Alcohol is known to facilitate memory if given after learning information in the laboratory; we aimed to investigate whether this effect can be found when alcohol is consumed in a naturalistic setting. Eighty-eight social drinkers were randomly allocated to either an alcohol self-dosing or a sober condition. The study assessed both retrograde facilitation and alcohol induced memory impairment using two independent tasks. In the retrograde task, participants learnt information in their own homes, and then consumed alcohol ad libitum. Participants then undertook an anterograde memory task, of alcohol impairment when intoxicated. Both memory tasks were completed again the following day. Mean amount of alcohol consumed was 82.59 grams over the evening. For the retrograde task, as predicted, both conditions exhibited similar performance on the memory task immediately following learning (before intoxication) yet performance was better when tested the morning after encoding in the alcohol condition only. The anterograde task did not reveal significant differences in memory performance post-drinking. Units of alcohol drunk were positively correlated with the amount of retrograde facilitation the following morning. These findings demonstrate the retrograde facilitation effect in a naturalistic setting, and found it to be related to the self-administered grams of alcohol.

Performance in response-inhibition paradigms is typically attributed to inhibitory control. Here we examined the idea that stopping may largely depend on the outcome of a sensory detection process. Subjects performed a speeded go task, but they were instructed to withhold their response when a visual stop signal was presented. The stop signal could occur in the centre of the screen or in the periphery. On half of the trials, perceptual distractors were presented throughout the trial. We found that these perceptual distractors impaired stopping, especially when stop signals could occur in the periphery. Furthermore, the effect of the distractors on going was smallest in the central stop-signal condition, medium in a condition in which no-signals could occur, and largest in the condition in which stop signals could occur in the periphery. The results show that an important component of stopping is finding a balance between ignoring irrelevant information in the environment and monitoring for the occurrence of occasional stop signals. These findings highlight the importance of sensory detection processes when stopping and could shed new light on a range of phenomena and findings in the response-inhibition literature.

OBJECTIVE: Early evidence suggests that ketamine may be an effective treatment to sustain abstinence from alcohol. The authors investigated the safety and efficacy of ketamine compared with placebo in increasing abstinence in patients with alcohol use disorder. An additional aim was to pilot ketamine combined with mindfulness-based relapse prevention therapy compared with ketamine and alcohol education as a therapy control. METHODS: in a double-blind placebo-controlled phase 2 clinical trial, 96 patients with severe alcohol use disorder were randomly assigned to one of four conditions: 1) three weekly ketamine infusions (0.8 mg/kg i.v. over 40 minutes) plus psychological therapy, 2) three saline infusions plus psychological therapy, 3) three ketamine infusions plus alcohol education, or 4) three saline infusions plus alcohol education. The primary outcomes were self-reported percentage of days abstinent and confirmed alcohol relapse at 6-month follow-up. RESULTS: Ninety-six participants (35 women; mean age, 44.07 years [SD=10.59]) were included in the intention-to-treat analysis. The treatment was well tolerated, and no serious adverse events were associated with the study drug. Although confidence intervals were wide, consistent with a proof-of-concept study, there were a significantly greater number of days abstinent from alcohol in the ketamine group compared with the placebo group at 6-month follow-up (mean difference=10.1%, 95% CI=1.1, 19.0), with the greatest reduction in the ketamine plus therapy group compared with the saline plus education group (15.9%, 95% CI=3.8, 28.1). There was no significant difference in relapse rate between the ketamine and placebo groups. CONCLUSIONS: This study demonstrated that treatment with three infusions of ketamine was well tolerated in patients with alcohol use disorder and was associated with more days of abstinence from alcohol at 6-month follow-up. The findings suggest a possible beneficial effect of adding psychological therapy alongside ketamine treatment.

RATIONALE: Rumination is a repetitive, negative, self-focused thinking style associated with various forms of psychopathology. Recent studies suggest that rumination increases craving for alcohol and predicts harmful drinking and alcohol-related problems. However, the acute effects of alcohol on rumination have not been previously studied. It is proposed that alcohol may reduce ruminative thinking through decreasing negative mood. OBJECTIVES: in the present study, we aimed to test the previously unexplored effects of acute alcohol consumption on rumination in a hazardous drinking population. METHODS: We conducted a randomised placebo-controlled laboratory study to examine the effect of low (0.4 g kg-1) and high doses (0.8 g kg-1) of alcohol on state rumination compared to placebo. Participants completed a rumination induction task prior to receiving drinks. We then measured state rumination and mood at repeated time points; 30 min, 60 min and 90 min post-drinks consumption. RESULTS: We found a significant decrease in state rumination in the low-dose alcohol group compared to placebo at 30 min post-alcohol consumption, but no difference was observed between the high-dose alcohol and placebo groups. Mediation analysis provided evidence for an indirect effect of alcohol on state rumination through concurrent changes in negative mood. CONCLUSIONS: These findings suggest that acute alcohol consumption can regulate negative mood and concurrently rumination, providing preliminary evidence for the role of rumination in alcohol use disorders. Rumination may be a treatment target in alcohol use disorders.

