Claire Mokrysz

Power failure: why small sample size undermines the reliability of neuroscience

A study with low statistical power has a reduced chance of detecting a true effect, but it is less well appreciated that low power also reduces the likelihood that a statistically significant result reflects a true effect. Here, we show that the average statistical power of studies in the neurosciences is very low. The consequences of this include overestimates of effect size and low reproducibility of results. There are also ethical dimensions to this problem, as unreliable research is inefficient and wasteful. Improving reproducibility in neuroscience is a key priority and requires attention to well-established but often ignored methodological principles.

Keep off the grass? Cannabis, cognition and addiction

In an increasing number of states and countries, cannabis now stands poised to join alcohol and tobacco as a legal drug. Quantifying the relative adverse and beneficial effects of cannabis and its constituent cannabinoids should therefore be prioritized. Whereas newspaper headlines have focused on links between cannabis and psychosis, less attention has been paid to the much more common problem of cannabis addiction. Certain cognitive changes have also been attributed to cannabis use, although their causality and longevity are fiercely debated. Identifying why some individuals are more vulnerable than others to the adverse effects of cannabis is now of paramount importance to public health. Here, we review the current state of knowledge about such vulnerability factors, the variations in types of cannabis, and the relationship between these and cognition and addiction.

Acute and chronic effects of cannabinoids on effort-related decision-making and reward learning: an evaluation of the cannabis 'amotivational' hypotheses.

RationaleAnecdotally, both acute and chronic cannabis use have been associated with apathy, amotivation, and other reward processing deficits. To date, empirical support for these effects is limited, and no previous studies have assessed both acute effects of Δ-9-tetrahydrocannabinol (THC) and cannabidiol (CBD), as well as associations with cannabis dependence.ObjectivesThe objectives of this study were (1) to examine acute effects of cannabis with CBD (Cann + CBD) and without CBD (Cann-CBD) on effort-related decision-making and (2) to examine associations between cannabis dependence, effort-related decision-making and reward learning.MethodsIn study 1, 17 participants each received three acute vaporized treatments, namely Cann-CBD (8xa0mg THC), Cann + CBD (8xa0mg THCxa0+xa010xa0mg CBD) and matched placebo, followed by a 50xa0% dose top-up 1.5xa0h later, and completed the Effort Expenditure for Rewards Task (EEfRT). In study 2, 20 cannabis-dependent participants were compared with 20 non-dependent, drug-using control participants on the EEfRT and the Probabilistic Reward Task (PRT) in a non-intoxicated state.ResultsCann-CBD reduced the likelihood of high-effort choices relative to placebo (pxa0=xa00.042) and increased sensitivity to expected value compared to both placebo (pxa0=xa00.014) and Cann + CBD (pxa0=xa00.006). The cannabis-dependent and control groups did not differ on the EEfRT. However, the cannabis-dependent group exhibited a weaker response bias than the control group on the PRT (pxa0=xa00.007).ConclusionsCannabis acutely induced a transient amotivational state and CBD influenced the effects of THC on expected value. In contrast, cannabis dependence was associated with preserved motivation alongside impaired reward learning, although confounding factors, including depression, cannot be disregarded. This is the first well powered, fully controlled study to objectively demonstrate the acute amotivational effects of THC.

The effects of nicotine dependence and acute abstinence on the processing of drug and non-drug rewards

RationaleDrug addiction may be characterised by a hypersensitivity to drug rewards and a hyposensitivity to non-drug rewards. This imbalance may become further polarised during acute abstinence.Objectives(i) Examine the differences between dependent and occasional smokers in choices for, motivation for and self-reported wanting and liking of cigarette and non-drug rewards. (ii) Examine the effects of 12-h nicotine abstinence on these metrics.MethodsDependent (nu2009=u200920) and occasional, non-dependent smokers (nu2009=u200920) were tested after ad libitum smoking and ≥12-h of nicotine abstinence. A novel task was developed (Drug, Reward and Motivation–Choice (DReaM-Choice)) in which different rewards (cigarettes, music and chocolate) could be won. In each trial, participants chose between two rewards and then could earn the chosen reward via repeated button-pressing. Participants subsequently ‘consumed’ and rated subjective liking of the rewards they had won.ResultsCompared with occasional smokers, dependent smokers made more choices for (pu2009<u20090.001), pressed more for (pu2009=u20090.046) and reported more wanting (pu2009=u20090.007) and liking (pu2009<u20090.001) of cigarettes, and also made fewer choices for chocolate (pu2009=u20090.005). There were no differences between the groups on button-pressing for chocolate or music. However, the balance between drug and non-drug reward processing was different between the groups across all metrics. Twelve-hour nicotine abstinence led to more cigarette choices (pu2009<u20090.001) and fewer music choices (pu2009=u20090.042) in both groups.ConclusionsNicotine dependence was associated with a hypersensitivity to cigarette rewards, but we found little evidence indicating a hyposensitivity to non-drug rewards. Our findings question the moderating influence of dependence on how acute nicotine abstinence affects reward processing.

