Role of Anterior Cingulate Cortex in Physician and Emotional Symptoms of Opioid Withdrawal

With the number of opioid-related deaths continuing to rise, the demand for an effective treatment for opioid use disorder (OUD) is growing. While opioid antagonists are effective, compliance is an issue since they induce withdrawal. The botanical compound, TGIR-C is a promising non-opioid alternative that treats detoxification without inducing withdrawal. Further research on its neural mechanisms would assist in the clinical adoption of TGIR-C under development by Resilience Biosciences Inc. A hallmark of opioid withdrawal is hyperkatifeia, which is a heightened awareness of aversive events and a shift in positive events towards a negative valence. Addicts try to counteract hyperkatifeia by taking more drug, creating a vicious cycle of abuse. Hyperkatifeia depends on changes in the anterior cingulate cortex (ACC) that are likely driven by withdrawal-induced elevations in dopamine (DA). Preliminary in vivo neurochemical evidence suggests that TGIR-C acts as a DA “stabilizer”. Building on this, we propose that TGIR-C is therapeutically effective because it stabilizes DA levels in the ACC during withdrawal, thereby abolishing hyperkatifeia and effectively removing the motivation for continued drug use. We will test this possibility using electrophysiology and fiber photometry in order to gain a better understanding of the therapeutic potential of TGIR-C.

Faculty Supervisor:

Jeremy Seamans

Student:

Partner:

Resilience Biosciences Inc.

Discipline:

Life Sciences

Sector:

Manufacturing; Professional, scientific and technical services

University:

The University of British Columbia

Program: