Mainline/ˈmeɪnlaɪn/ Definition 1 of 4Pro Tip 1/2Drug Usage Used to describe someone injecting drugs, usually illicit substances, directly into veins. Celebrities who mainlined fell into serious health issues. Pro Tip 2/2Colloquial Warning Considered very informal and offensive in non-drug related discussions. Never use 'mainline' casually in professional settings.