A single 1 mg/kg dose of psilocybin did not alter decision-making in probability or delay discounting tasks and did not reduce motivation in a progressive ratio task in healthy male and female rats. Psilocybin did produce the expected increase in head twitch responses, confirming the drug was pharmacologically active. These results suggest psilocybin may not impair or improve reward-based decision-making or motivation, indicating that its therapeutic effects in mental health disorders may not involve changes to brain systems underlying reward and decision-making. The findings also imply that widespread cognitive impairments may not occur even with chronic psilocybin treatment.
Psilocybin, the prodrug to the psychoactive compound in 'magic' mushrooms, is being studied as a treatment for depression and anxiety. Previous biosynthesis in E. coli using genes from Psilocybe cubensis achieved maximum titers of 1.16 g/L. This work tested genes from four psilocybin-producing mushroom species and found that psiD and psiK from P. cubensis performed best, while psiM from Psilocybe cyanescens increased selectivity for the intermediate baeocystin. The strain Gymdi30, with psiM from Gymnopilus dilepis, produced 1.46 ± 0.13 g/L psilocybin, the highest reported titer to date. Comparative proteomic analysis during high and low productivity identified metabolic bottlenecks. This represents a significant improvement toward a biosynthetic manufacturing route for psilocybin.