Attentional bias and treatment adherence in substitute-prescribed opiate users

BACKGROUNDnAttentional bias (AB) is implicated in the development and maintenance of substance dependence and in treatment outcome. We assessed the effects of attentional bias modification (ABM), and the relationship between AB and treatment adherence in opiate dependent patients.nnnMETHODnAn independent groups design was used to compare 23 opiate dependent patients with 21 healthy controls. Participants completed an AB task before either a control or an ABM task designed to train attention away from substance-related stimuli. Pre- and post-ABM AB and craving were assessed to determine any changes. Relationships between treatment adherence (using on top of prescribed opiates or not) and AB, craving and psychopathology were also examined.nnnRESULTSnThere was no baseline difference in AB between patients and controls, and no significant effect of ABM on AB or substance craving. However, treatment adherent patients who did not use illicit opiates on top of their prescribed opiates had statistically significantly greater AB away from substance-related stimuli than both participants using on top and controls, and reported significantly lower levels of craving than non-treatment adherent patients.nnnCONCLUSIONnWhilst we did not find any significant effects of ABM on AB or craving, patients who were treatment adherent differed from both those who were not and from controls in their attentional functioning and substance craving. These findings are the first to suggest that AB may be a within-treatment factor predictive of adherence to pharmacological treatment and potentially of recovery in opiate users.

Predictors of Age of Diagnosis and Survival of Alzheimer’s Disease in Down Syndrome

Background: People with Down syndrome (DS) are an ultra-high risk population for Alzheimer’s disease (AD). Understanding the factors associated with age of onset and survival in this population could highlight factors associated with modulation of the amyloid cascade. Objective: This study aimed to establish the typical age at diagnosis and survival associated with AD in DS and the risk factors associated with these. Methods: Data was obtained from the Aging with Down Syndrome and Intellectual Disabilities (ADSID) research database, consisting of data extracted from clinical records of patients seen by Community Intellectual Disability Services (CIDS) in England. Survival times when considering different risk factors were calculated. Results: The mean age of diagnosis was 55.80 years, SD 6.29. Median survival time after diagnosis was 3.78 years, and median age at death was approximately 60 years. Survival time was associated with age of diagnosis, severity of intellectual disability, living status, anti-dementia medication status, and history of epilepsy. Age at diagnosis and treatment status remained predictive of survival time following adjustment. Conclusion: This study provides the best estimate of survival in dementia within the DS population to date, and is in keeping with previous estimates from smaller studies in the DS population. This study provides important estimates and insights into possible predictors of survival and age of diagnosis of AD in adults with DS, which will inform selection of participants for treatment trials in the future.

Cannabis dampens the effects of music in brain regions sensitive to reward and emotion

Abstract Background Despite the current shift towards permissive cannabis policies, few studies have investigated the pleasurable effects users seek. Here, we investigate the effects of cannabis on listening to music, a rewarding activity that frequently occurs in the context of recreational cannabis use. We additionally tested how these effects are influenced by cannabidiol, which may offset cannabis-related harms. Methods Across 3 sessions, 16 cannabis users inhaled cannabis with cannabidiol, cannabis without cannabidiol, and placebo. We compared their response to music relative to control excerpts of scrambled sound during functional Magnetic Resonance Imaging within regions identified in a meta-analysis of music-evoked reward and emotion. All results were False Discovery Rate corrected (P<.05). Results Compared with placebo, cannabis without cannabidiol dampened response to music in bilateral auditory cortex (right: P=.005, left: P=.008), right hippocampus/parahippocampal gyrus (P=.025), right amygdala (P=.025), and right ventral striatum (P=.033). Across all sessions, the effects of music in this ventral striatal region correlated with pleasure ratings (P=.002) and increased functional connectivity with auditory cortex (right: P< .001, left: P< .001), supporting its involvement in music reward. Functional connectivity between right ventral striatum and auditory cortex was increased by cannabidiol (right: P=.003, left: P=.030), and cannabis with cannabidiol did not differ from placebo on any functional Magnetic Resonance Imaging measures. Both types of cannabis increased ratings of wanting to listen to music (P<.002) and enhanced sound perception (P<.001). Conclusions Cannabis dampens the effects of music in brain regions sensitive to reward and emotion. These effects were offset by a key cannabis constituent, cannabidol.

