Harriet de Wit

Harriet de Wit
University of Chicago | UC · Department of Psychiatry and Behavioral Neuroscience

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682
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Publications

Publications (682)
Preprint
Psychoactive drugs modulate learning and emotional processes in ways that could impact their recreational and medical use. Recent work has revealed how drugs impact different stages of processing emotional episodic memories, including encoding (formation of memory traces), consolidation (stabilization of memory traces), and retrieval (accessing mem...
Article
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Rationale Classical psychedelics, including psilocybin and lysergic acid diethylamide (LSD), are under investigation as potential therapeutic agents in psychiatry. Whereas most studies utilize relatively high doses, there are also reports of beneficial effects of “microdosing,” or repeated use of very low doses of these drugs. The behavioral and ne...
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Rationale Greater availability of cannabis in the USA has raised concerns about adverse effects of the drug, including possible amotivational states. Lack of motivation may be assessed by examining acute effects of cannabinoids on reward processing. Objectives This study examined single doses of delta-9-tetrahydrocannabinol (∆9-THC; 7.5, 15 mg ora...
Article
Background: This study examined effects of oral delta-9-tetrahydrocannabinol (THC) in women at two phases of the menstrual cycle differing in circulating levels of estrogen (E). Pre-clinical findings indicate that E increases sensitivity to THC and other cannabinoids, raising the possibility that higher E may be a risk factor for adverse responses...
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Background The use of cannabis has been clinically associated with decreased motivation to engage in normally rewarding activities. However, evidence from previous controlled studies is mixed. Method In this study, we examined the effects of acute delta-9-tetrahydrocannabinol (THC) versus placebo on a task measuring willingness to exert effort for...
Article
Importance: The concurrent use of both tobacco and alcohol causes substantial disease and early mortality, and smokers who drink heavily tend to be less successful in smoking cessation than smokers who do not. Although varenicline combined with nicotine replacement therapy for smoking cessation has been examined among smokers who do not drink heav...
Article
Increased cannabis availability has contributed to increased use with concomitant incidence of adverse effects. One risk factor for adverse drug reactions may be age. There is preclinical evidence that acute effects of delta-9-tetrahydrocannabinol (THC), the primary active constituent of cannabis, are greater during adolescence, but this has not be...
Article
The resurgence of interest in using psychedelic drugs, including lysergic acid diethylamide (LSD), in psychiatry has drawn attention to the medically unsupervised practice of 'microdosing'. Thousands of users claim that very low doses of LSD, taken at 3-4-day intervals, improve mood and cognitive function., However, few controlled studies have desc...
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Methamphetamine (MA) abuse remains an urgent public health problem. Understanding how the drug affects brain function will help to identify how it leads to abuse and dependence. Previous studies indicate that MA and other stimulants have complex effects on resting state functional connectivity. Here, we used a hypothesis-free approach to examine th...
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Stimuli previously paired with drugs of dependence can produce cravings that are associated with increased dopamine (DA) levels in limbic and striatal brain areas. Positron Emission Tomography (PET) imaging with [ ¹¹ C]-(+)-PHNO allows for a sensitive measurement of changes in DA levels. The purpose of the present study was to investigate changes i...
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Purpose of Review Many drug users claim to use drugs to cope with negative emotions, which may, in turn, result in persistent emotional blunting or anhedonia even when they are not using drugs. The purpose of this review is to describe the ways acute administration of psychoactive drugs impacts brain regions during emotion-related tasks, as a first...
Article
Despite substantial progress in the use of mind-altering drugs to treat psychiatric disorders, the psychological processes through which these drugs change mood or behavior are poorly understood. Controlled laboratory studies with well-defined psychological constructs are valuable to understand how these drugs manifest their therapeutic benefit. Ho...
Article
Poor inhibitory control and heightened feelings of stimulation after alcohol are two well-established risk factors for alcohol use disorder (AUD). Although these risk factors have traditionally been viewed as orthogonal, recent evidence suggests that the two are related and may share common neurobiological mechanisms. Here we examined the degree to...
Article
Background It is commonly believed that drugs, including stimulants, are used recreationally because of their ability to induce pleasurable subjective effects. However, recreational drug use sometimes occurs in the absence of positive subjective effects, suggesting that other factors contribute. Here, we examine the extent to which the direct subje...
Preprint
Full-text available
Stimuli previously paired with drugs of dependence can produce cravings that are associated with increased dopamine (DA) levels in limbic and striatal brain areas. Positron Emission Tomography (PET) imaging with [11C]-(+)-PHNO allows for a sensitive measurement of changes in DA levels. The purpose of the present study was to investigate changes in...
Article
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 exp...
Article
Alcohol abuse and dependence remain significant public health issues, and yet the brain circuits that are involved in the rewarding effects of alcohol are poorly understood. One promising way to study the effects of alcohol on neural activity is to examine its effects on functional connectivity between brain areas involved in reward and other funct...
Article
Background Alcohol use disorder (AUD) remains an unresolved source of morbidity and mortality. Psychopharmacological challenge studies and neuroimaging experiments are two methods used to identify risk of problematic substance use. The present study combined these two approaches by examining associations between self-reported stimulation, sedation,...
Article
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 i...
Article
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...
Article
Full-text available
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 re...
Article
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 Her...
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Full-text available
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...
Article
Full-text available
The detection of changes in mental states such as those caused by psychoactive drugs relies on clinical assessments that are inherently subjective. Automated speech analysis may represent a novel method to detect objective markers, which could help improve the characterization of these mental states. In this study, we employed computer-extracted sp...
Book
