Can neuroimaging help combat the opioid epidemic? A systematic review of clinical and pharmacological challenge fMRI studies with recommendations for future research

Abstract

The current opioid epidemic is an urgent public health problem, with enormous individual, societal, and healthcare costs. Despite effective, evidence-based treatments, there is significant individual variability in treatment responses and relapse rates are high. In addition, the neurobiology of opioid-use disorder (OUD) and its treatment is not well understood. This review synthesizes published fMRI literature relevant to OUD, with an emphasis on findings related to opioid medications and treatment, and proposes areas for further research. We conducted a systematic literature review of Medline and Psychinfo to identify (i) fMRI studies comparing OUD and control participants; (ii) studies related to medication, treatment, abstinence or withdrawal effects in OUD; and (iii) studies involving manipulation of the opioid system in healthy individuals. Following application of exclusionary criteria (e.g., insufficient sample size), 45 studies were retained comprising data from ~1400 individuals. We found convergent evidence that individuals with OUD display widespread heightened neural activation to heroin cues. This pattern is potentiated by heroin, attenuated by medication-assisted treatments for opioids, predicts treatment response, and is reduced following extended abstinence. Nonetheless, there is a paucity of literature examining neural characteristics of OUD and its treatment. We discuss limitations of extant research and identify critical areas for future neuroimaging studies, including the urgent need for studies examining prescription opioid users, assessing sex differences and utilizing a wider range of clinically relevant task-based fMRI paradigms across different stages of addiction.

Fig. 1

Prevalence of male and female participants across reviewed fMRI studies. Across all studies, 208 (14.7%) of participants were female

Fig. 2

Regional effects of opioidergic agents on neural function. Summarizes primary findings for selected brain regions from fMRI studies involving manipulation of the opioid system. OFC orbitofrontal cortex, INS insula, HIP hippocampus, AMY amygdala, ACC anterior cingulate, IFG inferior frontal gyrus, THA thalamus, STR striatum, MBN midbrain, SMT sensorimotor, OUD opioid use disorder, HC healthy control, NS no results. Based on data reported in refs [, , , , , , , –, –98, 100]. For studies including multiple conditions, e.g., ref. [89], results reported for neutral or resting state conditions were used for figure generation (see Supplemental Table 1 for details). Refer to Tables 1–4 of the primary manuscript for additional summaries of study findings