Maternal Substance Use and Early-Life Adversity: Inducing Drug Dependence in Offspring, Interactions, Mechanisms, and Treatments

Document Type : Review Article(s)


1 Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran

2 1 Neuroscience Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran 2 Department of Health Sciences, Faculty of Health, University of Waterloo, Waterloo, Ontario, Canada



The likelihood of substance dependency in offspring is increased in cases when there is a family history of drug or alcohol 
use. Mothering is limited by maternal addiction because of the separation. Maternal separation (MS) leads to the development 
of behavioural and neuropsychiatric issues in the future. Despite the importance of this issue, empirical investigations of the 
influences of maternal substance use and separation on substance use problems in offspring are limited, and studies that 
consider both effects are rare. This study aims to review a few studies on the mechanisms, treatments, genetics, epigenetics, 
molecular and psychological alterations, and neuroanatomical regions involved in the dependence of offspring who underwent 
maternal addiction and separation. The PubMed database was used. A total of 95 articles were found, including the most 
related ones in the review. The brain’s lateral paragigantocellularis (LPGi), nucleus accumbens (NAc), caudate-putamen (CPu), 
prefrontal cortex (PFC), and hippocampus, can be affected by MS. Dopamine receptor subtype genes, alcohol biomarker 
minor allele, and preproenkephalin mRNA may be affected by alcohol or substance use disorders. After early-life adversity, 
histone acetylation in the hippocampus may be linked to brain-derived neurotrophic factor (BDNF) gene epigenetics and 
glucocorticoid receptors (GRs). The adverse early-life experiences differ in offspring›s genders and rewire the brain›s dopamine 
and endocannabinoid circuits, making offspring more susceptible to dependence. Related psychological factors rooted in earlylife stress (ELS) and parental substance use disorder (SUD). Treatments include antidepressants, histone deacetylase inhibitors, 
lamotrigine, ketamine, choline, modafinil, methadone, dopamine, cannabinoid 1 receptor agonists/antagonists, vitamins, 
oxytocin, tetrahydrocannabinol, SR141716A, and dronabinol. Finally, the study emphasizes the need for multifaceted strategies 
to prevent these outcomes.


Maysam Fadaei-kenarsary: (Google Scholar) (PubMed)

Khadijeh Esmaeilpour: (Google Scholar) (PubMed)

Mohammad Shabani: (Google Scholar) (PubMed)

Vahid Sheibani: (Google Scholar) (PubMed)


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