Discussion
MDD
Esmethadone is a low potency uncompetitive NMDAR antagonist [HAP studies provide important data for predicting recreational use in the community and provide information for labeling and for drug scheduling under the Controlled Substances Act (CSA). In both HAP studies, all three esmethadone doses (25 mg [therapeutic], 75 mg [3x therapeutic], and 150 mg [6x therapeutic and MTD]) had meaningful and statistically significant lower scores compared with positive control (oxycodone or ketamine) on the primary endpoint of Drug Liking VAS EWe presented results for the Completer Population as indicated in the FDA 2017 Guidance [In summary, the results of these two, randomized, double-blind, active- and placebo-controlled, crossover studies testing the abuse potential of esmethadone in recreational drug users are consistent with the profile of a drug without meaningful abuse potential and are similar to results observed for unscheduled drugs without abuse potential such as eslicarbazepine and difelikefalin [Considering that MDD is a highly prevalent and life-threatening condition and available treatments have limited and delayed efficacy and metabolic and neurological side effects, an unmet need exists for safe, well-tolerated, and rapidly effective antidepressants. Patients in need should not have restricted or delayed access to potentially safe, well-tolerated, and life-saving drugs [In conclusion, the results of these two HAP studies, in accordance with results in preclinical models [