Development of a digital intervention for psychedelic preparation (DIPP).

Psychedelic substances induce profound alterations in consciousness. Careful preparation is therefore essential to limit adverse reactions, enhance therapeutic benefits, and maintain user safety. This paper describes the development of a self-directed, digital intervention for psychedelic preparation. Drawing on elements from the UK Medical Research Council (MRC) framework for developing complex interventions, the design was informed by a four-factor model of psychedelic preparedness, using a person-centred approach. Our mixed-methods investigation consisted of two studies. The first involved interviews with 19 participants who had previously attended a 'high-dose' psilocybin retreat, systematically exploring their preparation behaviours and perspectives on the proposed intervention. The second study engaged 28 attendees of an ongoing psilocybin retreat in co-design workshops, refining the intervention protocol using insights from the initial interviews. The outcome is a co-produced 21-day digital course (Digital Intervention for Psychedelic Preparation (DIPP)), that is organised into four modules: Knowledge-Expectation, Psychophysical-Readiness, Safety-Planning, and Intention-Preparation. Fundamental components of the course include daily meditation practice, supplementary exercises tied to the weekly modules, and mood tracking. DIPP provides a comprehensive and scalable solution to enhance psychedelic preparedness, aligning with the broader shift towards digital mental health interventions.

Development and psychometric validation of a novel scale for measuring 'psychedelic preparedness'.

Preparing participants for psychedelic experiences is crucial for ensuring these experiences are safe and, potentially beneficial. However, there is currently no validated measure to assess the extent to which participants are well-prepared for such experiences. Our study aimed to address this gap by developing, validating, and testing the Psychedelic Preparedness Scale (PPS). Using a novel iterative Delphi-focus group methodology ('DelFo'), followed by qualitative pre-test interviews, we incorporated the perspectives of expert clinicians/researchers and of psychedelic users to generate items for the scale. Psychometric validation of the PPS was carried out in two large online samples of psychedelic users (N = 516; N = 716), and the scale was also administered to a group of participants before and after a 5-7-day psilocybin retreat (N = 46). Exploratory and confirmatory factor analysis identified four factors from the 20-item PPS: Knowledge-Expectations, Intention-Preparation, Psychophysical-Readiness, and Support-Planning. The PPS demonstrated excellent reliability (ω = 0.954) and evidence supporting convergent, divergent and discriminant validity was also obtained. Significant differences between those scoring high and low (on psychedelic preparedness) before the psychedelic experience were found on measures of mental health/wellbeing outcomes assessed after the experience, suggesting that the scale has predictive utility. By prospectively measuring modifiable pre-treatment preparatory behaviours and attitudes using the PPS, it may be possible to determine whether a participant has generated the appropriate mental 'set' and is therefore likely to benefit from a psychedelic experience, or at least, less likely to be harmed.

Do mindfulness-based interventions change brain function in people with substance dependence? A systematic review of the fMRI evidence.

BACKGROUND: Substance use disorders (SUDs) affect ~ 35 million people globally and are associated with strong cravings, stress, and brain alterations. Mindfulness-based interventions (MBIs) can mitigate the adverse psychosocial outcomes of SUDs, but the underlying neurobiology is unclear. Emerging findings were systematically synthesised from fMRI studies about MBI-associated changes in brain function in SUDs and their associations with mindfulness, drug quantity, and craving. METHODS: PsycINFO, Medline, CINAHL, PubMed, Scopus, and Web of Science were searched. Seven studies met inclusion criteria. RESULTS: Group by time effects indicated that MBIs in SUDs (6 tobacco and 1 opioid) were associated with changes in the function of brain pathways implicated in mindfulness and addiction (e.g., anterior cingulate cortex and striatum), which correlated with greater mindfulness, lower craving and drug quantity. CONCLUSIONS: The evidence for fMRI-related changes with MBI in SUD is currently limited. More fMRI studies are required to identify how MBIs mitigate and facilitate recovery from aberrant brain functioning in SUDs.

Perceived coercion, perceived pressures and procedural justice arising from global lockdowns during the COVID-19 pandemic: A scoping review.

