Abstract
Opioid addiction is a chronic and complex disease characterized by relapse and remission. In the past decade, the opioid epidemic or opioid crisis in the United States has raised public awareness. Methadone, buprenorphine, and naloxone have proven their effectiveness in treating addicted individuals, and each of them has different effects on different opioid receptors. Classic and molecular genetic research has provided valuable information and revealed the possible mechanism of individual differences in vulnerability for opioid addiction. The polygenic risk score based on the results of a genome-wide association study (GWAS) may be a promising tool to evaluate the association between phenotypes and genetic markers across the entire genome. A novel gene editing approach, clustered, regularly-interspaced short palindromic repeats (CRISPR), has been widely used in basic research and potentially applied to human therapeutics such as mental illness; many applications against addiction based on CRISPR are currently under research, and some are successful in animal studies. In this article, we summarized the biological mechanisms of opioid addiction and medical treatments, and we reviewed articles about the genetics of opioid addiction, the promising approach to predict the risk of opioid addiction, and a novel gene editing approach. Further research on medical treatments based on individual vulnerability is needed.
Highlights
Opioid addiction is a chronic mental illness that causes the addicted individuals to experience many relapses and remissions throughout their life, and they suffer from many uncomfortable symptoms, including tolerance development and withdrawal [1,2]
Methadone causes fewer withdrawal symptoms and is less reinforcing due to its longer half-life [52]; the addicted individuals under the maintenance treatment (MMT) are no longer preoccupied with compulsive drug seeking and craving, and they are more willing to remain in treatment, improving their psychosocial function with help from the health care providers [53,54,55]
In the United States, billions of dollars have been lost due to opioid addiction, and thousands of deaths have been caused by opioid addiction annually [117,118]
Summary
Opioid addiction is a chronic mental illness that causes the addicted individuals to experience many relapses and remissions throughout their life, and they suffer from many uncomfortable symptoms, including tolerance development and withdrawal [1,2]. The risk of relapse is heightened due to the craving feeling with terrible withdrawal symptoms, as well as neurobiological changes in brain caused by the repeated abuse of opioids. Naloxone’s affinity is the highest for the MOR and is used to treat respiratory depression in addicted individuals with a severe opioid overdose Naltrexone binds to both the MOR and the κ opioid receptor (KOR), and a long-acting form of injectable naltrexone has a continuous effect to decrease the frequency and dosage of heroin use [28]. Prolonged exposure to drugs of abuse can change the brain reward circuits and enhance the KOR function through the hypothalamic–pituitary–adrenal axis, promoting opioid addiction relapse [46,47]; stress due to prolonged exposure to drugs can produce a dysphoric feeling. The DOR binds with enkephalins, and it can reduce levels of anxiety and attenuate depressive symptoms [48]
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