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A laboratory-scale up-flow anaerobic sludge blanket (UASB) reactor was deployed in this study to examine the relationship between pharmaceutical compounds and anaerobic process performance. The reactor successfully biotransformed up to 87–99% of psychostimulant caffeine, anti-diabetic drug gliclazide, and anti-hypertensive drug prazosin during 92 days of operation. At the same time, fluctuations were recorded for the methane gas production, and also the domination of acetic acid and propionic acid in the presence of pharmaceutical compounds was measured. The results from 16s rRNA sequencing revealed that these compounds stimulated the growth of hydrogenotrophic methanogens, mainly Methanobrevibacter and Methanobacterium, while shifting the compositions of hydrolytic and fermentative bacteria. These outcomes proved the capability of the pharmaceutical compounds to influence the …