Neural correlates of naturalistic single-trial appetitive conditioning.

BACKGROUND: Prior research suggests naturalistic single-trial appetitive conditioning may be a potent phenomenon in humans, capable of modulating both motivation and attention. In this study, we aimed to characterise the neural correlates of this phenomenon using functional Magnetic Resonance Imaging (fMRI) paradigms METHODS: Twenty-three healthy adults (12 males) underwent conditioning during which they ate a novel 3D object made from white chocolate (CS+) and handled a similar object made from plastic (CS-). Brain activity was recorded before and after conditioning during a passive viewing paradigm RESULTS: A naturalistic CS+ was rated as more highly craved, better-liked and elicited greater expectancies for chocolate than the CS- after conditioning. An exploration of the interaction between time (pre- and post-conditioning) and CS type (CS+, CS-) during the passive viewing task suggested enhanced activation from pre- to post-conditioning in the right superior frontal gyrus (R.SFG) in response to the CS-. CONCLUSION: Results reveal neural correlates of single-trial appetitive conditioning and highlight a possible role of response inhibition during learning about non-rewards, perhaps optimizing motivated behaviour. These findings contribute to our understanding of the neural mechanisms underpinning rapid reward and non-reward learning, and may inform development of behavioural interventions for reward-driven overeating.

A Systematic Review and Activation Likelihood Estimation Meta-Analysis of fMRI Studies on Sweet Taste in Humans.

BACKGROUND: The reward value of palatable foods is often cited as an important influence on eating behaviors, including intake of sugars. However, human neuroimaging studies have generated conflicting evidence on the basic neural representation of taste and reward responses to caloric sweeteners (sucrose and glucose), and most relevant studies have used small subject numbers. OBJECTIVE: We conducted a systematic review and a coordinate-based meta-analysis of studies reporting brain responses to oral sugar solutions. METHODS: A systematic search of MEDLINE, Scopus, and PsycINFO through October 2019 identified fMRI studies (in healthy human adults, including those with overweight or obesity) assessing differences in responses to purified sweet and nonsweet taste stimuli. Data were extracted with the primary objective of quantifying evidence for the activation of brain regions associated with caloric sweet taste sensation. We used activation likelihood estimation meta-analysis methods. We also performed multiple sensitivity analyses to assess the generality of effects. RESULTS: Of 455 unique articles, 15 met the criteria for inclusion. These contributed to 2 primary meta-analyses: 1) sucrose (13 experiments, 179 coordinates, n = 241) and 2) sucrose + glucose (16 experiments, 209 coordinates, n = 262). Consistent activation was apparent in primary taste areas: insula (69.2% of studies) and opercular cortex (76.9% of studies), precentral gyri (53.9% of studies), and globus pallidus and postcentral gyrus (30.8% of studies for each). Evidence of reward activity (caudate) was seen in the primary analyses (30.8% of studies) but not in sensitivity analysis. CONCLUSIONS: We confirm the importance of primary taste areas for gustatory processing in human adults. We also provide tentative evidence for reward-related caudate activity in relation to the sweet taste of caloric sugars. A number of factors affect the observation and interpretation of brain responses, including reward-related activity. Firm conclusions require confirmation with large data set studies.

Exploring the munchies: An online survey of users' experiences of cannabis effects on appetite and the development of a Cannabinoid Eating Experience Questionnaire.

BACKGROUND: Cannabis intoxication is commonly reported to increase appetite and enhance appreciation of food (the 'munchies'). These effects are attributed to activation of the endocannabinoid system. However, the psychological changes that underlie these phenomena are under-researched. We report here the results of an extensive online survey of cannabis users with an exploratory Cannabinoid Eating Experience Questionnaire (CEEQ). METHOD: Frequent cannabis users completed a 46-item questionnaire about their eating behaviour under the influence of cannabis. An English-speaking sample (n=591) provided data for the initial exploratory validation of the scale. A second Dutch-language survey (n=163) was used for confirmatory factor analysis. Test-retest reliability was based on a third English-speaking sample (n=40) who completed the revised, 28-item CEEQ twice across 2 weeks. RESULTS: Principal components analysis provided a two-factor solution. Factor 1 (hedonic) comprised 14 items that related primarily to the enjoyment and altered sensory aspects of eating. Factor 2 (appetitive) comprised a further 14 items related to motivational factors that instigate or promote eating. The two-factor structure was supported by confirmatory factor analysis. Both the hedonic and appetitive subscales had good internal reliability (α=0.92 for each subscale, in two independent samples). Good test-retest reliability was obtained for the revised 28-item questionnaire (ps<.01 for Total CEEQ and each subscale). CONCLUSION: The Cannabinoid Eating Experience Questionnaire provided a valid, reliable assessment of the psychological features of cannabis-induced alterations to appetite. Our data confirm that cannabis principally influences the motivational factors that lead to the initiation of eating and the hedonic factors implicated in maintaining eating.

