A systematic review of 12 studies examined two psychoactive compounds, psilocybin and esketamine, for treating depression. Esketamine, a laboratory-made substance, showed significant reduction in depressive symptoms and suicidal ideation shortly after intake and after one month, compared to baseline and standard antidepressants. Psilocybin, a naturally occurring psychedelic, produced antidepressant effects one day after intake and after 6–7 weeks, with benefits lasting up to 6 or 8 months. One study suggested psilocybin's effects are comparable to and may be superior to escitalopram. Both compounds demonstrated rapid and sustained effects, indicating potential as novel antidepressant agents after addressing limitations.
MDMA (ecstasy) and nicotine activate shared neuronal pathways. In male Swiss mice, a single injection of MDMA (1 mg/kg) or MDMA combined with nicotine (0.05 mg/kg) improved memory consolidation in a passive avoidance test. MDMA also increased locomotor activity in mice that had developed behavioral sensitization to nicotine. The study reports for the first time strong behavioral and biochemical interactions between the two drugs, including effects on oxidative stress and α7 nicotinic acetylcholine receptor expression in the prefrontal cortex and hippocampus. These findings may help explain why people often co-use MDMA and nicotine.