Prodrugs as Treatments for Cannabis Use Disorder: N-Acetylcysteine as a Case Example

Abstract

An important strategy for pharmacotherapy research is the development of prodrugs. These precursor compounds undergo in vivo transformation to pharmacologically active agents and offer the prospect for improved stability, absorption, and/or penetration when limitations exist in the pharmacokinetics of the active compounds. To date, only one prodrug has been extensively researched as a candidate treatment for cannabis use disorder (CUD). N-acetylcysteine (NAC), a prodrug of the amino acid cysteine, was shown in animal models to reduce drug seeking and reinstatement. This led to human laboratory and clinical trials research to examine NAC as a candidate pharmacotherapy for substance use disorders. Specific to CUD, large-scale randomized controlled trials have been conducted among adolescents and adults, and ongoing work aims to elucidate NAC’s optimal role CUD treatment. An overview of research to date on NAC for CUD is summarized in this chapter and offered as an example to inform the development of other prodrugs to treat CUD.