Objectives: Amphetamines are stimulants and addictive drugs. Saudi officials announced in 2023 a huge campaign against abused drugs. Numerous studies have shown that amphetamines abuse may affect the functions and structures of the brain and result in damage and psychiatric disorders. Nothing evidence was gathered and summarized for all available mechanisms to induce psychiatric disorders. Therefore, we summarized the alterations that cause psychiatric disorders. Methods: We are accessed the studies included in our scope by conducting a literature review involves using engines of the health database such as APA, PubMed, Cochrane Review, Scopus, Google Scholar, Medline, and EMBASE to collect the data and identify the materials that describe the topic by using multi-key words including amphetamines, methamphetamine, ecstasy which known as (MDMA) 3,4-Methylenedioxymethamphetamine , mechanisms of psychiatric disorders; substance-induced psychiatric disorders; psychosis; abuse mechanisms; cognitive-behavioral abnormalities. Results: Psychiatric Disorders induced by amphetamines is a result of direct mechanisms such as abnormalities in the levels of dopamine, glutamate, and GABA, in addition to high dopamine in the midbrain and forebrain, neuronal network dysregulation, and ultimately, cortical and subcortical damage. Indirect mechanisms are confirmed, such as long-term use, high doses, sleep deprivation, genetics, and reactive oxygen species. Dopamine functions and sensitization are confirmed in schizophrenia and drug-induced psychiatric disorders. Conclusion: Mechanisms that induce psychiatric disorders are complex and interrelated. Research focuses on alterations of dopaminergic, sensitization, glutamatergic, neuronal inflammation, cortical GABAergic neurons, apoptosis following neurotoxicity, and mediators of protein kinases. Amphetamine-induced psychiatric disorders could be avoided by early prevention and detoxification.
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