Psychedelic and substance-assisted therapies are attracting renewed scientific, clinical, and public interest as potential interventions for mental health disorders, particularly treatment-resistant depression, post-traumatic stress disorder, and substance use disorders. However, as the field moves from early efficacy trials toward clinical implementation, major questions remain regarding therapeutic mechanisms, psychological support models, safety, ethics, accessibility, and the role of subjective experience. This editorial introduces the Brain and Behavior special issue "Psychedelics in Mental Health: Opportunities and Challenges," which brings together empirical studies, reviews, clinical perspectives, a case report, and commentaries addressing these emerging priorities. Across the special issue, a central theme is that psychedelic therapy cannot be understood as a pharmacological intervention alone. Contributions highlight the importance of therapeutic relationships, preparation, integration, music, touch, external therapist involvement, peer support, cultural context, and patient expectations in shaping outcomes. Several manuscripts examine the phenomenology of psychedelic and ketamine experiences, emphasizing that subjective meaning-making, expectancy, and altered states are not incidental features but potentially central aspects of therapeutic change and clinical risk. Other articles consider implementation challenges, including models of care for veterans, the perspectives of peer support workers, global mental health equity, and culturally responsive access. Mechanistic and translational work further broadens the field by examining neuroplasticity, rapid-acting interventions for suicidality, and developmental perspectives on psychedelic use. Collectively, the articles in this special issue illustrate a field at an important inflection point. Psychedelic research requires greater conceptual precision, careful attention to safety and consent, and implementation frameworks that prioritize equity and cultural appropriateness. The promise of psychedelics in mental health lies not only in their potential for rapid symptom reduction, but also in their capacity to challenge and expand prevailing models of therapeutic change, integrating biological, psychological, relational, cultural, and systems-level perspectives on healing.
