Intense Sweetness Surpasses Cocaine Reward

BACKGROUND: Refined sugars (e.g., sucrose, fructose) were absent in the diet of most people until very recently in human history. Today overconsumption of diets rich in sugars contributes together with other factors to drive the current obesity epidemic. Overconsumption of sugar-dense foods or beverages is initially motivated by the pleasure of sweet taste and is often compared to drug addiction. Though there are many biological commonalities between sweetened diets and drugs of abuse, the addictive potential of the former relative to the latter is currently unknown. METHODOLOGY/PRINCIPAL FINDINGS: Here we report that when rats were allowed to choose mutually-exclusively between water sweetened with saccharin-an intense calorie-free sweetener-and intravenous cocaine-a highly addictive and harmful substance-the large majority of animals (94%) preferred the sweet taste of saccharin. The preference for saccharin was not attributable to its unnatural ability to induce sweetness without calories because the same preference was also observed with sucrose, a natural sugar. Finally, the preference for saccharin was not surmountable by increasing doses of cocaine and was observed despite either cocaine intoxication, sensitization or intake escalation-the latter being a hallmark of drug addiction. CONCLUSIONS: Our findings clearly demonstrate that intense sweetness can surpass cocaine reward, even in drug-sensitized and -addicted individuals. We speculate that the addictive potential of intense sweetness results from an inborn hypersensitivity to sweet tastants. In most mammals, including rats and humans, sweet receptors evolved in ancestral environments poor in sugars and are thus not adapted to high concentrations of sweet tastants. The supranormal stimulation of these receptors by sugar-rich diets, such as those now widely available in modern societies, would generate a supranormal reward signal in the brain, with the potential to override self-control mechanisms and thus to lead to addiction

Inventory and Analysis of Controlled Trials of Mobile Phone Applications Targeting Substance Use Disorders: A Systematic Review

Background: Less than 20% of people with addictions have access to adequate treatment. Mobile health could improve access to care. No systematic review evaluates effectiveness of mobile health applications for addiction.Objectives: First aim was to describe controlled trials evaluating the effectiveness of smartphone applications targeting substance use disorders and addictive behaviors. Secondly, we aimed to understand how the application produced changes in behavior and craving management.Method: A systematic review based on PRISMA recommendations was conducted on MEDLINE, CENTRAL, and PsycINFO. Studies had to be controlled trials concerning addictive disorders (substance/behavior), mobile application-based interventions, assessing effectiveness or impact of those applications upon use, published after 2008. Relevant information was systematically screened for synthesis. Quality and risk of bias were evaluated with JADAD score.Results: Search strategy retrieved 22 articles (2014-2019) corresponding to 22 applications targeting tobacco, alcohol, other substances and binge eating disorder. Control groups had access to usual treatments or a placebo-application or no treatment. Eight applications showed reduced use. Most of the applications informed about risks of use and suggestions for monitoring use. Twelve applications managed craving.Discussion: Heterogeneity limited study comparisons. Duration of studies was too short to predict sustainable results. A reduction of craving seemed related to a reduction in use.Conclusion: There is a lack of robust and comparable studies on mHealth applications for addiction treatment. Such applications could become significant contributors in clinical practice in the future so longer-termed double-blind studies are needed. Targeting craving to prevent relapse should be systematic

Smartphone-Based Virtual Agents Can Help the General Population Concerned by Sleep Complaints: A Proof-of-Concept Study During COVID-19 Confinement

Background: The COVID-19 crisis induces psychosocial stress and sleep complaints that require early management. KANOPEE is a smartphone-based application, providing an interaction with a virtual agent dedicated to screen and deliver behavioral interventions to fight sleep disorders. This paper describes the feasibility study of this application, during the context of COVID-19 confinement in France. Method: 2,069 users of aged 18 years and over downloaded the app during the inclusion period (between 22 April and 5 May 2020). Users first answered a screening interview based on the insomnia severity index (ISI) that was conducted by the virtual agent. If participants were positive for insomniac complaints (ISI > 14), they could join a two-stage intervention program: a) complete an electronic sleep diary for one week, and b) follow personalized sleep recommendations for 10 days. Measures collected included socio-demographic information, ISI and sleep/wake schedules; and acceptance and trust of the agent.Bordeaux Region Aquitaine Initiative for NeurosciencePhénotypage humain et réalité virtuell