Pre- and postprandial variation in implicit attention to food images reflects appetite and sensory-specific satiety.

Implicit attentional processes are biased toward food-related stimuli, with the extent of that bias reflecting relative motivation to eat. These interactions have typically been investigated by comparisons between fasted and sated individuals. In this study, temporal changes in implicit attention to food were assessed in relation to natural, spontaneous changes in appetite occurring before and after an anticipated midday meal. Non-fasted adults performed an emotional blink of attention (EBA) task at intervals, before and after consuming preferred, pre-selected sandwiches to satiety. Participants were required to detect targets within a rapid visual stream, presented after task-irrelevant food (preferred or non-preferred sandwiches, or desserts) or non-food distractor images. All categories of food distractor preferentially captured attention even when appetite levels were low, but became more distracting as appetite increased preprandially, reducing task accuracy maximally as hunger peaked before lunch. Postprandially, attentional capture was markedly reduced for images of the specific sandwich type consumed and, to a lesser extent, for images of other sandwich types that had not been eaten. Attentional capture by images of desserts was unaffected by satiation. These findings support an important role of selective visual attention in the guidance of motivated behaviour. Naturalistic, meal-related changes in appetite are accompanied by changes in implicit attention to visual food stimuli that are easily detected using the EBA paradigm. Preprandial enhancement of attention capture by food cues likely reflects increases in the incentive motivational value of all food stimuli, perhaps providing an implicit index of wanting. Postprandial EBA responses confirm that satiation on a particular food results in relative inattention to that food, supporting an important attentional component in the operation of sensory-specific satiety.

Persuasive techniques used in television advertisements to market foods to UK children.

The aim of this study was to quantify the nature and extent of use of persuasive marketing techniques in television advertisements (adverts) to promote foods to children. Popular UK commercial television channels broadcasting children's/family viewing were recorded for 2 days (6 am-10 pm) every month in 2008 and recordings were screened for adverts. Eighteen thousand eight hundred and eighty eight adverts were for food and these were coded for peak/non-peak children's viewing time and representation of core (healthy)/non-core (unhealthy)/miscellaneous foods. The analysis assessed use of persuasive appeals, premium offers, promotional characters (brand equity and licensed characters), celebrity endorsers and website promotion in food adverts. Promotional characters, celebrity endorsers and premium offers were used more frequently to promote non-core than core foods, even on dedicated children's channels. Brand equity characters featured on a greater proportion of food adverts than licensed characters. A food brand website was promoted in a third of food adverts (websites are not covered by the statutory regulation on food advertising). This extensive analysis of television adverts demonstrated that the use of persuasive marketing techniques to promote unhealthy foods was extensive in broadcasting popular with children despite regulations. Further studies should incorporate an analysis of the content of websites promoted during food adverts.

The extent of food advertising to children on UK television in 2008.

