Epigenetic pharmacotherapy for substance use disorder

Abstract

Identifying novel therapeutics for the treatment of substance use disorder (SUD) is an area of intensive investigation. Prior strategies that have attempted to modify one or a few neurotransmitter receptors have had limited success, and currently there are no FDA-approved medications for the treatment of cocaine, methamphetamine, and marijuana use disorders. Because drugs of abuse are known to alter the expression of numerous genes in reward-related brain regions, epigenetic-based therapies have emerged as intriguing targets for therapeutic innovation. Here, I evaluate potential therapeutic approaches and challenges in targeting epigenetic factors for the treatment of SUD and highlight examples of promising strategies and future directions.

Keywords: Addiction; Cocaine; Epigenetics; Substance use disorder; Therapeutics.

Figure 1:. Timeline of milestones in SUD treatments and epigenetics.

(Top) Relatively few FDA-approved treatments for SUD are currently available, and most treatments target neurotransmitter receptors. There are no FDA-approved medications for cocaine, methamphetamine, and cannabis use disorders. (Bottom) The majority of histone and DNA-modifying proteins were identified in the last few decades. Multiple epigenetic-based therapies have received FDA-approval in recent years for the treatment of cancer, but there are currently no FDA-approved, epigenetic-related treatments for SUD. AUD, alcohol use disorder; FDA, Food and Drug Administration; HATs, histone acetyltransferases; HDACs, histone deacetylases; HMTs, histone methyltransferases; NUD, nicotine use disorder; OUD, opioid use disorder.