Figure 1.

Unified model of ketamine’s properties. Ketamine modulation of reward centres causes immediate short-term antidepressant effects which are maintained by the sub-acute increase in neuroplasticity. Depending on the dose, metabolization rate, previous exposure and context, ketamine can modify synaptic gain to cause a transitory dissociative state by inducing a relaxation of the precision weighting of ‘bodily’ self-representation priors encoded in SN nodes or a transitory psychedelic state by inducing a relaxation of the precision weighting of ‘narrative’ self-representation priors encoded in DMN nodes. The sub-acute stimulation of neuroplasticity has a permissive role for maintaining changes in self-representation which may confer long-lasting benefits.

ACC: anterior cingulate cortex; DMN: default-mode network; LHb: lateral habenula nucleus; SN: salience network.