Functional evaluation of NK1 antagonism on cue reactivity in opiate dependence; An fMRI study

Abstract

Background Opiate addiction is a major health challenge with substantial societal cost. Though harm minimisation strategies have been effective, there is a growing need for new treatments for detoxification and relapse prevention. Preclinical research has found neurokinin 1 (NK 1 ) receptors have prominent effects on opiate reward and reinforcement, and human studies have found NK 1 antagonism led to reductions in craving and withdrawal. However, its effect on brain mechanisms in opiate addiction has not yet been examined. Methods This study aims to assess the impact of NK 1 antagonist aprepitant on heroin cue-elicited changes in blood-oxygenation level dependent (BOLD) signal in opiate dependent individuals undergoing detoxification. Participants will attend two scanning sessions and receive a single dose of aprepitant (320 mg) and a placebo in a randomised, cross-over design. During functional magnetic resonance imaging participants will undergo two runs of a cue reactivity task, which consists of passive viewing of drug cues or neutral cues in a block design fashion. We hypothesise that NK 1 antagonism will attenuate the BOLD response to drug cues in the caudate nucleus and amygdala. Regions of interest were selected based on NK 1 receptor density and their role in cue reactivity and craving.

The Neurokinin-1 Receptor: Structure Dynamics and Signaling

“…State agencies have only approved using human NK-1R antagonists for the treatment of chemotherapy-induced nausea and vomiting [118]. Basic experimental research provided much information on the potential efficacy of NK-1R antagonists in other pathological entities related to substance abuse, pain, some types of cancer, and psychiatric disorders, among others [119][120][121][122][123]. The drawbacks have come from the poor efficacy observed in some clinical assays, possibly associated with low receptor occupancy or other factors, and the need to simultaneously target different types of NK receptors for specific pathologies to attain effectiveness [93].…”

Stronger connectivity among reward, cognitive, and attention networks in people with severe Opioid Use Disorder compared with healthy controls.

“…Only data from the placebo scanning session was used in these analyses described below. A detailed description of the study design can be found elsewhere 13 , and a description of the MID and Cue Reactivity tasks can be found in Supplementary Materials, Methods.…”

“…This study is not a clinical trial and therefore was not registered as a clinical trial. The study design and planned analytical approach for the primary analyses was pre-registered 13 . This paper consists of secondary analyses which were not primary considerations when designing the research study that collected the data.…”

“…In order to explore the underlying neurocircuitry in sOUD, we used data from the Neural Correlates of Reward and Emotion in opiate dependence (NCORE) study 13 . The NCORE study collected task fMRI data from HCs and methadone-dependent (MD) people with sOUD.…”