Genetics-Informed Treatment & Gene Therapy Can Improve Rehab Outcomes
Addiction is a complex problem. The path to long-term recovery from addiction is different for everyone, but is often reached with the help of a variety of therapeutic elements, including detox and withdrawal management, counseling, cognitive behavioral interventions, relapse prevention skills training, and diligent aftercare efforts.
In some ways, addiction treatment is like a puzzle – one in which the patient, the patient’s family and addiction specialists must work together to find lasting solutions. Yet, in the future, there’s likely to be one crucial additional piece to this puzzle – one with the potential to make a huge positive difference to the well-being of addiction sufferers: the impact of genetics on addiction treatment.
A growing body of research suggests that our genetic makeup is a vital determinant not just of our likelihood to become addicted to a substance, but also of the severity of that addiction. Our understanding of this genetically determined addiction vulnerability will undoubtedly have significant implications for modern drug and alcohol addiction treatment.
Understanding Genetics and Addiction
To better comprehend the promise of genetics research on addiction treatment, we have to start with a broad understanding of how genes and the addiction process work.
What are Genes?
The U.S. National Library of Medicine’s Genetics Home Reference defines genes as the “basic physical and functional unit of heredity.” In more basic terms,genes are molecular sub-components of our DNA which contain the instructions that determine the characteristics of a biological life-form. Based on our current understanding of human genetics, there are roughly 20,000 genes in the human body, each of which plays some determining role in our individual characteristics.
These variables, of course, include immediately visible characteristics such as body shape or eye color, but some also have a causal link to a number of medical conditions. For example, there are specific genes which impart a tendency for a person to develop asthma and other allergic conditions. Similarly, there are other genes that may make a person more susceptible to heart disease or muscular dystrophy.
When it comes to genetics and susceptibility though, there’s one really important point to keep in mind: certain genes influence whether you’re at risk for a medical condition, but they don’t mean you absolutely will develop that condition.
What is Addiction?
Addiction (or a substance use disorder) is a chronic condition that can alter how the brain processes reward and motivation. In many cases, it is both a mental and physical condition in which a person develops a physiological dependence on a substance which, in turn, can change how that person thinks, feels, and behaves with regard to the substance in question.
When addiction is severe, people will often withdraw from everyday life. They may anticipate or obsess over the effects of a substance to the point that it consumes all other thoughts and becomes the central fixation of their lives.
Abruptly stopping the use of a substance to which someone has developed a dependence, therefore, can be exceedingly difficult, physically uncomfortable, and – if not dealt with correctly – life-threatening. For a more detailed guide to the nature of addiction and how it affects the body, click here.
The Impact of Genetics on Addiction
Scientists are still discovering the precise nature of the relationship between genetics and addiction. As mentioned earlier, we know it’s a complex relationship with no single gene governing the addiction process (though evidence suggests that genetic factors account for roughly half the incidence of several types of addictive disorders—a concept known as heritability).
For example, a 2008 review paper published by the National Institute on Alcohol Abuse and Alcoholism (NIAAA) found that genetic factors may contribute to as much as 50 to 60 percent of the variance in risk for developing alcohol dependence. We also know that if a person has a close relative who struggles with addiction they have a greatly increased likelihood of experiencing addiction themselves.
So, while we still have a lot to learn about how genetics and addiction work, we know that genetics play a crucial role in addiction development. The research also strongly suggests that people with a genetic vulnerability to addiction are more likely to experience a slower recovery than those without this factor working against them.
The Potential for Genetics-Informed Treatment and Gene Therapy in Addiction Treatment
When we talk about the role genetics may play in the treatment of alcohol and substance abuse, we can look to two different areas of research:
- Genetics-informed treatment, based on pharmacogenetic testing to help clinicians to know which medications are most likely to benefit a patient based on their individual genetic makeup.
- Gene therapy, which aims to manipulate an individual’s genes in order to limit or reverse susceptibility to substance abuse disorders or to develop new treatments for them.
Though we tend to think of prescription medications in black and white terms, the way a patient responds to specific drugs is influenced by their unique, genetically-determined physiology which could include differences in various metabolic processes. Because differences at a genetic level can cause patients to absorb, distribute, metabolize and eliminate medications in very different ways, it’s possible for one patient to experience therapeutic benefits from a course of prescription drugs while another encounters significant side effects.
