Food-related attentional bias and its associations with appetitive motivation and body weight: A systematic review and meta-analysis.

Theoretical models suggest that food-related visual attentional bias (AB) may be related to appetitive motivational states and individual differences in body weight; however, findings in this area are equivocal. We conducted a systematic review and series of meta-analyses to determine if there is a positive association between food-related AB and: (1.) body mass index (BMI) (number of effect sizes (k) = 110), (2.) hunger (k = 98), (3.) subjective craving for food (k = 35), and (4.) food intake (k = 44). Food-related AB was robustly associated with craving (r = 0.134 (95% CI 0.061, 0.208); p < .001), food intake (r = 0.085 (95% CI 0.038, 0.132); p < .001), and hunger (r = 0.048 (95% CI 0.016, 0.079); p = .003), but these correlations were small. Food-related AB was unrelated to BMI (r = 0.008 (95% CI -0.020, 0.035); p = .583) and this result was not moderated by type of food stimuli, method of AB assessment, or the subcomponent of AB that was examined. Furthermore, in a between-groups analysis (k = 22) which directly compared participants with overweight/obesity to healthy-weight control groups, there was no evidence for an effect of weight status on food-related AB (Hedge's g = 0.104, (95% CI -0.050, 0.258); p = .186). Taken together, these findings suggest that food-related AB is sensitive to changes in the motivational value of food, but is unrelated to individual differences in body weight. Our findings question the traditional view of AB as a trait-like index of preoccupation with food and have implications for novel theoretical perspectives on the role of food AB in appetite control and obesity.

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.

Does regular cannabis use affect neuroanatomy? An updated systematic review and meta-analysis of structural neuroimaging studies.

Regular cannabis use is associated with adverse cognitive and mental health outcomes that have been ascribed to aberrant neuroanatomy in brain regions densely innervated with cannabinoid receptors. Neuroanatomical differences between cannabis users and controls have been assessed in multiple structural magnetic resonance imaging (sMRI) studies. However, there is heterogeneity in the results leading to cautious interpretation of the data so far. We examined the sMRI evidence to date in human cannabis users, to establish more definitely whether neuroanatomical alterations are associated with regular cannabis use. The regional specificity and association with cannabis use indices (i.e. cumulative dosage, duration) were also explored. We systematically reviewed and meta-analysed published sMRI studies investigating regional brain volumes (cortical, subcortical and global) in cannabis users and non-user controls. Three electronic databases were searched (PubMed, Scopus, and PsycINFO). A total of 17 meta-analyses were conducted (one for each cortical, subcortical and global volume) using the generic inverse variance method, whereby standardised mean difference in volume was calculated between users and non-users. Exploratory meta-regressions were conducted to investigate the association between cannabis use indices and regional brain volumes. A total of 30 articles were eligible for inclusion, contributing 106 effect sizes across 17 meta-analyses. Regular cannabis users had significantly smaller volumes of the hippocampus (SMD = 0.14, 95% CIs [0.02, 0.27]; Z = 2.29, p = 0.02, I2 = 74%) and orbitofrontal cortex {medial (SMD = 0.30, 95% CIs [0.15, 0.45]; Z = 3.89, p = 0.0001, I2 = 51%), lateral (SMD = 0.19, 95% CIs [0.07, 0.32]; Z = 3.10, p = 0.002, I2 = 26%)} relative to controls. The volumes of the hippocampus and orbitofrontal cortex were not significantly associated with cannabis duration and dosage. Our findings are consistent with evidence of aberrance in brain regions involved in reward, learning and memory, and motivation circuits in the regular use of substances other than cannabis, pointing to commonality in neurobiological abnormalities between regular users of cannabis and of other substances.

Updating of working memory in ecstasy polydrug users: Findings from fNIRS.

AIMS/OBJECTIVES: Cognitive deficits are now well documented in ecstasy (MDMA) users with type and relative demand of task emerging as important factors. The updating component of executive processes appears to be particularly affected. The study reported here used functional near infrared spectroscopy imaging to investigate changes in cortical haemodynamics during memory updating. METHOD: Twenty ecstasy users and 20 non-users completed verbal and spatial memory updating tasks and brain blood oxygenation and deoxygenation change was measured using functional near infrared spectroscopy. RESULTS: There was no interaction between group and difficulty on the updating tasks, though there was a significant main effect of difficulty on both tasks. The effects of group approached significance on the verbal updating task. There were significant differences in blood oxygenation and deoxygenation change at optodes centred over the right and left dorsolateral prefrontal cortex, with ecstasy users showing greater blood oxygenation than the other groups. DISCUSSION: The lack of a behavioural difference on both tasks but presence of blood oxygenation and deoxygenation changes in letter updating provides support for the notion that ecstasy-polydrug users are investing more effort to achieve the same behavioural output. Total lifetime dose was high, and recency of use was significantly related to most changes, suggesting that heavy and recent use may be particularly detrimental.

