Concluding Remarks
Metabolomics constitutes a powerful approach for revealing the impact of exposure on the overall biochemistry of an individual or system. Establishing the concise relationship between the phenotype and specific drug use is confounded by many types of exposure that an individual can simultaneously experience (e.g., drugs, chemical, nutrition, or stress), and by the impact of these exposures over a lifetime. Thus, studies in animal models and cell systems are critical for controlling experimental conditions and demonstrating links for validation in human cohorts. Important areas for such controlled dose- and time-to-response studies in animal models include using metabolomics to: (i) investigate peripheral metabolites that correlate with biochemical perturbations in the brain caused by opiate receptor binding; (ii) determine the impact of in utero exposure and neonatal exposure to opiates on biochemical processes later in life; (iii) investigate sex differences in response to opiate exposure; (iv) determine the impact of specific nutrient intake concurrent with opiate exposure on addiction-related responses; and (v) reveal the role of opiate receptor binding and metabolism on the gut microbiota (see Outstanding Questions and Box 1) [50,51]. We propose that, if addiction constitutes an overall metabolic disturbance in the organism, interventions that regulate metabolism might be used to treat and/or prevent SUDs. For instance, we recognize that optimum levels of folic acid are important in contributing to healthy pregnancies [52] and combatting the development of cancers, and that both low levels and high levels of folic acid have been associated with increased cancer risks [53,54]. Together, these insights have led us to hypothesize that opiate addiction, and related cancer risks, could be reduced through nutritional interventions, and we propose that extensive studies are warranted to further explore this hypothesis. We anticipate that using metabolomics for the analysis of human biospecimens, from a variety of studies, including the Golestan Cohort, will facilitate the discovery of diagnostic biomarkers and nutritional targets that may aid in intervention strategies to treat substance abuse, addiction, and withdrawal.
