Insights into the Neurobiology of Craving in Opioid Use Disorder

Abstract

Purpose of review: Opioids remain the most potent form of pain relief currently available, yet have a high abuse liability. Here we discuss underlying neurobiological changes in Opioid Use Disorder (OUD) that likely contribute to drug craving, which in turn drives continued drug use and relapse.

Recent findings: Craving has emerged as a strong indicator in drug-seeking and relapse. Studies have demonstrated a number of allostatic changes in circuitry that facilitate learning of drug-stimuli relationships, thereby augmenting cue-triggered drug use and relapse.

Summary: This review will focus on key neurobiological changes in underlying circuitry observed during the initial and continued exposure to opioids that result in an increase in neural-reactivity to drug-related intrinsic and extrinsic drug cues, and to enhanced learning of drug-context correlations. This sensitized learning state may be an indication of the underlying framework that drives craving and ultimately, motivates increased salience of drug cues and drives drug-seeking.

Keywords: Drug craving; Incentive sensitization; Negative affect; Negative reinforcement; Opioid Use Disorder; Stress.

Figure 1.

Allostatic changes in neurocircuitry following repeated opioid exposure in OUD. Following repeated opioid use, allostatic changes are observed in circuitry that mediates reward and motivation (a switch from “liking” to “wanting”), stress and negative affect (decreases in anti-stress; increases in stress), as well as cognitive function (decreases in executive function, and increased incentive sensitization to drug cues); Amy, amygdala; dlPFC, dorsal lateral PFC; DS, Dorsal striatum; Hipp, hippocampus; Hypothal, hypothalamus; NAc, nucleus accumbens; OFC, orbitofrontal cortex; vlPFC, ventral lateral PFC; vmPFC, ventral medial PFC; VP, ventral pallidum; VTA, ventral tegmental area. Figure created with Biorender.com.