Imaging and Treatment Development for Substance Use Disorders
Diana Martinez, MD
Columbia University Irving Medical Center
New York State Psychiatric Institute
While treatment options exist for some substance use disorders (SUD), there has been a lack of novel therapies despite the clinical need. Human brain using Positron Emission Tomography (PET) has the potential to identify the neurotransmitter systems involved in relapse and treatment retention. Many of these studies have focused on striatal dopamine transmission and show that addiction is associated with a decrease in dopamine D2/3 receptors and blunted pre-synaptic dopamine release. Additionally, these imaging studies also show that low striatal dopamine signaling is associated with compulsive drug use.
Although dopamine is thought to drive much of the positive reinforcement in substance use, the kappa opioid receptor (KOR)/dynorphin system plays a significant role in modulating the negative aspects of addiction. Activation of this receptor system exacerbates stress induced reinstatement in animal models of SUD, while blocking the receptor reduces it. We recently completed a PET imaging study of KOR in cocaine use disorder that investigates stress induced cocaine seeking behavior. The results suggest that this receptor serves as a target for medication development in this disorder.
Despite these findings, there has been little advancement in medication development for SUD. As a result, our current focus is on developing transcranial magnetic stimulation (TMS) as a potential treatment for alcohol use disorder and chronic pain with opioid misuse. The rationale and early results from these studies will be presented.