This aim of this scoping review is to map what is known about perceived coercion, perceived pressures and procedural justice within the context of the general population's experience of 'lockdowns' imposed by governments worldwide in response to the increased transmission of COVID-19. Arksey & O'Malley's (2005) framework for conducting scoping reviews was chosen. A sensitive search strategy was devised and conducted using PubMed, Scopus, and Web of Science using the following search terms: (adherence OR acceptance OR agreement OR trust OR distrust OR compliance OR willing*) OR (perceived coerc* OR percept* coerc* OR pressure OR force OR influence OR control OR threat OR justice) AND (lockdown) AND (COVID OR SARS-CoV-2 OR COVID-19). The database search initially produced 41,628 articles to screen. A total of 40 articles were included in this review and the following five themes were identified from the studies: perceived acceptability and willingness to adhere to lockdown; perceived control during lockdown; perceived pressures arising from lockdown; perceived threat of sanction from others and the procedural (in)justice of lockdown. Our synthesis suggests that i) individuals experienced an initial willingness and tolerance of lockdown that lessened over time as perceptions of personal control decreased; ii) that social influences may pressure individuals to follow or break lockdown rules; and iii) that justifiability and proportionality together with individuals' perceptions of harm from COVID-19 may impact the extent to which individuals adhere to lockdown. Furthermore, the review found an absence of information regarding specific individual characteristics and circumstances that increase the likelihood of experiencing perceived coercion and its related constructs and highlights a need for a better understanding of the cultural and socioeconomic factors affecting perceptions of, and adherence to, lockdown.

A bioelectronic route to compassion: Rationale and study protocol for combining transcutaneous vagus nerve stimulation (tVNS) with compassionate mental imagery.

BACKGROUND: The vagus nerve (VN) is a neural nexus between the brain and body, enabling bidirectional regulation of mental functioning and peripheral physiology. Some limited correlational findings suggest an association between VN activation and a particular form of self-regulation: compassionate responding. Interventions that are geared towards strengthening self-compassion in particular, can serve as an antidote to toxic shame and self-criticism and improve psychological health. OBJECTIVE: We describe a protocol for examining the role of VN activation on 'state' self-compassion, self-criticism, and related outcomes. By combining transcutaneous vagus nerve stimulation (tVNS) with a brief imagery-based self-compassion intervention, we aim to preliminarily test additivity versus synergy between these distinct bottom-up and top-down methods for putatively regulating vagal activity. We also test whether the effects of VN stimulation accumulate with daily stimulation and daily compassionate imagery practice. METHODS: Using a randomized 2 x 2 factorial (stimulation x imagery condition) design, healthy volunteers (n = 120) receive active (tragus) or sham (earlobe) tVNS plus standardized (audio-recorded) self-compassionate or sham mental imagery instructions. These interventions are delivered in a university-based psychological laboratory in two sessions, one week apart, as well as being self-administered between sessions by participants at home. Pre-stimulation, peri-stimulation and post-imagery measures of state self-compassion, self-criticism and related self-report outcomes are assessed in two lab sessions, separated by a week (Days 1 and 8). Heart rate variability is used as a physiological metric of vagal activity and an eye-tracking task assesses attentional bias to compassionate faces during the two lab sessions. On Days 2-7, participants continue their randomly assigned stimulation and imagery tasks at home, and complete state measures at the end of each remote session. DISCUSSION: Demonstrating modulation of compassionate responding using tVNS would support a causal link between VN activation and compassion. This would provide a basis for future studies of bioelectronic approaches to augmenting therapeutic contemplative techniques. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov, Identifier: NCT05441774 (Date: July 1st 2022). OSF REGISTRATION: https://osf.io/4t9ha.

Meditation trips: A thematic analysis of the combined naturalistic use of psychedelics with meditation practices.