OBJECTIVE: To provide the most comprehensive analysis to date of the extent of food advertising on UK television channels popular with young people following regulatory reform of this type of marketing activity. METHODS: UK television was recorded 06:00-22:00 h for a weekday and a weekend day every month between January and December 2008 for 14 of the most popular commercial channels broadcasting children's/family viewing. Recordings were screened for advertisements, which were coded according to predefined categories including whether they were broadcast in peak/non-peak children's viewing time. Food advertisements were coded as core (healthy)/non-core (unhealthy)/miscellaneous foods. RESULTS: Food and drinks were the third most heavily advertised product category, and there were a significantly greater proportion of advertisements for food/drinks during peak compared to non-peak children's viewing times. A significantly greater proportion of the advertisements broadcast around soap operas than around children's programmes were for food/drinks. Children's channels broadcast a significantly greater proportion of non-core food advertisements than the family channels. There were significant differences between recording months for the proportion of core/non-core/miscellaneous food advertisements. CONCLUSIONS: Despite regulation, children in the UK are exposed to more TV advertising for unhealthy than healthy food items, even at peak children's viewing times. There remains scope to strengthen the rules regarding advertising of HFSS foods around programming popular with children and adults alike, where current regulations do not apply. Ongoing, systematic monitoring is essential for evaluation of the effectiveness of regulations designed to reduce children's exposure to HFSS food advertising on television in the UK.

Food commercials increase preference for energy-dense foods, particularly in children who watch more television.

OBJECTIVE: Our aim was to determine if levels of television viewing (a proxy measure for habitual commercial exposure) affect children's food preference responses to television food commercials. METHODS: A total of 281 children aged 6 to 13 years from northwest England viewed toy or food television commercials followed by a cartoon on 2 separate occasions; they then completed 3 food preference measures, a commercial recognition task, and a television viewing questionnaire. RESULTS: After viewing the food commercials, all children selected more branded and nonbranded fat-rich and carbohydrate-rich items from food preference checklists compared with after viewing the toy commercials. The food preferences of children with higher habitual levels of television viewing were more affected by food commercial exposure than those of low television viewers. After viewing food commercials, high television viewing children selected a greater number of branded food items compared with after the toy commercials as well as compared with the low television viewers. Children correctly recognized more food commercials than toy commercials. CONCLUSIONS: Exposure to television food commercials enhanced high television viewers' preferences for branded foods and increased reported preferences for all food items (branded and nonbranded) relative to the low television viewers. This is the first study to demonstrate that children with greater previous exposure to commercials (high television viewers) seemed to be more responsive to food promotion messages than children with lower previous advertising exposure.

Pharmacological management of appetite expression in obesity.

For obese individuals, successful weight loss and maintenance are notoriously difficult. Traditional drug development fails to exploit knowledge of the psychological factors that crucially influence appetite, concentrating instead on restrictive criteria of intake and weight reduction, allied to a mechanistic view of energy regulation. Drugs are under development that may produce beneficial changes in appetite expression in the obese. These currently include glucagon-like peptide-1 analogs such as liraglutide, an amylin analog davalintide, the 5-HT(2C) receptor agonist lorcaserin, the monoamine re-uptake inhibitor tesofensine, and a number of combination therapies such as pramlintide and metreleptin, bupropion and naltrexone, phentermine and topiramate, and bupropion and zonisamide. However, the effects of these treatments on eating behavior remain poorly characterized. Obesity is typically a consequence of overconsumption driven by an individual's natural sensitivity to food stimuli and the pleasure derived from eating. Intuitively, these processes should be effective targets for pharmacotherapy, and behavioral analysis can identify drugs that selectively affect desire to eat, enjoyment of eating, satiation or postmeal satiety. Rational interventions designed specifically to modulate these processes could limit the normally aversive consequences of caloric restriction and maximize an individual's capacity to successfully gain control over their appetite.

Cannabinoids and appetite: food craving and food pleasure.

The ability of Cannabis sativa to promote eating has been documented for many centuries, with the drug reported by its users to promote strong cravings for, and an intensification of the sensory and hedonic properties of food. These effects are now known to result from the actions of cannabinoid molecules at specific cannabinoid receptor sites within the brain, and to reflect the physiological role of their natural ligands, the endocannabinoids, in the control of appetite. Recent developments in the biochemistry and pharmacology of endocannabinoid systems have generated convincing evidence from animal models for a normal role of endocannabinoids in the control of eating motivation. The availability of specific cannabinoid receptor agonists and antagonists raises the possibility of improved therapies for disorders of eating and body weight: not only in the suppression of appetite to counter our susceptibility to the over-consumption of highly pleasurable and energy-dense foods; but also in the treatment of conditions that involve reduced appetite and weight loss. Here, we outline some of the findings of the past decade that link endocannabinoid function appetite control, and the possible clinical applications of that knowledge.

