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2.
J Psychopharmacol ; : 269881119862533, 2019 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-31407943

RESUMO

BACKGROUND: Acute consumption of cannabis or its primary psychoactive ingredient ∆9-tetrahydrocannabinol has been shown to impair memory, reaction time, time perception, and attention. However, it is difficult to measure these impairments in a brief test that can be used in a non-laboratory setting. AIMS: We aim to develop and validate a prototype for a mobile phone application to measure ∆9-tetrahydrocannabinol-induced cognitive impairment. METHODS: We conducted two double-blind, within-subjects studies examining impairments after oral doses of ∆9-tetrahydrocannabinol (0, 7.5, 15 mg) using both standardized computer-based tasks and our novel phone-based tasks. The tasks measured cognitive speed, reaction time, fine motor ability, and working memory and, in the second study, time perception. Study 1 (n=24) provided initial data, and Study 2 (n=24) was designed to refine the measures. In both studies, healthy non-daily cannabis users participated in three four-hour experimental sessions in which they received capsules containing ∆9-tetrahydrocannabinol (7.5, 15 mg) or placebo. Subjective and cardiovascular measures were obtained at regular intervals, and at the time of peak drug effect subjects completed both standardized, computer-based and brief, phone-based tasks. RESULTS: ∆9-Tetrahydrocannabinol-induced impairment was detected on most of the computer tasks, but was not evident on most of the phone tasks. CONCLUSIONS: The phone tasks were brief, to facilitate use in a non-laboratory setting, but it is likely that this made them less sensitive to the impairing effects of ∆9-tetrahydrocannabinol. These findings confirm that ∆9-tetrahydrocannabinol impairs performance on several tasks at two recreationally relevant doses, but raises question about the feasibility of designing a phone application as a sensitive field sobriety test for cannabis.

3.
Biol Psychiatry ; 2019 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-31331617

RESUMO

BACKGROUND: Numerous anecdotal reports suggest that repeated use of very low doses of lysergic acid diethylamide (LSD), known as microdosing, improves mood and cognitive function. These effects are consistent both with the known actions of LSD on serotonin receptors and with limited evidence that higher doses of LSD (100-200 µg) positively bias emotion processing. Yet, the effects of such subthreshold doses of LSD have not been tested in a controlled laboratory setting. As a first step, we examined the effects of single very low doses of LSD (0-26 µg) on mood and behavior in healthy volunteers under double-blind conditions. METHODS: Healthy young adults (N = 20) attended 4 laboratory sessions during which they received 0 (placebo), 6.5, 13, or 26 µg of LSD in randomized order at 1-week intervals. During expected peak drug effect, they completed mood questionnaires and behavioral tasks assessing emotion processing and cognition. Cardiovascular measures and body temperature were also assessed. RESULTS: LSD produced dose-related subjective effects across the 3 doses (6.5, 13, and 26 µg). At the highest dose, the drug also increased ratings of vigor and slightly decreased positivity ratings of images with positive emotional content. Other mood measures, cognition, and physiological measures were unaffected. CONCLUSIONS: Single microdoses of LSD produced orderly dose-related subjective effects in healthy volunteers. These findings indicate that a threshold dose of 13 µg of LSD might be used safely in an investigation of repeated administrations. It remains to be determined whether the drug improves mood or cognition in individuals with symptoms of depression.

4.
Artigo em Inglês | MEDLINE | ID: mdl-31209507

RESUMO

RATIONALE: One risk factor for alcohol and substance misuse is hypomanic experiences, or periods of mood elevation. Young people who report hypomanic states are more likely to develop bipolar disorder (BP), and BP and other mood disorders increase the risk of addiction. We recently reported that young adults with a history of mood elevation experience less subjective effects from a low dose of alcohol, which may be predictive of future alcohol use. The finding with alcohol raised the question of whether this dampened response to a drug also applies to other drugs, such as amphetamine. OBJECTIVE: This study assessed responses of d-amphetamine in healthy young adults with varying experiences of mood elevation, as measured by the Mood Disorders Questionnaire (MDQ). METHODS: Healthy 18-19-year-olds (N = 30) with a range of MDQ scores participated in three 4-h laboratory sessions in which they received placebo, 10 mg, or 20 mg d-amphetamine. They completed mood questionnaires and cardiovascular measures. RESULTS: Individuals with higher MDQ scores reported less stimulation and euphoria after 10 mg, but not 20 mg, d-amphetamine, than individuals with lower scores. MDQ scores were not related to cardiovascular responses to the drug. CONCLUSIONS: A history of mood elevation experiences or hypomania states is related to dampened response to a low dose of a psychostimulant drug, extending previous findings with dampened response to alcohol. This phenotype for mood disorders of dampened responses to drugs may contribute to risk for subsequent drug use or misuse.

