Classical psychedelics show therapeutic promise for mental health conditions, but their acute subjective effects—while possibly enhancing outcomes—also pose clinical challenges. This review examines the phenomenology, benefits, risks, and implementation issues tied to these subjective experiences. Emerging research on nonhallucinogenic analogues may preserve neuroplastic benefits without inducing intense subjective effects. The authors argue that a debate over the necessity of acute subjective effects may be avoidable, and clinical psychiatry should accommodate both approaches. Future research should explore both the role of subjective experience and alternative compounds to expand treatment options.
Set and setting—the mindset a person brings to therapy and the environment in which it occurs—are foundational to MDMA-assisted therapy for PTSD and critically influence its efficacy. Drawing on experience conducting clinical trials in the Veterans Health Administration, this article describes advantages and challenges of implementing this intervention in large healthcare systems. Specific, practical suggestions are offered for optimizing set and setting from both participant and clinician perspectives, aiming to leverage opportunities and adapt to challenges. These recommendations are intended to inform future research and potential clinical implementation efforts in traditional healthcare settings.