About

Professor Harriet de Wit directs the Human Behavioral Pharmacology Laboratory (HBPL), which focuses on investigating the effects of psychoactive drugs in human volunteers. The laboratory studies the determinants and consequences of drug use by measuring the drugs' effects on physiology, behavior, and subjective state. Under her leadership, the HBPL operates at the intersection of human behavior and pharmacology, aiming to understand how psychoactive substances influence various aspects of human functioning.

Research topics

• Psychiatry
• Medicine
• Biology
• Genetics
• Psychology
• Chemistry

Selected publications

• Acute and delayed effects of THC on memories of stress in healthy adults

  Psychopharmacology · 2026-04-15

  articleOpen accessSenior author

  Many cannabis users claim that one reason they use cannabis is to relieve stress or dampen effects of stressful memories. However, the processes by which cannabis or its primary constituent, Δ9-tetrahydrocannabinol (THC) alleviate stressful experiences remains unclear. Here, we assessed whether low oral doses of THC reduce emotional or physiological responses to memories of a standardized social stress procedure in healthy volunteers. Healthy adults (18–35 years) received placebo, 5, or 10 mg THC groups (n = 12 per group) under double-blind conditions before retrieving memories of a stressful event. They participated in three sessions: (1) social stress procedure to establish stress memories, (2) pretreatment with THC or placebo followed by presentation of stress session images, and (3) re-presentation of stress images without drug. During Session 1, participants underwent a Trier Social Stress Test (TSST) and a non-stress control task to create individualized stress and neutral memory images. During Session 2 one week later, participants received THC (5 or 10 mg) or placebo before viewing images from Session 1. Dependent measures included subjective and physiological responses to the stress and control images, during a memory retrieval task. During Session 3, conducted one week after Session 2, image-elicited responses were reassessed without administration of drug. During the stress memory retrieval on Session 2, the TSST-images significantly increased distress and arousal relative to control images. However, THC (5 and 10 mg) did not dampen most of the subjective or physiological responses to the images. The only measure on which THC reduced responses was on affective facial emotional expressions during presentation of stress images. No lasting effects of the drug were observed on Session 3. Although the small sample raised questions about power, Bayes factor analyses supported the conclusion of null findings. Using this novel procedure, images established with a social stress procedure elicited stress responses one week later. However, low doses of THC failed to diminish most of the subjective or physiological responses to stress-related images. Future work should examine whether these findings can be replicated in larger samples.

  PublisherOA PDFDOI

• Author response: Methamphetamine-induced adaptation of learning rate dynamics depend on baseline performance

  2025-06-24

  peer-reviewOpen access

  The ability to calibrate learning according to new information is a fundamental component of an organism’s ability to adapt to changing conditions. Yet, the exact neural mechanisms guiding dynamic learning rate adjustments remain unclear. Catecholamines appear to play a critical role in adjusting the degree to which we use new information over time, but individuals vary widely in the manner in which they adjust to changes. Here, we studied the effects of a low dose of methamphetamine (MA), and individual differences in these effects, on probabilistic reversal learning dynamics in a within-subject, double-blind, randomized design. Participants first completed a reversal learning task during a drug-free baseline session to provide a measure of baseline performance. Then they completed the task during two sessions, one with MA (20 mg oral) and one with placebo (PL). First, we showed that, relative to PL, MA modulates the ability to dynamically adjust learning from prediction errors. Second, this effect was more pronounced in participants who performed moderately low at baseline. These results present novel evidence for the involvement of catecholaminergic transmission on learning flexibility and highlights that baseline performance modulates the effect of the drug.

  PublisherDOI

• Δ9-Tetrahydrocannabinol Alters Limbic and Frontal Functional Brain Connectomes Among Young Adult Cannabis Users

  Biological Psychiatry Cognitive Neuroscience and Neuroimaging · 2025-09-14

  articleOpen access

  BACKGROUND: -tetrahydrocannabinol (THC) disrupts brain connectivity. Few studies have examined this on a whole-brain level. We examined the effects of a single moderate dose of THC on resting-state functional brain networks among young adult cannabis users. METHODS: In a within-subject, double-blind, randomized study, 33 healthy occasional cannabis users received THC (7.5 mg, oral) and placebo before completing resting-state functional magnetic resonance imaging (rs-fMRI) during peak intoxication. Group-information-guided independent component analysis was performed on resting-state brain data to identify whole-brain networks associated with each scan. Within-samples t tests assessed for differences in intrinsic network functional connectivity and between-network functional connectivity after THC versus placebo. Additional linear models examined relationships between brain connectivity, subjective drug effects, and past-month cannabis use. RESULTS: THC reduced within-network intrinsic connectivity in corticostriatal circuits and other networks associated with sensory systems, interoceptive experiences, and spatial reasoning. THC reduced connectivity between 2 networks characterized by the anterior cingulate cortex and dorsal insula regions as well as the ventral insula and lingual gyrus, respectively. Network connectivity during THC (vs. placebo) was not related to subjective measures of drug effect or recent cannabis use. CONCLUSIONS: Our findings add to a growing literature showing that THC decreases rs-fMRI throughout the brain, impacting networks linked to the many behavioral and perceptual changes associated with THC. Future work is needed to extend these findings to clinical samples and to assess the extent to which these networks are associated with negative outcomes of chronic THC use.