5.
Nat Neurosci ; 22(7): 1196, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31168101

RESUMO

Several occurrences of the word 'schizophrenia' have been re-worded as 'liability to schizophrenia' or 'schizophrenia risk', including in the title, which should have been "GWAS of lifetime cannabis use reveals new risk loci, genetic overlap with psychiatric traits, and a causal effect of schizophrenia liability," as well as in Supplementary Figures 1-10 and Supplementary Tables 7-10, to more accurately reflect the findings of the work.

6.
Psychopharmacology (Berl) ; 236(8): 2413-2423, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31165207

RESUMO

RATIONALE: Methamphetamine (MA) use is steadily increasing and thus constitutes a major public health concern. Women seem to be particularly vulnerable to developing MA use disorder, as they initiate use at a younger age and transition more quickly to problematic use. Initial drug responses may predict subsequent use, but little information exists on potential gender differences in the acute effects of MA prior to dependence. OBJECTIVE: We examined gender differences in the acute effects of MA on subjective mood and reward-related behavior in healthy, non-dependent humans. METHODS: Men (n = 44) and women (n = 29) completed 4 sessions in which they received placebo or MA under double-blind conditions twice each. During peak drug effect, participants completed the monetary incentive delay task to assess reaction times to cues signaling potential monetary losses or gains, in an effort to determine if MA would potentiate reward-motivated behavior. Cardiovascular and subjective drug effects were assessed throughout sessions. RESULTS: Overall, participants responded more quickly to cues predicting incentivized trials, particularly large-magnitude incentives, than to cues predicting no incentive. MA produced faster reaction times in women, but not in men. MA produced typical stimulant-like subjective and cardiovascular effects in all participants, but subjective ratings of vigor and (reduced) sedation were greater in women than in men. CONCLUSIONS: Women appear to be more sensitive to the psychomotor-related behavioral and subjective effects of MA. These findings provide initial insight into gender differences in acute effects of MA that may contribute to gender differences in problematic MA use.

7.
Psychopharmacology (Berl) ; 236(5): 1407-1409, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31172224
8.
Neuropsychopharmacology ; 44(10): 1698-1705, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31042696

RESUMO

The psychostimulant drug ±3,4-methylenedioxymethamphetamine (MDMA) reportedly produces distinctive feelings of empathy and closeness with others. MDMA increases social behavior in animal models and has shown promise in psychiatric disorders, such as autism spectrum disorder (ASD) and post-traumatic stress disorder (PTSD). How it produces these prosocial effects is not known. This behavioral and psychophysiological study examined the effects of MDMA, compared with the prototypical stimulant methamphetamine (MA), on two measures of social behavior in healthy young adults: (i) responses to socially relevant, "affective" touch, and (ii) visual attention to emotional faces. Men and women (N = 36) attended four sessions in which they received MDMA (0.75 or 1.5 mg/kg), MA (20 mg), or a placebo in randomized order under double-blind conditions. Responses to experienced and observed affective touch (i.e., being touched or watching others being touched) were assessed using facial electromyography (EMG), a proxy of affective state. Responses to emotional faces were assessed using electrooculography (EOG) in a measure of attentional bias. Subjective ratings were also included. We hypothesized that MDMA, but not MA, would enhance the ratings of pleasantness and psychophysiological responses to affective touch and increase attentional bias toward positive facial expressions. Consistent with this, we found that MDMA, but not MA, selectively enhanced ratings of pleasantness of experienced affective touch. Neither drug altered the ratings of pleasantness of observed touch. On the EOG measure of attentional bias, MDMA, but not MA, increased attention toward happy faces. These results provide new evidence that MDMA can enhance the experience of positive social interactions; in this case, pleasantness of physical touch and attentional bias toward positive facial expressions. The findings are consistent with evidence that the prosocial effects are unique to MDMA relative to another stimulant. Understanding the behavioral and neurobiological processes underlying the distinctive social effects of MDMA is a key step to developing the drug for psychiatric disorders.

9.
Addict Biol ; : e12775, 2019 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-31099141

RESUMO

Chronic use of methamphetamine impairs frontostriatal structure and function, which may result in increased incentive-motivational responses to drug cues and decreased regulation of drug-seeking behavior. However, less is known regarding how the drug affects these circuits after acute administration. The current study examined the effects of a single dose of methamphetamine on resting state frontostriatal functional connectivity in healthy volunteers. Participants (n = 22, 12 female) completed two sessions in which they received methamphetamine (20 mg) and placebo before a resting state scan during functional magnetic resonance imaging. Participants also provided self-report measures of euphoria and stimulation at regular intervals. We conducted seed-based voxelwise functional connectivity analyses using three bilateral striatal seed regions: nucleus accumbens (NAcc), caudate, and putamen and compared connectivity following methamphetamine versus placebo administration. Additionally, we conducted correlational analyses to assess if drug-induced changes in functional connectivity were related to changes in subjective response. Methamphetamine increased NAcc functional connectivity with medial frontal regions (ie, orbitofrontal cortex, medial frontal gyrus, and superior frontal gyrus) and decreased NAcc functional connectivity with subgenual anterior cingulate cortex (ACC). Methamphetamine also increased functional connectivity between putamen and left inferior frontal gyrus (IFG), and individuals who displayed greater drug-induced increase in connectivity reported less euphoria and stimulation. These findings provide important information regarding the effects of methamphetamine on brain function in nonaddicted individuals. Further studies will reveal whether such effects contribute to the abuse potential of the drug and whether they are related to the frontostriatal impairments observed after chronic methamphetamine use.

10.
Neuroimage ; 196: 188-194, 2019 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-30974242

RESUMO

Individuals with impulsive and addictive disorders, including drug addiction, binge eating/obesity, and problem gambling, exhibit both impaired control over behavior and heightened sensitivity to reward. However, it is not known whether such deviation in inhibitory and reward circuitry among clinical populations is a cause or consequence of the disorders. Recent evidence suggests that these constructs may be related at the neural level, and together, increase risk for engaging in maladaptive behaviors. The current study examined the degree to which brain function during inhibition relates to brain function during receipt of reward in healthy young adults who have not yet developed problem behaviors. Participants completed the stop signal task to assess inhibitory control and the doors task to assess reactivity to monetary reward (win vs loss) during functional magnetic resonance imaging (fMRI). Brain activation during response inhibition was negatively correlated with brain activation during reward. Specifically, less brain activation in right prefrontal regions during inhibition, including the right inferior frontal gyrus, middle frontal gyrus, and supplementary motor area, was associated with greater brain activation in left ventral striatum during receipt of monetary reward. Moreover, these associations were stronger in binge drinkers compared to non-binge drinkers. These findings suggest that the systems are related even before the onset of impulsive or addictive disorders. As such, it is possible that the association between inhibitory and reward circuitry may be a prospective marker of risk.

11.
Artigo em Inglês | MEDLINE | ID: mdl-30998058

RESUMO

Risk-taking behavior can result in a range of maladaptive behaviors such as illicit substance use, unsafe driving, and high-risk sexual behavior. Perception of risk and preference for engaging in risky behaviors have been measured using both self-report measures and a range of behavioral tasks designed for the purpose, and these may predict future risk-taking behavior. However, the interrelationships between these measures and the latent constructs underlying them are poorly understood. In the present study, we examined data from over 1,000 men and women who completed measures of risk-related behaviors, including self-reports of perception of risk, propensity to engage in risky behaviors, and incentivized performance on tasks that involve risk. We conducted principal component analyses (PCAs) to understand the underlying latent structure of these measures. A PCA with the full sample revealed 5 distinct components, corresponding to measures of (a) health/ethical risks, (b) discounting of uncertain rewards, (c) risk of personal finances, (d) preferences in recreational hobbies and social interactions that involve risk, and (e) behavior involving risks in interpersonal interactions. Although we found sex differences on several of the measures, the sex-adjusted PCA components were similar to those of the unadjusted full sample PCA. These findings add to a growing literature revealing different components of the broad category of risk perception and risk-taking behaviors. A better understanding of the multidimensionality of risk preference will help lay the foundation for more refined measures, develop better predictors of future risk-taking behavior, and ultimately to study the genetic or other biological basis of risk-taking. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