This volume provides an empirical and conceptual overview of advances in our understanding of impulsivity and impulsive behaviors. Prominent scientists review the range of behavioral phenomena referred to as ‘impulsive’, as well as the defining features and psychological, neurocognitive and behavioral processes that underlie of the manifestation of...
Article
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...
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Full-text available
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...
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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 experien...
Preprint
Full-text available
With the sharply increasing prevalence of 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...
Article
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...
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Full-text available
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 o...
Article
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, place...
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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 Figure...
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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 clea...
Article
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 em...
Article
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 sing...
Article
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...
Chapter
Persistent maladaptive decision-making is central to several psychiatric conditions, particularly addiction. Decision-making measures may serve as promising intermediate phenotypes (i.e. intervening mechanisms that link genetic variation to clinical vulnerability) and thus elucidate biological mechanisms that increase risk for addiction and related...
Article
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 dis...
Article
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 pros...
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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.
Article
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., educa...
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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 m...
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Humans vary substantially in their willingness to take risks. In a combined sample of over one million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. We identified 611 approximately independent genetic loci associ...
Preprint
Full-text available
Humans vary substantially in their willingness to take risks. In a combined sample of over one million individuals, we conducted genome-wide association studies (GWAS) of general risk tolerance, adventurousness, and risky behaviors in the driving, drinking, smoking, and sexual domains. We identified 611 approximately independent genetic loci associ...
Article
Background Delay-discounting has been proposed as a potential endophenotype for various neuropsychiatric diseases, including drug and alcohol abuse. Although this trait is heritable, it remains unclear which genes/loci influence delay-discounting. Methods In collaboration with the genetics company 23andMe, Inc., we performed a genome-wide associat...
Article
Background Genetic factors contribute to the risk for developing alcohol use disorder (AUD). Previous studies have estimated the heritability of AUD to be between 40–60% and have explored the role of specific candidate genes, including genes for alcohol-metabolizing enzyme like ADH1B, ALDH2. More recently, Genome-Wide Association Studies (GWAS) hav...
Article
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 wit...
Preprint
Background Impulsive personality traits are complex heritable traits that are governed by frontal-subcortical circuits and are associated with numerous neuropsychiatric disorders, particularly drug abuse. Methods In collaboration with the genetics company 23andMe, Inc., we performed several genome-wide association studies ( GWAS ) on measures of i...
Article
Full-text available
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...
Preprint
Full-text available
Risk-taking behavior affects many aspects of life, including maladaptive behaviors such as illicit substance use, unsafe driving, and risky sexual behavior. Risk-taking has been measured using both self-report measures and behavioral tasks designed for the purpose, but there is little consensus in the associations among measures and our understandi...
Article
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-r...
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Full-text available
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 stim...
Article
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...
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Full-text available
In the version of this article initially published, the consortium authorship was not presented correctly. The 23andMe Research Team was listed as the last author, rather than the fourth, and a line directing readers to the Supplementary Note for a list of members did appear but was not directly associated with the consortium name. Also, the Supple...
Article
Introduction Preclinical and clinical evidence suggest that the neuropeptide oxytocin may be of value in treating alcohol use disorder, either by reducing the rewarding effects of alcohol or reducing negative affect induced by alcohol withdrawal. However, the effect of a single dose of oxytocin on subjective and psychomotor responses to alcohol in...
Article
Background: It is well established that the main psychoactive constituent of cannabis, Δ9-tetrahydrocannabinol (THC), impairs episodic memory encoding and modulates emotional processing, but little is known about the impact of THC during the retrieval of emotional episodic memories. With the rise of cannabis to treat medical conditions, including...
Article
Introduction: Despite widespread knowledge of the dangers of cigarette consumption, smoking continues to be a public health concern. One compound that has shown potential for treatment in preclinical models is the neuropeptide oxytocin (OT). The purpose of the present study was to examine the effects of intranasal oxytocin on cigarette craving, be...
Article
Both preclinical and clinical evidence suggests that the endogenous opioid system is involved in responses to stress. For example, in animal models opioid agonists reduce isolation distress whereas opioid antagonists increase isolation distress. We recently reported that the mixed mu agonist and kappa antagonist buprenorphine dampened responses to...
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Full-text available
Background: Drugs are typically used in social settings. Here, we consider two factors that may contribute to this observation: (i) the presence of other people may enhance the positive mood effects of a drug, and conversely, (ii) drugs may enhance the value of social stimuli. Methods: We review evidence from controlled laboratory studies with h...
Preprint
Full-text available
Liability to alcohol dependence (AD) is heritable, but little is known about its complex polygenic architecture or its genetic relationship with other disorders. To discover loci associated with AD and characterize the relationship between AD and other psychiatric and behavioral outcomes, we carried out the largest GWAS to date of DSM - IV diagnose...
Article
Full-text available
One known risk factor for drug use and abuse is sensitivity to rewarding effects of drugs. It is not known whether this risk factor extends to sensitivity to non-drug rewards. In this study with healthy young adults, we examined the association between sensitivity to the subjective rewarding effects of amphetamine and a neural indicator of anticipa...