Depression involves disrupted communication between the frontal cortex and striatum. In 48 patients with treatment-resistant depression, those with lower baseline connectivity in these circuits showed greater symptom improvement after a single low-dose (0.2 mg/kg) ketamine infusion, but not after a higher dose (0.5 mg/kg) or placebo. Reduced connectivity between the superior frontal cortex and striatum predicted treatment response. Patients had weaker frontostriatal connections than healthy controls.
Chronic MDMA use damages serotonin transporters (SERT) in the brain, which is linked to addiction and impaired decision-making. In rats, the cough suppressant dextromethorphan (DM) partially reversed this damage: co-administration with MDMA restored SERT binding by about 23% after 14 days compared to MDMA alone. Behavioral tests showed that MDMA-induced reward and hyperactivity were associated with lower SERT activity, and DM helped restore both SERT levels and serotonin fiber density. The findings suggest DM may protect against MDMA's neurotoxic effects on the brain's reward and motivation circuits.