12.
Behav Processes ; 162: 157-161, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30876880

RESUMO

Delayed reward discounting (DRD) is a behavioral economic measure of impulsivity, reflecting how rapidly a reward loses value based on its temporal distance. In humans, more impulsive DRD is associated with susceptibility to a number of psychiatric diseases (e.g., addiction, ADHD), health outcomes (e.g., obesity), and lifetime outcomes (e.g., educational attainment). Although the determinants of DRD are both genetic and environmental, this review focuses on its genetic basis. Both rodent studies using inbred strains and human twin studies indicate that DRD is moderately heritable, a conclusion that was further supported by a recent human genome-wide association study (GWAS) that used single nucleotide polymorphisms (SNP) to estimate heritability. The GWAS of DRD also identified genetic correlations with psychiatric diagnoses, health outcomes, and measures of cognitive performance. Future research priorities include rodent studies probing putative genetic mechanisms of DRD and human GWASs using larger samples and non-European cohorts. Continuing to characterize genomic influences on DRD has the potential to yield important biological insights with implications for a variety of medically and socially important outcomes.


Assuntos
Desvalorização pelo Atraso , Genômica , Comportamento Impulsivo , Recompensa , Animais , Comportamento Aditivo , Economia Comportamental , Estudo de Associação Genômica Ampla , Humanos , Polimorfismo de Nucleotídeo Único
13.
J Neurosci ; 39(13): 2562-2572, 2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30718321

RESUMO

Impulsive personality traits are complex heritable traits that are governed by frontal-subcortical circuits and are associated with numerous neuropsychiatric disorders, particularly drug abuse and attention-deficit/hyperactivity disorder (ADHD). In collaboration with the genetics company 23andMe, we performed 10 genome-wide association studies on measures of impulsive personality traits [the short version of the UPPS-P Impulsive Behavior Scale, and the Barratt Impulsiveness Scale (BIS-11)] and drug experimentation (the number of drug classes an individual had tried in their lifetime) in up to 22,861 male and female adult human research participants of European ancestry. Impulsive personality traits and drug experimentation showed single nucleotide polymorphism heritabilities that ranged from 5 to 11%. Genetic variants in the CADM2 locus were significantly associated with UPPS-P Sensation Seeking (p = 8.3 × 10-9, rs139528938) and showed a suggestive association with Drug Experimentation (p = 3.0 × 10-7, rs2163971; r 2 = 0.68 with rs139528938). Furthermore, genetic variants in the CACNA1I locus were significantly associated with UPPS-P Negative Urgency (p = 3.8 × 10-8; rs199694726). The role of these genes was supported by single variant, gene- and transcriptome-based analyses. Multiple subscales from both UPPS-P and BIS showed strong genetic correlations (>0.5) with Drug Experimentation and other substance use traits measured in independent cohorts, including smoking initiation, and lifetime cannabis use. Several UPPS-P and BIS subscales were genetically correlated with ADHD (r g = 0.30-0.51), supporting their validity as endophenotypes. Our findings demonstrate a role for common genetic contributions to individual differences in impulsivity. Furthermore, our study is the first to provide a genetic dissection of the relationship between different types of impulsive personality traits and various psychiatric disorders.SIGNIFICANCE STATEMENT Impulsive personality traits (IPTs) are heritable traits that are governed by frontal-subcortical circuits and are associated with neuropsychiatric disorders, particularly substance use disorders. We have performed genome-wide association studies of IPTs to identify regions and genes that account for this heritable variation. IPTs and drug experimentation were modestly heritable (5-11%). We identified an association between single nucleotide polymorphisms in CADM2 and both sensation seeking and drug experimentation; and between variants in CACNA1I and negative urgency. The role of these genes was supported by single variant, gene- and transcriptome-based analyses. This study provides evidence that impulsivity can be genetically separated into distinct components. We showed that IPT are genetically associated with substance use and ADHD, suggesting impulsivity is an endophenotype contributing to these psychiatric conditions.

