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1.
Alcohol Clin Exp Res ; 2020 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-33201577

RESUMO

INTRODUCTION: Alcohol is among the most commonly used psychoactive drugs, yet it can produce markedly different subjective effects in different people. Certain effects, including both heightened stimulatory effects and lesser sedative effects, are thought to predict repeated or excessive use. However, we do not fully understand the nature of these individual differences or their relationships to alcohol consumption. This controlled laboratory study examined subjective and physiologic responses to a moderate dose of alcohol in social drinkers in relation to the subjects' decision to consume alcohol. METHODS: Healthy adult volunteers (N = 95) participated in a 5-session double-blind alcohol choice study. On the first 4 sessions, they received alcohol (0.8 g/kg) and placebo in alternating order, and on the fifth session, they chose and consumed whichever of the 2 they preferred. During each session, participants completed the Profile of Mood States (POMS) and Biphasic Alcohol Effects Scale (BAES) questionnaires and had their vitals recorded every 30 minutes. We compared subjective and physiologic response to alcohol during the sampling sessions in participants who chose alcohol or placebo on session 5. RESULTS: Of the 95 participants, 55 chose alcohol (choosers) and 40 chose placebo (nonchoosers). In the full sample, alcohol produced its expected effects (e.g., increased friendliness, elation, and vigor (POMS), and stimulation and sedation (BAES)). The chooser and nonchooser groups did not differ in demographic characteristics, blood alcohol levels, or cardiovascular measures. However, the choosers experienced greater alcohol-induced increases in positive mood (POMS) and liked the drug more, whereas the nonchoosers experienced greater anger, anxiety (POMS), and sedation (BAES) after alcohol. CONCLUSION: Both greater positive mood effects and lesser sedative effects after alcohol predicted preference under controlled conditions, suggesting that both factors can predict future consumption of alcohol.

2.
Artigo em Inglês | MEDLINE | ID: mdl-33202256

RESUMO

Dopamine (DA) plays a key role in reward processing and is implicated in psychological disorders such as depression, substance use, and schizophrenia. The role of DA in reward processing is an area of highly active research. One approach to this question is drug challenge studies with drugs known to alter DA function. These studies provide good experimental control and can be performed in parallel in laboratory animals and humans. This review aimed to summarize results of studies using pharmacological manipulations of DA in healthy adults. 'Reward' is a complex process, so we separated 'phases' of reward, including anticipation, evaluation of cost and benefits of upcoming reward, execution of actions to obtain reward, pleasure in response to receiving a reward, and reward learning. Results indicated that i) DAergic drugs have different effects on different phases of reward; ii) the relationship between DA and reward functioning appears unlikely to be linear; iii) our ability to detect the effects of DAergic drugs varies depending on whether subjective, behavioral, imaging measures are used.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32505126

RESUMO

One well-known phenotypic risk factor for the development of alcohol use disorder is sensitivity to the rewarding effects of alcohol. In the present study, we examined whether individuals who are sensitive to alcohol reward are also sensitive to nondrug rewards, thereby reflecting a broader individual difference risk factor. Specifically, we tested the hypothesis that subjective response to acute rewarding effects of alcohol would be related to neural activation during monetary reward receipt relative to loss (in the absence of alcohol). Community-recruited healthy young social drinkers (N = 58) completed four laboratory sessions in which they received alcohol (0.8 g/kg) and placebo in alternating order under double-blind conditions, providing self-report measures of subjective response to alcohol at regular intervals. At a separate visit 1-3 weeks later, they completed a reward-guessing game, the 'Doors' task, during fMRI in a drug-free state. Participants who reported greater motivation (i.e., wanting) to consume more alcohol after a single moderate dose of alcohol also exhibited greater neural activation in the bilateral ventral caudate and the nucleus accumbens during reward receipt relative to loss. Striatal activation was not related to other subjective ratings including alcohol-induced sedation, stimulation, or pleasure (i.e., feeling, liking). Our study is the first to show that measures of alcohol reward are related to neural indices of monetary reward in humans. These results support growing evidence that individual differences in responses to drug and nondrug reward are linked and together form a risk profile for drug use or abuse, particularly in young adults.

