Psychedelic-assisted psychotherapy may work by reducing activity and functional connectivity within the default-mode network (DMN), a brain system linked to self-referential thought and rumination. The review suggests that psychedelics like psilocybin and LSD temporarily disrupt DMN integrity, allowing for a more flexible, less rigid pattern of brain activity that could help patients break out of maladaptive thought patterns. This neural change is proposed as a key indicator of therapeutic effectiveness for conditions such as depression, anxiety, and addiction. The authors call for further research to confirm the causal relationship between DMN modulation and clinical outcomes.
Endogenous N,N-dimethyltryptamine (DMT) is a naturally occurring psychedelic compound with unique biological and physiological properties that may influence nervous system function. The review describes DMT's biosynthesis, metabolism, and interactions with receptors, particularly sigma-1 and trace amine-associated receptors, beyond its well-known action at serotonin 5-HT2A receptors. It discusses DMT's potential roles in neuroplasticity, neuroprotection, and modulation of consciousness, as well as its possible involvement in endogenous states such as dreaming, near-death experiences, and psychosis. The authors suggest that DMT may act as a neurotransmitter or neuromodulator with effects on cognitive and emotional processes, highlighting its therapeutic potential for neurodegenerative and psychiatric disorders.