Food and non-alcoholic beverage marketing in children and adults: A systematic review and activation likelihood estimation meta-analysis of functional magnetic resonance imaging studies.

Food marketing impacts the food behaviors of children and adults, but the underpinning neural mechanisms are poorly understood. This systematic review and meta-analysis pooled evidence from neuroimaging studies of exposure to food marketing stimuli (vs. control) on brain activations in children and adults to clarify regions associated with responding. Databases were searched for articles published to March 2022. Inclusion criteria included human functional magnetic resonance imaging (fMRI) studies employing a contrast between a food marketing stimulus and a non-food/non-exposure control, published in English in a peer-reviewed journal, reporting whole brain (not Region of Interest [ROI] only) co-ordinates. Eleven studies met inclusion criteria, of which eight were included in the quantitative synthesis (Activation Likelihood Estimation [ALE] meta-analysis). Food marketing exposures (vs. controls) produced greater activation in two clusters lying across the middle occipital gyrus, lingual gyrus, and cuneus (cluster 1), and the postcentral gyrus, precentral gyrus, and the inferior parietal lobule/supramarginal gyrus (cluster 2). Brain responses to food marketing are most consistently observed in areas relating to visual processing, attention, sensorimotor activity, and emotional processing. Subgroup analyses (e.g., adults vs. children) were not possible because of the paucity of data, and sensitivity analyses highlighted some instability in the clusters; therefore, conclusions remain tentative pending further research.

Cannabis Dependence is Associated with Reduced Hippocampal Subregion Volumes Independently of Sex: Findings from an ENIGMA Addiction Working Group Multi-Country Study.

Background: Males and females who consume cannabis can experience different mental health and cognitive problems. Neuroscientific theories of addiction postulate that dependence is underscored by neuroadaptations, but do not account for the contribution of distinct sexes. Further, there is little evidence for sex differences in the neurobiology of cannabis dependence as most neuroimaging studies have been conducted in largely male samples in which cannabis dependence, as opposed to use, is often not ascertained. Methods: We examined subregional hippocampus and amygdala volumetry in a sample of 206 people recruited from the ENIGMA Addiction Working Group. They included 59 people with cannabis dependence (17 females), 49 cannabis users without cannabis dependence (20 females), and 98 controls (33 females). Results: We found no group-by-sex effect on subregional volumetry. The left hippocampal cornu ammonis subfield 1 (CA1) volumes were lower in dependent cannabis users compared with non-dependent cannabis users (p<0.001, d=0.32) and with controls (p=0.022, d=0.18). Further, the left cornu ammonis subfield 3 (CA3) and left dentate gyrus volumes were lower in dependent versus non-dependent cannabis users but not versus controls (p=0.002, d=0.37, and p=0.002, d=0.31, respectively). All models controlled for age, intelligence quotient (IQ), alcohol and tobacco use, and intracranial volume. Amygdala volumetry was not affected by group or group-by-sex, but was smaller in females than males. Conclusions: Our findings suggest that the relationship between cannabis dependence and subregional volumetry was not moderated by sex. Specifically, dependent (rather than non-dependent) cannabis use may be associated with alterations in selected hippocampus subfields high in cannabinoid type 1 (CB1) receptors and implicated in addictive behavior. As these data are cross-sectional, it is plausible that differences predate cannabis dependence onset and contribute to the initiation of cannabis dependence. Longitudinal neuroimaging work is required to examine the time-course of the onset of subregional hippocampal alterations in cannabis dependence, and their progression as cannabis dependence exacerbates or recovers over time.

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.

Brain Anatomical Alterations in Young Cannabis Users: Is it All Hype? A Meta-Analysis of Structural Neuroimaging Studies.

