The Sonoran Desert Toad (Incilius alvarius) is the only vertebrate known to produce the powerful psychedelic, 5-MeO-DMT, which is easily-accessible form the animal’s exterior glands. This paper seeks to present the biocultural (ecological and cultural) history, and conservation concerns of I. alvarius. Discovery of 5-MeO-DMT in I. alvarius was first reported in 1965 and 1967 (Erspamer et al.), and eventually led to the popular psychedelic use of this species after a pamphlet was published in 1984 (Most). Its mostly unmitigated use in for-profit spirituality, wellness, and adventurism has driven erroneous, coerced, and exploitive narratives of ancient Indigenous use – increasing: exploitation of I. alvarius, biocultural erosion, and malpractice of 5-MeO-DMT. Reconciliation of diverse needs is intellectually and financially challenging. It must be careful of approaches that are implicitly biased by a demand that extracts, appropriates, and trades in Indigenous and wellness motifs – but can be reached from the reconciliation and intersection of Indigenous and Western science and priorities. Few conservation-oriented studies and outreach elements concerning I. alvarius exist, and most have been supported by crowdfunding.