Midomafetamine

Overview

An N-substituted amphetamine analog. It is a widely abused drug classified as a hallucinogen and causes marked, long-lasting changes in brain serotonergic systems. It is commonly referred to as MDMA or ecstasy. It is a widely abused drug classified as a hallucinogen and causes marked, long-lasting changes in brain serotonergic systems.

Mechanism of Action

It enters neurons via carriage by the monoamine transporters. Once inside, MDMA inhibits the vesicular monoamine transporter, which results in increased concentrations of serotonin, norepinephrine, and dopamine into the cytoplasm, and induces their release by reversing their respective transporters through a process known as phosphorylation. It also acts as a weak 5-HT1 and 5-HT2 receptor agonist. MDMA's unusual entactogenic effects have been hypothesized to be, at least partly, the result of indirect oxytocin secretion via activation of the serotonin system. Oxytocin is a hormone released following events like hugging, orgasm, and childbirth, and is thought to facilitate bonding and the establishment of trust. Based on studies in rats, MDMA is believed to cause the release of oxytocin, at least in part, by both directly and indirectly agonizing the serotonin 5-HT1A receptor.

Indications

MDMA-assisted therapy was investigated in Phase 3 clinical trials (MAPP1 and MAPP2) for post-traumatic stress disorder (PTSD). In August 2024, the FDA rejected the NDA submitted by Lykos Therapeutics, citing functional unblinding as a core evidentiary concern and requesting an additional Phase 3 trial. MDMA has also been studied for anxiety associated with terminal cancer. MDMA is one of the four most widely used illicit drugs in the U.S.

• Post-traumatic stress disorder