“…Sex differences are also apparent in the pharmacokinetic, metabolic, and analgesic effects of oxycodone (Chan et al, 2008;Holtman and Wala, 2006;Neelakantan et al, 2015) , and subtle differences have been observed in the liability for opioid abuse (Collins et al, 2016;Mavrikaki et al, 2017) . Therefore animal studies show that, relative to males, females self-administer more opioids, are more vulnerable to their reinforcing effects, and become more physically dependent, (Alexander et al, 1978;Boyer et al, 1998;Cicero et al, 2003Cicero et al, , 2002aGraziani and Nisticò, 2016b;Hadaway et al, 1979;Lofwall et al, 2012;Lynch, 2018;Lynch et al, 2002;Serdarevic et al, 2017) . In our work presented here, when rats were given a choice between a water bottle and an oxycodone-containing bottle, both sexes readily drank oxycodone and escalated their intake, but females self-administered twice as much oxycodone by body weight as did males, with a resultant five-fold increase in blood levels.…”