Current preclinical studies on neuroinflammation and changes in blood-brain barrier integrity by MDMA and methamphetamine.
Esther O'Shea, Andrés Urrutia, Alfred Richard Green, María Isabel Colado
Neuropharmacology December 2014 DOI: 10.1016/j.neuropharm.2014.02.015 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | MDMA |
| Keywords | 3,4-methylenedioxymethamphetamine Basal lamina proteins Blood–brain barrier disruption Igg extravasation Neuroinflammation |
| Key findings | The review reports that MDMA and methamphetamine disrupt the blood-brain barrier, as shown by IgG extravasation and Evans Blue leakage. Methamphetamine decreases basal lamina protein expression alongside increased matrix metalloproteinase activity, while MDMA effects appear related to MAPK JNK1/2 activation. The authors state that the consequences remain to be established, but propose links to behavioural sensitization, reward, and AIDS-related neurologic disease in methamphetamine users. |
Abstract
The blood-brain barrier (BBB) is essential in the maintenance of brain homeostasis both by preserving normal brain functioning and also by protecting the brain from exposure to a range of potentially harmful substances. This review presents some of the evidence of BBB disruption following exposure to the substituted amphetamines 3,4-methylenedioxymethamphetamine (MDMA, 'ecstasy') and methamphetamine (METH), two drugs of abuse which are widely consumed recreationally by younger sectors of the population. Both MDMA and METH have been shown to produce disruption of the BBB as reflected by IgG extravasation and Evans Blue leakage. In particular, METH decreases the expression of basal lamina proteins associated with an increase in matrix metalloproteinase activity. These changes in BBB integrity appear to be related to MDMA-induced activation of the mitogen-activated protein kinase (MAPK) JNK1/2. The consequences of the disruption in the BBB by these two drugs remain to be established, but there is evidence in the literature that, at least in the case of METH, increased matrix metalloproteinase (MMP) activity may be related to increased behavioural sensitization and reward perhaps because of the modification of the passage of the drug into the CNS. In addition, the high incidence of AIDS-related neurologic disease in METH users may also be related to increased entry into the brain of virally derived neurotoxic products. This article is part of the Special Issue entitled 'CNS Stimulants'.
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 6
- Ecstasy (3,4-methylenedioxymethamphetamine): cardiovascular effects and mechanisms. European Journal of Pharmacology May 7, 2021
- Examining the Role of Oxytocinergic Signaling and Neuroinflammatory Markers in the Therapeutic Effects of MDMA in a Rat Model for PTSD. Pharmaceuticals June 27, 2024
- Dantrolene sodium fails to reverse robust brain hyperthermia induced by MDMA and methamphetamine in rats. Psychopharmacology April 1, 2023
- Repeated Administration of 3,4-Methylenedioxymethamphetamine (MDMA) Elevates the Levels of Neuronal Nitric Oxide Synthase in the Nigrostriatal System: Possible Relevance to Neurotoxicity. Neurotoxicity Research November 2018
- 3,4-Methylenedioxymethamphetamine (MDMA, ecstasy) produces edema due to BBB disruption induced by MMP-9 activation in rat hippocampus. Neuropharmacology March 16, 2017
and 1 more in the library
Cites 15
- In vivo evidence for free radical involvement in the degeneration of rat brain 5‐HT following administration of MDMA (‘ecstasy’) and p‐chloroamphetamine but not the degeneration following fenfluramine British Journal of Pharmacology July 1, 1997
- Is MDMA (‘Ecstasy’) Neurotoxic in Humans? An Overview of Evidence and of Methodological Problems in Research Neuropsychobiology 2000
- The mechanisms involved in the long‐lasting neuroprotective effect of fluoxetine against MDMA (‘ecstasy’)‐induced degeneration of 5‐HT nerve endings in rat brain British Journal of Pharmacology September 1, 2001
- Role of hyperthermia in the protective action of clomethiazole against MDMA (‘ecstasy’)‐induced neurodegeneration, comparison with the novel NMDA channel blocker AR‐R15896AR British Journal of Pharmacology June 1, 1998
- Studies on the effect of MDMA (‘ecstasy’) on the body temperature of rats housed at different ambient room temperatures British Journal of Pharmacology July 4, 2005
and 10 more in the library