4.
Drug Alcohol Depend ; 212: 107989, 2020 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-32386922

RESUMO

BACKGROUND: Controlled drug challenge studies provide valuable information about the acute behavioral effects of drugs, including individual differences that may affect risk for abuse. One question that arises in such studies is whether a single administration of a drug (and placebo) provides an accurate measure of response to the drug. METHODS: Here, we examined data from two studies, one with alcohol and one with amphetamine, in which participants received two administrations of the drug and placebo. In this analysis we assess the stability of acute subjective and cardiovascular responses to the drugs across the two administrations. We examine i) systematic increases or decreases to the drugs from the first to the second administration, ii) test-retest reliability within individuals and iii) the accuracy of the acute drug responses to predict drug choice in a later session. RESULTS: Responses were largely stable across sessions, although on the second session amphetamine "liking" was higher, and subjective responses to placebo including "liking" and "want more" decreased in both studies. Test-retest reliability within individuals was high. Responses during the first drug administration were as accurate in predicting drug choice as responses during both administrations combined. CONCLUSIONS: Our findings indicate that a single administration of drug (and placebo) provides a good index of an individual's responses to alcohol or amphetamine, when participants are tested under controlled experimental conditions.

5.
Neuropsychopharmacology ; 45(11): 1807-1816, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32386395

RESUMO

With the increasing prevalence of legal cannabis use and availability, there is an urgent need to identify cognitive impairments related to its use. It is widely believed that cannabis, or its main psychoactive component Δ9-tetrahydrocannabinol (THC), impairs working memory, i.e., the ability to temporarily hold information in mind. However, our review of the literature yielded surprisingly little empirical support for an effect of THC or cannabis on working memory. We thus conducted a study with three main goals: (1) quantify the effect of THC on visual working memory in a well-powered sample, (2) test the potential role of cognitive effects (mind wandering and metacognition) in disrupting working memory, and (3) demonstrate how insufficient sample size and task duration reduce the likelihood of detecting a drug effect. We conducted two double-blind, randomized crossover experiments in which healthy adults (N = 23, 23) performed a reliable and validated visual working memory task (the "Discrete Whole Report task", 90 trials) after administration of THC (7.5 and/or 15 mg oral) or placebo. We also assessed self-reported "mind wandering" (Exp 1) and metacognitive accuracy about ongoing task performance (Exp 2). THC impaired working memory performance (d = 0.65), increased mind wandering (Exp 1), and decreased metacognitive accuracy about task performance (Exp 2). Thus, our findings indicate that THC does impair visual working memory, and that this impairment may be related to both increased mind wandering and decreased monitoring of task performance. Finally, we used a down-sampling procedure to illustrate the effects of task length and sample size on power to detect the acute effect of THC on working memory.

6.
Artigo em Inglês | MEDLINE | ID: mdl-32033922

RESUMO

BACKGROUND: The practice of "microdosing," or the use of repeated, very low doses of lysergic acid diethylamide (LSD) to improve mood or cognition, has received considerable public attention, but empirical studies are lacking. Controlled studies are needed to investigate both the therapeutic potential and the neurobiological underpinnings of this pharmacologic treatment. METHODS: The present study was designed to examine the effects of a single low dose of LSD (13 µg) versus placebo on resting-state functional connectivity and cerebral blood flow in healthy young adults. Twenty men and women, 18 to 35 years old, participated in 2 functional magnetic resonance imaging scanning sessions in which they received placebo or LSD under double-blind conditions. During each session, the participants completed drug effect and mood questionnaires, and physiological measures were recorded. During expected peak drug effect, they underwent resting-state blood oxygen level-dependent and arterial spin labeling scans. Cerebral blood flow as well as amygdala and thalamic connectivity were analyzed. RESULTS: LSD increased amygdala seed-based connectivity with the right angular gyrus, right middle frontal gyrus, and the cerebellum, and decreased amygdala connectivity with the left and right postcentral gyrus and the superior temporal gyrus. This low dose of LSD had weak and variable effects on mood, but its effects on positive mood were positively correlated with the increase in amygdala-middle frontal gyrus connectivity strength. CONCLUSIONS: These preliminary findings show that a very low dose of LSD, which produces negligible subjective changes, alters brain connectivity in limbic circuits. Additional studies, especially with repeated dosing, will reveal whether these neural changes are related to the drug's purported antidepressant effect.

