The present invention is based, in part, on flagellin adjuvants that enhance immune responses directed against drugs of abuse. Provided are conjugates comprising a flagellin adjuvant covalently linked to a drug of abuse or an immunologically similar derivative thereof. Also provided are methods of making the conjugates of the invention and use thereof for administration to a subject, e.g., to produce an immune response in the subject against the drug of abuse, to prevent addiction to the drug of abuse in the subject, to reduce the effect of the drug of abuse in the subject, to reduce the level of the drug of abuse in the brain of the subject, and/or to reduce the addiction in the subject to the drug of abuse.