Endocannabinoids and the non-homeostatic control of appetite.

The usual physiological perspective on appetite and food intake regards control of eating simplistically, as merely the reflexive behavioural component of a strict homeostatic regulatory system. Hunger is seen to arise in response to energy deficit; meal size is determined by the passage of nutrients into the gut and the stimulation of multiple satiety signals; and overall energy intake is modified to reflect the balance of fuel reserves and energy expenditure. But everyday experience shows that we rarely eat simply through need. Rather, food stimuli exert a powerful influence over consumption through their appeal to innate and learned appetites, generating the psychological experiences of hunger, craving and delight independently of energy status. That these important and influential subjective experiences are mediated through complex neurochemical processes is self-evident; but the chemical nature of our infatuation with, and subservience to, the motivating properties of foods are overshadowed by mechanistic, peripherally anchored models that take little account of psychological factors, and which consequently struggle to explain the phenomenon of obesity. This chapter discusses recent developments that suggest the endocannabinoids are key components of the central mechanisms that give rise to the emotional and motivational experiences that lead us to eat and to overconsume.

The effect of Korean pine nut oil (PinnoThin) on food intake, feeding behaviour and appetite: a double-blind placebo-controlled trial.

Certain free fatty acids have been shown to have potent effects on food intake and self-reported changes in appetite; effects associated with increases in the release of endogenous cholecystokinin (CCK) and glucagon like peptide-1 (GLP-1). In the current study, the effects of a Korean pine nut oil product, PinnoThin, at doses 2 g, 4 g and 6 g triglyceride (TG) and 2 g free fatty acid (FFA), on food intake and appetite were examined in a cross-over double-blind placebo-controlled randomised counter-balanced design in 42 overweight female volunteers. 2 g FFA PinnoThin, given 30 minutes prior to an ad-libitum buffet test lunch, significantly reduced food intake (gram) by 9% (F(4,164) = 2.637, p = 0.036) compared to olive oil control. No significant effect of PinnoThin on macronutrient intake or ratings of appetite were observed. Given the recent data showing that the TG form of PinnoThin may also reduce appetite by increasing CCK release, the lack of any effect of the TG form found in this study could be attributed to the timing of the dosing regime. Collectively, these data suggest that PinnoThin may exert satiating effects consistent with its known action on CCK and GLP-1 release, and previously observed effects on self-reported appetite ratings.

Taranabant cuts the fat: new hope for cannabinoid-based obesity therapies?

Endocannabinoid/cannabinoid receptor signaling acts centrally and peripherally to govern appetite and energy balance. While system stimulation promotes eating and energy storage, receptor blockade can reduce food intake and facilitate weight loss. In this issue of Cell Metabolism, Addy et al. (2008) test the therapeutic antiobesity potential of taranabant, a cannabinoid 1 receptor inverse agonist.

Cannabinoids and ghrelin have both central and peripheral metabolic and cardiac effects via AMP-activated protein kinase.

Endocannabinoids and ghrelin are potent appetite stimulators and are known to interact at a hypothalamic level. However, both also have important peripheral actions, including beneficial effects on the ischemic heart and increasing adipose tissue deposition, while ghrelin has direct effects on carbohydrate metabolism. The AMP-activated protein kinase (AMPK) is a heterotrimeric enzyme that functions as a fuel sensor to regulate energy balance at both cellular and whole body levels, and it may mediate the action of anti-diabetic drugs such as metformin and peroxisome proliferator-activated receptor gamma agonists. Here we show that both cannabinoids and ghrelin stimulate AMPK activity in the hypothalamus and the heart, while inhibiting AMPK in liver and adipose tissue. These novel effects of cannabinoids on AMPK provide a mechanism for a number of their known actions, such as the reduction in infarct size in the myocardium, an increase in adipose tissue, and stimulation of appetite. The beneficial effects of ghrelin on heart function, including reduction of myocyte apoptosis, and its effects on lipogenesis and carbohydrate metabolism, can also be explained by its ability to activate AMPK. Our data demonstrate that AMPK not only links the orexigenic effects of endocannabinoids and ghrelin in the hypothalamus but also their effects on the metabolism of peripheral tissues.

