Abstract:
Background: Despite its negative consequences, substance addiction is a persistent, relapsing 
disorder characterized by compulsive drug-seeking behaviour. Substance use and addiction 
have been rapidly increasing public health problems all over the world. According to empirical 
evidence, substances directly affect individuals' memory, attention, decision-making, and 
executive functions, impacting various regions of the brain. Neural circuitry and 
neurotransmitter changes associated with substance addiction are leading causes of cognitive 
impairment.  
Objective: To reveal the specific neural mechanisms associated with cognitive deficits in the 
human brain  
Methods: Scientific evidence was gathered by referring to more than 20 articles that are 
included in Google Scholar, PubMed, and ELSEVIER databases. This study was mainly 
conducted by referring to scientific articles that have been published within 10 years.  
Results: Results revealed that the ventral tegmental area and nucleus accumbens internalize the 
reward stimuli regulating the dopaminergic system that can be induced by psychoactive 
substances. Then, long-term substance use associated with serotonergic and GABA activity 
leads to changes in the executive functions in the prefrontal cortex and the inhibitory control. 
Conclusion: Considering the empirical evidence, prolonged usage of substances is capable of 
deteriorating individuals’ cognitive functions drastically. Hence, a multidisciplinary approach 
including neurology, genetics, public health, and psychology is a crucial requirement to 
manage these substance-related cognitive impairments. Early identification can be used to 
mitigate the severity of the impairments.