Methylenedioxymethamphetamine (MDMA): Serotonergic and dopaminergic mechanisms related to its use and misuse
Susan Schenk, Quenten Highgate
Journal of Neurochemistry March 12, 2021 DOI: 10.1111/jnc.15348 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Review Peer reviewed |
|---|---|
| Topics | MDMA Serotonin |
| Keywords | Amphetamine 5-HT Receptor Pharmacology Neurotransmission Dopaminergic Hallucinogen Neurotransmitter Inhibitory postsynaptic potential |
| Citations | 47 |
| Key findings | Serotonin inhibits the acquisition of MDMA self-administration, while dopamine is critical for its maintenance in laboratory animals. |
Abstract
Abstract Methylenedioxymethamphetamine (MDMA) is an amphetamine analogue that preferentially stimulates the release of serotonin (5HT) and results in relatively small increases in synaptic dopamine (DA). The ratio of drug‐stimulated increases in synaptic DA, relative to 5HT, predicts the abuse liability; drugs with higher DA:5HT ratios are more likely to be abused. Nonetheless, MDMA is a drug that is misused. Clinical and preclinical studies have suggested that repeated MDMA exposure produces neuroadaptive responses in both 5HT and DA neurotransmission that might explain the development and maintenance of MDMA self‐administration in some laboratory animals and the development of a substance use disorder in some humans. In this paper, we describe the research that has demonstrated an inhibitory effect of 5HT on the acquisition of MDMA self‐administration and the critical role of DA in the maintenance of MDMA self‐administration in laboratory animals. We then describe the circuitry and 5HT receptors that are positioned to modulate DA activity and review the limited research on the effects of MDMA exposure on these receptor mechanisms. image
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 26
- The Psychedelic Future of Post-Traumatic Stress Disorder Treatment Current Neuropharmacology January 5, 2024
- Pilot study suggests DNA methylation of the glucocorticoid receptor gene (NR3C1) is associated with MDMA-assisted therapy treatment response for severe PTSD Frontiers in Psychiatry February 6, 2023
- Role of the gut-brain axis via the subdiaphragmatic vagus nerve in stress resilience of 3,4-methylenedioxymethamphetamine in mice exposed to chronic restrain stress. Neurobiology of Disease December 1, 2023
- Ayahuasca blocks ethanol preference in an animal model of dependence and shows no acute toxicity Journal of Ethnopharmacology November 22, 2021
- The mechanistic divide in psychedelic neuroscience: An unbridgeable gap? Neurotherapeutics January 25, 2024
and 21 more in the library
Cites 50
- Control of Serotonergic Function in Medial Prefrontal Cortex by Serotonin-2A Receptors through a Glutamate-Dependent Mechanism Journal of Neuroscience December 15, 2001
- Mood and cognitive effects of ± 3,4‐methylenedioxymethamphetamine (MDMA, ‘ecstasy’): week‐end ‘high’ followed by mid‐week low Addiction July 1, 1997
- Carrier‐Mediated Release of Serotonin by 3,4‐Methylenedioxymethamphetamine: Implications for Serotonin‐Dopamine Interactions Journal of Neurochemistry 1996
- Chronic tolerance to recreational MDMA (3,4-methylenedioxymethamphetamine) or Ecstasy Journal of Psychopharmacology 2005
- Human psychobiology of MDMA or ‘Ecstasy’: an overview of 25 years of empirical research Human Psychopharmacology: Clinical and Experimental July 1, 2013
and 45 more in the library