Similarities between meditative and psychedelic states have long been recognized. Recently, parallels in the psychological mechanisms mediating the beneficial effects of mindfulness and psychedelic treatments-as well as their potential therapeutic complementarity-have been noted. However, empirical research in this area remains limited. Here, we explore the naturalistic use of meditation practices among psychedelic users recruited outside of treatment/retreat or research settings. Participants with ≥ 1 psychedelic drug experience(s) were included in an online survey. The majority (n = 875; 66.5%) indicated that they engaged in meditation, 39.4% (n = 345) of whom had combined psychedelic use with meditation practices on ≥ 1 occasion. The majority (74.2%; n = 256) provided written accounts describing their experiences of "psychedelic-meditation," which were the basis for the present thematic analytic study. Six overarching themes were identified: (1) Compatibility Between Psychedelic and Meditative States; (2) Enhancement of the Meditative and Psychedelic Experience; (3) Beneficial Changes in Relating to the Internal and External World (encompassing acceptance, connection, peacefulness, and transformation); (4) Negative Effects of Combined Use; (5) Meditation as a Preparatory and Navigational Tool; and (6) Contextual Considerations (including reflections upon, and practical advice about, combining meditation and psychedelics). Participants' experiences appear to support recent empirical and theoretical work on the parallels and complementarity between psychedelic drug effects and meditation. The findings identify facilitating conditions for combining psychedelics with meditation, which may have implications for their combined therapeutic use. For example, the use of meditation techniques might represent a "psychedelic-sparing" strategy, potentially enabling therapeutically important psychedelic effects to emerge at lower doses. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

A systematic review of the pharmacological modulation of autobiographical memory specificity.

Background: Over-general autobiographical memory (AM) retrieval is proposed to have a causal role in the maintenance of psychological disorders like depression and PTSD. As such, the identification of drugs that modulate AM specificity may open up new avenues of research on pharmacological modeling and treatment of psychological disorders. Aim: The current review summarizes randomized, placebo-controlled studies of acute pharmacological modulation of AM specificity. Method: A systematic search was conducted of studies that examined the acute effects of pharmacological interventions on AM specificity in human volunteers (healthy and clinical participants) measured using the Autobiographical Memory Test. Results: Seventeen studies were identified (986 total participants), of which 16 were judged to have low risk of bias. The presence and direction of effects varied across drugs and diagnostic status of participants (clinical vs. healthy volunteers). The most commonly studied drug-hydrocortisone-produced an overall impairment in AM specificity in healthy volunteers [g = -0.28, CI (-0.53, -0.03), p = 0.03], although improvements were reported in two studies of clinical participants. In general, studies of monoamine modulators reported no effect on specificity. Conclusion: Pharmacological enhancement of AM specificity is inconsistent, although monaminergic modulators show little promise in this regard. Drugs that reduce AM specificity in healthy volunteers may be useful experimental-pharmacological tools that mimic an important transdiagnostic impairment in psychological disorders. Systematic review registration: PROSPERO, identifier CRD42020199076, https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42020199076.

Accelerated forgetting of a trauma-like event in healthy men and women after a single dose of hydrocortisone.

Posttraumatic stress disorder (PTSD) is characterised by dysregulated hypothalamic-pituitary-adrenal axis activity and altered glucocorticoid receptor sensitivity. Early treatment with glucocorticoids may reduce PTSD risk, although the effect of such treatment on the aetiologically critical step of traumatic-memory-formation remains unclear. Here we examine the effects of exogenous cortisol (hydrocortisone) in a preclinical model of PTSD, using a factorial (Drug × Sex), randomised-controlled, double-blind design. Healthy men and women (n = 120) were randomised to receive 30 mg oral hydrocortisone or matched placebo immediately after watching a stressful film. Effects on film-related intrusions were assessed acutely in the lab, and ecologically using daily memory diaries for one week. We found that participants receiving hydrocortisone showed a faster reduction in daily intrusion frequency. Voluntary memory was assessed once, at the end of the week, but was unaffected by hydrocortisone. Exploratory analyses indicated sex-dependent associations between intrusions and baseline estradiol and progesterone levels. In men receiving hydrocortisone, higher baseline estradiol levels were associated with fewer intrusions, whereas women exhibited the opposite pattern. By contrast, progesterone levels were positively associated with intrusions only in men treated with hydrocortisone. The findings suggest that hydrocortisone promotes an accelerated degradation of sensory-perceptual representations underlying traumatic intrusive memories. In addition, while sex alone was not an important moderator, the combination of sex and sex-hormone levels (especially estradiol) influenced hydrocortisone's effects on involuntary aversive memories. Future well-powered experimental studies may provide a basis for a precision-psychiatry approach to optimising early post-traumatic glucocorticoid treatments that target intrusive memories, based on individual endocrinological profiles.

