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.
Ketamine, a drug used for depression and anesthesia, causes dose-dependent increases in dissociation and intoxication, reduces emotional insensitivity, and raises stress as measured by cortisol. It alters brain connectivity, particularly between reward and negative affect circuits and thalamic sub-regions. Increased coupling between the amygdala and anteroventral thalamus correlates with greater dissociation and intoxication, while decreased coupling of anteromedial and posterior parietal thalamus correlates with increased sensory reward responsiveness. Drug-altered connectivity involving the nucleus accumbens and thalamic sub-regions shows negative associations with anxiety. These findings help disentangle the brain states underlying ketamine's acute effects, informing its therapeutic use and abuse risk.