Rethinking dose-response effects of cannabis use in adolescence

Cannabis is increasingly a prescribed drug and is even legal in some countries. It is timely then that a recent study by Edmund Silins and colleagues in The Lancet Psychiatry reported associations between cannabis use in adolescence and a range of impor tant life outcomes. Combining data at a participant level from three longitudinal cohort studies in Australia and New Zealand, and controlling for an impressive number of confounding variables, Silins and colleagues report that increased frequency of cannabis use before age 17 years predicted reduced likelihood of completing high school or gaining a university degree along side increased risk of cannabis dependence, use of other illicit drugs, and attempted suicide. Silins and colleagues conclude that the reported associations showed a dose-response relation with cannabis exposure. The models they tested assumed a linear eff ect of cannabis according to maximum reported frequency of use (never, less than monthly, monthly or more, weekly or more, or daily) before age 17 years. These proxies of use might not reflect actual dose (of delta-9tetra hydrocannabinol) because of variation in cannabis potency and patterns of use. Nevertheless, it is reasonable to assume that dose increased pro gressively but in a nonlinear manner from never to daily user groups. For example, the diff erence between never and less than monthly might reflect a tiny amount of cannabis (perhaps a few joints in one’s lifetime), whilst escalating from weekly or more to daily can reflect a large increase in cannabis consumption. The authors report that categorical representations of cannabis use did not improve the model fi t over and above a linear model. However, we believe that a categorical analysis could supplement their fi ndings and aid interpretation of dose-response effects. Silins and colleagues assert that strongest eff ects were shown in daily users, which seems to be true for cannabis dependence, but not for the other outcomes that were robust to confounding. Daily users did not fare worse than weekly users for rates of school completion or degree attainment, whereas use of other illicit drugs was 4% lower, and suicide attempts were 6% lower in daily than weekly users (fi gure). It is possible that these trends in the raw data can be explained by confounding or sampling error or both in the daily use group because of low frequencies, especially in rare outcomes like suicide attempts. Alternatively, daily use might not carry greater risk for these outcomes than weekly use. If so, this absence of a clear dose-response profile might either suggest a non-linear relation or, more likely, question the argument of causality. Cannabis comes in many forms with some types like skunk or sinsemilla containing very high levels of delta9-tetrahydrocannabinol, but without cannabidiol, an ingredient that offsets some harmful eff ects of delta-9tetrahydrocannabinol on cognition and mental health. As legislative changes pave the way for the next generation of cannabis users, future prospective longitudinal cohort studies could benefi t from biological quantification of concentrations of major cannabinoids ingested and biological indicators of degree of use to more clearly characterise doseresponse eff ects.

Commentary on Meier et al. (2018): Smoke and mirrors-are adolescent cannabis users vulnerable to cognitive impairment?

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Resisting the urge to smoke: inhibitory control training in cigarette smokers

Impaired response inhibition is an important factor in tobacco dependence. We examined the effects of inhibitory control training (ICT) on inhibition, smoking resistance and cigarette use. Smokers (nu2009=u200955) abstained from smoking for 12u2009h prior to testing. On the test day, participants recorded cigarette use and completed pre-training measures of global and cue-specific (smoking-related) response inhibition. Participants were randomized to either an active or a control ICT group. The active group was required to repeatedly inhibit a response towards smoking cues (100%), while the control group was required to inhibit a response towards smoking and neutral cues with equal frequency (50%). Participants performed post-training measures of response inhibition, smoking resistance and cigarette use. Inhibition data did not indicate time (pre-training, post-training)u2009×u2009group (active training, control training) or timeu2009×u2009groupu2009×u2009cue (smoking, neutral) interactions. There was weak evidence that smokers in the active group were more likely to resist smoking than those in the control group. Cigarette use data did not indicate a timeu2009×u2009group interaction. Our data suggest that ICT may enhance the ability to resist smoking, indicating that training may be a promising adjunct to smoking pharmacotherapy.