In a double-blind, placebo-controlled trial, 16 adults with subthreshold PTSD symptoms and early life trauma but no current psychiatric disorders were given 120 mg of MDMA or placebo. Participants were split into two groups based on baseline brain activity in the amygdala in response to nonconscious threat cues: those with high amygdala reactivity (NTNA+) and those with low reactivity (NTNA-). MDMA, compared with placebo, reduced activity in the amygdala and subgenual anterior cingulate cortex (sgACC), increased connectivity between the sgACC and amygdala, and increased liking of threatening facial expressions, but only in the NTNA+ subgroup. These findings suggest that baseline neural circuit profiles can identify who may benefit most from MDMA therapy and point to possible biomarkers for personalized treatment.
High-grade gliomas integrate into serotonergic circuits via dorsal and median raphe projections, which drive calcium-mediated proliferation. Psilocybin, a serotonergic psychedelic selective for 5-HT2A with activity at TrkB, significantly increased proliferation in glioblastoma and DMG xenografts after a single dose, with effects persisting for at least two weeks. Calcium transients in glioma cells appeared within 30 minutes and remained detectable for two weeks. Genetic knockout of 5-HT2A nearly abolished psilocybin-induced proliferation, while TrkB knockout partially reduced it. These findings indicate that psilocybin promotes sustained glioma growth primarily through 5-HT2A activation, with a modulatory role for TrkB, suggesting caution for clinical use in brain tumor patients.