Reframing Addiction and Therapeutic Strategies: Neurodegenerative Signatures and Developmental Vulnerability

Wednesday, May 20, 2026 | 2:00 to 3:00 p.m. ET

Yasmin Hurd, PhD

Professor, Neuroscience

Professor, Pharmacological Sciences

Professor, Psychiatry

Icahn School of Medicine at Mount Sinai

yasmin.hurd@mssm.edu

Website

Dr. Yasmin Hurd is the Ward-Coleman Chair of Translational Neuroscience and the Director of the Addiction Institute at Mount Sinai.
Dr. Hurd's multidisciplinary research investigates the neurobiology underlying addiction disorders and related psychiatric illnesses. A translational approach is used to examine molecular and neurochemical events in the human brain and comparable animal models in order to ascertain neurobiological correlates of behavior. A major focus of the research is directed to risk factors of addiction disorders including genetics as well as developmental exposure to drugs of abuse such as cannabis. The group also conducts human clinical trials in developing novel therapies for opioid use disorder.

Summary

Substance use disorders, particularly involving opioids and cannabis, represent a major public health crisis with profound neurobiological and societal consequences. This lecture highlights translational research integrating human postmortem brain analyses, animal models, and clinical studies to elucidate molecular mechanisms underlying addiction and related psychiatric risk. Studies of individuals with opioid use disorder reveal overlapping transcriptional and epigenetic signatures, including disruptions in oxidative phosphorylation pathways, tau-related mechanisms, and PRC2-mediated gene silencing. These findings suggest that chronic opioid exposure engages neurodegenerative-like processes linked to drug-seeking behavior and impaired cognitive flexibility. Such alterations also converge with perturbations in synaptic regulatory proteins, further linking addiction-related plasticity to broader neurodegenerative and neuroimmune processes within cortico-striatal circuits. While substance use disorders and psychiatric illnesses are often framed as adult conditions, this work also emphasizes a strong developmental component. The lecture extends these addiction-related mechanisms to developmental vulnerability, demonstrating that prenatal and adolescent cannabis exposure disrupts placental immune signaling, brain development, and long-term behavioral outcomes, including anxiety and other phenotypes associated with psychiatric risk. These effects converge on shared pathways involving synaptic function, oxidative stress, and immune dysregulation, suggesting that early-life cannabinoid exposure may prime neurobiological systems that later intersect with addiction-related and potentially neurodegenerative processes. The lecture further emphasizes leveraging these mechanistic insights to inform therapeutic development, including targeting epigenetic regulators and advancing cannabidiol as a potential intervention to reduce craving, anxiety, and stress responses. Collectively, this work bridges fundamental mechanistic discovery with translational strategies aimed at developing effective, non-addictive treatments for substance use disorders

Learning Objectives: 

1. To understand transcriptional and epigenetic mechanisms underlying opioid use disorder, including their overlap with neurodegenerative-like processes and implications for cognitive and behavioral dysfunction.
2. To examine how prenatal and adolescent cannabis exposure influences neurodevelopment, contributing to long-term behavioral and psychiatric risk through placental and brain-based mechanisms.
3. To assess translational strategies for medication development in substance use disorders, including targeting epigenetic regulators and the therapeutic potential of cannabidiol.