Altered energy production, lowered antioxidant potential, and inflammatory processes mediate CNS damage associated with abuse of the psychostimulants MDMA and methamphetamine.
Luke A. Downey, Jennifer M Loftis
European Journal of Pharmacology March 15, 2014 DOI: 10.1016/j.ejphar.2014.01.032 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | MDMA |
| Keywords | 2-fluoro-2-deoxy-d-glucose pubchem cid 3,4-Methylenedioxy-N-Methylamphetamine MDMA Bioenergetics Cocaine pubchem cid Inflammation Methamphetamine pubchem cid Neurodegenerative diseases Oxidative stress |
| Key findings | Psychostimulant dependence, particularly MDMA and methamphetamine use, may involve ongoing central nervous system damage affecting brain energy regulation and immune response. The authors contend that neuropsychiatric impairments persisting after abstinence, such as cognitive deficits, depression, and anxiety, are linked to poorer treatment outcomes including increased relapse and lower retention. They propose that matching molecular changes to specific substances and use patterns could inform new addiction treatments. |
Abstract
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.
Comparable studies
Other narrative reviews on MDMA, most cited first.
| Study | Year | Design | Participants |
|---|---|---|---|
| Human Pharmacology of MDMA | 2004 | Review | |
| Human psychopharmacology of Ecstasy (MDMA): a review of 15 years of empirical research | 2001 | Review | |
| 3,4‐Methylenedioxymethamphetamine (MDMA, “Ecstasy”): pharmacology and toxicology in animals and humans | 1994 | Review | |
| (±)3,4-Methylenedioxymethamphetamine (‘Ecstasy’)-Induced Serotonin Neurotoxicity: Studies in Animals | 2000 | Review | |
| Amphetamine toxicities | 2010 | Review |
Citations in the library
Cited by 4
- Associations between MDMA/ecstasy use and physical health in a U.S. population-based survey sample Journal of Psychopharmacology October 1, 2022
- Longitudinal Examination of Learning and Memory in Rats Following Adolescent Exposure to 3,4-Methylenedioxymethamphetamine or 5-Methoxy-N,N-Diisopropyltryptamine Journal of Behavioral and Brain Science 2017
- Network Pharmacology Reveals the Potential Mechanism of Ketamine in Improving Cognitive Impairment in Patients With Depression. Alpha psychiatry August 2026
- Amphetamine-related drugs neurotoxicity in humans and in experimental animals: Main mechanisms. Progress in Neurobiology August 2017
Cites 15
- Neurometabolic Effects of Psilocybin, 3,4-Methylenedioxyethylamphetamine (MDE) and d-Methamphetamine in Healthy Volunteers A Double-Blind, Placebo-Controlled PET Study with [18F]FDG Neuropsychopharmacology June 1, 1999
- Decreased cerebral cortical serotonin transporter binding in ecstasy users: a positron emission tomography/[11C]DASB and structural brain imaging study Brain May 17, 2010
- MDMA in humans: factors which affect the neuropsychobiological profiles of recreational ecstasy users, the integrative role of bioenergetic stress Journal of Psychopharmacology March 1, 2006
- Mechanisms of MDMA (Ecstasy)-Induced Oxidative Stress, Mitochondrial Dysfunction, and Organ Damage Current Pharmaceutical Biotechnology June 27, 2010
- Memory impairment and hippocampus specific protein oxidation induced by ethanol intake and 3, 4‐Methylenedioxymethamphetamine (MDMA) in mice Journal of Neurochemistry March 25, 2013
and 10 more in the library