7.
Drug Alcohol Depend ; 206: 107725, 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-31757518

RESUMO

BACKGROUND: Drug addiction and dependence continue as an unresolved source of morbidity and mortality. Two approaches to identifying risk for abuse and addiction are psychopharmacological challenge studies and neuroimaging experiments. The present study combined these two approaches by examining associations between self-reported euphoria or liking after a dose of d-amphetamine and neural-based responses to anticipation of a monetary reward. METHODS: Healthy young adults (N = 73) aged 19 and 26, without any history of alcohol/substance dependence completed four laboratory sessions in which they received oral d-amphetamine (20 mg) or placebo, and completed drug effect questionnaires. On a separate session they underwent a functional magnetic resonance imaging scan while they completed a monetary incentive delay task. During the task, we recorded neural signal related to anticipation of winning $5 or $1.50 compared to winning no money (WinMoney-WinZero), in reward related regions. RESULTS: Liking of amphetamine during the drug sessions was related to differences in activation during the WinMoney-WinZero conditions - in the amygdala (positive), insula (negative) and caudate (negative). In posthoc analyses, liking of amphetamine was also positively correlated with activation of the amygdala during anticipation of large rewards and negatively related to activation of the left insula to both small and large anticipated rewards. CONCLUSIONS: These findings suggest that individual differences in key regions of the reward network are related to rewarding subjective effects of a stimulant drug. To further clarify these relationships, future pharmacofMRI studies could probe the influence of amphetamine at the neural level during reward anticipation.

8.
Psychopharmacology (Berl) ; 237(3): 825-832, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31832721

RESUMO

RATIONALE AND OBJECTIVE: Poor inhibitory control is a well-established risk factor for alcohol use disorder (AUD). Similarly, greater sensitivity to the stimulant effects and less sensitivity to the sedative effects of alcohol are also strongly linked to risk for AUD. Traditionally, these two risk factors have been considered to be orthogonal, and thus they have been studied independently. However, recent evidence from animal and human studies suggests that they may be related. The current study examined the relationship between inhibitory control and subjective responses to alcohol in a sample of healthy young adults. METHODS: Moderate social drinkers (N = 69) first completed the stop signal task to assess inhibitory control. They then participated in four sessions in which they received an oral dose of ethanol (0.8 g/kg) or placebo in alternating order, providing self-report measures of stimulation and sedation on the Biphasic Alcohol Effects Scale (BAES) at regular intervals. RESULTS: Linear mixed effects models showed that poor inhibitory control was associated with greater stimulation and less sedation following alcohol compared with placebo. CONCLUSION: These findings provide the first direct evidence that individuals with poor inhibitory control experience greater sensitivity to the rewarding, stimulant effects of alcohol, and less sensitivity to the negative, sedative effects. These findings suggest that inhibition and subjective response to alcohol are not independent risk factors, and that together they constitute a heightened profile of risk for AUD.

9.
Exp Clin Psychopharmacol ; 28(1): 55-64, 2020 Feb.
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) 2020 APA, all rights reserved).


Assuntos
Comportamentos de Risco à Saúde , Assunção de Riscos , Autorrelato , Comportamento Sexual , Comportamento Social , Adolescente , Adulto , Condução de Veículo , Feminino , Administração Financeira , Humanos , Masculino , Fenótipo , Análise de Componente Principal , Recompensa , Transtornos Relacionados ao Uso de Substâncias , Adulto Jovem
10.
Nicotine Tob Res ; 22(1): 89-95, 2020 01 27.
Artigo em Inglês | MEDLINE | ID: mdl-30085292

RESUMO

BACKGROUND: 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 OT on stress-induced cigarette craving in regular smokers after 12 h of abstinence. METHOD: Daily smokers (n = 48) completed a stress induction task and a nonstressful 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 was 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.

11.
Addict Biol ; 25(3): e12775, 2020 May.
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.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31668830

RESUMO

BACKGROUND: With the growing acceptance of cannabis use, it is crucial to understand the drug's effects on episodic memory accuracy and distortion. We investigated the impact of the administration of Δ9-tetrahydrocannabinol (THC), the main psychoactive constituent of cannabis, on a context-based memory illusion. METHODS: In a double-blind, placebo-controlled, within-subjects design, healthy infrequent cannabis users (N = 24) memorized object pictures that were superimposed over scenes (e.g., gray cat on beach) after pretreatment with placebo or THC (15 mg oral). Two days later under sober conditions, memory for the object pictures was tested by asking participants to discriminate between previously seen objects or perceptually similar lures (e.g., different gray cat). Context reinstatement was manipulated by presenting objects on their original or different scenes (e.g., beach or forest). RESULTS: THC impaired memory for perceptual details of objects compared with placebo, and the context illusion was obtained in each condition: context reinstatement increased high-confidence false recognition along with correct recognition of previously seen objects. Although THC did not interact with these context effects overall, post hoc analyses showed that THC magnified the context illusion when objects were semantically congruent with their encoding contexts but abolished the context illusion when objects were incongruent with their encoding contexts. CONCLUSIONS: These results are consistent with the hypothesis that THC impairs the encoding of specific object information more than item-context associations. As a result, THC may spare the distorting effects of context reinstatement on memory. In fact, THC may increase these distorting effects under conditions when objects are semantically congruent with context.

