How Genetic Testing is Being Used to Reduce the Opiate EpidemicAnna Ciulla
Could genetic testing help reduce the opiate epidemic? The question is more than academic. Eradicating the opiate scourge has proven difficult since the epidemic began in 1999 with the explosion in use of opioid medications and illicit opiate substances. Clearly, a multifaceted approach is necessary. Rampant overprescription of opioid medications for pain management in the early 2000s led to overdose deaths from both prescribed opioids and the illegal drug heroin of more than 500,000 Americans between 2000 and 2015, averaging 91 deaths per day. Increased public awareness of opioids, along with more scrutiny of doctors’ opioids prescribing habits by federal and state agencies and Medicare ramped up in 2010. Abuse-deterrent preparations of the painkiller OxyContin helped decrease use of that opiate, yet it led to a subsequent increase in illicit heroin use. The Centers for Disease Control and Prevention (CDC) recommended new prescription guidelines for opioids in early 2016 and in the fall of 2017, the opioid epidemic in America was declared a public health emergency and top governmental priority by President Donald Trump.
Yet the battle to eradicate the opiate epidemic is far from over, leading for calls for improved access to treatment for opiate addiction, stronger monitoring of opioid prescriptions, and research, development and approval of new non-addicting painkiller drugs. In addition, the White House has declared that genetic testing be used to help further knowledge of the predisposition, presence and likelihood of various diseases, potentially including the ability to test for or predict drug addiction.
OPIOID VS. OPIATE
The National Institute on Drug Abuse (NIDA) defines opioids as a class of drugs that include the illegal drug heroin, synthetic opioids such as fentanyl, and pain reliever drugs available through prescription and illicitly such as oxycodone (brand name OxyContin), hydrocodone (brand name Vicodin), morphine, codeine and others. Opiates are chemical compounds that are either extracted or refined from the natural plant matter of poppies (fibers and sap). Opium, morphine, codeine and heroin are examples of opiates. Opioids, on the other hand, are mostly synthesized or made in the lab and are not derived from natural plant matter, although oxycodone, hydrocodone, and hydromorphone may be partially synthesized from opium’s chemical compound. Both opiates and opioids are narcotics and highly addictive. Fentanyl is of major concern, as this illicitly produced synthetic opioid is 50-100 times stronger than morphine and is primarily responsible for an approximately fivefold increase in drug overdose deaths in 2016, per data from the CDC.
The opiates list is lengthy and changes frequently with the approval by the Food and Drug Administration (FDA) of new formulations for specific diseases and conditions. Xanax (alprazolam) is a benzodiazepine, not an opioid, but using Xanax in combination with an opioid can result in “profound sedation, respiratory depression, coma and death.” Opana ER is an opioid agonist, used for managing long-term, round-the-clock pain for which there is no other treatment. It, too, can prove life-threatening when used concomitantly with a benzodiazepine. Vicodin and Lortab are opiate drugs containing hydrocodone and acetaminophen, and Percocet and Tylox are opiate drugs containing oxycodone and acetaminophen.
IS ADDICTION GENETIC?
While researchers have long speculated on a genetic component to addiction, pointing to studies of twins showing addiction to alcohol and family history of alcoholism played out in offspring and subsequent generations and pinpointing specific genes, identifying a propensity or likelihood of addiction to alcohol or drugs is still in the initial stages. Although studies on genetic predisposition to addiction have postulated that genetic factors play a significant role in influencing the development of an addiction –ranging from 40 to 60 percent – much work remains to be done in prospective longitudinal and clinical studies of efficacy. Furthermore, even if a genetic test points to a vulnerability to drug addiction, it does not mean the person will ultimately become addicted. The answer to the question, is drug addiction genetic, is a qualified “maybe.” There is, however, certainly ample evidence to suggest a strong genetics component to drug addiction.
