Fuschia Serre

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.

Cocaine is low on the value ladder of rats: possible evidence for resilience to addiction.

Background 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 in the investigation of craving and substance use in daily life: A systematic review

BACKGROUND Craving is viewed as a major determinant of relapse in persons with substance addiction, but this association remains poorly understood due to its time-limited nature and the biases associated with retrospective reporting. Ecological momentary assessment (EMA) offers new opportunities to examine both craving and substance use with strong ecological validity by collecting real-time data in daily life. This review examined all published studies using EMA to: (1) assess the link between craving and substance use; and (2) identify relevant moderators of craving among substance users. METHODS We searched PubMed and PsycInfo databases up to October 31, 2013. RESULTS Ninety-one studies were selected, involving mostly tobacco smokers (73%). A majority of studies (92%) reported a positive relationship between craving and substance use, concurrently and prospectively, and among users with different levels of use for both legal and illegal substances. Results suggest that craving is a stronger predictor of relapse episodes when assessed in close temporal proximity to substance use. EMA data also confirmed the influence of diverse within-person and between-person sources of variation in daily life craving reports. CONCLUSIONS This review provides strong support for the link between craving and substance use, and underscores the importance of the timing of assessments.

Extended Heroin Access Increases Heroin Choices Over a Potent Nondrug Alternative

Epidemiological research shows that the proportion of drug users who become addicted to heroin is higher than to cocaine. Here we tested whether this difference could be due to a difference in the addiction liability between the two drugs. Addiction liability was assessed under a discrete-trials choice procedure by measuring the proportion of rats that prefer the drug over a potent alternative reward (ie, water sweetened with saccharin). Previous research on choice between self-administration of i.v. cocaine or sweet water showed that the proportion of cocaine-preferring rats remains relatively low and invariable (ie, 15%), even after extended drug access and regardless of past drug consumption (ie, total drug use before choice testing). By contrast, the present study shows that under similar choice conditions, the proportion of heroin-preferring rats considerably increases with extended heroin access (6–9 h per day for several weeks) and with past heroin consumption, from 11 to 51% at the highest past drug consumption level. At this level, the proportion of drug-preferring rats was about three times higher with heroin than with cocaine (51% vs 15%). This increase in the rate of heroin preference after extended heroin access persisted even after recovery from acute heroin withdrawal. Overall, these findings show that choice procedures are uniquely sensitive to different drugs and suggest that heroin is more addictive than cocaine. This higher addiction liability may contribute to explain why more drug users become addicted to heroin than to cocaine in epidemiological studies.

Ecological momentary assessment in alcohol, tobacco, cannabis and opiate dependence: A comparison of feasibility and validity

BACKGROUND Despite growing use of computerized ambulatory monitoring in substance dependence research, little is known about the comparative feasibility and validity of these novel methods by substance type. This study compares the feasibility and validity of computerized ambulatory monitoring in outpatients seeking treatment for alcohol, tobacco, cannabis or opiate dependence. METHODS A total of 109 participants were recruited from an outpatient treatment center and completed standard clinical instruments followed by 2 weeks of computerized ambulatory monitoring of daily life experiences and substance use. RESULTS Individuals with cannabis dependence had the lowest rates of study acceptance (31%) as well as compliance with the repeated electronic interviews (79.9%), while those with tobacco dependence had the highest rates (62% and 91.0%, respectively). Concurrent validity was found between scores from standard clinical instruments and similar constructs assessed in daily life, with no difference by substance group. While no fatigue effects were detected, change in some variables was observed as a function of time in the study. CONCLUSIONS Computerized ambulatory protocols are feasible and provide valid data in individuals with diverse forms of dependence, but compliance to repeated sampling methodology may vary by substance type.

Choosing Under the Influence: A Drug-Specific Mechanism by Which the Setting Controls Drug Choices in Rats

Ample evidence shows that the setting can control drug choices in both humans and animals. Here we reveal in rats that a major mechanism of this control involves a regulation of the drug influence on other competing options at the time of choice. Briefly, rats were offered a choice between a drug dose (cocaine or heroin) and a brief access to water sweetened with saccharin in two different settings. In one setting, choosing under the influence was not possible and rats largely preferred saccharin over either cocaine or heroin. In contrast, when the same rats were shifted to a setting where choosing under the influence was possible, they chose the drug either nonexclusively or exclusively depending on whether the drug enhanced or suppressed sweet reward, respectively. Thus, when rats were under the orexigenic influence of heroin at the time of choice, they more frequently chose saccharin in alternation with heroin. In contrast, when rats were under the anorexic influence of cocaine, they stopped choosing saccharin and continued taking cocaine exclusively. These setting- and drug-specific changes in preference were rapid and reversible, and could be induced by passively administering cocaine or heroin before choice. Finally, rats behaved as if they were oblivious to the drug influence on their choices. This behavior could explain why rats are vulnerable to harm themselves, sometimes to the point of death, in settings where choices are made under the drug influence, notably if this influence excludes other important options or, conversely, enhances harmful ones.

Association between morningness/eveningness, addiction severity and psychiatric disorders among individuals with addictions.

