Liquid, gel, and semi-solid compositions containing naloxone base, or isomers or derivatives thereof, with one or more non-aqueous solvents, and optional viscosity adjusting agents, are provided. Methods of treating an individual exhibiting symptoms of respiratory depression associated with known or suspected opioid overdose including administering a liquid, gel, or semi-solid formulation containing a solution of naloxone base, or an isomer or a derivative thereof, in one or more non-aqueous solvents, are also provided.