Endocannabinoids and food intake: newborn suckling and appetite regulation in adulthood.

The appetite-stimulating effects of the cannabis plant (Cannabis sativa) have been known since ancient times, and appear to be effected through the incentive and rewarding properties of foods. Investigations into the biological basis of the multiple effects of cannabis have yielded important breakthroughs in recent years: the discovery of two cannabinoid receptors in brain and peripheral organ systems, and endogenous ligands (endocannabinoids) for these receptors. These advances have greatly increased our understanding of how appetite is regulated through these endocannabinoid receptor systems. The presence of endocannabinoids in the developing brain and in maternal milk have led to evidence for a critical role for CB1 receptors in oral motor control of suckling during neonatal development. The endocannabinoids appear to regulate energy balance and food intake at four functional levels within the brain and periphery: (i) limbic system (for hedonic evaluation of foods), (ii) hypothalamus and hindbrain (integrative functions), (iii) intestinal system, and (iv) adipose tissue. At each of these levels, the endocannabinoid system interacts with a number of better known molecules involved in appetite and weight regulation, including leptin, ghrelin, and the melanocortins. Therapeutically, appetite stimulation by cannabinoids has been studied for several decades, particularly in relation to cachexia and malnutrition associated with cancer, acquired immunodeficiency syndrome, or anorexia nervosa. The recent advances in cannabinoid pharmacology may lead to improved treatments for these conditions or, conversely, for combating excessive appetite and body weight, such as CB1 receptor antagonists as antiobesity medications. In conclusion, the exciting progress in the understanding of how the endocannabinoid CB receptor systems influence appetite and body weight is stimulating the development of therapeutic orexigenic and anorectic agents. Furthermore, the role of cannabinoid CB1 receptor activation for milk suckling in newborns may open new doors toward understanding nonorganic failure-to-thrive in infants, who display growth failure without known organic cause.

Endocannabinoid receptor antagonists: potential for obesity treatment.

Obesity has been described as a global epidemic. Its increasing prevalence is matched by growing costs, not only to the health of the individual, but also to the medical services required to treat a range of obesity-related diseases. In most instances, obesity is a product of progressively less energetic lifestyles and the over-consumption of readily available, palatable, and highly caloric foods. Past decades have seen massive investment in the search for effective anti-obesity therapies, so far with limited success. An important part of the process of developing new pharmacologic treatments for obesity lies in improving our understanding of the psychologic and physiologic processes that govern appetite and bodyweight regulation. Recent discoveries concerning the endogenous cannabinoids are beginning to give greater insight into these processes. Current research indicates that endocannabinoids may be key to the appetitive and consummatory aspects of eating motivation, possibly mediating the craving for and enjoyment of the most desired, most fattening foods. Additionally, endocannabinoids appear to modulate central and peripheral processes associated with fat and glucose metabolism. Selective cannabinoid receptor antagonists have been shown to suppress the motivation to eat, and preferentially reduce the consumption of palatable, energy-dense foods. Additionally, these agents act to reduce adiposity through metabolic mechanisms that are independent of changes in food intake. Given the current state of evidence, we conclude that the endocannabinoids represent an exciting target for new anti-obesity therapies.

The cannabinoid CB1 receptor antagonist SR141716 blocks the orexigenic effects of intrahypothalamic ghrelin.

The paraventricular nucleus (PVN) of the hypothalamus plays a key role in the control of appetite and energy balance. Both ghrelin and cannabinoid receptor agonists increase food intake when administered into this nucleus: this study investigated possible interactions between the two systems in relation to eating. The orexigenic effect of ghrelin (100 pmol) when infused in to the PVN was reversed by a small, systemic dose of the CB(1) cannabinoid receptor antagonist SR141716 (1 mg kg(-1)). This is the first demonstration of a functional relationship between brain ghrelin and endocannabinoid systems, and, although it needs to be further investigated, the effect of ghrelin on food intake when injected into the PVN seems to be mediated by stimulation of cannabinoid release.

