Project Grant F32DA062467

Award Date 4/1/25
Completion Date 3/31/28
Dollars Obligated $74K
Federal Grant Program
93.279
Assistance Type
Project Grant
Place of Performance
Ithaca, NY, USA
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This Project Grant award from the National Institute of Mental Health (NIMH), under the Mental Health Research Grants program (CFDA 93.242), is providing $627,945 to Cornell University to investigate the role of cortical GABAergic interneurons in the effects of the psychedelic drug psilocybin. The research aims to: 1) measure the spiking activity of different interneuron subtypes in response to psilocybin administration, 2) determine if serotonin receptors expressed in the interneurons...
The National Institute of Mental Health (NIMH) awarded a 5-year, $679,118 Project Grant under the Mental Health Research Grants program (CFDA 93.242) to the University of California Santa Cruz (UCSC) to investigate the cellular and circuit mechanisms underlying the long-lasting therapeutic effects of the psychedelic drug psilocybin in the stressed brain. The key objectives are to: Determine the acute and enduring effects of psilocybin on synaptic plasticity, cortical functional networks,...
This Project Grant award from the National Institute on Drug Abuse (NIDA) under the Drug Use and Addiction Research Programs (CFDA 93.279) provides $495,024 to The Trustees of the University of Pennsylvania to conduct research on the effects of psilocybin on neurocognitive function and motivation in individuals with opioid use disorder. The 2-year project aims to examine psilocybin's impact on brain activity, cognition, and behavior across three key domains: motivation, inhibitory control,...
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This federal Project Grant award in the amount of $131,990 from the National Institute on Drug Abuse (NIDA), under the Drug Use and Addiction Research Programs (CFDA 93.279), will investigate the effects of psychedelic 5-HT2A agonist drugs on reversing aberrant reward-seeking behavior in an animal model of early-life adversity. The research, to be conducted by the University of California, Irvine, aims to replicate and extend previous findings showing that a single dose of the psychedelic...
This $509,279 Project Grant award from the National Institute on Drug Abuse (CFDA 93.279 - Drug Use and Addiction Research Programs) supports research into the role of 5-HT2A receptor signaling in treating stimulant use disorder. The principal investigator and prime awardee, The Medical College of Wisconsin, Inc., will conduct studies examining how 5-HT2A receptor agonists, including psychedelic drugs, can suppress the reinforcing effects of methamphetamine, promote neuroplasticity, and...
This Project Grant award from the National Institute on Drug Abuse (NIDA), under the Drug Use and Addiction Research Programs (CFDA 93.279), provides $1,603,784 to Brigham & Women's Hospital to study the effects of psilocybin on a neuroimmune circuit that controls stress behaviors relevant to substance use disorders. The project aims to define how psilocybin impacts peripheral immune cells, understand how these immune cells regulate astrocytes in the nucleus accumbens, and evaluate the...
This Project Grant award from the National Institute of Mental Health (NIMH) under the Mental Health Research Grants program (CFDA 93.242) provides $237,000 to the University of California, San Diego (UC San Diego) to study the efficacy of psychedelic agents in reversing depression-relevant behaviors and associated EEG biomarkers in mice. The 2-year project aims to assess whether chronic corticosterone treatment, short-active winter-like photoperiod, and the acetylcholinesterase inhibitor...
