There are almost 1000 species of Acacia sensu stricto in Australia, while the 44 species and 4 subspecies in southern Africa were taxonomically revised in the year 2011 to Senegalia and Vachellia. There are rumors of a chemical similarity between the Australian Acacia and their southern African sister genera. Chemical analysis has unequivocally demonstrated the presence of tryptamines (i.e., DMT), β-carbolines, histamines, and phenethylamines in Australian species. However, reliable published data were not found in support of similar alkaloids in southern African (or even African) species, indicating the need for exploratory phytochemical analysis. Interestingly, the Australian species are more like the Vachellia and Senegalia from the Americas. While many reliable chemical studies have been found, there are several more that report only tentative results. Tentative data and anecdotal accounts are included in the current review to guide researchers to areas where further work can be done. For example, the current review encourages further phytochemical work to confirm if the two metabolite families, tryptamine and β-carboline alkaloids, occur together in a single specimen. Tryptamines and β-carbolines are the prerequisite ingredients of the South American psychotropic drink ayahuasca, which utilizes two different species to create this synergistic combination. These observations and others are discussed in light of geochemical variability, the potential ethnobotanical implications, and the need for further research to confirm or nullify anecdotal reports and tentative chromatographic/spectroscopic data in southern African species. Keywords: dimethyltryptamine (DMT); 5-methoxydimethyltryptamine; tryptamine; phenethylamine; psychopharmacology.