The presently disclosed subject matter provides solid, oral, extended release, pharmaceutical particulate and multi-particulate dosage forms with abuse deterrent and overdose protection features / characteristics comprising at least one or two populations of particulates. In certain embodiments, the first population of particulates comprises a therapeutically effective amount of at least one opioid embedded in a polymer matrix, a primary functional coat layer (FC 1), a secondary functional coat layer (FC 2), and an over coat； wherein FC 1 comprises a nonionic water-insoluble polymer and, optionally, at least one of a cationic polymer, a nonionic water-soluble polymer, and a water-soluble plasticizer； FC 2 comprises a cationic polymer and, optionally, a nonionic water- insoluble polymer； and the over coat comprises a nonionic water-soluble polymer. The second population of particulates comprises an alkaline agent and, optionally, a pH- stabilizing agent. In certain embodiments, the extended release pharmaceutical dosage form contains at least three different populations of multi-particulates. Each population of particulates is designed for a specific function to accomplish the desired combination of abuse deterrence and overdose protection. The presently disclosed subject matter also provides methods related to the solid, oral, extended release, particulate and multi-particulate dosage forms.