The effects of response inhibition training following binge memory retrieval in young adults binge eaters: a randomised-controlled experimental study.

Binge eating is increasingly prevalent among adolescents and young adults and can have a lasting harmful impact on mental and physical health. Mechanistic insights suggest that aberrant reward-learning and biased cognitive processing may be involved in the aetiology of binge eating. We therefore investigated whether recently developed approaches to catalyse brief interventions by putatively updating maladaptive memory could also boost the effects of cognitive bias modification training on binge eating behaviour. A non-treatment-seeking sample of 90 binge eating young adults were evenly randomised to undergo either selective food response inhibition training, or sham training following binge memory reactivation. A third group received training without binge memory reactivation. Laboratory measures of reactivity and biased responses to food cues were assessed pre-post intervention and bingeing behaviour and disordered eating assessed up to 9 months post-intervention. The protocol was pre-registered at https://osf.io/82c4r/ . We found limited evidence of premorbid biased processing in lab-assessed measures of cognitive biases to self-selected images of typical binge foods. Accordingly, there was little evidence of CBM reducing these biases and this was not boosted by prior 'reactivation' of binge food reward memories. No group differences were observed on long-term bingeing behaviour, caloric consumption or disordered eating symptomatology. These findings align with recent studies showing limited impact of selective inhibition training on binge eating and do not permit conclusions regarding the utility of retrieval-dependent memory 'update' mechanisms as a treatment catalyst for response inhibition training.

Pharmacological modelling of dissociation and psychosis: an evaluation of the Clinician Administered Dissociative States Scale and Psychotomimetic States Inventory during nitrous oxide ('laughing gas')-induced anomalous states.

RATIONALE: A significant obstacle to an improved understanding of pathological dissociative and psychosis-like states is the lack of readily implemented pharmacological models of these experiences. Ketamine has dissociative and psychotomimetic effects but can be difficult to use outside of medical and clinical-research facilities. Alternatively, nitrous oxide (N2O) - like ketamine, a dissociative anaesthetic and NMDAR antagonist - has numerous properties that make it an attractive alternative for modelling dissociation and psychosis. However, development and testing of such pharmacological models relies on well-characterized measurement instruments. OBJECTIVES: To examine the factor structures of the Clinician Administered Dissociative States Scale (CADSS) and Psychotomimetic States Inventory (PSI) administered during N2O inhalation in healthy volunteers. METHODS: Secondary analyses of data pooled from three previous N2O studies with healthy volunteers. RESULTS: Effect sizes for N2O-induced dissociation and psychotomimesis were comparable to effects reported in experimental studies with sub-anaesthetic ketamine in healthy volunteers. Although, like ketamine, a three-factor representation of N2O-induced dissociation was confirmed, and a more parsimonious two-factor model might be more appropriate. Bayesian exploratory factor analysis suggested that N2O-induced psychosis-like symptoms were adequately represented by two negative and two positive symptom factors. Hierarchical cluster analysis indicated minimal item overlap between the CADSS and PSI. CONCLUSION: N2O and ketamine produce psychometrically similar dissociative states, although parallels in their psychosis-like effects remain to be determined. The CADSS and PSI tap largely non-overlapping experiences under N2O and we propose the use of both measures (or similar instruments) to comprehensively assess anomalous subjective states produced by dissociative NMDAR antagonists.

Stimulating meditation: a pre-registered randomised controlled experiment combining a single dose of the cognitive enhancer, modafinil, with brief mindfulness training.