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NEURAL MECHANISMS OF PSILOCYBIN ACTION IN THE FRONTAL CORTEX - PROJECT SUMMARY SEROTONERGIC PSYCHEDELICS ARE BEST KNOWN FOR ALTERING PERCEPTION, COGNITION, AND MOOD. RECENTLY, THERE HAS BEEN A RESURGENCE IN CLINICAL TRIALS INVESTIGATING PSYCHEDELICS FOR THEIR POTENTIAL IN TREATING NEUROPSYCHIATRIC ILLNESSES, SUCH AS SUBSTANCE USE DISORDER. PSILOCYBIN-ASSISTED THERAPY, FOR EXAMPLE, HOLDS PROMISE IN TREATING ALCOHOL, OPIOID, OR STIMULANT ADDICTION. IT HAS RECEIVED ATTENTION FOR SHOWING POSITIVE, LONG-LASTING EFFECTS AFTER ONLY A SINGLE TREATMENT. STILL, IT IS UNKNOWN HOW PSILOCYBIN ACTS ON THE BRAIN IMMEDIATELY AFTER ADMINISTRATION TO BEGIN ALTERING NEURONAL PROCESSING. THIS PROPOSAL AIMS TO DETERMINE PSILOCYBIN'S CELLULAR AND MICROCIRCUIT MECHANISMS OF ACTION IN THE MOUSE MEDIAL FRONTAL CORTEX, WITH A SPECIFIC FOCUS ON GABAERGIC INTERNEURONS AND SOMA-DENDRITE COUPLING. INTERNEURONS IN THE FRONTAL CORTEX EXPRESS SEROTONIN RECEPTORS AND LIKELY RESPOND TO PSILOCYBIN TO MEDIATE CHANGES IN CORTICAL INFORMATION PROCESSING. MEANWHILE, SOMA-DENDRITE COUPLING CONTROLS THE EFFICIENCY OF INFORMATION FLOW IN PYRAMIDAL NEURONS, THEREBY GOVERNING SPIKE OUTPUT, AND IT IS ASSOCIATED WITH COGNITIVE PROCESSING. IN THE MEDIAL FRONTAL CORTEX, PSILOCYBIN-DRIVEN CHANGES IN MICROCIRCUIT ACTIVITY AND SOMA-DENDRITE COUPLING MAY THEREFORE UNDERLIE THE COGNITIVE STATE THAT ACCOMPANIES A PSYCHEDELIC EXPERIENCE. MORE IMPORTANTLY, THESE CELLULAR AND MICROCIRCUIT-LEVEL CHANGES MAY BE LINKED TO PSILOCYBIN'S THERAPEUTIC EFFECTS. IN AIM 1 OF THIS PROPOSAL, WE WILL USE TWO-PHOTON CALCIUM IMAGING TO DETERMINE HOW PSILOCYBIN INFLUENCES THE ACTIVITY OF THREE DENDRITE-MODULATING INTERNEURON POPULATIONS IN THE MEDIAL FRONTAL CORTEX. ADDITIONALLY, WE WILL EXAMINE WHETHER THE OBSERVED ACTIVITY CHANGES ARE MEDIATED BY SPECIFIC SEROTONIN RECEPTORS EXPRESSED IN THESE INTERNEURON POPULATIONS. IN AIM 2, WE WILL USE MULTI-PLANE CALCIUM IMAGING TO DETERMINE HOW PSILOCYBIN INFLUENCES SOMA-DENDRITE COUPLING IN PYRAMIDAL NEURONS OF THE MEDIAL FRONTAL CORTEX. WE WILL ALSO PERTURB THE ACTIVITY OF THE THREE DENDRITE-MODULATING INTERNEURON POPULATIONS TO DETERMINE THEIR ROLE IN SHAPING SOMA-DENDRITE COUPLING DURING PSILOCYBIN ACTION. THE PROPOSED EXPERIMENTS ARE DESIGNED TO ELUCIDATE HOW PSILOCYBIN SHAPES CORTICAL COMPUTATIONS. IN DOING SO, THIS PROPOSAL WILL ADVANCE OUR UNDERSTANDING OF THE NEUROBIOLOGY OF PSYCHEDELICS, SPECIFICALLY IN THE CIRCUITS THAT ARE IMPORTANT FOR EXECUTIVE FUNCTION AND IMPULSE CONTROL, WHICH WILL LEAD TO IMPROVED TREATMENTS FOR ADDICTION.

Posted 3/19/25, 12:00 AM