The dynorphin story – that it agonizes the kappa opioid receptor, which more or less antagonizes the mu opioid receptor, which, being where heroin et al bind, reduces addiction – continues to impress. This is a nice summary of the clinical opportunities and likely future treatment approaches.
Eduardo R. Butelman, Vadim Yuferov,Mary Jeanne Kreek. κ-opioid receptor/dynorphin system: genetic and pharmacotherapeutic implications for addiction. Trends in Neurosciences Volume 35, Issue 10, October 2012, Pages 587–596
Addictions to cocaine or heroin/prescription opioids [short-acting μ-opioid receptor (MOPr) agonists] involve relapsing cycles, with experimentation/escalating use, withdrawal/abstinence, and relapse/re-escalation. κ-Opioid receptors (KOPr; encoded by OPRK1), and their endogenous agonists, the dynorphins (encoded by PDYN), have counter-modulatory effects on reward caused by cocaine or MOPr agonist exposure, and exhibit plasticity in addictive-like states. KOPr/dynorphin activation is implicated in depression/anxiety, often comorbid with addictions. In this opinion article we propose that particular stages of the addiction cycle are differentially affected by KOPr/dynorphin systems. Vulnerability and resilience can be due to pre-existing (e.g., genetic) factors, or epigenetic modifications of the OPRK1 or PDYN genes during the addiction cycle. Pharmacotherapeutic approaches limiting changes in KOPr/dynorphin tone, especially with KOPr partial agonists, may hold potential for the treatment of specific drug addictions and psychiatric comorbidity.