BACKGROUND: Mindfulness-meditation has a variety of benefits on well-being. However, individuals with primary attentional impairments (e.g. attention deficit disorder) or attentional symptoms secondary to anxiety, depression or addiction, may be less likely to benefit, and require additional mindfulness-augmenting strategies. AIMS: To determine whether a single dose of the cognitive enhancer, modafinil, acutely increases subjective and behavioural indices of mindfulness, and augments brief mindfulness training. METHODS: A randomised, double-blind, placebo-controlled, 2 (drug: placebo, modafinil) × 2 (strategy: mindfulness, relaxation control) experiment was conducted. Seventy-nine meditation-naïve participants were assigned to: placebo-relaxation, placebo-mindfulness, modafinil-relaxation or modafinil-mindfulness. Pre-drug, post-drug and post-strategy state mindfulness, affect and autonomic activity, along with post-strategy sustained attention and mind-wandering were assessed within a single lab session. After the session, participants were instructed to practice their assigned behavioural strategy daily for one week, with no further drug administration, after which, follow-up measures were taken. RESULTS: As predicted, modafinil acutely increased state mindfulness and improved sustained attention. Differential acute strategy effects were found following mindfulness on autonomic activity but not state mindfulness. There were no strategy or drug effects on mind-wandering. However, exploratory analyses indicated that participants receiving modafinil engaged in more strategy practice across strategy conditions during follow-up. CONCLUSIONS: Modafinil acutely mimicked the effects of brief mindfulness training on state mindfulness but did not enhance the effects of this training. Limitations of the current study, and recommendations for future research examining modafinil as an adjunct to mindfulness- (or relaxation-) based treatments are discussed.

Rewarding Subjective Effects of the NMDAR Antagonist Nitrous Oxide (Laughing Gas) Are Moderated by Impulsivity and Depressive Symptoms in Healthy Volunteers.

BACKGROUND: Nitrous oxide (N2O) is an anesthetic gas with both therapeutic and abuse potential. Because N2O is an NMDA receptor (NMDAR) antagonist, its effects are expected to resemble those of the prototypical NMDAR antagonist, ketamine. In this study, we examined the subjective rewarding effects of N2O using measures previously employed in studies of ketamine. We also tested for moderation of these effects by bipolar phenotype, depressive symptoms, and impulsivity. METHODS: Healthy volunteers were randomly assigned to either 50% N2O (n = 40) or medical air (n = 40). Self-reported rewarding (liking and wanting), and alcohol-like effects were assessed pre-, peri- and post inhalation. RESULTS: Effect sizes for the various rewarding/alcohol-like effects of N2O were generally similar to those reported in studies of moderate-dose ketamine. Impulsivity moderated the subjective reinforcing (liking) effects of inhaled gas, while depressive symptoms moderated motivational (wanting [more]) effects. However, depression and impulsivity had opposite directional influences, such that higher impulsivity was associated with higher N2O liking, and higher depression, with lower N2O wanting. CONCLUSION: To the extent that static (versus longitudinal) subjective rewarding effects are a reliable indicator of future problematic drug use, our findings suggests that impulsivity and depression may predispose and protect, respectively, against N2O abuse. Future studies should examine if these moderators are relevant for other NMDAR antagonists, including ketamine, and novel ketamine-like therapeutic and recreational drugs. Similarities between moderate-dose N2O and moderate-dose ketamine in the intensity of certain subjective effects suggest that N2O may, at least to some extent, serve as substitute for ketamine as a safe and easily implemented experimental tool for probing reward-related NMDAR function and dysfunction in humans.

Long-term behavioural rewriting of maladaptive drinking memories via reconsolidation-update mechanisms.

BACKGROUND: Alcohol use disorders can be conceptualised as a learned pattern of maladaptive alcohol-consumption behaviours. The memories encoding these behaviours centrally contribute to long-term excessive alcohol consumption and are therefore an important therapeutic target. The transient period of memory instability sparked during memory reconsolidation offers a therapeutic window to directly rewrite these memories using targeted behavioural interventions. However, clinically-relevant demonstrations of the efficacy of this approach are few. We examined key retrieval parameters for destabilising naturalistic drinking memories and the ability of subsequent counterconditioning to effect long-term reductions in drinking. METHODS: Hazardous/harmful beer-drinking volunteers (N = 120) were factorially randomised to retrieve (RET) or not retrieve (No RET) alcohol reward memories with (PE) or without (No PE) alcohol reward prediction error. All participants subsequently underwent disgust-based counterconditioning of drinking cues. Acute responses to alcohol were assessed pre- and post-manipulation and drinking levels were assessed up to 9 months. RESULTS: Greater long-term reductions in drinking were found when counterconditioning was conducted following retrieval (with and without PE), despite a lack of short-term group differences in motivational responding to acute alcohol. Large variability in acute levels of learning during counterconditioning was noted. 'Responsiveness' to counterconditioning predicted subsequent responses to acute alcohol in RET + PE only, consistent with reconsolidation-update mechanisms. CONCLUSIONS: The longevity of behavioural interventions designed to reduce problematic drinking levels may be enhanced by leveraging reconsolidation-update mechanisms to rewrite maladaptive memory. However, inter-individual variability in levels of corrective learning is likely to determine the efficacy of reconsolidation-updating interventions and should be considered when designing and assessing interventions.

