Recent reports suggest co-administration of high doses of ethanol with controlled release opioid formulations may break down the controlled release matrix resulting in the sudden release of high doses of the opioid. This study evaluated the effects of ethanol on the safety, PD, and PK of a morphine oral solution in opiate naïve, moderate drinkers. This was a restricted-randomized, double blind, cross-over, placebo controlled study. In part 1, twelve subjects received immediate release (IR) morphine 50 mg alone, ethanol 20% (0.7 g/kg) alone and (IR) morphine 50 mg with ethanol 20% (0.7 g/kg). Therefore, the study emulated the worst case scenario of dose dumping. In part 2, ten subjects who had tolerated part 1 treatments, received IR morphine 80 mg alone and with ethanol 20% (0.7 g/kg). Subjects completed PD assessments (VASs, Pupillometry, Capnography, Choice Reaction Time, Digit Symbol Substitution Test and Divided Attention Task) using validated computerized tests (SMS, Ventana Clinical Research Corp). PD data and PK samples were collected over 8 hours post dosing. Except for VAS for Intoxication, none of the PD measures distinguished between the effects of morphine alone and morphine co-administrated with ethanol. Pupillometry was a sensitive measure of morphine effect and was unaltered by ethanol co-administration. The PK of morphine and its metabolites were unaffected by the co-administration of ethanol. No severe adverse events (AEs) were reported. Administration of morphine alone and with ethanol induced AEs of moderate intensity or less. No clinically relevant decreases in vital signs or oxygen saturation were observed. The results of this study indicate that at the doses administered pharmacodynamic or pharmacokinetic interactions between ethanol and morphine are rather limited and of minimal clinical importance. In vitro effects of ethanol on dissolution of morphine formulations do not substitute for clinical interaction studies to establish the actual risk in humans.