J Med Internet Res

Background: The COVID-19 crisis and consequent confinement restrictions have caused significant psychosocial stress and reports of sleep complaints, which require early management, have increased during recent months. To help individuals concerned about their sleep, we developed a smartphone-based app called KANOPEE that allows users to interact with a virtual agent dedicated to autonomous screening and delivering digital behavioral interventions. Objective: Our objective was to assess the feasibility of this app, in terms of inclusion rate, follow-up rate, perceived trust and acceptance of the virtual agent, and effects of the intervention program, in the context of COVID-19 confinement in France. Methods: The virtual agent is an artificial intelligence program using decision tree architecture and interacting through natural body motion and natural voice. A total of 2069 users aged 18 years and above downloaded the free app during the study period (April 22 to May 5, 2020). These users first completed a screening interview based on the Insomnia Severity Index (ISI) conducted by the virtual agent. If the users were positive for insomnia complaints (ISI score >14), they were eligible to join the 2-stage intervention program: (1) complete an electronic sleep diary for 1 week and (2) follow personalized sleep recommendations for 10 days. We collected and analyzed the following measures: sociodemographic information, ISI scores and sleep/wake schedules, and acceptance and trust of the agent. Results: Approximately 76% (1574/2069) of the app users completed the screening interview with the virtual agent. The virtual agent was well accepted by 27.4% (431/1574) of the users who answered the acceptance and trust questionnaires on its usability, satisfaction, benevolence, and credibility. Of the 773 screened users who reported sleep complaints (ISI score >14), 166 (21.5%) followed Step 1 of the intervention, and only 47 of those (28.3%) followed Step 2. Users who completed Step 1 found that their insomnia complaints (baseline mean ISI score 18.56, mean ISI score after Step 1 15.99; P21) did not respond to either intervention. Conclusions: These preliminary results suggest that the KANOPEE app is a promising solution to screen populations for sleep complaints and that it provides acceptable and practical behavioral advice for individuals reporting moderately severe insomnia.Bordeaux Region Aquitaine Initiative for NeurosciencePhénotypage humain et réalité virtuell

Front Psychiatry

The rate of individuals with addiction who are currently treated are low, and this can be explained by barriers such as stigma, desire to cope alone, and difficulty to access treatment. These barriers could be overcome by mobile technologies. EMI (Ecological Momentary Intervention) is a treatment procedure characterized by the delivery of interventions (messages on smartphones) to people in their daily lives. EMI presents opportunities for treatments to be available to people during times and in situations when they are most needed. Craving is a strong predictor of relapse and a key target for addiction treatment. Studies using Ecological Momentary Assessment (EMA) method have revealed that, in daily life, person-specific cues could precipitate craving, that in turn, is associated with a higher probability to report substance use and relapse in the following hours. Assessment and management of these specific situations in daily life could help to decrease addictive use and avoid relapse. The Craving-Manager smartphone app has been designed to diagnose addictive disorders, and assess and manage craving as well as individual predictors of use/relapse. It delivers specific and individualized interventions (counseling messages) composed of evidence-based addiction treatments approaches (cognitive behavioral therapy and mindfulness). The Craving-Manager app can be used for any addiction (substance or behavior). The objective of this protocol is to evaluate the efficacy of the Craving-Manager app in decreasing use (of primary substance(s)/addictive behavior(s)) over 4 weeks, among individuals on a waiting list for outpatient addiction treatment. This multicenter double-blind randomized controlled trial (RCT) will compare two parallel groups: experimental group (full interventional version of the app, 4 weeks, EMA + EMI), versus control group (restricted version of the app, 4 weeks, only EMA). Two hundred and seventy-four participants will be recruited in 6 addiction treatment centers in France. This RCT will provide indication on how the Craving-Manager app will reduce addictive use (e.g., better craving management, better stimulus control) in both substance and behavioral addictions. If its efficacy is confirmed, the app could offer the possibility of an easy to use and personalized intervention accessible to the greatest number of individuals with addiction. ClinicalTrials.gov: NCT04732676