An assessment of rapamycin for weakening binge-eating memories via reconsolidation: a pre-registered, double-blind randomised placebo-controlled experimental study.

BACKGROUND: Maladaptive learning linking environmental food cues to high-palatability food reward plays a central role in overconsumption in obesity and binge eating disorders. The process of memory reconsolidation offers a mechanism to weaken such learning, potentially ameliorating over-eating behaviour. Here we investigated whether putatively interfering with synaptic plasticity using the mammalian target of rapamycin (mTOR) inhibitor, rapamycin, could weaken retrieved chocolate reward memories through blockade of reconsolidation. METHODS: Seventy five healthy volunteers with a tendency to binge eat chocolate were randomised to retrieve chocolate reward memory under 10 mg rapamycin (RET + RAP, active condition), or placebo (RET + PBO), or they received 10 mg rapamycin without subsequent retrieval (NO RET + RAP). Indices of chocolate reward memory strength were assessed one week pre and post manipulation and at one month follow-up. RESULTS: Contrary to hypotheses, the RET + RAP group did not show any greater reduction than control groups on indices of motivational salience of chocolate cues, motivation to consume chocolate or liking of chocolate. Mild evidence of improvement in the RET + RAP group was found, but this was limited to reduced chocolate binge episodes and improved healthy food choices. CONCLUSIONS: We did not find convincing evidence of comprehensive naturalistic chocolate reward memory reconsolidation blockade by rapamycin. The effects on chocolate bingeing and food choices may warrant further investigation. These limited positive findings may be attributable to insufficient interference with mTOR signalling with 10 mg rapamycin, or failure to destabilise chocolate memories during retrieval.

Author Correction: Ketamine can reduce harmful drinking by pharmacologically rewriting drinking memories.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Reduction in the occurrence of distressing involuntary memories following propranolol or hydrocortisone in healthy women.

BACKGROUND: Pharmacological treatments targeting the neuroendocrine stress response may hold special promise in secondary prevention of posttraumatic stress disorder (PTSD). However, findings from clinical trials have been inconsistent and the efficacy of specific drugs, their temporal window of efficacy, effective doses and the characteristics of likely treatment responders remain unclear. METHOD: Using an experimental human model of distressing involuntary memory formation, we compare the effects of two drugs that have theoretical or empirical support as secondary preventive agents in PTSD. Eighty-eight healthy women (average age: 23.5 years) received oral propranolol (80 mg), hydrocortisone (30 mg), or matched placebo immediately after viewing a 'trauma film'. They then completed daily, time-stamped intrusion diaries for 1 week, at the end of which, voluntary memory was tested. RESULTS: While neither drug affected voluntary memory for the trauma narrative, propranolol treatment was associated with 42% fewer, and hydrocortisone with 55% fewer intrusions across the week, relative to placebo. Additionally, propranolol reduced general trauma-like symptoms, and post-drug cortisol levels were negatively correlated with intrusion frequency in the hydrocortisone group. CONCLUSIONS: Overall, this study shows substantial reductions in intrusive memories and preserved voluntary narrative-declarative memory following either propranolol or hydrocortisone in an experimental model of psychological trauma. As such, despite some inconsistencies in clinical trials, our findings support continued investigation of propranolol and hydrocortisone as secondary preventive agents for re-experiencing symptoms of PTSD. The findings also suggest that it is critical for future research to identify the conditions governing the preventive efficacy of these drugs in PTSD.

The role of self-compassion and self-criticism in binge eating behaviour.

