MDMA, better known as ecstasy, molly, or one of a number of other street names, is a stimulant drug with unique prosocial effects. In this video, I discuss the current understanding of how MDMA acts on the brain to produce its effects.

TRANSCRIPT:

MDMA, better known as ecstasy, molly, or one of a number of other street names, is a stimulant drug that is chemically related to amphetamine. Like other stimulants, MDMA causes increased alertness and a positive mood. But MDMA’s effects are also distinct from the effects of other stimulants, as the drug causes unique prosocial effects such as strong feelings of trust, openness, and closeness with others.

Although we don’t have a full understanding of the effects of MDMA on the brain, MDMA’s mechanism is similar in many ways to the mechanism of other amphetamines. MDMA inhibits the function of proteins called transporter proteins, which typically remove neurotransmitters like serotonin, dopamine, and norepinephrine from the space between neurons known as the synaptic cleft. By inhibiting transporter proteins, MDMA causes serotonin, dopamine, and norepinephrine to accumulate in the synaptic cleft, increasing neurotransmitter activity there. In contrast to other amphetamines, MDMA inhibits the serotonin transporter more potently than the dopamine or norepinephrine transporter. MDMA also uses transporter proteins to enter neurons; once inside, MDMA disrupts the storage of neurotransmitters in synaptic vesicles, causing the buildup of serotonin, dopamine, and norepinephrine inside neurons; then, MDMA facilitates the release of these neurotransmitters into the synaptic cleft, leading to increased neurotransmitter levels and activity. In addition to these mechanisms, MDMA also binds to a number of receptors directly, including specific subtypes of the serotonin receptor; these interactions may contribute to the effects of MDMA.

It’s not clear what mechanism accounts for the unique prosocial effects of MDMA. A number of studies have found that MDMA promotes the release of the hormone oxytocin, which itself has been linked to prosocial effects. At the same time, most studies have failed to find a link between increasing oxytocin levels and the prosocial effects of MDMA, leaving these effects still unexplained.


REFERENCES:

Dunlap LE, Andrews AM, Olson DE. Dark Classics in Chemical Neuroscience: 3,4-Methylenedioxymethamphetamine. ACS Chem Neurosci. 2018 Oct 17;9(10):2408-2427. doi: 10.1021/acschemneuro.8b00155. Epub 2018 Jul 12. PMID: 30001118; PMCID: PMC6197894.

Oeri HE. Beyond ecstasy: Alternative entactogens to 3,4-methylenedioxymethamphetamine with potential applications in psychotherapy. J Psychopharmacol. 2021 May;35(5):512-536. doi: 10.1177/0269881120920420. Epub 2020 Sep 10. PMID: 32909493; PMCID: PMC8155739.

Schenk S, Highgate Q. Methylenedioxymethamphetamine (MDMA): Serotonergic and dopaminergic mechanisms related to its use and misuse. J Neurochem. 2021 Jun;157(5):1714-1724. doi: 10.1111/jnc.15348. Epub 2021 Mar 25. PMID: 33711169.