Background: Methylenedioxymethamphetamine (MDMA) is widely consumed as are creational psychoactive substance, and its ability to induce persistent or irreversible injury to serotonergic axons has raised major public health concerns. Identifying agents capable of reducing or reversing MDMA-related neurotoxicity is therefore essential. This study evaluated the protective and restorative effects of Moringa oleifera aqueous leaf extract on MDMA-induced neuronal damage within the prefrontal cortex.

Materials and Methods: Thirty adult male Wistar rats were randomly assigned into five groups (n = 6) and treated for 14 consecutive days. Group A served as the untreated control; Group B received M. oleifera extract alone (200 mg/kg); Group C received only MDMA (5 mg/kg); Group D was administered MDMA for days 1–7 followed by M. oleifera for days 8–14; and Group E received MDMA in the morning (5 mg/kg) and M. oleifera in the evening (200 mg/kg). After treatment, brains were excised, weighed and the prefrontal cortex was sectioned for histological and immunohistochemical evaluations.

Results: Exposure to MDMA resulted in marked neuronal injury and degeneration of myelin sheaths. Treatment with M. oleifera extract promoted structural recovery, characterized by improved neuronal integrity and remyelination.

Conclusion: Aqueous leaf extract of Moringa oleifera demonstrated both protective and therapeutic effects against MDMA-induced neurotoxicity in the prefrontal cortex, indicating its potential as a natural neuroprotective agent.