Relaciones entre el sistema endocanabinoide y apetito: nuevos horizontes en el manejo de la obesidad

La obesidad ha sido reconocida como una epidemia global. En la mayoría de los casos, la obesidad es el producto de un estilo de vida cada vez más sedentario aunado al consumo excesivo de alimentos asequibles, altamente apetitosos y calóricamente densos. Las décadas pasadas han sido testigo del gran esfuerzo dedicado a la búsqueda de tratamientos efectivos contra la obesidad, sin embargo los resultados obtenidos hasta el momento no han sido satisfactorios. Un aspecto importante del proceso de desarrollo de nuevos tratamientos farmacológicos para la obesidad se basa en el entendimiento de los procesos psicológicos y fisiológicos que gobiernan el apetito y la regulación del peso corporal. Los descubrimientos recientes referentes a los canabinoides endógenos han comenzado a esclarecer dichos procesos. Los conocimientos actuales indican que el sistema endocanabinoide parece ejercer un papel clave en las fases apetitiva y consumatoria de la motivación alimentaria, posiblemente mediando las ansias y el placer por las comidas más deseadas que son, generalmente, los alimentos calóricamente más densos. Además, los endocanabinoides parecen modular componentes centrales y periféricos asociados con el metabolismo de las grasas y de la glucosa. Los antagonistas selectivos de los receptores canabinoides han demostrado ser capaces de suprimir la motivación para la ingesta y reducir preferencialmente el consumo de alimentos apetitosos con alto valor energético. La siguiente revisión resume los avances recientes y las teorías actuales en este campo concluyendo que los endocanabinoides representan un blanco apasionante en la investigación sobre nuevas tratamientos anti-obesidad.

Obesity has been described as a global epidemic. In most instances, obesity is a product of progressively less energetic lifestyles and the overconsumption of readily available, palatable, and highly caloric foods. Past decades have seen massive investment in the search for effective anti-obesity therapies, so far with limited success. An important part of the process of developing new pharmacological treatments for obesity lies in bettering our understanding of the psychological and physiological processes that govern appetite and body weight regulation. Recent discoveries concerning the endogenous cannabinoids are beginning to give greater insight into these processes. Current research indicates that endocannabinoids may be key to the appetitive and consummatory aspects of eating motivation, possibly mediating the craving for and enjoyment of the most desired, most fattening foods. Additionally, endocannabinoids appear to modulate central and peripheral processes associated with fat and glucose metabolism. Selective cannabinoid receptor antagonist drugs have been shown to suppress motivation to eat, and preferentially reduce the consumption of palatable, energy- dense foods. Here we review the background to these developments, and current theoretical accounts. We conclude that endocannabinoids represent an exciting target for new anti-obesity therapies.

Cannabinoid influences on palatability: microstructural analysis of sucrose drinking after delta(9)-tetrahydrocannabinol, anandamide, 2-arachidonoyl glycerol and SR141716.

RATIONALE: Central cannabinoid systems have been implicated in appetite control through the respective hyperphagic and anorectic actions of CB1 agonists and antagonists. The motivational changes underlying these actions remain to be determined, but may involve alterations to food palatability. OBJECTIVES: The mode of action of cannabinoids on ingestion was investigated by examining the effects of exogenous and endogenous agonists, and a selective CB1 receptor antagonist, on licking microstructure in rats ingesting a palatable sucrose solution. METHODS: Microstructural analyses of licking for a 10% sucrose solution was performed over a range of agonist and antagonist doses administered to non-deprived, male Lister hooded rats. RESULTS: Delta(9)-tetrahydrocannabinol (0.5, 1 and 3 mg/kg) and anandamide (1 mg/kg and 3 mg/kg) significantly increased total number of licks. This was primarily due to an increase in bout duration rather than bout number. There was a non-significant increase in total licks following administration of 2-arachidonoyl glycerol (0.2, 1.0 and 2.0 mg/kg), whereas administration of the CB1 antagonist SR141716 (1 mg/kg and 3 mg/kg) significantly decreased total licks. All drugs, with the exception of anandamide, significantly decreased the intra-bout lick rate. An exponential function fitted to the cumulative lick rate curves for each drug revealed that all compounds altered the asymptote of this function without having any marked effects on the exponent. CONCLUSIONS: These data are consistent with endocannabinoid involvement in the mediation of food palatability.