Entry 1 sense Webster, 1913 mainline /(mān"līn`)/ · main·line · IPA /ˈmeɪnˌlaɪn/ 01 v. t. to inject (illegal drugs) into the vein; as, he preferred to mainline heroin rather than sniff coke. 1. to inject (illegal drugs) into the vein; as, he preferred to mainline heroin rather than sniff coke.