Abstract: The present invention provides genetically modified fungi, such as non-hallucinogenic psychedelic fungi, in which a biochemical pathway to produce a bioactive alkaloid is disrupted. In some aspects, the psilocybin biosynthesis pathway is disrupted, resulting in non-hallucinogenic psychedelic fungi which do not produce or contain psilocybin, or which produce or contain a substantially reduced amount of psilocybin relative to wild-type fungi. Also provided are methods of making genetically modified fungi, for example by disrupting or rebalancing a biochemical pathway therein, such as the psilocybin biosynthesis pathway, such as by using gene editing techniques, including gene inactivation by small interfering RNAs (siRNAs), microRNAs (miRNAs), and CRISPR/Cas9. Also provided are compositions of genetically modified fungi, such as compositions of non-hallucinogenic psychedelic fungi, and methods of their use, including as functional foods, nootropics, legal microdoses, nutraceuticals, and therapeutics.