A journey with psychedelic mushrooms: From historical relevance to biology, cultivation, medicinal uses, biotechnology, and beyond

Psychedelic mushrooms that contain psilocybin and related tryptamines have a long history of traditional use, and recent evidence suggests they may have therapeutic value for neurological and psychiatric disorders. This review covers the diversity and distribution of these mushrooms, methods for quantifying tryptamines and related metabolites, and the biosynthetic pathways that produce them. It also describes how psilocybin and related tryptamines are metabolized in humans and their pharmacological effects, including both beneficial and hazardous health implications. The authors discuss opportunities for using biotechnology and machine learning to engineer mushroom secondary metabolite profiles and outline a roadmap for future research.

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Abstract

Psychedelic mushrooms containing psilocybin and related tryptamines have long been used for ethnomycological purposes, but emerging evidence points to the potential therapeutic value of these mushrooms to address modern neurological, psychiatric health, and related disorders. As a result, psilocybin containing mushrooms represent a re-emerging frontier for mycological, biochemical, neuroscience, and pharmacology research. This work presents crucial information related to traditional use of psychedelic mushrooms, as well as research trends and knowledge gaps related to their diversity and distribution, technologies for quantification of tryptamines and other tryptophan-derived metabolites, as well as biosynthetic mechanisms for their production within mushrooms. In addition, we explore the current state of knowledge for how psilocybin and related tryptamines are metabolized in humans and their pharmacological effects, including beneficial and hazardous human health implications. Finally, we describe opportunities and challenges for investigating the production of psychedelic mushrooms and metabolic engineering approaches to alter secondary metabolite profiles using biotechnology integrated with machine learning. Ultimately, this critical review of all aspects related to psychedelic mushrooms represents a roadmap for future research efforts that will pave the way to new applications and refined protocols.