Several hundred psychoactive plants and fungi are known from different families. These produce specialized metabolites, which upon ingestion affect the function of the nervous system inducing sedative, stimulant, euphoric, deliriant or hallucinogenic effects. Several examples include cannabinoids which modulate the endocannabinoid system (eCBS); the group of serotonin 2A receptor (5-HT2AR) agonists such as psilocin, mescaline and N,N-dimethyltryptamine (DMT); the kappa opioid receptor (KOR) agonist salvinorin A; the tropane alkaloids which act as acetylcholine inhibitors; the iboga alkaloids which affect multiple neurotransmitter systems; the kavalactones which modulate γ-aminobutyric acid (GABA) receptors, and many others. In the last decade, there has been a growing revival of clinical research on the potential therapeutic benefits of these bioactive compounds for drug development. However, knowledge about the molecular and biochemical basis in the different species, along with their evolutionary significance, are largely lacking.

Today's technological advances, including efficient de novo genome sequencing, and mass spectrometry based approaches for structure elucidation and spatial metabolite mapping, concede the discovery of previously unavailable knowledge on the biochemistry of psychoactive plants. In this Research Topic, we therefore wish to include studies that will tackle uncharted metabolic pathways of specialized metabolites in psychoactive plants and fungi. This includes gene discovery by genomic and transcriptomic sequencing and metabolic identification and spatial mapping of psychoactive compounds across the species’ organs, tissues and cell types. Papers describing the synthetic biology-driven metabolic engineering of psychoactive compounds in heterologous systems will be highly encouraged, as well as those confronting the role/s that the psychoactive compounds play in the species. Given the large diversity of psychoactive compounds from different plant families, we will also welcome studies exploring the evolution and domestication of these compounds across different taxonomies.

We are most interested in manuscripts containing original research, given the low availability of this data in the scientific literature. We will also consider review papers related to biochemistry, genetics and evolution of psychoactive compounds across plant families.

We are interested in specific topics, such as:

• “omics” studies of psychoactive species: Metabolomics, transcriptomics and/or proteomics in plant-pathogen relationships, de novo assembly of psychoactive plant transcriptomes/genomes, and biosynthesis of psychoactive small molecules
• Functional characterization of co-expressed transcripts, metabolic response to environmental conditions
• Evolution: Inheritance of chemical phenotypes, breeding and domestication, synthetic biology, evolution across different taxonomies
• Metabolic characterization and spatial mapping of psychoactive small molecules and their biosynthetic pathways

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Frontiers in Plant Science

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