Self-criticism and low self-compassion are implicated in the development and maintenance of binge eating. However, the association between these self-attitudes and binge eating symptoms remains unclear. Women with symptoms of Bulimia Nervosa (BN) or Binge Eating Disorder (BED) were randomised to either a self-compassion (n = 30) or self-critical rumination (n = 30) strategy following a negative mood induction. Responses to food cues (cue reactivity and affect) and calorie consumption in a 'taste test' were assessed. The self-compassion strategy was associated with a greater improvement in positive and negative affect following the negative mood induction. Despite the differential effects on mood, self-compassion and self-critical rumination led to similar self-reported food cravings and physiological reactivity to cues. However, participants in the self-compassion condition consumed significantly fewer calories, rated the consumed food as less pleasurable, and reported less desire to continue eating. The findings suggest that therapeutic strategies for cultivating self-compassion are associated with improved food-related self-regulation in the context of negative mood.

Ketamine can reduce harmful drinking by pharmacologically rewriting drinking memories.

Maladaptive reward memories (MRMs) are involved in the development and maintenance of acquired overconsumption disorders, such as harmful alcohol and drug use. The process of memory reconsolidation - where stored memories become briefly labile upon retrieval - may offer a means to disrupt MRMs and prevent relapse. However, reliable means for pharmacologically weakening MRMs in humans remain elusive. Here we demonstrate that the N-methyl D-aspartate (NMDA) antagonist ketamine is able to disrupt MRMs in hazardous drinkers when administered immediately after their retrieval. MRM retrieval + ketamine (RET + KET) effectively reduced the reinforcing effects of alcohol and long-term drinking levels, compared to ketamine or retrieval alone. Blood concentrations of ketamine and its metabolites during the critical 'reconsolidation window' predicted beneficial changes only following MRM reactivation. Pharmacological reconsolidation interference may provide a means to rapidly rewrite maladaptive memory and should be further pursued in alcohol and drug use disorders.

The effects of licit and illicit recreational drugs on prospective memory: a meta-analytic review.

RATIONALE: There are no recent reports summarising the magnitude of prospective memory (PM) impairments in recreational drug users. OBJECTIVE: We performed a meta-analysis of studies (with a parallel group design) examining PM performance in users of common recreational drugs (including alcohol and tobacco) who were not intoxicated during testing. Studies were also evaluated for the presence of methodological bias. METHODS: Twenty-seven studies were included in the meta-analysis following literature searches of MEDLINE, EMBASE and PsycINFO. Effect sizes (standardised mean difference; SMD) were calculated separately for the effects of alcohol, cannabis, ecstasy, methamphetamine and tobacco use. The influences of drug use and study characteristics on effect sizes were explored using meta-regressions. Sources of study bias were also assessed. RESULTS: Heavy drinkers and regular drug users tended to perform worse than controls on event and time-based PM tasks. Effect sizes (standardised mean differences; SMDs) for event-based PM impairment across the different drug-using groups/heavy drinkers ranged between - 1.10 and - 0.49, with no 95% CI crossing 0.00. SMDs for time-based PM ranged between - 0.98 and - 0.70. Except for the CIs associated with the ES for smokers' time-based PM performance, no CIs crossed 0.00. CONCLUSIONS: Although all drug-using groups showed moderate-large impairments in event and time-based PM, effect sizes had low precision and moderate-high levels of heterogeneity. In addition, several methodological and reporting issues were identified in the majority of studies. As such, considerable uncertainty remains regarding the role of confounds and the magnitude of PM impairments in non-intoxicated recreational drug users.

Prospects for reconsolidation-focused treatments of substance use and anxiety-related disorders.

Memories are often conceptualized as permanent entities; however, retrieval of memories via stimulus prompts can return them to an active state, which initiates a period of lability before the memories are reconsolidated into long-term storage. Importantly, during this period, memories can be disrupted/altered. A growing body of work has focused on translating animal and experimental science into reconsolidation-based interventions for clinical disorders maintained by maladaptive memories. Interventions targeting reward-based and fear-based memories undergirding substance use and anxiety-related disorders, respectively, have shown significant potential. There are several promising pharmacological agents and behavioral approaches that have been used to therapeutically target memory reconsolidation. Here, we discuss the current state of science with special emphasis on the clinical utility of these approaches.