The role of nutrition in psychedelics clinical trials: Key considerations and recommendations for 5-methoxy-N,N-dimethyltryptamine (5-MeO-DMT)
Abstract
ABSTRACT Psychedelic compounds exhibit diverse pharmacological and clinical effects, underscoring the need for further research and the development of clear guidelines to support their safe and effective clinical use. Growing interest in psychedelics has also increased attention toward the relationship between nutrition, dietary habits, and psychiatric disorders. This narrative review presents the hypothesis that nutritional status, dietary patterns, body composition, gut microbiota, and selected food–drug interactions may influence the pharmacokinetics, pharmacodynamics, efficacy, or safety of 5-MeO-DMT. This hypothesis is based on the pharmacological properties of 5-MeO-DMT, current knowledge of serotonergic signaling, and indirect evidence from nutritional psychiatry, psychopharmacology, and preclinical research. Direct clinical evidence supporting these interactions is currently unavailable. 5-MeO-DMT exhibits its highest affinity for the 5-HT1A receptor while also interacting with 5-HT2A receptors, providing a biological rationale for investigating potential interactions between nutrition and psychedelic treatment. Rather than proposing established clinical recommendations, this review identifies biologically plausible mechanisms, summarizes the available indirect evidence, and highlights key knowledge gaps that warrant prospective investigation. We propose that incorporating standardized nutritional assessments into future clinical trials may improve the interpretation…
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