Effectiveness and Acceptance of a Smartphone-Based Virtual Agent Screening for Alcohol and Tobacco Problems and Associated Risk Factors During COVID-19 Pandemic in the General Population

Background: During the current COVID-19 pandemic, alcohol, and tobacco are the most available substances for managing stress and can induce a risk of addiction. KANOPEE is a smartphone application available to the general population using an embodied conversational agent (ECA) to screen for experiences of problems with alcohol/tobacco use and to provide follow-up tools for brief intervention.Objectives: This study aimed to determine if the smartphone KANOPEE application could identify people at risk for alcohol and/or tobacco use disorders in the context of the current COVID-19 pandemic, to assess adherence to a 7-day follow-up use diary, and to evaluate trust and acceptance of the application.Methods: The conversational agent, named Jeanne, interviewed participants about perceived problems with the use of alcohol and tobacco since the pandemic and explored risk for tobacco and alcohol use disorder with the five-item Cigarette Dependence Scale (CDS-5) and “Cut Down, Annoyed, Guilty, Eye-opener” (CAGE) questionnaire and experience of craving for each substance. Descriptive, univariate, and multivariate analyses were performed to specify personalized associations with reporting a problem with alcohol/tobacco use; descriptive analysis reported the experience with the intervention and acceptance and trust in the application.Results: From April 22 to October 26, 2020, 1,588 French participants completed the KANOPEE interview, and 318 answered the acceptance and trust scales. Forty-two percent of tobacco users and 27% of alcohol users reported problem use since the pandemic. Positive screening with CDS-5 and CAGE and craving were associated with reported problem use (p < 0.0001). Lockdown period influenced alcohol (p < 0.0005) but not tobacco use (p > 0.05). Eighty-eight percent of users reported that KANOPEE was easy to use, and 82% found Jeanne to be trustworthy and credible.Conclusion: KANOPEE was able to screen for risk factors for substance use disorder (SUD) and was acceptable to users. Reporting craving and being at risk for SUD seem to be early markers to be identified. Alcohol problem use seems to be more reliant on contextual conditions such as confinement. This method is able to offer acceptable, brief, and early intervention with minimal delay for vulnerable people.Bordeaux Region Aquitaine Initiative for NeurosciencePhénotypage humain et réalité virtuell

The daily association between affect and alcohol use: a meta-analysis of individual participant data

