How Psychedelics Work

There is now extensive evidence that serotonin 5-HT2A receptor acting psychedelic drugs such as psilocybin LSD and DMT work by producing a profound disruption of ongoing oscillatory activity in the brain. This disrupts the segregation of key brain networks and leads to increased crosstalk between them. in this state of increased disorder [entropy] abnormal thinking processes such as rumination that underpin disorders such as depression and addiction become temporally disrupted allowing the patient to “escape” from them. also the increased connectivity allows the person to discover new insights in their past and develop new thoughts about the future which can endure well after the trip is over. this prolonged benefit can be accentuated by psychotherapy and also by the serotonin receptor stimulation that in rodent models can be shown to increase dendrite growth and  synaptogenesis. Our recent neuroimaging studies of depressed patients recovering after psilocybin treatment reveals that the increased connectivity seen during the trip persists for weeks afterwards and is associated with increased flexibility of brain function, an outcome not seen with traditional antidepressant treatments. We think this increased flexibility may explain the experiences of increased connectedness with the world that patients often report and the improved wellbeing scores they register.