Dissociative experiences from ketamine, often seen as undesirable side effects, may be essential for its antidepressant action in certain depression subtypes. The 'relaxed prior hypothesis' proposes that ketamine enhances sensitivity to bodily signals by blocking glutamate, improving short-term plasticity. Two patients with 'depersonalized depression' (Entfremdungsdepression) in a six-month esketamine program showed that induced dissociation, particularly disembodiment, could suspend ingrained patterns of feeling and behavior. This creates a window of psychological plasticity, allowing the body to regain responsiveness to emotional cues. The findings suggest esketamine's dissociative effects may be especially beneficial for those with compromised interoceptive awareness and interaffectivity.
Psychotherapeutic change can be modeled using biophysical principles from synergetics and the free energy principle. Introducing sensory surprise into the patient-therapist system may trigger self-organization and the formation of new attractor states, disrupting entrenched patterns of thoughts, emotions, and behaviors. The therapist can facilitate this by cultivating epistemic trust and modulating embodied attention, allowing surprising affective states into shared awareness. Transient increases in free energy enable updates to generative models, expanding the phenomenal field. Increased entropy, complexity, and lower determinism at behavioral and physiological levels are proposed as markers and predictors of therapeutic gains. Future research should explore how the therapist's openness to novelty shapes outcomes.