For example, researchers now know that impairment of a particular gene, casein kinase1-epsilon (CSNK1E), not only increases susceptibility to opioid addiction, it also increases vulnerability to binge eating (in women, but not in men). The dysfunction of CSNK1E, say researchers at Boston University Medical Center, increases the euphoric response to opioids and produces a “marked sensitivity” to binge eating. They explained further that genetic variation in CSNK1E could serve as a potential risk factor “that influences the initial pleasurable/euphoric response to opioids,” which may have implications for choice of non-opioid treatment drug for pain relief and therapeutic opioid dosing. Researchers also suggested that CSNK1E may be involved in patients with alcohol use disorders, and that the “potential interaction” of the gene with circadian biology as it affects addiction is an area ripe for further exploration.
IS THERE A GENETIC TEST FOR ADDICTION?
Genetic testing for drug addiction is still evolving, yet the prospect of taking a simple cheek swab and having it sent to the lab for analysis to determine drug addiction or a genetic propensity to addiction is promising. The ability to identify patients at risk of addiction to opioids could be a potent weapon in the fight to curb the current opiate epidemic.
Genetic testing for drug addiction, in this case, for risk of opioid addiction, is a complex and evolving area of research as scientists search for specific alleles of specific genes that may contribute to developing drug addiction. Genetic testing involves, among other things, analysis of opioid receptor genes, such as mu, kappa and delta. Researchers know that the mu opioid receptor (OPRM1) is a primary target for opioid drugs and peptides and thus plays a significant role in the perception of pain and addiction. Genetic variants of OPRM1, such as the single nucleotide polymorphism A118G, researchers say, have been implicated in the predisposition to addiction and association with addiction to opioid drugs.
What entities perform genetic testing for drug addiction? While there is a growing list of companies that do so, one that performs genotyping of OPRM1 is Genelex. Buccal swabs and blood specimens are tested. Medicare does not currently cover this genetic testing and coverage by private insurance varies. While there are some companies marketing genetic testing to consumers, critics say the science isn’t yet conclusive and there may be many more genes involved in drug addiction that have not been discovered. An article published in Genome asserted that genetic tests marketed as a solution to the opioid epidemic are “dubious at best.” Indeed, one company, Proove Bioscience, is under court-ordered restructuring and may have criminal liability after claims that its opioid risk assessment test lacked evidence of either reliability or effectiveness.
Yet, in a 2017 study published in Precision Medicine (Bangalore), researchers argue that “unless the scientific community embraces genetic addiction risk coupled with potential precision or personalized medicine to induce ‘dopamine homeostasis,’ it will fail.”
A newly-released genome-wide association study has identified a regulatory variant of RGMA on chromosome 15 associated with opioid dependence on European Americans. Researchers are excited because this is the first study that demonstrates an association with RGMA and opioid dependence. The belief is that genetic studies can provide insight into the biology of opioid dependence and may help influence treatment and prevention.
In other research, Dr. Kenneth Blum, genetic researcher who co-developed the first-known addiction gene, and co-authors have laid out a comprehensive review of the future of addiction treatment through identifying vulnerability or risk for both drug and alcohol severity coupled with genetically directed therapies. One result of his extensive research and testing is the development of the Genetic Addiction Risk Score (GARS), which makes it possible for individuals to know his or her genetic vulnerability or risk for substance addiction to alcohol and/or drugs. Dr. Blum and his co-authors call the approach Precision Addiction Management, the future for GARS testing for those expressing all types of addictive behaviors.
What about direct-to-consumer DNA and genetic testing? Ancestry genetic testing and health risk testing that bypass traditional genetic service providers are a fast-growing industry that’s heavily marketed. Yet third-party genetic testing is not regulated by the Food and Drug Administration (FDA) and consumers may be ill-equipped to understand the test results, especially if those results point to an existing or downstream risk of disease – which may include a vulnerability or risk of opiate addiction. A study by Boston University researchers published in Translational Behavioral Medicine points out the need for better efforts to maximize the effectiveness of genome-based knowledge.