Influential psychological theories hypothesize that people consume alcohol in response to the experience of both negative and positive emotions. Despite two decades of daily diary and ecological momentary assessment research, it remains unclear whether people consume more alcohol on days they experience higher negative and positive affect in everyday life. In this preregistered meta-analysis, we synthesized the evidence for these daily associations between affect and alcohol use. We included individual participant data from 69 studies (N = 12,394), which used daily and momentary surveys to assess affect and the number of alcoholic drinks consumed. Results indicate that people are not more likely to drink on days they experience high negative affect, but are more likely to drink and drink heavily on days high in positive affect. People self-reporting a motivational tendency to drink-to-cope and drink-to-enhance consumed more alcohol, but not on days they experienced higher negative and positive affect. Results were robust across different operationalizations of affect, study designs, study populations, and individual characteristics. These findings challenge the long-held belief that people drink more alcohol following increases in negative affect. Integrating these findings under different theoretical models and limitations of this field of research, we collectively propose an agenda for future research to explore open questions surrounding affect and alcohol use.The present study was funded by the Canadian Institutes of Health Research Grant MOP-115104 (Roisin M. O’Connor), Canadian Institutes of Health Research Grant MSH-122803 (Roisin M. O’Connor), John A. Hartford Foundation Grant (Paul Sacco), Loyola University Chicago Research Support Grant (Tracy De Hart), National Institute for Occupational Safety and Health Grant T03OH008435 (Cynthia Mohr), National Institutes of Health (NIH) Grant F31AA023447 (Ryan W. Carpenter), NIH Grant R01AA025936 (Kasey G. Creswell), NIH Grant R01AA025969 (Catharine E. Fairbairn), NIH Grant R21AA024156 (Anne M. Fairlie), NIH Grant F31AA024372 (Fallon Goodman), NIH Grant R01DA047247 (Kevin M. King), NIH Grant K01AA026854 (Ashley N. Linden-Carmichael), NIH Grant K01AA022938 (Jennifer E. Merrill), NIH Grant K23AA024808 (Hayley Treloar Padovano), NIH Grant P60AA11998 (Timothy Trull), NIH Grant MH69472 (Timothy Trull), NIH Grant K01DA035153 (Nisha Gottfredson), NIH Grant P50DA039838 (Ashley N. Linden-Carmichael), NIH Grant K01DA047417 (David M. Lydon-Staley), NIH Grant T32DA037183 (M. Kushner), NIH Grant R21DA038163 (A. Moore), NIH Grant K12DA000167 (M. Potenza, Stephanie S. O’Malley), NIH Grant R01AA025451 (Bruce Bartholow, Thomas M. Piasecki), NIH Grant P50AA03510 (V. Hesselbrock), NIH Grant K01AA13938 (Kristina M. Jackson), NIH Grant K02AA028832 (Kevin M. King), NIH Grant T32AA007455 (M. Larimer), NIH Grant R01AA025037 (Christine M. Lee, M. Patrick), NIH Grant R01AA025611 (Melissa Lewis), NIH Grant R01AA007850 (Robert Miranda), NIH Grant R21AA017273 (Robert Miranda), NIH Grant R03AA014598 (Cynthia Mohr), NIH Grant R29AA09917 (Cynthia Mohr), NIH Grant T32AA07290 (Cynthia Mohr), NIH Grant P01AA019072 (P. Monti), NIH Grant R01AA015553 (J. Morgenstern), NIH Grant R01AA020077 (J. Morgenstern), NIH Grant R21AA017135 (J. Morgenstern), NIH Grant R01AA016621 (Stephanie S. O’Malley), NIH Grant K99AA029459 (Marilyn Piccirillo), NIH Grant F31AA022227 (Nichole Scaglione), NIH Grant R21AA018336 (Katie Witkiewitz), Portuguese State Budget Foundation for Science and Technology Grant UIDB/PSI/01662/2020 (Teresa Freire), University of Washington Population Health COVID-19 Rapid Response Grant (J. Kanter, Adam M. Kuczynski), U.S. Department of Defense Grant W81XWH-13-2-0020 (Cynthia Mohr), SANPSY Laboratory Core Support Grant CNRS USR 3413 (Marc Auriacombe), Social Sciences and Humanities Research Council of Canada Grant (N. Galambos), and Social Sciences and Humanities Research Council of Canada Grant (Andrea L. Howard)

Cocaine Is Low on the Value Ladder of Rats: Possible Evidence for Resilience to Addiction