Studies have shown that Evening-Type (ET) subjects used more stimulating and sedative substances, and presented more psychiatric disorders than Morning-Type (MT) subject. However, there is a lack of data on the chronotype of patients with addiction. The aim of our study was to describe chronotype and associated factors in a sample of outpatients beginning treatment for addiction. Subjects were assessed with the Morningness-Eveningness questionnaire of Hörne & Ostberg, the Addiction Severity Index and the Mini International Neuropsychiatric Interview. In the 333 subjects with an addiction, 20% were MT and 32% were ET. When comparing ET to MT, multivariate analysis showed that ET was significantly associated with poly-problematic addiction, non-substance addictions, cannabis addiction, and mood disorders, but not with severity of addiction. MT was associated with antisocial personality disorder. Results suggested that chronotype was associated with specific addiction pattern and psychiatric disorders.

Addiction severity pattern associated with adult and childhood Attention Deficit Hyperactivity Disorder (ADHD) in patients with addictions

Attention Deficit Hyperactivity Disorder (ADHD) is highly prevalent among adults with addictive disorders, but little is known about addiction patterns associated with ADHD diagnosis. This study examined addiction severity in patients with co-occurring addictive disorders and ADHD controlling for the potential influence of associated psychiatric comorbidity. Data were collected in French outpatient addiction treatment centers. A total of 217 patients seeking treatment for substance or gambling addiction were included. At treatment entry, participants were interviewed with the Addiction Severity Index, the Conners Adult ADHD Diagnosis Interview for the DSM-IV (CAADID), the Mini International Neuropsychiatric Interview (MINI) and the Structured Clinical Interview for DSM-IV Axis II for borderline personality disorder (SCID II). History of ADHD was associated with an earlier onset of addiction, poly-dependence (defined by presence of at least two current substance dependence diagnoses in addition to tobacco dependence if present) and borderline personality disorder. Persistence of ADHD during adulthood was associated with a higher prevalence of poly-dependence. This study highlights the need for early implementation of preventive interventions for substance use or behavioral addiction in children/adolescents with ADHD and the need to consider ADHD in the treatment of addictive disorders.

Predictors of craving and substance use among patients with alcohol, tobacco, cannabis or opiate addictions: Commonalities and specificities across substances

INTRODUCTION Craving has been proposed as a major contributor to addiction relapse and the influence of mood on craving and substance use has been extensively documented. However, information is lacking concerning the extent to which the magnitude of these effects may vary according to different types of substances. The aim of the present study was to compare the prospective links between emotions, craving and substance use in four groups of patients beginning treatment for alcohol, tobacco, cannabis, or opiate addiction. METHODS Ecological Momentary Assessment (EMA) was used over a two-week period. Data were analyzed using hierarchical linear modeling (HLM). RESULTS 159 participants were recruited (67.3% male; M = 36.7 years). The average response rate to the EMA assessments was 83.1%. The findings confirmed the strong predictive role of craving intensity on substance use reported at the next assessment of the day among the alcohol (γ = 0.224; p = .018), tobacco (γ = 0.133; p = .013) and cannabis groups (γ = 0.266; p = .019), but not for opiates (γ = 0.098; p = .142). Craving intensity was itself predicted by greater anxious mood (γ = 0.108; p = 0,029) and event negativity (γ = 0.107; p = .003) among tobacco patients, lower sad mood among cannabis patients (γ = -0.248; p = 0,002), and lower event negativity among opiate patients (γ = -0.201; p = .002). CONCLUSION While these results support the benefit of targeting craving in addiction treatment regardless of substance type, the substance-specific emotional risk factors for craving identified in this study may provide important insights for the development of personalized treatment strategies.

Effects of anxiety and mood disorders on craving and substance use among patients with substance use disorder: an ecological momentary assessment study

BACKGROUND Despite recognition of the negative impact of psychiatric comorbidity on addictive disorders, the mechanisms underlying this association remain poorly understood. The present investigation applied mobile technologies to examine the effect of comorbid mood or anxiety disorders on craving intensity and substance use within the natural conditions of daily life. METHODS A total of 159 participants were recruited from a French outpatient addiction clinic and completed two weeks of computerized ambulatory monitoring of daily life experiences using Ecological Momentary Assessment (EMA). Patients described in real-time their emotional states, craving intensity, and substance use. Current mood and/or anxiety disorders were diagnosed according to DSM-IV criteria. The main substances of dependence were alcohol (n = 48), tobacco (n = 43), cannabis (n = 35), or opiates (n = 33). RESULTS Craving intensity strongly predicted substance use reported over subsequent hours of the day both in groups with (OR = 1.13, p = .009, n = 95) and without (OR = 1.20, p = .002, n = 64) current comorbid psychiatric disorders. Current comorbid mood and/or anxiety disorders were associated with higher craving intensity (γ coef = 0.632, SE = 0.254, p = .014) and consequently more frequent substance use (γ coef = 0.162, SE = 0.052, p = .003). A portion of increased substance use associated with current mood and/or anxiety disorders was independent of increases in craving intensity. CONCLUSIONS Attention to craving management is particularly important for patients with substance use disorders and comorbid mood and/or anxiety disorders, but additional interventions are also needed that address other mechanisms through which these disorders lead to an increase in substance use frequency, independently from craving.