Is approving esketamine as an antidepressant for treatment resistant depression associated with recreational use and risk perception of ketamine? Results from a longitudinal and cross-sectional survey in nightlife attendees

Background Esketamine was licensed for use in treatment resistant depression by the European Medicines Agency in December 2019. It is unclear whether this new approval has lowered the risk perception of recreational ketamine use. This is important given a recent increase in recreational ketamine use. Methods This study expanded on an existing longitudinal online study of the nightlife scene, by adding an additional longitudinal assessment as well as a new cross-sectional sample. Participants had to be aged 18–34 years, reside in the UK and have attended at least 6 electronic music events in the past year. The likelihood of increasing recreational ketamine use due to the approval, attitudes towards and risk perception of medical ketamine use and experiences resulting from recreational ketamine use were collected after the approval. Changes in ketamine use and frequency were assessed longitudinally before and after the approval. Results The overall sample size was 2415: 414 longitudinal (57% retention rate) and 2001 new cross-sectional participants. The majority indicated no change in their likelihood of using recreational ketamine due to the approval of esketamine (87%). Longitudinal participants did not indicate an increase in past 12 month use or frequency after the approval. Only one-third of participants reported being aware of the approval. Participants previously aware showed greater overall support for medical use of ketamine than participants previously unaware of the change. However, an equally high risk was assigned to the recreational use of ketamine in both groups. Ketamine users indicated both increases as well as decreases in depression and anxiety as a result of ketamine use. Conclusion The introduction of esketamine as an antidepressant was not associated with a change in the risk perception of recreational ketamine use in most participants, nor was it longitudinally associated with increased use. Potential negative effects of recreational ketamine use on mental health, as users in this sample reported, should be clearly communicated when discussing the benefits of (es-) ketamine in a therapeutic context

The development and validation of a human screening model of tobacco abstinence

Introduction Given the low efficacy of smoking cessation methods, an experimental medicine model indicating smoking abstinence would be of great benefit to the development of new treatments. Hence the sensitivity of cognitive tasks and ambulatory craving measures to smoking abstinence were investigated. Methods Cognitive tasks and ambulatory ratings of craving were assessed for sensitivity to acute abstinence (experiment 1), and nicotine replacement therapy administration (NRT) (experiment 2). Results In experiment 1 go/no-go performance was improved (Mean Difference [MD] -0.99, 95% CI: −1.90 to −0.08) and craving was lower (Regression Coefficient [RC] −33.39, 95% CI: -39.96 to -26.82) in satiated compared with abstinent smokers. There was no clear evidence that N-back (MD 0.64, 95% CI: −0.42 to 2.51), delay discounting (MD 0.01, 95% CI: 0.001 to 0.005) or dot probe performance (MD 0.61, 95% CI: −0.87 to 1.54) were sensitive to acute abstinence. In experiment 2 go/no-go performance was improved (MD 1.12, 95% CI: 0.16–2.08) and craving was lower (RC −18.59, 95% CI: −24.63 to −12.55) smokers abstinent overnight receiving NRT compared with placebo. There was no clear evidence that N-back (MD −0.25, 95% CI: −1.45 to 0.94), delay discounting (MD 0.01, 95% CI: -0.002 to 0.004) or dot probe performance (MD −0.49, 95% CI: −1.61 to −0.64) were sensitive to NRT. Conclusions Findings from two experiments converge to suggest that abstinence in smokers reliably increases ambulatory craving assessments and, to a lesser extent, decreases go/no-go task performance. These findings can be utilized in the development of an experimental medicine model to test novel treatments for smoking cessation

Behavioral tasks sensitive to acute abstinence and predictive of smoking cessation success:a systematic review and meta-analysis

BACKGROUND AND AIMS: Performance on cognitive tasks may be sensitive to acute smoking abstinence and may also predict whether quit attempts fail. Our aim was to conduct a systematic review and meta-analysis to identify cognitive tasks sensitive to acute abstinence and predictive of smoking cessation success.METHODS: Embase, Medline, PsycInfo and Web of Science were searched up to March 2016. Studies were included if they enrolled adults and assessed smoking using used a quantitative measure. Studies were combined in a random effects meta-analysis.RESULTS: We included 42 acute abstinence studies and 13 cessation studies were included. There was evidence for an effect of abstinence on delay discounting [d = 0.26, 95% CI 0.07 to 0.45, p = 0.005], response inhibition [d = 0.48, 95% CI 0.26 to 0.70, p &lt; 0.001], mental arithmetic [d = 0.38, 95% CI 0.06 to 0.70, p = 0.018], and recognition memory [d = 0.46, 95% CI 0.23 to 0.70, p &lt; 0.001]. In contrast performance on the Stroop [d =0 .17, 95% CI -0.17 to 0.51, p = 0.333] and smoking Stroop [d = 0.03, 95% CI -0.11 to 0.17, p = 0.675] task was not influenced by abstinence. We found only weak evidence for an effect of acute abstinence on dot probe task performance [d = 0.15, 95% CI -0.01 to 0.32, p = 0.072]. The design of the cessation studies was too heterogeneous to permit meta-analysis.CONCLUSIONS: Compared with satiated smokers, acutely abstinent smokers display higher delay discounting, lower response inhibition, impaired arithmetic, and recognition memory performance. However, reaction time measures of cognitive bias appear to be unaffected by acute tobacco abstinence. Conclusions about cognitive tasks that predict smoking cessation success were limited by methodological inconsistencies.</p

The effects of cannabidiol on impulsivity and memory during abstinence in cigarette dependent smokers