Introduction: Cannabis use has a high prevalence in young youth and is associated with poor psychosocial outcomes. Such outcomes have been ascribed to the impact of cannabis exposure on the developing brain. However, findings from individual studies of volumetry in youth cannabis users are equivocal. Objectives: Our primary objective was to systematically review the evidence on brain volume differences between young cannabis users and nonusers aged 12-26 where profound neuromaturation occurs, accounting for the role of global brain volumes (GBVs). Our secondary objective was to systematically integrate the findings on the association between youth age and volumetry in youth cannabis users. Finally, we aimed to evaluate the quality of the evidence. Materials and Methods: A systematic search was run in three databases (PubMed, Scopus, and PsycINFO) and was reported using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We run meta-analyses (with and without controlling for GBV) of brain volume differences between young cannabis users and nonusers. We conducted metaregressions to explore the role of age on volumetric differences. Results: Sixteen studies were included. The reviewed samples included 830 people with mean age 22.5 years (range 14-26 years). Of these, 386 were cannabis users (with cannabis use onset at 15-19 years) and 444 were controls. We found no detectable group differences in any of the GBVs (intracranium, total brain, total white matter, and total gray matter) and regional brain volumes (i.e., hippocampus, amygdala, orbitofrontal cortex, and total cerebellum). Age and cannabis use level did not predict (standardized mean) volume group differences in metaregression. We found little evidence of publication bias (Egger's test p>0.1). Conclusions: Contrary to evidence in adult samples (or in samples mixing adults and youth), previous single studies in young cannabis users, and meta-analyses of brain function in young cannabis users, this early evidence suggests nonsignificant volume differences between young cannabis users and nonusers. While prolonged and long-term exposure to heavy cannabis use may be required to detect gross volume alterations, more studies in young cannabis users are needed to map in detail cannabis-related neuroanatomical changes.

Neurological and cognitive alterations induced by MDMA in humans.

3,4 Methylenedioxymethamphetamine generally referred to as MDMA or 'ecstasy' is a ring-substituted phenethylamine stimulant which produces powerful empathogenic effects. Use of MDMA remains popular despite prohibition, and potential long-term negative consequences of repeated use. MDMA produces its acute subjective effects primarily by stimulating the release of serotonin via action at the serotonin transporter (SERT). There is evidence that MDMA administration may lead to long lasting neurotoxic effects on serotonin neurons in primates, and reductions in markers of central serotonin axons, and axon terminals in animals. In humans, demonstration of serotonergic neurotoxicity is much more difficult to identify, and much of the research is complicated by confounding issues of polysubstance use, genetic and environmental factors and reliance on self-reports of previous drug use. We do not review the mechanisms for neurotoxicity in detail as they are covered elsewhere in this special issue. There is a large body of literature, however, which has investigated potential cognitive and neurocognitive consequences of repeated MDMA use. Here we review the literature on cognition, and neuroimaging studies that have investigated structural and functional brain changes associated with ecstasy use.

Mechanisms of weight regain.

Weight regain following weight loss is frequent problem that people with obesity face. This weight recidivism is often attributed to the lack of compliance with appropriate food habits and exercise. On the contrary, it is known that body weight and fat mass are regulated by numerous physiological mechanisms, far beyond voluntary food intake and physical exercise. Thus, the aim of this paper is to review the main peripheral and central mechanisms involved in weight regain. Gut hormone secretion profiles impact upon predisposition to weight regain according to an individual variability, although it is recognised a usual pattern of compensatory changes: a reduction in anorectic hormones secretion and an increase in orexigenic hormone. These changes lead to both increased appetite and reward value of food leading to increased energye intake. In addition, resting energy expenditure after weight loss is lower than expected according to body composition changes. This gap between observed and predicted energy expenditure following weight loss is named metabolic adaptation, which has been suggested to explain partly weight regain. This complicated scenario, beyond patient motivation, makes weight regain a challenge in long-term management interventions in patients with obesity.

Do comorbid personality disorders in cocaine dependence exacerbate neuroanatomical alterations? A structural neuroimaging study.

Cocaine dependence (CD) is highly comorbid with personality disorders, with implications for poorer treatment response. The neurobiological mechanisms of this comorbidity are unclear. We aimed to test the role of comorbid personality disorders in the neuroanatomy of CD. We examined 4 groups using high-resolution structural neuroimaging, psychological questionnaires and cognitive tests: CD (n = 19), CD and personality disorder type B (CD + B, n = 21), CD and personality disorder C (CD + C, n = 13) and 21 controls. We compared groups in neuroanatomy and hypothesised that (i) CD would show altered striatal areas ascribed to reward processing (i.e., accumbens, caudate and putamen), (ii) CD + B and CD + C would show altered areas supporting emotional regulation/social valuation and anxiety/avoidance (i.e., OFC and amygdala). The CD + B group had larger caudate volumes than CD (p = .01, d = 0.94) and reduced lateral OFC thickness than CD + C (p = .056, d = 0.71). Exploratory correlations showed that altered neural integrity of the OFC and of the caudate nucleus in these groups exacerbated with worse personality disorder severity and impulsivity scores. CD with and without comorbid personality disorders may have partially distinct underlying mechanisms and targets for treatment.

