The intersection between psychedelics and schizophrenia spectrum disorders: Reevaluating risk and therapeutic potential.

Summary

Psychedelic compounds have gained renewed interest as potential therapies, but their relationship with psychosis and schizophrenia spectrum disorders (SSDs) requires further understanding. This review discusses the historical ties between psychedelics and SSDs, highlighting both similarities and differences in experiences. While psychedelics can worsen existing psychotic conditions or trigger psychosis in susceptible individuals, there may be therapeutic potential for specific symptoms in stable patients using low doses. Recommendations for managing psychosis-related risks are also provided.

Study at a glance

Abstract

In the past decade, interest in studying psychedelic compounds as potential therapeutic agents has resurged. These studies carefully exclude individuals at risk for developing psychotic symptoms in response to psychedelic use. Given the potential for psychedelics to be established as treatments in psychiatry, it is important to more robustly understand their link with psychosis and schizophrenia spectrum disorders (SSDs). In this narrative review, we examine the historical and theoretical relationship between psychedelic drugs and SSDs, including the origins of the psychotomimetic hypothesis. For key psychedelic compounds, we review their phenomenological manifestations in relation to the experiential alterations characteristic of SSDs, revealing both areas of overlap and important qualitative differences that challenge the uniform psychotomimetic classification. We also review putative neural mechanisms underlying altered experiential states associated with psychedelic use and SSDs, with attention to serotonergic, dopaminergic, and glutamatergic contributions. Clinical evidence demonstrates that psychedelics can exacerbate pre-existing psychotic illness and may trigger psychosis in vulnerable individuals, though the magnitude of these risks remains inadequately quantified. However, phenomenological and mechanistic distinctions suggest that potential therapeutic applications may exist for carefully selected symptoms (negative symptoms, depression) in stable patients using low-dose, controlled approaches. Based on published work, we provide recommendations regarding psychosis-related risk and potential avenues for the treatment of SSDs as psychedelics gain traction as therapeutics.

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