International audienceBACKGROUND:Assessing the relative value of cocaine and how it changes with chronic drug use represents a long-standing goal in addiction research. Surprisingly, recent experiments in rats--by far the most frequently used animal model in this field--suggest that the value of cocaine is lower than previously thought.METHODOLOGY/PRINCIPAL FINDINGS:Here we report a series of choice experiments that better define the relative position of cocaine on the value ladder of rats (i.e., preference rank-ordering of different rewards). Rats were allowed to choose either taking cocaine or drinking water sweetened with saccharin--a nondrug alternative that is not biologically essential. By systematically varying the cost and concentration of sweet water, we found that cocaine is low on the value ladder of the large majority of rats, near the lowest concentrations of sweet water. In addition, a retrospective analysis of all experiments over the past 5 years revealed that no matter how heavy was past cocaine use most rats readily give up cocaine use in favor of the nondrug alternative. Only a minority, fewer than 15% at the heaviest level of past cocaine use, continued to take cocaine, even when hungry and offered a natural sugar that could relieve their need of calories.CONCLUSIONS/SIGNIFICANCE:This pattern of results (cocaine abstinence in most rats; cocaine preference in few rats) maps well onto the epidemiology of human cocaine addiction and suggests that only a minority of rats would be vulnerable to cocaine addiction while the large majority would be resilient despite extensive drug use. Resilience to drug addiction has long been suspected in humans but could not be firmly established, mostly because it is difficult to control retrospectively for differences in drug self-exposure and/or availability in human drug users. This conclusion has important implications for preclinical research on the neurobiology of cocaine addiction and for future medication development

Ecological Momentary Assessment (EMA) to explore craving in daily life : influence of conditioned stimuli and relationship with substance use

Le craving est considéré comme une composante centrale de l’addiction, potentiellement impliquée dans les processus de rechute, et influencée par de nombreux facteurs. Les études ayant examiné le lien entre craving et rechute montrent cependant des résultats contradictoires. Ces divergences pourraient s’expliquer par les limites méthodologiques rencontrées pour évaluer le craving de façon rétrospective ou pour l’induire expérimentalement en laboratoire. La méthode EMA (Ecological Momentary Assessment) utilise des technologies mobiles afin d’évaluer les sujets dans leur environnement naturel et de récolter des données en temps réel. Cette approche est particulièrement intéressante pour étudier les fluctuations rapides du craving, capturer l’influence des variables environnementales, ainsi que pour examiner le lien prospectif entre plusieurs variables. L’objectif général de cette thèse était d’utiliser la méthode EMA afin d’examiner en vie quotidienne le craving, ses modérateurs, et son lien avec l’usage de substances chez des sujets dépendants débutant une prise en charge pour une addiction à une substance. L’analyse de la littérature révèle que la majorité des études EMA examinant le craving concerne le tabac et l’alcool, et que peu d’études ont examiné ce phénomène pour des substances illégales. La partie expérimentale de cette thèse a permis de 1) démontrer la faisabilité et la validité de la méthode EMA chez des sujets dépendants, quelle que soit la substance de dépendance (tabac, alcool, cannabis ou opiacés), 2) montrer un lien prospectif unidirectionnel entre l’intensité du craving et l’usage de substances pour les 4 groupes de substances, et 3) mettre en évidence une augmentation du craving face à des stimuli conditionnés (cues) rencontrés en vie quotidienne, augmentation d’autant plus importante qu’il s’agissait de cues individuels (personnels à chaque sujet). Cette étude démontre l’intérêt de la méthode EMA dans l’étude des addictions, souligne le rôle du craving dans les processus de rechute, et encourage le développement de protocoles d’extinction de la réactivité aux cues centrés sur des cues individuels propres à chaque sujet.Craving is a central component of addiction, involved in relapse process and under the influence of many factors. However, studies examining the link between craving and relapse have revealed some contradictory results. These inconsistencies could be due to limits encountered to assess craving in laboratory or clinical settings. Ecological Momentary Assessment (EMA) methods use mobile technologies to assess subjects in their daily life, and collect data in real time. EMA is particularly well suited to assess fluctuations of craving, capture influence of environmental moderators, and examine prospective link between variables. The objective of this thesis was to use EMA to examine craving, its moderators, and its link with substance use in daily life among substance-dependent outpatients evaluated at treatment intake. Review of the literature revealed that majority of EMA studies examining craving concerned tobacco and alcohol, but only few examined illegal substances. The experimental part of this thesis 1) demonstrated that EMA methods are feasible and provide valid data in individuals with dependence for different types of substances (tobacco, alcohol, cannabis, opiates), 2) showed a prospective unidirectional association between craving and subsequent substance use in the 4 groups of substances, and 3) confirmed that conditioned stimuli (cues) encountered in daily life are associated with an increase of craving intensity, and showed that individual personalized cues elicit a more robust effect on craving compared to standard cues. These results highlight the relevance of using EMA methods to study addiction, suggest that craving has a key place in the relapse process, and encourage to develop tailorised extinction protocols centered on individual cues rather than standard non-specific cues