How effective are pharmaceuticals for cognitive enhancement in healthy adults? A series of meta-analyses of cognitive performance during acute administration of modafinil, methylphenidate and D-amphetamine.

Modafinil, methyphenidate (MPH) and d-amphetamine (d-amph) are putative cognitive enhancers. However, efficacy of cognitive enhancement has yet to be fully established. We examined cognitive performance in healthy non-sleep-deprived adults following modafinil, MPH, or d-amph vs placebo in 3 meta-analyses, using subgroup analysis by cognitive domain; executive functions (updating, switching, inhibitory control, access to semantic/long term memory), spatial working memory, recall, selective attention, and sustained attention. We adhered to PRISMA. We identified k = 47 studies for analysis; k = 14 studies (64 effect sizes) for modafinil, k = 24 studies (47 effect sizes) for Methylphenidate, and k = 10 (27 effect sizes) for d-amph. There was an overall effect of modafinil (SMD=0.12, p=.01). Modafinil improved memory updating (SMD=0.28, p=.03). There was an overall effect of MPH (SMD=0.21, p=.0004) driven by improvements in recall (SMD=0.43, p=.0002), sustained attention (SMD=0.42, p=.0004), and inhibitory control (SMD=0.27, p=.03). There were no effects for d-amph. MPH and modafinil show enhancing effects in specific sub-domains of cognition. However, data with these stimulants is far from positive if we consider that effects are small, in experiments that do not accurately reflect their actual use in the wider population. There is a user perception that these drugs are effective cognitive enhancers, but this is not supported by the evidence so far.

Perceived harm, motivations for use and subjective experiences of recreational psychedelic 'magic' mushroom use.

BACKGROUND: Data on actual harm of magic mushrooms suggest that toxicity and abuse potential is low, however, their legal status suggests otherwise. We aimed to gauge perception of harm of magic mushrooms in both users and mushroom-naïve participants. We also aimed to observe differences in expectations of effects between users and mushroom-naïve participants, and whether motivations for use predicted their expected effects. METHOD: In total, 73 polydrug users with experience of using magic mushrooms and 78 mushroom-naïve participants completed an online survey. We asked participants to rank a list of 10 substances from most dangerous to least dangerous and questioned them about expectation of effect using a modified magic mushroom expectation questionnaire. Users were asked about their motivations for using magic mushrooms. RESULTS: Both groups perceive mushrooms to be safer than heroin, cocaine, prescription painkillers, gamma-hydroxybutyrate (GHB), ecstasy, tobacco and alcohol. However, the mushroom-naïve group ranked mushrooms as significantly more dangerous than the user group. Non-users reported greater expectancy for negative intoxication. Users reported greater expected entactogenic, prosocial, aesthetic and mood effects, and perceptual alterations. Finally, expectant effects of mushroom use were associated with different motivations for use, for example using for personal psychotherapy was associated with expectation of increased entactogenic effects and decreased negative effects. CONCLUSION: Our data suggest a general perception of harm that is in line with data on actual harm, but at odds with current legal classifications. Future clinical investigations may require management of negative intoxication expectation of participants with no prior experience of psilocybin.

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.

Is (poly-) substance use associated with impaired inhibitory control? A mega-analysis controlling for confounders.

Many studies have reported that heavy substance use is associated with impaired response inhibition. Studies typically focused on associations with a single substance, while polysubstance use is common. Further, most studies compared heavy users with light/non-users, though substance use occurs along a continuum. The current mega-analysis accounted for these issues by aggregating individual data from 43 studies (3610 adult participants) that used the Go/No-Go (GNG) or Stop-signal task (SST) to assess inhibition among mostly "recreational" substance users (i.e., the rate of substance use disorders was low). Main and interaction effects of substance use, demographics, and task-characteristics were entered in a linear mixed model. Contrary to many studies and reviews in the field, we found that only lifetime cannabis use was associated with impaired response inhibition in the SST. An interaction effect was also observed: the relationship between tobacco use and response inhibition (in the SST) differed between cannabis users and non-users, with a negative association between tobacco use and inhibition in the cannabis non-users. In addition, participants' age, education level, and some task characteristics influenced inhibition outcomes. Overall, we found limited support for impaired inhibition among substance users when controlling for demographics and task-characteristics.

MDMA and brain activity during neurocognitive performance: An overview of neuroimaging studies with abstinent 'Ecstasy' users.

