Altered energy production, lowered antioxidant potential, and inflammatory processes mediate CNS damage associated with abuse of the psychostimulants MDMA and methamphetamine.
Central nervous system (CNS) damage associated with psychostimulant dependence may be an ongoing, degenerative process with adverse effects on neuropsychiatric function. However, the molecular mechanisms regarding how altered energy regulation affects immune response in the context of substance use disorders are not fully understood. This review summarizes the current evidence regarding the effects of psychostimulant [particularly 3,4-methylenedioxy-N-methylamphetamine (MDMA) and methamphetamine] exposure on brain energy regulation, immune response, and neuropsychiatric function. Importantly, the neuropsychiatric impairments (e.g., cognitive deficits, depression, and anxiety) that persist following abstinence are associated with poorer treatment outcomes - increased relapse rates, lower treatment retention rates, and reduced daily functioning. Qualifying the molecular changes within the CNS according to the exposure and use patterns of specifically abused substances should inform the development of new therapeutic approaches for addiction treatment.
Centre for Human Psychopharmacology, Swinburne University of Technology, Hawthorn, VIC 3122, Australia; Department of Psychology, Swansea University, Swansea, Wales, UK.
Luke A
LA
Downey
Research & Development Service, Portland VA Medical Center, 3710 SW US Veterans Hospital Road, Portland, OR 97239 USA; Department of Psychiatry, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239-3098, USA; Methamphetamine Abuse Research Center, Oregon Health & Science University, Portland VA Medical Center, Portland, OR, USA. Electronic address: loftisj@ohsu.edu.
Jennifer M
JM
Loftis
D019969:Amphetamine-Related Disorders / Q000150:complications* / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000534:rehabilitation; D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D000697:Central Nervous System Stimulants / Q000009:adverse effects; D004734:Energy Metabolism / Q000187:drug effects*; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D008694:Methamphetamine / Q000009:adverse effects*; D018817:N-Methyl-3,4-methylenedioxyamphetamine / Q000009:adverse effects*; D018384:Oxidative Stress / Q000187:drug effects*; D012008:Recurrence; D013375:Substance Withdrawal Syndrome / Q000209:etiology / Q000378:metabolism
D000697:Central Nervous System Stimulants; D018836:Inflammation Mediators; D008694:Methamphetamine; D018817:N-Methyl-3,4-methylenedioxyamphetamine
2-Fluoro-2-deoxy-d-glucose (PubChem CID: 315411); 3,4-Methylenedioxy-N-methylamphetamine (MDMA); 3,4-Methylenedioxy-N-methylamphetamine (MDMA) (PubChem CID: 1615); 3,4-Methylenedioxyethamphetamine (MDE) (PubChem CID: 105039); Bioenergetics; Cocaine (PubChem CID: 5760); Inflammation; Methamphetamine; Methamphetamine (PubChem CID: 10836); Neurodegenerative diseases; Oxidative stress