The Effects of Drugs of Abuse on ABC Transporters

ATP-binding cassette (ABC) transporters are a superfamily of integral membrane proteins located in several places in the human body, including the blood-brain barrier (BBB), and are involved in substrate translocation and tissue protection from harmful substances, including drugs of abuse. A growing body of evidence indicates that the ABC transporters are involved in clinically relevant actions of drugs of abuse, including their primary subjective effects, adverse effects, drug resistance, and drug-drug interactions. Moreover, evidence suggest that drugs of abuse can alter the function and/or expression of these transporters, meaning that ABC transporters influence the distribution of these drugs to the CNS. Opioids, cannabinoids, stimulants, and other classes of abused drugs interact with ABC transporters in various ways. Although there is clearly evidence for a role of ABC transporters in the actions of drugs of abuse, and potentially in drug dependence, the relationship between ABC transporters and drugs of abuse remains understudied and underappreciated. In this chapter, pre-clinical and clinical studies demonstrating the interaction of ABC transporters with drugs of abuse will be explored, with emphasis on their effects on the expression and function of ABC transporters.