Characterising the neurobiology of detoxification in opiate dependence: is there a role for NK1 antagonism to improve outcomes?

Background: Opiate dependence is a major health challenge of increasing concern globally. Treatment typically involves psychosocial interventions, harm minimisation and opiate substitution therapy. Whilst this has been effective at reducing harms, there is a growing need for new pharmacological treatments to aid detoxification. Preclinical research has shown neurokinin 1 (NK1) receptors play an important role in opiate reward and reinforcement. Human studies have found NK1 antagonism led to reductions in craving, however its effects on brain mechanisms in opiate dependence have not been well characterised.

Methods: Our MRC-funded Neural Correlates of Reward and Emotion in opioid dependence (NCORE) study is using functional Magnetic Resonance Imaging (fMRI) to assess the impact of NK1 antagonist, aprepitant, on brain mechanisms in opiate dependent individuals undergoing methadone dose reduction. Participants attend two scanning sessions in which they are administered a single dose of aprepitant (320mg) and a placebo in a double-blind, randomised, cross-over design. Scanning sessions employ several fMRI paradigms including a monetary reward task, a heroin-cue reactivity task and an aversive images task. We hypothesise that compared with healthy controls, opiate dependent individuals will display a blunted striatal blood-oxygen level dependent (BOLD) response during monetary reward anticipation, an elevated frontostriatal BOLD response to salient cues during the cue reactivity task, and an elevated amygdala BOLD response to aversive images compared with neutral images. We hypothesise that in opiate dependent individuals NK1 antagonism will 'normalise' the BOLD responses during these tasks, which will be indicative of clinical benefit.

Results: Data collection is ongoing and preliminary findings from behavioural and neuroimaging data will be presented.

Conclusion: If NK1 antagonism is found to modulate brain mechanisms in a direction indicative of clinical benefit, it will be important to examine the clinical utility of NK1 antagonism in opiate dependence through clinical trials.