Historical Review: Opiate Addiction and Opioid Receptors

Substance use disorders (SUDs), defined as a collection of symptoms including tolerance and withdrawal, are chronic illnesses characterized by relapse and remission. In the United States, billions of dollars have been lost due to SUDs. In the past 30 years, effective medications and behavioral interventions have played a major role in preventing relapse and facilitating longer periods of abstinence. From the late 1990s to the present, the opioid epidemic or opioid crisis in the United States has raised public awareness of SUDs. Methadone, buprenorphine, and naloxone have proven their effectiveness in treating addicted individuals, and each of them has different effects on different opioid receptors. Methadone and buprenorphine target mu opioid receptors (MORs) in the brain to treat opioid dependence by reducing withdrawal and craving, whereas naloxone is an opioid antagonist used to treat opioid overdose. Mu, kappa, and delta are opioid receptor subtypes with common analgesic effects, and each also has unique effects and distribution in the brain. MORs in distinct brain regions, such as the nucleus accumbens and basolateral amygdala, trigger the euphoria and incentive properties of rewarding stimuli. Kappa opioid receptors can trigger anti-reward effects and produce dysphoric effects. Delta opioid receptors can induce anxiolytic effects. Though effective medications are available, relapse is still common due to neurobiological changes in brain pathways and tolerance of opioid receptors with repeated abuse of substances. In this article, I summarize the biological mechanisms of opioid dependence and opioid receptors and review previous articles about medications used to treat SUDs and their clinical effects.