Should we skip the trip? Clinical implications of psychedelic-associated subjective effects and the potential role of non-hallucinogenic alternatives.

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.

Study at a glance

Abstract

The resurgence of interest in classical psychedelics brings both promise and challenges to psychiatric care. Increasing evidence supports the therapeutic potential of psychedelics for a range of mental health conditions, and approval for clinical use appears inevitable. The psychedelic-associated acute subjective experience may mediate or enhance therapeutic outcomes, but also presents significant clinical challenges. This review explores the role of psychedelic-associated subjective effects in psychiatric treatment, including their phenomenology, therapeutic benefit, potential risks, and challenges for implementation. We also explore emerging research on nonhallucinogenic psychedelic analogues that may retain neuroplastic effects while minimizing or eliminating the acute subjective effects. We argue that a debate over the necessity of acute subjective effects of psychedelics may be avoidable and that clinical psychiatry warrants space for both perspectives. Future research should continue to explore the clinical implications of psychedelic-associated subjective experience, while also exploring alternative compounds that broaden the breadth of treatment options for patients.