14.
Psychopharmacology (Berl) ; 236(6): 1741-1748, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30604184

RESUMO

RATIONALE: The behavioral and reward-related effects of stimulant drugs have been studied extensively; yet the effect of stimulants on sensory processing is still relatively unknown. Prior brain imaging studies have shown that single doses of stimulant drugs increase neural function during cognitive and attentional processes. However, it is not clear if stimulant drugs such as methamphetamine (MA) affect neural responses to novel sensory stimuli, and whether these effects depend on the visual features of the stimuli. OBJECTIVE: In this study, we examined the effects of a single dose of MA (20 mg oral) on neural activation in response to visual stimuli that varied on "non-straight edges" (NSE), a low-level visual feature that quantifies curved/fragmented edges and is related to perceived image complexity. METHODS: Healthy adult participants (n = 18) completed two sessions in which they received MA and placebo in counterbalanced order before an fMRI scan where they viewed both high and low NSE images. Participants also completed measures of subjective drug effects throughout both sessions. RESULTS: During both sessions, high NSE images activated primary visual cortex to a greater extent than low NSE images. Further, MA increased activation only for low NSE images in three areas of visual association cortex: left fusiform, right cingulate/precuneus, and posterior right middle temporal gyrus. This interaction was unrelated to subjective drug effects. CONCLUSIONS: These findings suggest that stimulant drugs may change the relative sensitivity of higher order sensory processing to increase visual attention when viewing less complex stimuli. Moreover, MA-induced alterations in this type of sensory processing appear to be independent of the drugs' ability to increase feelings of well-being.

15.
Nat Neurosci ; 22(3): 503, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30622366

RESUMO

The author list was in the wrong order in the HTML version of the original article and in the HTML version of the original correction notice. This has been corrected to show the 23andMe Research Team as the fourth author and Abraham A. Palmer as the last author in both places.

16.
Artigo em Inglês | MEDLINE | ID: mdl-30265060

RESUMO

Delayed reward discounting (DRD) is a behavioral economic measure of impulsivity that has been consistently associated with addiction. It has also been identified as a promising addiction endophenotype, linking specific sources of genetic variation to individual risk. A challenge in the studies to date is that levels of DRD are often confounded with prior drug use, and previous studies have also had limited genomic scope. The current investigation sought to address these issues by studying DRD in healthy young adults with low levels of substance use (N = 986; 62% female, 100% European ancestry) and investigating genetic variation genome-wide. The genome-wide approach used a prioritized subset design, organizing the tests into theoretically and empirically informed categories and apportioning power accordingly. Three subsets were used: (a) a priori loci implicated by previous studies; (b) high-value addiction (HVA) markers from the recently developed SmokeScreen array; and (c) an atheoretical genome-wide scan. Among a priori loci, a nominally significant association was present between DRD and rs521674 in ADRA2A. No significant HVA loci were detected. One statistically significant genome-wide association was detected (rs13395777, p = 2.8 × 10-8), albeit in an intergenic region of unknown function. These findings are generally not supportive of the previous candidate gene studies and suggest that DRD has a complex genetic architecture that will require considerably larger samples to identify genetic associations more definitively. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

17.
Nicotine Tob Res ; 2018 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30085292

RESUMO

Introduction: Cigarette smoking is a well-known public health concern, and there is an urgent need to develop new treatments to reduce smoking or facilitate abstinence. One factor that is known to contribute to relapse is stress, making the stress response an important target for treatment. The neuropeptide oxytocin (OT) is believed to have stress-reducing effects, and in addition there is evidence that it reduces drug craving. The purpose of the present study was to examine the effects of intranasal oxytocin on stress-induced cigarette craving in regular smokers after 12 hours of abstinence. Method: Daily smokers (n= 48) completed a stress induction task and a non-stressful control task at two different sessions, receiving intranasal OT (40 IU) or placebo (PBO) before or after the task. Subjects were randomly assigned to one of three groups: Group PP (N=16) received PBO before and after the stress/control tasks, Group OP (N=16) received OT before the tasks and PBO after, and Group PO (N=16) received PBO before the tasks and OT shortly after completing the tasks. Cigarette craving as well as subjective and physiological responses to stress were assessed. Results: OT did not alter responses to stress, whether it was administered before or after the stressful task, on measures of cigarette craving, anxiety, heart rate, blood pressure, and cortisol levels. Conclusions: The current study findings do not support several previous reports that OT reduced either stress or drug craving. Implications: This study finds a null result of the neuropeptide oxytocin on stress-induced cigarette craving. Reporting null findings is part of the process of identifying potential treatments for addictive disorders.