Ecological Momentary Assessment (EMA) to explore craving in daily life : influence of conditioned stimuli and relationship with substance use

Le craving est considéré comme une composante centrale de l’addiction, potentiellement impliquée dans les processus de rechute, et influencée par de nombreux facteurs. Les études ayant examiné le lien entre craving et rechute montrent cependant des résultats contradictoires. Ces divergences pourraient s’expliquer par les limites méthodologiques rencontrées pour évaluer le craving de façon rétrospective ou pour l’induire expérimentalement en laboratoire. La méthode EMA (Ecological Momentary Assessment) utilise des technologies mobiles afin d’évaluer les sujets dans leur environnement naturel et de récolter des données en temps réel. Cette approche est particulièrement intéressante pour étudier les fluctuations rapides du craving, capturer l’influence des variables environnementales, ainsi que pour examiner le lien prospectif entre plusieurs variables. L’objectif général de cette thèse était d’utiliser la méthode EMA afin d’examiner en vie quotidienne le craving, ses modérateurs, et son lien avec l’usage de substances chez des sujets dépendants débutant une prise en charge pour une addiction à une substance. L’analyse de la littérature révèle que la majorité des études EMA examinant le craving concerne le tabac et l’alcool, et que peu d’études ont examiné ce phénomène pour des substances illégales. La partie expérimentale de cette thèse a permis de 1) démontrer la faisabilité et la validité de la méthode EMA chez des sujets dépendants, quelle que soit la substance de dépendance (tabac, alcool, cannabis ou opiacés), 2) montrer un lien prospectif unidirectionnel entre l’intensité du craving et l’usage de substances pour les 4 groupes de substances, et 3) mettre en évidence une augmentation du craving face à des stimuli conditionnés (cues) rencontrés en vie quotidienne, augmentation d’autant plus importante qu’il s’agissait de cues individuels (personnels à chaque sujet). Cette étude démontre l’intérêt de la méthode EMA dans l’étude des addictions, souligne le rôle du craving dans les processus de rechute, et encourage le développement de protocoles d’extinction de la réactivité aux cues centrés sur des cues individuels propres à chaque sujet.Craving is a central component of addiction, involved in relapse process and under the influence of many factors. However, studies examining the link between craving and relapse have revealed some contradictory results. These inconsistencies could be due to limits encountered to assess craving in laboratory or clinical settings. Ecological Momentary Assessment (EMA) methods use mobile technologies to assess subjects in their daily life, and collect data in real time. EMA is particularly well suited to assess fluctuations of craving, capture influence of environmental moderators, and examine prospective link between variables. The objective of this thesis was to use EMA to examine craving, its moderators, and its link with substance use in daily life among substance-dependent outpatients evaluated at treatment intake. Review of the literature revealed that majority of EMA studies examining craving concerned tobacco and alcohol, but only few examined illegal substances. The experimental part of this thesis 1) demonstrated that EMA methods are feasible and provide valid data in individuals with dependence for different types of substances (tobacco, alcohol, cannabis, opiates), 2) showed a prospective unidirectional association between craving and subsequent substance use in the 4 groups of substances, and 3) confirmed that conditioned stimuli (cues) encountered in daily life are associated with an increase of craving intensity, and showed that individual personalized cues elicit a more robust effect on craving compared to standard cues. These results highlight the relevance of using EMA methods to study addiction, suggest that craving has a key place in the relapse process, and encourage to develop tailorised extinction protocols centered on individual cues rather than standard non-specific cues