MDMA/Ecstasy has had a resurgence in popularity, with recent supplies comprising higher strength MDMA, potentially leading to increased drug-related harm. Neurocognitive problems have been widely reported in ecstasy users, equally some studies report null findings, and it remains unclear which factors underlie the development of neurocognitive impairments. This review covers the empirical research into brain activity during neurocognitive performance, using fMRI, fNIRS, and EEG. Our main conclusion is that chronic repeated use of recreational ecstasy can result in haemodynamic and electrophysiological changes that reflect recruitment of additional resources to perform cognitive tasks. Findings are consistent with serotonergic system changes, although whether this reflects neurotoxicity or neuroadaptation, cannot be answered from these data. There is a degree of heterogeneity in the methodologies and findings, limiting the strengths of current conclusions. Future research with functional neuroimaging paired with molecular imaging, genetics or pharmacological challenges of the serotonin system may help to decipher the link between serotonergic and cognitive changes in ecstasy users.

The effect of beliefs about alcohol's acute effects on alcohol priming and alcohol-induced impairments of inhibitory control.

Acute alcohol administration can lead to a loss of control over drinking. Several models argue that this 'alcohol priming effect' is mediated by the effect of alcohol on inhibitory control. Alternatively, beliefs about how alcohol affects behavioural regulation may also underlie alcohol priming and alcohol-induced inhibitory impairments. Here two studies examine the extent to which the alcohol priming effect and inhibitory impairments are moderated by beliefs regarding the effects of alcohol on the ability to control behaviour. In study 1, following a priming drink (placebo or .5g/kg of alcohol), participants were provided with bogus feedback regarding their performance on a measure of inhibitory control (stop-signal task; SST) suggesting that they had high or average self-control. However, the bogus feedback manipulation was not successful. In study 2, before a SST, participants were exposed to a neutral or experimental message suggesting acute doses of alcohol reduce the urge to drink and consumed a priming drink and this manipulation was successful. In both studies craving was assessed throughout and a bogus taste test which measured ad libitum drinking was completed. Results suggest no effect of beliefs on craving or ad lib consumption within either study. However, within study 2, participants exposed to the experimental message displayed evidence of alcohol-induced impairments of inhibitory control, while those exposed to the neutral message did not. These findings do not suggest beliefs about the effects of alcohol moderate the alcohol priming effect but do suggest beliefs may, in part, underlie the effect of alcohol on inhibitory control.

Tailoring pharmacotherapy to specific eating behaviours in obesity: Can recommendations for personalised therapy be made from the current data?

Pharmacotherapy provides an adjunct to behaviour modification in the management of obesity. There are a number of new drug therapies purportedly targeting appetite; liraglutide, and bupropion/naltrexone, which are European Medicines Agency and US Food and Drug Administration (FDA) approved, and lorcaserin and phentermine/topiramate, which have FDA approval only. Each of the six drugs, used singly or in combination, has distinct pharmacological, and presumably distinct behavioural, mechanisms of action, thus the potential to provide defined therapeutic options to personalise the management of obesity. Yet, with regard to pharmacotherapy for obesity, we are far from true personalised medicine. We review the limited mechanistic data with four mono and combination pharmacotherapies, to assess the potential for tailoring their use to target specific obesogenic behaviours. Potential treatment options are considered, but in the absence of adequate research in respect to effects of these drugs on eating behaviour, neural activity and psychological substrates that underlie poorly controlled eating, we are far from definitive therapeutic recommendations. Specific mechanistic studies and broader behavioural phenotyping, possibly in conjunction with pharmacogenetic research, are required to characterise responders for distinct pharmacotherapeutic options.

Recreational 3,4-methylenedioxymethamphetamine or 'ecstasy': Current perspective and future research prospects.

AIMS: The purpose of this article is to debate current understandings about the psychobiological effects of recreational 3,4-methylenedioxymethamphetamine (MDMA or 'ecstasy'), and recommend theoretically-driven topics for future research. METHODS: Recent empirical findings, especially those from novel topic areas were reviewed. Potential causes for the high variance often found in group findings were also examined. RESULTS AND CONCLUSIONS: The first empirical reports into psychobiological and psychiatric aspects from the early 1990s concluded that regular users demonstrated some selective psychobiological deficits, for instance worse declarative memory, or heightened depression. More recent research has covered a far wider range of psychobiological functions, and deficits have emerged in aspects of vision, higher cognitive skill, neurohormonal functioning, and foetal developmental outcomes. However, variance levels are often high, indicating that while some recreational users develop problems, others are less affected. Potential reasons for this high variance are debated. An explanatory model based on multi-factorial causation is then proposed. FUTURE DIRECTIONS: A number of theoretically driven research topics are suggested, in order to empirically investigate the potential causes for these diverse psychobiological deficits. Future neuroimaging studies should study the practical implications of any serotonergic and/or neurohormonal changes, using a wide range of functional measures.