RATIONALE: Social functioning is modulated by the endogenous opioid system. In opioid use disorder, social functioning appears disrupted, but little research has delineated the nature of these deficits and their relationship to acute opioid use. OBJECTIVES: the current study aimed to assess both emotional and cognitive empathy, along with subjective and physiological responses to social exclusion in opioid users who were either acutely intoxicated or non-intoxicated from using opioids. METHODS: Individuals on an opioid substitution medication (OSM) were divided into 'intoxicated users' (had taken their OSM the same day as testing, n = 20) and 'non-intoxicated users' (had taken their OSM > 12 h ago, n = 20) and compared with opioid-naïve controls (n = 24). Empathy was assessed using the multifaceted empathy test and self-report questionnaire. Participants also underwent a period of social exclusion (Cyberball Game) and completed measures of mood and physiological responses (salivary cortisol and heart rate). RESULTS: Non-intoxicated users had significantly lower emotional empathy (the ability to experience others' emotions), as well as greater anger after social exclusion when compared with the intoxicated users and controls. Anger did not change with social exclusion in the intoxicated user group and cortisol levels were lower overall. CONCLUSIONS: Reduced ability to spontaneously share the emotions of others was reported in non-intoxicated users, particularly regarding positive emotions. There was some support for the idea of hyperalgesia to social pain, but this was restricted to an enhanced anger response in non-intoxicated users. Equivalent rates of empathy between the intoxicated users and controls could indicate some remediating effects of acute opioids.

BACKGROUND: 3,4-Methylenedioxymethamphetamine (MDMA) is widely known for its positive acute effects on social behaviour, such as increasing empathy, whilst also attenuating the negative impact of social exclusion. However there is a scarcity of research that investigates the long-term impact of recreational MDMA use on these fundamental social processes. METHOD: Sixty-seven individuals were split into three groups based on their drug-use history: poly-drug MDMA users ( n = 25), poly-drug users who do not use MDMA ( n = 19), alcohol-only users ( n = 23), and were tested in an independent groups design. Participants completed both a self-report measure of emotional and cognitive empathy, along with the Multifaceted Empathy Task - a computerised assessment of empathy - and the Cyberball Game - a social exclusion paradigm. RESULTS: MDMA users had significantly greater subjective emotional empathy, and greater cognitive empathy on the computer task compared with the poly-drug users who do not use MDMA. There were no significant differences in subjective responses to social exclusion between the groups. Indices of MDMA use did not correlate with empathy. CONCLUSIONS: Long-term MDMA users in this sample exhibited normal psychosocial functioning in regard to empathy and social pain and had higher subjective emotional empathy. This conflicts with previous suggestions that moderate, long-term MDMA use may cause heightened social distress, and is further evidence of the safety of the drug, which is relevant to considerations of its therapeutic use.

Social anxiety disorder (SAD) has been related to alcohol use disorder (AUD). Shyness can be considered a subclinical analogue of SAD, yet there is little research into the effect of alcohol on anxiety levels in highly-shy individuals. This naturalistic study investigated acute and sub-acute effects of alcohol in high and low shy social drinkers. 97 individuals were tested at home and assigned to either consume alcohol to normal levels (n = 50) or to remain sober (n = 47). Baseline measures of AUD symptoms, shyness and social phobia were taken. Measures of state anxiety were taken at baseline, following a period of alcohol consumption or sobriety, and the following morning. Marginally decreased acute anxiety resulting from alcohol consumption in high shyness was observed. A significant increase in anxiety the day following drinking was observed in highly-shy participants. There was a significant correlation between anxiety elevation on the second day and AUDIT scores in highly-shy participants. This study suggests anxiety during hangover is linked to AUD symptoms in highly-shy individuals, providing a potential marker for increased AUD risk, which could inform prevention and treatment.

BACKGROUND: Worldwide, alcohol abuse is a burgeoning problem. Abstinence is key to allow recovery of physical and mental health as well as quality of life, but treatment for alcohol dependence is associated with high relapse rates. Preliminary data have suggested that a combined repeated ketamine and psychological therapy programme may be effective in reducing relapse in severe alcohol use disorder. This non-commercial proof-of-concept trial is aimed at making a preliminary assessment of the effectiveness of this combined treatment in this patient group. METHODS/DESIGN: This is a phase II, randomised, double-blind, placebo-controlled, parallel-group clinical trial taking place in two sites in the UK: the South West of England and London. Ninety-six recently detoxified alcoholics, with comorbid depressive symptoms, will be randomised to one of four treatment arms. Patients will receive either three sessions of ketamine (0.8 mg/kg administered intravenously (IV) over 40 minutes) or placebo (50 ml saline 0.9% IV over 40 minutes) plus either seven sessions of manualised psychological therapy or an alcohol education control. Patients will be assessed at 3 and 6 months on a range of psychological and biological variables. The primary endpoints are (1) relapse rates at 6 months and (2) percentage days abstinent at 6 months. Secondary endpoints include 3 and 6 month percentage days abstinence, tolerability (indicated by dropout), adverse events, depressive symptoms, craving and quality of life. DISCUSSION: This study will provide important information on a new combined psychological and pharmacological intervention aimed at reducing relapse rates in alcoholics. The findings would have broad application given the worldwide prevalence of alcoholism and its associated medical, psychological and social problems. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02649231. Registered on 5 January 2016.