  PublisherDOI

• Methamphetamine modulates functional connectivity signatures of sustained attention and arousal

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-21 · 1 citations

  preprintOpen access

  Building on evidence that psychostimulants modulate whole-brain functional connectivity signatures of sustained attention, we examined how a single dose of methamphetamine (MA, 20 mg) changes network-level functional organization and sustained attention in healthy adults. Using a within-subject, placebo-controlled design, we tested whether MA selectively affects behavioral and fMRI connectivity signatures of sustained attention and arousal. Under MA, participants showed improved sustained attention task performance as well as functional connectivity signatures of higher sustained attention and arousal. These network changes emerged consistently across resting-state and task-based fMRI, indicating that MA influences attention- and arousal-related networks regardless of cognitive context. Furthermore, a support vector classifier distinguished functional connectivity patterns observed during the MA and placebo conditions, identifying connections overlapping with networks related to arousal. Together, these findings align with prior work on other psychostimulants like methylphenidate, showing that MA modulates sustained attention and related large-scale brain networks. By revealing how MA modulates attention-relevant brain connectivity patterns, our results highlight the utility of psychostimulants as causal tools for probing the robustness, generalizability, and interpretability of brain-based biomarkers of behavior.

  PublisherOA PDFDOI

• Prescription Opioid Medication Survey: A Tool to Collect Deep Phenotypic Data on the Multifactorial Pathways to Opioid Use Disorder in Clinical and Population-Based Cohorts

  Complex Psychiatry · 2025-05-17

  articleOpen access

  Introduction: We are in the midst of an opioid epidemic. In the USA, more than a third of the country knows someone who has died from an opioid overdose. Prescription opioids (e.g., oxycodone, hydrocodone, and fentanyl) are commonly used and misused, and it has been estimated that approximately 8-12% of individuals who misuse opioids will subsequently develop an opioid use disorder (OUD). While emphasis has been placed on understanding OUD and the associated adverse effects, there remains a critical gap in systematically characterizing the multifactorial pathways (e.g., behavioral, clinical, genetic, and socio-demographic characteristics) that contribute to the transition from initial use to misuse to OUD. Methods: To address this gap, we introduce the Prescription Opioid Medication Survey (POMS), an online 120-item assessment that compiles multiple validated and standardized instruments. POMS is intended for individuals with any lifetime prescription opioid use. POMS captures various aspects of prescription opioid use including data on opioid use patterns, subjective effects (e.g., euphoria, nausea), problematic use, withdrawal, OUD, overdose, treatment history, and remission. It also addresses comorbid risk factors such as surgical history, chronic pain, other substance use disorders (SUD; e.g., nicotine, alcohol, cannabis, stimulants), other addictive behaviors (i.e., gambling, sexual behaviors, and gaming), and family history of SUD and other addictive behaviors. Mental health assessments, including screening for depression and anxiety, self-reports of eight psychiatric disorders (anxiety, depression, bipolar, schizophrenia, attention-deficit/hyperactivity disorder, post-traumatic stress disorder, obsessive-compulsive disorder, eating disorders), and related mental health conditions (e.g., loneliness, suicide, trauma) are included, along with data on personality traits (e.g., risk-taking, delay discounting, wisdom) and socio-demographic factors. POMS is intended to be administered in clinical settings and large population-based cohorts, facilitating data collection that can enable discoveries to inform better prevention and intervention strategies for OUD. Conclusion: POMS offers a comprehensive tool for systematically capturing the multifactorial risk factors associated with opioid misuse and OUD, providing insights that can inform prevention and intervention strategies.

  PublisherOA PDFDOI

• Author response: Methamphetamine-induced adaptation of learning rate dynamics depend on baseline performance

  2025-07-21

  peer-reviewOpen access
  PublisherDOI

• Effects of methamphetamine on human effort task performance are unrelated to its subjective effects