13.
Neuropsychopharmacology ; 45(1): 217-239, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31391575
14.
Sci Rep ; 9(1): 17583, 2019 11 26.
Artigo em Inglês | MEDLINE | ID: mdl-31772290

RESUMO

We investigated the association between impulsivity related traits and BMI at the observational and genetic epidemiology level in a cross-sectional population of healthy young American-European adults. We studied 998 students and university staff of European ancestry recruited from Chicago (Illinois) and Athens (Georgia). We measured 14 impulsivity variables using three broad categories: impulsive choice, action and personality. Weight and height of participants were measured by research assistants. The single-nucleotide polymorphism (SNP) rs3751812 in the fat mass and obesity-associated (FTO) gene was genotyped using the Illumina PsychArray BeadChip platform. Within the three broad domains of impulsivity, 4 parameters (delay discounting of rewards area under the curve and average of k indexes, Conner's continuous performance test, and negative urgency) were associated with BMI. The FTO rs3751812 minor allele T was associated with higher BMI. Of the 14 impulsivity variables, rs3751812 T was associated with more premeditation and perseverance, before and after adjusting for BMI. The association between FTO rs3751812 and BMI adjusted for premeditation remained significant, but disappeared after adjusting for perseverance and for both perseverance and premeditation traits. Our observational and genetic data indicate a complex pattern of association between impulsive behaviors and BMI in healthy young American-European adults.

15.
BJPsych Open ; 5(3): e38, 2019 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-31685074

RESUMO

Heavy alcohol use is pervasive and one of our most significant global health burdens. Early theories posited that certain alcohol response phenotypes, notably low sensitivity to alcohol ('low-level response') imparts risk for alcohol use disorder (AUD). However, other theories, and newer measures of subjective alcohol responses, have challenged that contention and argued that high sensitivity to some alcohol effects are equally important for AUD risk. This study presents results of a unique longitudinal study in 294 young adult non-dependent drinkers examined with alcohol and placebo testing in the laboratory at initial enrolment and repeated 5 years later, with regular follow-up intervals assessing AUD (trial registration: http://clinicaltrials.gov/ct2/show/NCT00961792). Findings showed that alcohol sedation was negatively correlated with stimulation across the breath alcohol curve and at initial and re-examination testing. A higher rather than lower alcohol response phenotype was predictive of future AUD. The findings underscore a new understanding of factors increasing vulnerability to AUD.

16.
J Psychopharmacol ; 33(9): 1160-1169, 2019 09.
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.

17.
Biol Psychiatry ; 86(10): 792-800, 2019 Nov 15.
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.

18.
Psychopharmacology (Berl) ; 236(11): 3363-3370, 2019 Nov.
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.


Assuntos
Comportamento Aditivo/diagnóstico , Comportamento Aditivo/psicologia , Estimulantes do Sistema Nervoso Central/administração & dosagem , Dextroanfetamina/administração & dosagem , Euforia/efeitos dos fármacos , Adolescente , Afeto/efeitos dos fármacos , Afeto/fisiologia , Comportamento Aditivo/induzido quimicamente , Estimulantes do Sistema Nervoso Central/efeitos adversos , Dextroanfetamina/efeitos adversos , Relação Dose-Resposta a Droga , Método Duplo-Cego , Euforia/fisiologia , Feminino , Humanos , Masculino , Inquéritos e Questionários , Adulto Jovem
19.
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.


Assuntos
Afeto/efeitos dos fármacos , Estimulantes do Sistema Nervoso Central/farmacologia , Metanfetamina/farmacologia , Tempo de Reação/efeitos dos fármacos , Recompensa , Caracteres Sexuais , Adolescente , Adulto , Afeto/fisiologia , Transtornos Relacionados ao Uso de Anfetaminas/psicologia , Sinais (Psicologia) , Método Duplo-Cego , Feminino , Voluntários Saudáveis , Humanos , Masculino , Motivação/efeitos dos fármacos , Motivação/fisiologia , Tempo de Reação/fisiologia , Adulto Jovem
20.
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.

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