This is the final version of the article. Available from Springer Nature via the DOI in this record.The dataset generated during the current study are available from the corresponding author on reasonable request.Acute nicotine abstinence in cigarette smokers results in deficits in performance on specific cognitive processes, including working memory and impulsivity which are important in relapse. Cannabidiol (CBD), the non-intoxicating cannabinoid found in cannabis, has shown pro-cognitive effects and preliminary evidence has indicated it can reduce the number of cigarettes smoked in dependent smokers. However, the effects of CBD on cognition have never been tested during acute nicotine withdrawal. The present study therefore aimed to investigate if CBD can improve memory and reduce impulsivity during acute tobacco abstinence. Thirty, non-treatment seeking, dependent, cigarette smokers attended two laboratory-based sessions after overnight abstinence, in which they received either 800 mg oral CBD or placebo (PBO), in a randomised order. Abstinence was biologically verified. Participants were assessed on go/no-go, delay discounting, prose recall and N-back (0-back, 1-back, 2-back) tasks. The effects of CBD on delay discounting, prose recall and the N-back (correct responses, maintenance or manipulation) were null, confirmed by a Bayesian analysis, which found evidence for the null hypothesis. Contrary to our predictions, CBD increased commission errors on the go/no-go task. In conclusion, a single 800 mg dose of CBD does not improve verbal or spatial working memory, or impulsivity during tobacco abstinence.This research was funded by a PhD Studentship from the Medical Research Council (MRC) to the C.H. and an MRC DPFS award (MR/K015524/1) to HVC and CJAM.TPF is funded by a Senior Academic Fellowship from the Society for the Study of Addiction

Measurement of the Cross Section Asymmetry of the Reaction gp-->pi0p in the Resonance Energy Region Eg = 0.5 - 1.1 GeV

The cross section asymmetry Sigma has been measured for the photoproduction of pi0-mesons off protons, using polarized photons in the energy range Eg = 0.5 - 1.1 GeV. The CM angular coverage is Theta = 85 - 125 deg with energy and angle steps of 25 MeV and 5 deg, respectively. The obtained Sigma data, which cover the second and third resonance regions, are compared with existing experimental data and recent phenomenological analyses. The influence of these measurements on such analyses is also considered

The Sensitivity of HAWC to High-Mass Dark Matter Annihilations

The High Altitude Water Cherenkov (HAWC) observatory is a wide field-of-view detector sensitive to gamma rays of 100 GeV to a few hundred TeV. Located in central Mexico at 19 degrees North latitude and 4100 m above sea level, HAWC will observe gamma rays and cosmic rays with an array of water Cherenkov detectors. The full HAWC array is scheduled to be operational in Spring 2015. In this paper, we study the HAWC sensitivity to the gamma-ray signatures of high-mass (multi- TeV) dark matter annihilation. The HAWC observatory will be sensitive to diverse searches for dark matter annihilation, including annihilation from extended dark matter sources, the diffuse gamma-ray emission from dark matter annihilation, and gamma-ray emission from non-luminous dark matter subhalos. Here we consider the HAWC sensitivity to a subset of these sources, including dwarf galaxies, the M31 galaxy, the Virgo cluster, and the Galactic center. We simulate the HAWC response to gamma rays from these sources in several well-motivated dark matter annihilation channels. If no gamma-ray excess is observed, we show the limits HAWC can place on the dark matter cross-section from these sources. In particular, in the case of dark matter annihilation into gauge bosons, HAWC will be able to detect a narrow range of dark matter masses to cross-sections below thermal. HAWC should also be sensitive to non-thermal cross-sections for masses up to nearly 1000 TeV. The constraints placed by HAWC on the dark matter cross-section from known sources should be competitive with current limits in the mass range where HAWC has similar sensitivity. HAWC can additionally explore higher dark matter masses than are currently constrained.Comment: 15 pages, 4 figures, version to be published in PR

Drug use changes at the individual level : Results from a longitudinal, multisite survey in young europeans frequenting the nightlife scene

Background: Monitoring emerging trends in the increasingly dynamic European drug market is vital; however, information on change at the individual level is scarce. In the current study, we investigated changes in drug use over 12 months in European nightlife attendees. Method: In this longitudinal online survey, changes in substances used, use frequency in continued users, and relative initiation of use at follow-up were assessed for 20 different substances. To take part, participants had to be aged 18–34 years; be from Belgium, Italy, the Netherlands, Sweden, or the UK; and have attended at least 6 electronic music events in the past 12 months at baseline. Of 8,045 volunteers at baseline, 2,897 completed the survey at both time points (36% follow-up rate), in 2017 and 2018. Results: The number of people using ketamine increased by 21% (p < 0.001), and logarithmized frequency of use in those continuing use increased by 15% (p < 0.001; 95% CI: 0.07–0.23). 4-Fluoroamphetamine use decreased by 27% (p < 0.001), and logarithmized frequency of use in continuing users decreased by 15% (p < 0.001, 95% CI: −0.48 to −0.23). The drugs with the greatest proportion of relative initiation at follow-up were synthetic cannabinoids (73%, N = 30), mephedrone (44%, N = 18), alkyl nitrites (42%, N = 147), synthetic dissociatives (41%, N = 15), and prescription opioids (40%, N = 48). Conclusions: In this European nightlife sample, ketamine was found to have the biggest increase in the past 12 months, which occurred alongside an increase in frequency of use in continuing users. The patterns of uptake and discontinuation of alkyl nitrates, novel psychoactive substances, and prescription opioids provide new information that has not been captured by existing cross-sectional surveys. These findings demonstrate the importance of longitudinal assessments of drug use and highlight the dynamic nature of the European drug landscape