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.

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.

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.

© 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.

Is human Pavlovian conditioning driven by a unitary, propositional system (as claimed by Mitchell, De Houwer, & Lovibond, 2009) or by dual systems; one under conscious control, symbolic in nature, and requiring effort to deploy, and the other utilizing associative processes and automatic in its operation (McLaren, Green, & Mackintosh, 1994)? Past research has suggested that for electrodermal conditioning to occur in humans, conscious awareness of the contingencies is necessary to produce conditioned responding (e.g. Hinchy, Lovibond, & Ter-Horst, 1995), as predicted by single process theories that attribute the conditioned response (CR) to conscious expectancy of the shock. In this article, the authors examined the Perruchet effect (Perruchet, 1985), using an electrodermal paradigm to determine whether there is any role for associative processes in human electrodermal conditioning. The authors attempted to replicate the basic effect, whereby expectancy of an unconditioned stimulus (US) increases over a run of nonreinforced trials while the CR to the conditional stimulus (CS) declines, and the complementary pattern in which expectancy decreases over a run of reinforced trials while the CR to the CS grows in strength. In line with these patterns, the change in skin conductance response (our CR) as a function of US run length was found to follow a linear trend opposite to that of conscious expectancy of shock with respect to US run length. This dissociation supports a dual-processing system account of human Pavlovian conditioning, with conscious, controlled processes governing expectancy (and subject to the gambler's fallacy), whereas automatic, associative processes determine at least some of the strength of the CR to the CS.