18.
Nat Neurosci ; 21(9): 1161-1170, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30150663

RESUMO

Cannabis use is a heritable trait that has been associated with adverse mental health outcomes. In the largest genome-wide association study (GWAS) for lifetime cannabis use to date (N = 184,765), we identified eight genome-wide significant independent single nucleotide polymorphisms in six regions. All measured genetic variants combined explained 11% of the variance. Gene-based tests revealed 35 significant genes in 16 regions, and S-PrediXcan analyses showed that 21 genes had different expression levels for cannabis users versus nonusers. The strongest finding across the different analyses was CADM2, which has been associated with substance use and risk-taking. Significant genetic correlations were found with 14 of 25 tested substance use and mental health-related traits, including smoking, alcohol use, schizophrenia and risk-taking. Mendelian randomization analysis showed evidence for a causal positive influence of schizophrenia risk on cannabis use. Overall, our study provides new insights into the etiology of cannabis use and its relation with mental health.

19.
Neuropsychopharmacology ; 43(13): 2532-2538, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-30093699

RESUMO

Individuals who experience greater stimulation and less sedation from alcohol are at increased risk for alcohol-related problems. However, little is known regarding the neurobiological mechanisms underlying subjective response to alcohol. The current study examined the degree to which alcohol-induced brain activation correlates with ratings of stimulation and sedation, using a within-subjects, double-blind, placebo-controlled design. Participants (N = 34 healthy adults with no history of alcohol use disorder) completed three sessions: a calibration session to determine the duration of infusion needed to bring the breath alcohol to 80 mg/dl for each subject, and two counterbalanced fMRI sessions with placebo and alcohol administration. During the fMRI sessions, participants underwent 50 min scans, which included a 10 min baseline period, the IV infusion period needed to bring breath alcohol concentration (BrAC) to a peak 80 mg/dl (on the alcohol session), followed by a post-peak decline period. Participants rated their subjective stimulation and sedation at regular intervals throughout the scan. A priori VOI analyses showed that the time course of stimulation correlated with BOLD signal in the striatum. The time course of sedation did not correlate with BOLD signal in any VOIs. There were no correlations in primary visual cortex, which served as a control. These findings are the first to show that alcohol effects in the striatum are linked to the positive, stimulant-like effects of the drug and advance our understanding of the neurobiological mechanisms underlying individual differences in subjective responses to alcohol, and more broadly, risk for alcohol use disorders.

20.
Cogn Neurosci ; 9(3-4): 89-99, 2018 Jul - Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30044718

RESUMO

Alcohol and other pharmacologically similar sedatives (i.e., GABAA positive allosteric modulators or PAMs) impair the encoding of new episodic memories but retroactively facilitate the consolidation of recently encoded memories. These effects are consistent for recollection (i.e., the retrieval of details) but some mixed results have been reported for familiarity (i.e., a feeling of knowing a stimulus was presented). Here, with dual-process models, we reanalyzed prior work testing the effects of GABAA PAMs at encoding or consolidation. Contrary to previous conclusions, we show that GABAA PAMs at encoding consistently impair both recollection and familiarity when an independence correction is applied to familiarity-based responses. These findings were further confirmed and extended in a dual-process signal detection analysis of a recent study on the effects of alcohol during encoding or consolidation: Alcohol at encoding impaired both recollection and familiarity, whereas alcohol at consolidation enhanced both recollection and familiarity. These findings speak to the ability of alcohol and other GABAA PAMs to induce 'blackouts,' highlighting the importance of dual-process approaches when analyzing drug manipulations at different phases of episodic memory.

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