Biologics to treat substance use disorders: Current status and new directions.

Biologics (vaccines, monoclonal antibodies (mAb), and genetically modified enzymes) offer a promising class of therapeutics to treat substance use disorders (SUD) involving abuse of opioids and stimulants such as nicotine, cocaine, and methamphetamine. In contrast to small molecule medications targeting brain receptors, biologics for SUD are larger molecules that do not cross the blood-brain barrier (BBB), but target the drug itself, preventing its distribution to the brain and blunting its effects on the central nervous system (CNS). Active and passive immunization approaches rely on antibodies (Ab) that bind drugs of abuse in serum and block their distribution to the brain, preventing the rewarding effects of drugs and addiction-related behaviors. Alternatives to vaccines and anti-drug mAb are genetically engineered human or bacterial enzymes that metabolize drugs of abuse, lowering the concentration of free active drug. Pre-clinical and clinical data support development of effective biologics for SUD.