Mistuning of synaptic transmission may contribute to psychiatric disorders. Inhibiting glutamate transporters in hippocampal slices caused synaptic retuning, reducing synaptic strength and lowering the threshold for long-term potentiation (LTP). A rat model of depression with decreased glutamate transporters also showed a reduced LTP threshold. The antidepressant ketamine counteracted the effects of increased glutamate on synaptic retuning, suggesting its mechanism of action is restoring adequate synaptic tuning.
Psychedelic therapies face layered complexity from interactions between pharmacological and extra-pharmacological factors, and their embeddedness in societal, legal, and regulatory systems. This is compounded by epistemic fragmentation: dominant biomedical paradigms often clash with knowledge from social sciences, humanities, or Indigenous traditions. Though interdisciplinary engagement is increasingly recognized as necessary, existing calls rarely specify structural or pedagogical conditions for operationalizing it. Addressing these complexities requires moving beyond superficial collaboration; genuine interdisciplinary progress needs researchers capable of productive friction across epistemic cultures. The authors propose cultivating T-shaped competencies and intersectoral training as a structural response to these systemic challenges.