Psychedelic drugs have been used as treatments in indigenous cultures for thousands of years. Yet, due to their legal status, there has been limited scientific research into the therapeutic potential of these compounds for psychiatric disorders. In the absence of other effective treatments however, researchers have begun again to systematically investigate such compounds and there is now evidence pointing to the use of psychedelic drugs in the treatment of addiction. In this review we focus on human evidence for the effectiveness of preparations used by indigenous cultures in the Amazon (ayahausca) and Africa (ibogaine) and worldwide (psilocybin), and more recently synthetised drugs such as the serotonergic hallucinogen LSD and the dissociative anaesthetic ketamine. Potential mechanisms explored are anti-depressant effects, changes in neuroplasticity and existential psychological effects of these drugs.

Cognitive control theories attribute action control to executive processes that modulate behavior based
on expectancy or task rules. Here we examined corticospinal excitability and behavioral performance
in a go/no-go task. Go and no-go trials were presented in runs of 5, and runs alternated predictably. At
the beginning of each trial, subjects indicated whether they expected a go trial or a no-go trial.
Analyses revealed that subjects immediately adjusted their expectancy ratings when a new run started.
However, motor excitability was primarily associated with the properties of the previous trial, rather
than the predicted properties of the current trial. We also observed a large go latency cost at the
beginning of a go run. These findings indicate that actions in predictable environments are
substantially influenced by previous events, even if this goes against conscious expectancies about
upcoming events.

Recent research suggests that response-inhibition training can alter impulsive and compulsive behaviour. When stop signals are introduced in a gambling task, people not only become more cautious when executing their choice responses, they also prefer lower bets when gambling. Here we examined how stopping motor responses influences gambling. Experiment 1 showed that the reduced betting in stop-signal blocks was not caused by changes in information sampling styles or changes in arousal. In Experiments 2a-2b, people preferred lower bets when they occasionally had to stop their response in a secondary decision-making task, but not when they were instructed to respond as accurately as possible. Experiment 3 showed that merely introducing trials on which subjects could not gamble did not influence gambling preferences. Experiment 4 demonstrated that the effect of stopping on gambling generalised to different populations. Furthermore, two combined analyses suggest that the effect of stopping on gambling preferences was reliable but small. Finally, Experiment 5 showed that the effect of stopping on gambling generalised to a different task. Based on our findings and earlier research we propose that the presence of stop signals influences gambling by reducing approach behaviour and altering the motivational value of the gambling outcome.

Performance in response inhibition paradigms is typically attributed to inhibitory control. Here we examined the idea that stopping may largely depend on the outcome of a sensory detection process. Subjects performed a speeded go task, but they were instructed to withhold their response when a visual stop signal was presented. The stop signal could occur in the center of the screen or in the periphery. On half of the trials, perceptual distractors were presented throughout the trial. We found that these perceptual distractors impaired stopping, especially when stop signals could occur in the periphery. Furthermore, the effect of the distractors on going was smallest in the central stop-signal condition, medium in a condition in which no signals could occur, and largest in the condition in which stop signals could occur in the periphery. The results show that an important component of stopping is finding a balance between ignoring irrelevant information in the environment and monitoring for the occurrence of occasional stop signals. These findings highlight the importance of sensory detection processes when stopping and could shed new light on a range of phenomena and findings in the response inhibition literature. © 2014 the Author(s).

Response inhibition is typically considered a hallmark of deliberate executive control. In this article, we review work showing that response inhibition can also become a ‘prepared reflex’, readily triggered by information in the environment, or after sufficient training, a ‘learned reflex’ triggered by the retrieval of previously acquired associations between stimuli and stopping. We present new results indicating that people can learn various associations, which influence performance in different ways. To account for previous findings and our new results, we present a novel architecture that integrates theories of associative learning, Pavlovian conditioning, and executive response inhibition. Finally, we discuss why this work is also relevant for the study of ‘intentional inhibition’.

A recent study has shown that short-term training in response inhibition can make people more cautious for up to two hours when making decisions. However, the longevity of such training effects is unclear. In this study we tested whether training in the stop-signal paradigm reduces risky gambling when the training and gambling task are separated by 24 hours. Two independent experiments revealed that the aftereffects of stop-signal training are negligible after 24 hours. This was supported by Bayes factors that provided strong support for the null hypothesis. These findings indicate the need to better optimise the parameters of inhibition training to achieve clinical efficacy, potentially by strengthening automatic associations between specific stimuli and stopping.