Prestigious award seeks to advance new avenue of addiction treatment
A chemical biologist at Oregon Health & Science University has become just the second researcher in the institution’s history to receive a prestigious Avenir Award from the National Institute on Drug Abuse, known as NIDA, of the National Institutes of Health.
James Frank, Ph.D., assistant professor of chemical physiology and biochemistry in the OHSU School of Medicine and the Vollum Institute at OHSU, will use the award to develop new tools to improve understanding of an alternative suite of receptors in the brain believed to be involved in opioid addiction. Existing medications to treat opioid use disorder target the brain’s opioid receptors, yet the recent surge of fentanyl into the illicit drug supply has supercharged an opioid epidemic that now kills 80,000 Americans annually. Fentanyl is 100 times more potent than morphine, which makes existing medications to treat addiction less effective.
“Because fentanyl is so potent and sticks to its receptors so effectively, the opioid-targeting drugs that we have in our toolkit don’t work as well,” he said. “So, we’re trying to develop new therapies that act on receptors outside of the opiate system.”
Using chemical tools developed in his OHSU lab, Frank’s research will focus on an alternative suite of receptors, called cannabinoid receptors, that are involved in the functions of pain management and addiction in the brain. Specifically, he will target a cannabinoid receptor known as CB2, as well as other orphan cannabinoid receptors like GPR55 that haven’t been as intensively studied as the CB1 cannabinoid receptor.
All are part of the nervous system’s endocannabinoid system, which is most notably associated with the use of cannabis.
“There are many parallels between the opioid and cannabinoid systems, in terms of where they’re expressed in the brain’s reward circuits, as well as how they act on those cells once activated,” Frank said. “We think that if we can better understand specific cannabinoid receptors and in which specific brain pathways they become activated in addiction, it may be possible to design new drugs to treat substance use disorders.”
Further, unlike opioid receptors, Frank says, cannabinoid receptors do not induce respiratory depression that can lead to death:“They have a higher safety profile compared with the opioid drugs that are currently available.”
Read more about OHSU’s leadership in addiction medicine.
The lab is developing new chemical tools capable of activating cannabinoid receptors on specific brain circuits with light. Combined with the use of fluorescent dyes, the Frank lab will discern — with detailed time and space specificity — how the introduction of opioids to cells within a Petri dish and in live mice changes the expression of cannabinoid receptors.
By using these state-of-the-art chemical tools, the goal of the research is to illuminate signaling mechanisms that could be useful in drug development.
Frank joined OHSU in 2018 as a research assistant professor in the Vollum Institute, with support from the Vollum Fellowship. He was promoted in 2021 to assistant professor in the School of Medicine.
The award provides $2.1 million over five years. The Avenir Awards support early-career investigators proposing new areas of research for the genetics or epigenetics of addiction.
Frank’s project was one of just two Avenir Awards in Chemistry and Pharmacology Research granted this year. NIDA has three Avenir award programs: research in HIV, genetics and epigenetics of substance use, and chemistry and pharmacology of substance use. Only two OHSU scientists have received an Avenir in any category.
Jamie Lo, M.D., an associate professor of obstetrics and gynecology, was the first OHSU School of Medicine researcher to be awarded the prestigious grant: Lo received the Avenir Award in Genetics and Epigenetics in 2022 to develop research exploring how parents’ behavior and environment affects their offspring before birth, and, in some cases, before conception.
Frank’s award number is 1DP1DA060496-01 through the National Institute on Drug Abuse of the NIH.
All research involving animal subjects at OHSU must be reviewed and approved by the university’s Institutional Animal Care and Use Committee (IACUC). The IACUC’s priority is to ensure the health and safety of animal research subjects. The IACUC also reviews procedures to ensure the health and safety of the people who work with the animals. The IACUC conducts a rigorous review of all animal research proposals to ensure they demonstrate scientific value and justify the use of live animals.