Metabolic phenotyping of opioid and psychostimulant addiction: A novel approach for biomarker discovery and biochemical understanding of the disorder

Abstract

Despite the progress in characterising the pharmacological profile of drugs of abuse, their precise biochemical impact remains unclear. The metabolome reflects the multifaceted biochemical processes occurring within a biological system. This includes those encoded in the genome but also those arising from environmental/exogenous exposures and interactions between the two. Using metabolomics, the biochemical derangements associated with substance abuse can be determined as the individual transitions from recreational drug to chronic use (dependence). By understanding the biomolecular perturbations along this time course and how they vary across individuals, metabolomics can elucidate biochemical mechanisms of the addiction cycle (dependence/withdrawal/relapse) and predict prognosis (recovery/relapse). In this review, we summarise human and animal metabolomic studies in the field of opioid and psychostimulant addiction. We highlight the importance of metabolomics as a powerful approach for biomarker discovery and its potential to guide personalised pharmacotherapeutic strategies for addiction targeted towards the individual's metabolome.

Building Bridges In Neuropharmacology: New therapeutic approaches for psychiatric and neurodegenerative disorders

“…Understanding the biochemistry underlining opioid and psychostimulant use disorders is critical not only to develop effective pharmacotherapy but also to unravel the all‐important biomarkers that allow diagnosis and treatments of diseases and progression to be monitored (Caspani et al, 2022). As such, metabolomic approaches, that is, the analysis of the metabolome, offer a unique biochemical fingerprint that will help uncover the biomolecular perturbations that take place as people transition from recreational use of opioids and psychostimulants to chronic use/abuse and how that varies across individuals.…”

“…Indeed, drug discovery is complex, time-consuming and very costly. Understanding the biochemistry underlining opioid and psychostimulant use disorders is critical not only to develop effective pharmacotherapy but also to unravel the all-important biomarkers that allow diagnosis and treatments of diseases and progression to be monitored (Caspani et al, 2022). As such, metabolomic approaches, that is, the analysis of the metabolome, offer a unique biochemical fingerprint that will help uncover the biomolecular perturbations that take place as people transition from recreational use The above research areas all have clear aims to improve human health, but the maxim that good translational research must always be underpinned with good basic research is as true for neuropharmacology as it is for any other area of science.…”

NMR in Metabolomics: From Conventional Statistics to Machine Learning and Neural Network Approaches

“…[1][2][3]. The investigation and the recording of metabolites by target analysis, metabolic profiling and metabolic fingerprinting (i.e., extracellular metabolites) are fundamental steps for the discovery of biomarkers, helping in diagnoses and designing appropriate approaches for drug treatment of diseases [4,5]. There are many databases available with metabolomics data, including spectra acquired by nuclear magnetic resonance (NMR) and mass spectrometry (MS), but also metabolic pathways.…”

Mitochondria-Related Nuclear Gene Expression in the Nucleus Accumbens and Blood Mitochondrial Copy Number After Developmental Fentanyl Exposure in Adolescent Male and Female C57BL/6 Mice

“…In addition to the many neurobiological changes in reward related processing, and cycles of negative affect that are associated with opioid use, escalation of use, and substance use disorders (13)(14)(15)(16)(17)(18), opioid exposure is also associated with high degrees of oxidative stress and oxidative damage both centrally and peripherally (19)(20)(21)(22)(23). Patients with opioid use disorders show higher levels of oxidative and inflammatory markers in blood serum (24), and are more likely to show markers of metabolic syndrome, indicative of increased risk for mortality due to heart disease or diabetes (25).…”

“…Patients with opioid use disorders show higher levels of oxidative and inflammatory markers in blood serum ( 24 ), and are more likely to show markers of metabolic syndrome, indicative of increased risk for mortality due to heart disease or diabetes ( 25 ). Multiple pre-clinical studies have shown metabolic disruptions and oxidative damage in brain tissue after morphine or heroin exposure ( 19 , 26 ). Oxidative damage in the form of increased reactive oxygen species and decreased antioxidant enzyme activity caused by drug use can lead to mitochondrial dysfunction and neurotoxicity as well as other cellular damage ( 22 , 26 ).…”