Meanwhile, well-established tools to assess opioid risk include Current Opioid Misuse Measure (COMM-9) and the Opioid Risk Tool (ORT), both of which are quick, easy to use, and inexpensive. Genetic testing for drug addiction, on the other hand, is expensive, takes longer to obtain results, and hasn’t yet proven reliable. There may be a place for it as part of a predictive risk assessment portfolio for opioid addiction, and while the science apparently isn’t there yet, it remains promising.
ACS Chemical Biology. “An Advance in Prescription Opioid Vaccines: Overdose Mortality Reduction and Extraordinary Alteration of Drug Half-Life.” Retrieved January 19, 2018.
American Association for Clinical Chemistry. “Novel Genetic Test Could Help Combat the Opioid Epidemic by Identifying Patients at Risk of Addiction.” Retrieved February 14, 2018.
Biological Psychiatry. “Genome-Wide Association Study Identifies a Regulatory Variant of RGMA Associated with Opioid Dependence in European Americans.” Retrieved February 23, 2018.
Boston University Research. “At-Home Genetic Testing Leads to Misinterpretation of Results.” Retrieved March 10, 2018.
CNBC. “The genetic test that can help fix America’s opioid painkiller addiction.” Retrieved February 13, 2018.
European Journal of Pharmacology. “Opioid receptor and peptide gene polymorphisms: potential implications for addictions.” Retrieved February 16, 2018.
Genes, Brain and Behavior. “Further support for genetic factors underlying addictions.” Science Daily. Retrieved February 15, 2018.
Genome. “Genome Culture: Genetic Testing for Susceptibility to Opioid Addiction is a Risky Business.” Retrieved February 16, 2018.
Human Molecular Genetics. “Sequence variability and candidate gene analysis in complex disease: association of mu opioid receptor gene variation with substance dependence.” Retrieved February 16, 2018.
Indiana University. “Panel of 11 genes predicts alcoholism risk, gives new insights into the biology of the disease.” Retrieved February 13, 2018.
Journal of Biological Chemistry. “Allelic Expression Imbalance of Human mu Opioid Receptor (OPRM1) Caused by Variant A118G.” Retrieved February 16, 2018.
Journal of Pain and Palliative Care Pharmacotherapy. “The epidemic of prescription opioid abuse, the subsequent rising presence of heroin use, and the federal response.” Retrieved February 16, 2018.
Learn Genetics. “Genes and Addiction.” Retrieved February 13, 2018.
MedPage Today. “Fatal RX Opioid Overdoses Low, but Linked to Dosage.” Retrieved January 19, 2018.
MedPage Today. “Opioids: Can a Genetic Test Identify an Addict in the Making?” Retrieved February 16, 2018.
National Center for Biotechnology Information. “Genetic Testing for Opioid Pain Management: A Primer.” Retrieved February 13, 2018.
Oregon.gov. “’Opiates or Opioids’—What’s the difference?” Retrieved February 14, 2018.
Pain News Network. “Does Genetic Testing for Opioid Addiction Really Work?” Retrieved February 14, 2018.
Postgraduate Medicine. “Going beyond prescription pain relievers to understand the opioid epidemic: the role of illicit fentanyl, new psychoactive substances, and heroin.” Retrieved February 16, 2018.
Precision Medicine (Bangalore). “Global Opioid Epidemic: Doomed to Fail Without Genetically Based Precision Addiction Medicine (PAM): Lessons Learned from America.” Retrieved February 16, 2018.
Proceedings of the National Academy of Sciences. “Mouse model of OPRM1 (A118G) polymorphism has sex-specific effects on drug-mediated behavior.” Retrieved February 16, 2018.
Technology Networks. “Tackling the Opioid Crisis: Genetic Testing to identify addiction risk.” Retrieved February 13, 2018.
The Sober World. “Genetic Innovation for Addiction Recovery and Prevention.” Retrieved March 5, 2018.
U.S. News & World Report. “Fentanyl: the Scariest Opioid?” Retrieved February 14, 2018.
U.S. News & World Report. “Genetic Testing for Addiction: 5 Things to Know.” Retrieved February 13, 2018.