Mechanistic insights toward dissociating therapeutic from psychedelic effects: bridging the gap between psychedelic research and mental health care.

Clinical trials investigating psychedelic compounds for depression and anxiety-related disorders are yielding promising preliminary results. Psychedelics produce profound alterations in brain function-such as suppression of the default mode network and thalamocortical dysregulation-leading to intense subjective experiences including ego dissolution and mystical-type states.While often described as meaningful or therapeutic, these effects can also be unpredictable or distressing. Because of these effects, which require labor-intensive, potentially cost-challenging preparation, administration, integration sessions, and exclude individuals with psychiatric vulnerabilities (e.g., bipolar disorder, borderline personality disorder, schizophrenia), questions remain about their real-world scalability. Consequently, there is growing interest in the possibility of dissociating the therapeutic benefits of psychedelics from their consciousness-altering effects.In this perspective, we examine emerging clinical and preclinical evidence investigating this scientifically timely and pressing question. Pharmacological strategies such as serotonin 2A receptor (5-HT