Ultrasonic and ozone pre-treatment technologies were employed in this study to improve the anaerobic digestion efficiency of pharmaceutical waste activated sludge. The sludge solubilisation achieved 30.01% (150,000 kJ/kg TS) and 28.10% (0.1 g O-3/g TS) after ultrasonic treatment and ozone treatment. The anaerobic biodegradability after ultrasonic treatment was higher compared to ozonation due to the higher cumulative methane volume observed after 6 days (249 ml vs 190 ml). The ozonated sludge released the highest concentration of Cu2+ into the liquid phase (6.640 mg L-1) compared to 0.530 mg/L for untreated sludge and 0.991 mg/L for sonicated sludge. The acute toxicity test measured by luminescent bacteria showed that anaerobic digestion could degrade toxic compounds and result in a reduction in toxicity. The main mechanism of action led to some differences in the treated sludge exhibiting higher potential for methane production from pharmaceutical waste sludge with ultrasonic treatment. (C) 2015 Elsevier Ltd. All rights reserved.