  Psychopharmacology · 2025-07-08

  articleOpen accessSenior author

  RATIONALE: Stimulant drugs increase objective indices of reward-related behavior, including willingness to expend effort for reward, and also produce feelings of well-being and positive mood. However, it is not known to what extent these different measures are related to each other. OBJECTIVES: The present study was designed to assess the relationship between the behavioral measure of effort expenditure and positive subjective responses to methamphetamine (MA). METHODS: 96 healthy adults completed the Effort Expenditure for Rewards Task (EEfRT) during two laboratory sessions after receiving 20 mg MA or placebo (PL) under double blind conditions. They also self-reported their mood states and drug effects. RESULTS: MA (vs. PL) increased willingness to complete a high effort/high reward option vs. a low effort/low reward option during the EEfRT (N = 96), and this effect was greater in participants with low effort at baseline. A subjective value modeling analysis (N = 91) showed that MA decreased sensitivity to the perceived cost of effort for the low baseline performance group only. MA also increased self-reported positive affect (euphoria; N = 94, liking the drug; N = 92) in the full sample, but this increase was unrelated to either baseline EEfRT performance or MA-induced EEfRT performance changes (N = 91). CONCLUSIONS: As reported previously, MA increased choice of the high effort/high reward option, particularly in participants with low effort at baseline, who also showed drug-induced changes in effort sensitivity. These behavioral effects were not related to drug liking and drug-induced euphoria. These findings suggest that the effects of stimulants on reward-related behavior and mood are dissociable.

  PublisherDOI

• The mesocorticolimbic system in stimulant use disorder

  Molecular Psychiatry · 2025-09-10 · 3 citations

  reviewOpen accessSenior author

  Stimulant Use Disorder (StUD) is a pervasive and extremely dangerous form of addiction for which there are currently no approved medications. Discovering treatments will require a deep understanding of the neural mechanisms underlying the behavioral effects of stimulant drugs. A major target is the mesocorticolimbic system. Individual differences in mesocorticolimbic function can influence the propensity to initiate stimulant use and the risk for stimulant use disorders. Since repeated stimulant use can further alter mesocorticolimbic function, these pathways may serve as a target for both early interventions aimed at preventing the onset of harmful stimulant use and treatments designed to alleviate addiction symptoms. Here we review evidence from studies in both humans and laboratory animals, focusing on the neurotransmitter systems most strongly implicated in StUD, primarily dopamine and, to a lesser extent, glutamate. We identify evidence of (i) complex, non-linear perturbations to mesocorticolimbic function related to stimulant use, and (ii) gaps in knowledge and opportunities for research to improve our understanding of the determinants and consequences of StUD.

  PublisherOA PDFDOI

• Methamphetamine-induced adaptation of learning rate dynamics depend on baseline performance

  eLife · 2025-07-21

  articleOpen access

  The ability to calibrate learning according to new information is a fundamental component of an organism’s ability to adapt to changing conditions. Yet, the exact neural mechanisms guiding dynamic learning rate adjustments remain unclear. Catecholamines appear to play a critical role in adjusting the degree to which we use new information over time, but individuals vary widely in the manner in which they adjust to changes. Here, we studied the effects of a low dose of methamphetamine (MA), and individual differences in these effects, on probabilistic reversal learning dynamics in a within-subject, double-blind, randomized design. Participants first completed a reversal learning task during a drug-free baseline session to provide a measure of baseline performance. Then they completed the task during two sessions, one with MA (20 mg oral) and one with placebo (PL). First, we showed that, relative to PL, MA modulates the ability to dynamically adjust learning from prediction errors. Second, this effect was more pronounced in participants who performed moderately low at baseline. These results present novel evidence for the involvement of catecholaminergic transmission on learning flexibility and highlights that baseline performance modulates the effect of the drug.

  PublisherDOI

• Δ9-Tetrahydrocannabinol Impacts Frontolimbic Resting State Connectivity and Associations With Negative Affect Among Young Adults Who Use Cannabis

  Biological Psychiatry · 2025-04-09

  articleSenior author
  PublisherDOI

Recent grants

• Acquisition and persistence of drug cue conditioning in humans

  NIH · $2.3M · 2014–2021

• NIH Grant R21DA020773

  NIH · $418k · 2010

• NIH Grant R21DA031796

  NIH · $411k · 2016

• NIH Grant R01DA006176

  NIH · $610k · 1996

• NIH Grant R01DA003517

  NIH · $2.2M · 2001

Frequent coauthors

• Thomas Steckler

  4717 shared

• Robert L. Balster

  4273 shared

• Klaus A. Miczek

  4216 shared

• Jos Prickaerts

  Maastricht University

  3736 shared

• Craig A. Erickson

  Cincinnati Children's Hospital Medical Center

  3548 shared

• Kimberly A. Stigler

  Indiana University School of Medicine

  3548 shared

• Christopher J. McDougle

  Massachusetts General Hospital

  3547 shared

• David J. Posey

  Indiana University School of Medicine

  3520 shared

Education

• Ph.D., Psychiatry and Behavioral Neuroscience

  University of Chicago

  1990

• M.A., Psychology

  University of Chicago

  1985

• B.A., Psychology

  University of Chicago

  1982

Awards & honors

• Solvay Award for Outstanding Basic Psychopharmacological Res…
• Marian W. Fischman Memorial Lectureship Award, College of Pr…
• Distinguished Lecturer, Elizabeth Fitzgerald Sporar Endowmen…
• Distinguished Achievement Award, European Behavioural Pharma…
• Lifetime Achievement Award, Research Society on Alcoholism (…