Time to embrace the whole: considering the replacement of psilocybin with Psilocybe spp. in psychedelic research and therapy

Psilocybin, the main psychoactive compound in Psilocybe cubensis mushrooms, has gained considerable attention for its therapeutic potential. Current research focuses only on isolated psilocybin, neglecting the broader pharmacological and cultural use of the whole mushroom. This perspective advocates for an integrative approach that includes standardised P. cubensis extracts within the psychedelic research agenda. We review preclinical studies comparing whole-mushroom extracts with pure psilocybin, showing enhanced or distinct effects on synaptic proteins, metabolomic profiles, and behavioural outcomes, including in models of depression and obsessive-compulsive disorder. Furthermore, the use of whole extracts may promote more affordable, equitable, and publicly accessible treatment models, in contrast to high-cost synthetic psilocybin formulations. This article argues for the urgent need to explore whole-mushroom therapeutics, ensuring that decisions in psychedelic medicine are based on a full spectrum of evidence rather than solely on pharmaceutical feasibility.