It is native to Kansas, Oklahoma, and Texas and has spread to Missouri and New Mexico.

[4] Desmanthus leptolobus grows easily from seed in USDA Hardiness Zones 5–8, handling freezes to ~-20 °C.

[5] Seeds are thinner and more elongated than those of the closely related species Desmanthus illinoensis.

[6] Root bark of D. leptolobus has been found to contain a psychedelic compound called DMT and other related tryptamines.

While its only reported quantitative analysis found concentrations of 0.14% of DMT (lower than has been found in Desmanthus illinoensis), one person documented a "subjectively stronger response" than D.