Lysergic acid amide (LSA) from Argyreia nervosa seeds, often considered a natural substitute for LSD, shows weak psychedelic activity and should not be regarded as LSD-like. Computer models predicted LSA has highest affinity for α1A and α1B receptors, with clear affinity for several serotonin and dopamine receptors. In lab tests, LSA had lower binding affinities than LSD for all tested receptor subtypes, but showed clear affinity for 5-HT1A, 5-HT2, and α2 receptors. Other ergotalkaloids in the plant also prefer serotonin and dopamine receptors. Vegetative and psychotropic effects may arise from serotonin or dopamine receptor activation, but the psychedelic effect is weak.
A new synthetic method produces 4-hydroxytryptamines (the chemical family that includes psilocin and psilocybin) with high versatility for exploring how changes to the nitrogen atom affect biological activity. The approach uses a stable precursor and mild conditions to create sterically hindered, chiral, and electron-deficient variants, including close relatives of iprocin. Testing these compounds on serotonin receptors 1A and 2A revealed that adding bulkier groups to the nitrogen lowers affinity for the 5-HT2A receptor, while azetidinyl tryptamines with a terminal aryl group show remarkably high affinity.