rewards, whereas the other involved the discounting of sexual rewards (i.e., number of sex acts). RESULTS: Alcohol dependent individuals discounted sexual rewards at significantly higher rates than did controls. There was a trend toward, but not a similarly significant relation for the discounting of monetary rewards. CONCLUSIONS: Rates of sexual discounting are elevated in alcohol dependent individuals. If this relation is replicated in other at risk populations, the rapid devaluation of sexual rewards may be a laboratory marker of impulsive sexual choices.

Excessive discounting of delayed reinforcers as a trans-disease process contributing to addiction and other disease-related vulnerabilities: emerging evidence.

Delay discounting describes the devaluation of a reinforcer as a function of the delay until its receipt. Although all people discount delayed reinforcers, one consistent finding is that substance-dependent individuals tend to discount delayed reinforcers more rapidly than do healthy controls. Moreover, these higher-than-normal discounting rates have been observed in individuals with other behavioral maladies such as pathological gambling, poor health behavior, and overeating. This suggests that high rates of delay discounting may be a trans-disease process (i.e., a process that occurs across a range of disorders, making findings from one disorder relevant to other disorders). In this paper, we argue that delay discounting is a trans-disease process, undergirded by an imbalance between two competing neurobehavioral decision systems. Implications for our understanding of, and treatment for, this trans-disease process are discussed.

Are executive function and impulsivity antipodes? A conceptual reconstruction with special reference to addiction.

RATIONALE: Although there is considerable interest in how either executive function (EF) or impulsivity relate to addiction, there is little apparent overlap between these research areas. OBJECTIVES: The present paper aims to determine if components of these two constructs are conceptual antipodes--widely separated on a shared continuum. METHODS: EFs and impulsivities were compared and contrasted. Specifically, the definitions of the components of EF and impulsivity, the methods used to measure the various components, the populations of drug users that show deficits in these components, and the neural substrates of these components were compared and contrasted. RESULTS: Each component of impulsivity had an antipode in EF. EF, however, covered a wider range of phenomena, including compulsivity. CONCLUSIONS: Impulsivity functions as an antipode of certain components of EF. Recognition of the relationship between EF and impulsivity may inform the scientific inquiry of behavioral problems such as addiction. Other theoretical implications are discussed.

The behavioral economics and neuroeconomics of reinforcer pathologies: implications for etiology and treatment of addiction.

The current paper presents a novel approach to understanding and treating addiction. Drawing from work in behavioral economics and developments in the new field of neuroeconomics, we describe addiction as pathological patterns of responding resulting from the persistently high valuation of a reinforcer and/or an excessive preference for the immediate consumption of that reinforcer. We further suggest that, as indicated by the competing neurobehavioral decision systems theory, these patterns of pathological choice and consumption result from an imbalance between two distinct neurobehavioral systems. Specifically, pathological patterns of responding result from hyperactivity in the evolutionarily older impulsive system (which values immediate and low-cost reinforcers) and/or hypoactivity in the more recently evolved executive system (which is involved in the valuation of delayed reinforcers). This approach is then used to explain five phenomena that we believe any adequate theory of addiction must address.

Buprenorphine medication versus voucher contingencies in promoting abstinence from opioids and cocaine.

During a 12-week intervention, opioid dependent participants (N = 120) maintained on thrice-a-week (M, W, F) buprenorphine plus therapist and computer-based counseling were randomized to receive: (a) medication contingencies (MC = thrice weekly dosing schedule vs. daily attendance and single-day 50% dose reduction imposed upon submission of an opioid and/or cocaine positive urine sample); (b) voucher contingency (VC = escalating schedule for opioid and/or cocaine negative samples with reset for drug-positive samples); or (c) standard care (SC), with no programmed consequences for urinalysis results. VC resulted in better 12-week retention (85%) compared to MC (58%; p = 0.009), but neither differed from SC (76% retained). After adjusting for baseline differences in employment, and compared to SC, the MC group achieved 1.5 more continuous weeks of combined opioid/cocaine abstinence (p = 0.030), while the VC group had 2 more total weeks of abstinence (p = 0.048). Drug use results suggest that both the interventions were efficacious, with effects primarily in opioid rather than cocaine test results. Findings should be interpreted in light of the greater attrition associated with medication-based contingencies versus the greater monetary costs of voucher-based contingencies.

Cigarette smokers discount past and future rewards symmetrically and more than controls: is discounting a measure of impulsivity?

A considerable body of evidence indicates that consideration of the future and past are related. Future discounting studies indicate that cigarette smokers discount future outcomes more than non-smokers. The purpose of the present study was to determine if a similar profile of results could be obtained with a novel procedure evaluating the discounting of past outcomes, providing further support for future/past symmetry. Thirty cigarette smokers and 29 non-smokers participated in a computerized assessment of discounting of hypothetical future and past outcomes. Symmetry was supported, with a similar profile of results in future and past discounting procedures. These included: hyperbolic discounting, greater discounting of small-magnitude outcomes than large-magnitude outcomes, and greater discounting by cigarette smokers relative to non-smokers.

The relationship between temporal discounting and the prisoner's dilemma game in intranasal abusers of prescription opioids.

Previous research on college students has found that cooperation in iterated prisoner's dilemma game is correlated with preference for delayed rewards in studies of temporal discounting. The present study attempted to replicate this finding in a drug-dependent population. Thirty-one individuals who intranasally abuse prescription opioids participated in temporal discounting and iterated prisoner's dilemma game procedures during intake for a treatment study. Rate of temporal discounting was determined for each participant at two hypothetical reward magnitudes, as well as proportion of cooperation in a 60-trial iterated prisoner's dilemma game versus a tit-for-tat strategy. Cooperation in the prisoner's dilemma game and temporal discounting rates were significantly correlated in the predicted direction: individuals who preferred delayed rewards in the temporal discounting task were more likely to cooperate in the prisoner's dilemma game.

Discounting of past outcomes.

Drug use, abuse, and addiction are common behavioral manifestations of impulsiveness. A useful and popular laboratory analogue of impulsiveness is temporal discounting. Temporal discounting refers to the reduction in the present, subjective value of outcomes that are temporally distant in the future. The extensive literature on temporal discounting indicates hyperbolic discounting, the magnitude effect, and the sign effect. It is possible that the same principles may apply to other dimensions of psychological distance, including past temporal distance. The purpose of the present study was to examine the possibility that outcomes in the past are discounted hyperbolically and at a similar rate to outcomes in the future. The magnitude and sign effects were also examined in past discounting. Indifference points of college students were determined from a paper-and-pencil questionnaire of future and past discounting. The results demonstrate that humans discount temporally distant past outcomes similarly to future outcomes. Discounting of the future and past are qualitatively and quantitatively similar; discounting of past outcomes is orderly, hyperbolic, and consistent with most empirical observations from studies of future discounting, including the magnitude and sign effects. The present study indicates that the discounting of past outcomes is a quantifiable phenomenon, and the results are similar to observations from the established future-discounting literature. Past discounting may be of use in the study of drug-dependent and other impulsive populations. Implications of a relationship between future and past discounting are discussed.