Lysergic acid diethylamide (LSD) reduces reactivity in the left amygdala and right medial prefrontal cortex when processing fearful faces, compared to a placebo. In a double-blind, randomized, crossover study, 20 healthy adults received either 100 μg of LSD or a placebo before undergoing functional magnetic resonance imaging (fMRI). Plasma LSD levels were measured before and after the scan. A significant negative correlation emerged between the reduced amygdala response to fearful stimuli and the subjective drug effects reported by participants. These findings indicate that LSD alters the engagement of brain regions involved in emotional processing.
The acute response to MDMA (ecstasy) is shaped by both drug concentration in the blood and personal characteristics. Pooling data from 10 placebo-controlled studies with 194 healthy adults, the strongest predictor of effects was MDMA plasma level. After adjusting for dose by body weight, higher activity of the enzyme CYP2D6 predicted lower MDMA concentrations. People scoring high in openness to experience reported more closeness, less general inactivation, and stronger altered states of consciousness. Those with high neuroticism or trait anxiety were more likely to have unpleasant or anxious reactions. These findings highlight that both pharmacological and non-pharmacological factors influence MDMA's effects, which may inform its therapeutic use.