NIDA Awards UC San Diego $12.6 Million to Unite Alcohol and Drug Addiction Research Under One Roof

Addiction science has long been organized around a fault line that patients rarely experience in their own lives. Alcohol research developed in one set of laboratories, drug research in another, and the two fields published in largely separate journals, trained separate specialists, and built separate animal models. Yet in clinical reality, polysubstance use — the combined or alternating use of alcohol, opioids, stimulants and other substances — is common, and it is often associated with more severe outcomes than dependence on a single substance. A new five-year, $12.6 million award from the National Institute on Drug Abuse (NIDA) to University of California San Diego researchers is designed to dismantle that artificial boundary and replace it with an integrated, multiscale picture of what addiction does to the body and brain.

The funding establishes the Polysubstance Addiction Research Center, or PARC, a multidisciplinary center led by Olivier George, PhD, professor of psychiatry at UC San Diego School of Medicine. The center assembles investigators from psychiatry, medicine, obstetrics and gynecology and reproductive sciences, and computational biology and bioinformatics, in partnership with the Veterans Affairs San Diego Healthcare System. Its stated mission is to uncover the biological factors that contribute to addiction across multiple substances, rather than studying one drug class at a time.

George, who directs PARC, argues that the traditional division of the field does not reflect how addiction actually occurs. People frequently use more than one substance, he notes, so researchers need to understand what these substances have in common as well as what makes them different. By bringing psychostimulant research — a category that includes cocaine, which speeds up activity in the central nervous system — together with opioid and alcohol research under one organizational roof, the center hopes to identify biological mechanisms that may be shared across substances and others that are specific to particular drug classes.

The scientific scope of the center is deliberately broad. PARC will focus its experimental work on cocaine, oxycodone, alcohol, and the combination of cocaine and oxycodone, using a coordinated research strategy in which the same questions are asked across all four exposure conditions. Rather than examining a single biological system in isolation, the investigators will study behavior alongside changes in brain networks, gene activity, and processes involving the immune system, metabolism, and the gut-brain connection. The goal is to understand why some individuals develop more severe addiction-related behaviors than others, and to do so by looking at multiple biological systems simultaneously.

Central to this effort is what the center calls its One-Individual Multiscale Atlas, a framework for integrating information that ranges from genes and individual cells to brain circuits, peripheral organs, and behavior. In practical terms, the atlas is meant to connect measurements made at one biological level with measurements made at another: how a change in gene expression within a specific type of brain cell relates to altered communication across a neural network, and how both relate to observable behavior. Findings generated in the laboratory will then be compared with human genetic, brain imaging, and other biological datasets to determine whether the patterns observed in preclinical models align with variation seen in people.

Abraham Palmer, PhD, professor and vice chair of basic research in the Department of Psychiatry at UC San Diego School of Medicine, emphasizes the genetic dimension of this approach. Decades of research have established that genetic differences among individuals contribute to risk for addiction, and Palmer describes PARC as using cutting-edge techniques to understand how those individual differences shape addiction risk at the molecular, cellular, and brain circuit levels. The multiscale design is intended to bridge the gap between statistical genetic associations and the biological mechanisms those associations may point toward.

The center’s work is organized into three interconnected research projects. The first, a brain connectomics project, will examine how addiction changes the organization and communication of brain networks — asking, in effect, whether repeated exposure to cocaine, oxycodone, alcohol, or their combination produces measurable shifts in how regions of the brain talk to one another. The second, a brain transcriptomics project, will study changes in gene activity within specific types of brain cells, a level of resolution that has become possible with modern single-cell and cell-type-specific molecular methods. The third, a gut-vagus multiomics project, will investigate how the gut and the vagus nerve — the cranial nerve that connects the brain with organs throughout the body — may influence addiction-related behaviors, reflecting growing scientific interest in the role of peripheral physiology and the microbiome-gut-brain axis in neuropsychiatric conditions.

Together, these projects support the center’s first formal aim: identifying biological markers associated with vulnerability to addiction-related behaviors. Advanced computational and machine-learning methods will be used to integrate the different types of data the projects generate and to identify patterns that may help explain differences in addiction severity. The second aim goes a step further, moving from correlation to causation. Researchers will use medications and other interventions to test whether potential biological targets identified through the center’s research — including pathways involved in cellular stress, immune signaling, and communication between the gut and the brain — actually influence addiction-related behavior when manipulated. As George puts it, the goal is to go beyond simply finding a biological difference associated with addiction and to test whether changing that biological process changes the behavior itself, an approach he argues is more likely to yield targets that translate into new treatments.

The third aim is infrastructural. PARC will expand an addiction biobank that already contains more than 40,000 specimens collected from studies of addiction-related behaviors involving cocaine, oxycodone, and alcohol, a resource that has supported 75 external research projects to date. The center will also provide researchers with access to standardized behavioral models, computational tools, and shared datasets, with data deposited in National Institutes of Health repositories to support reproducibility and allow other laboratories to build on the center’s findings. In this respect, PARC is designed not only as a research program but as a national resource for addiction science.

The new center formalizes and expands a collaboration that has been building at UC San Diego for six years. During that period, PARC investigators have worked across more than a dozen laboratories, producing hundreds of publications and developing shared research resources. Barbara Jung, MD, associate vice chancellor and dean of UC San Diego School of Medicine, describes the award as a recognition of George’s leadership and his vision for bringing researchers across disciplines to address the complexities of addiction, and says the creation of PARC strengthens the school’s ability to lead collaborative research that can deepen understanding of addiction and help identify new approaches to prevention and treatment. By connecting biological information across multiple levels and bridging the historical divide between alcohol and drug research, PARC aims to move the field from isolated observations toward an integrated account of why addiction develops, why some people are more vulnerable than others, and why relapse occurs.

Subject of Research: A NIDA-funded multidisciplinary center studying the shared biology of polysubstance addiction across cocaine, oxycodone, and alcohol

Article Title: UC San Diego receives $12.6 million award to launch a new polysubstance addiction research center

Article References: UC San Diego receives $12.6 million award to launch a new polysubstance addiction research center. (n.d.). Original publication

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Keywords: polysubstance addiction, NIDA, UC San Diego, Olivier George, brain connectomics, transcriptomics, gut-brain axis, vagus nerve, cocaine, oxycodone, alcohol use disorder, biobank