Genetics-informed treatment, which draws from a branch of pharmacology called “pharmacogenetics,” aims to understand genetic factors in order to determine how a person is likely respond to different medications.
At Greenhouse’s genetics testing lab, patients’ DNA can currently be retrieved using a cheek swab and tested to detect the presence of gene variants known to impact the efficacy of different medications. This enables prescribers to estimate how patients will respond to different classes of medications, including those used in medication-assisted substance abuse treatment and the psychiatric medications used to treat co-occurring mental illness.
By personalizing prescription usage through genetics-informed treatment, prescribers can lessen the likelihood of unpleasant side effects and minimize unnecessary trial and error that delays appropriate treatment.
According to the Genetics Home Reference, gene therapy is “an experimental technique that uses genes to treat or prevent disease.” From the point of view of developing new treatments for inherited disease, this science has three main components:
- Replacing a mutated gene that causes disease
- Deactivating genes which have the potential to cause health problems
- Introducing a new gene into the body to fight disease.
While early research into gene therapy interventions are promising, it’s important to understand that this is an emerging field of research. The FDA has approved a limited number of gene therapy interventions but thus far, none of these relate to addiction treatment.
The following are some of the more promising avenues of gene therapy for treatment of addiction being explored today:
Illicit methamphetamine is a dangerous stimulant substance which can lead to organ failure, brain damage and a slew of other potentially life-threatening health problems. According to the National Survey on Drug Use and Health (NSDUH), close to a million people in the U.S. are known users of this highly addictive substance.
Early research by a team at the University of Arkansas suggests that gene therapy may provide a powerful tool for overcoming methamphetamine addiction. Essentially, the team has isolated a gene that produces potent anti-meth antibodies. These antibodies are able to bind and trap methamphetamine molecules, preventing them from passing through the blood-brain barrier.
The hope of this research is that a medication may eventually be developed which neutralizes the methamphetamine high, which would negate the reward of continued meth use. Such a medication could be a valuable pharmacologic tool in the treatment of methamphetamine dependence.
Similar findings have been discovered with alcohol—one of the most commonly used addictive substance in the world. Alcohol use is estimated to lead to more than three million fatalities each year, though the extreme social and financial toll of alcoholism is difficult to quantify.
Research into the genetic determinants of alcoholism has investigated the relatively low prevalence of problematic alcohol use and people of East Asian origin. Such studies have found that a certain genetic mutation frequently present in these individuals could confer as much as a 66-99% protection against addiction to alcohol.
Researchers determined that this group carried a genetic mutation for a gene that codes for an enzyme (aldehyde dehydrogenase) crucial to the metabolism of alcohol. In theory, gene therapies could eventually be developed which effectively mimic this genetic trait. As a result, those treated would experience strong negative side effects when imbibing alcohol, including flushing, dizziness, hypotension and palpitations (a reaction analogous to that experienced by people treated with disulfiram—an medication for alcohol dependence already in use). They would also, hopefully, gradually decrease their compulsive drinking behavior as a result of such an intervention.
Opioids are a class of drug which include heroin and synthetic substances such as fentanyl and oxycodone. Opioid addiction has reached epidemic proportions in the United States. It’s estimated that 11.1 million people over age 12 abused prescription opioids in 2017 and that there were more than 72,000 fatal opioid overdoses in 2017 alone.
Research conducted by the Military HIV Research Program (MHRP) suggests that gene therapy may lead to the development of a safe and effective vaccine by producing antibodies which block opioids from affecting the brain. Dr. Gary Matyas of the MHRP states that, “by blocking the effects of heroin in the brain, we hope to give people a window so they can overcome their addiction.”
The Future of Genetics Research on Addiction Treatment
Right now, the best modalities we have at our disposal for addiction treatment are behavioral therapeutic interventions and medication treatment (specifically for opioids and alcohol dependence) combined with after-care and support. These and other treatment strategies can be individualized to a patient’s strengths, needs, abilities and preferences, as Greenhouse does through our comprehensive medical and psychological assessments.
In the future though, gene therapy may play a vital role in solving the addiction puzzle. Early forays into the genetic determinants of addiction have been promising, and it’s certain that the scientific community will continue to study them as we go forward.
Through a deeper understanding of the impact of genetics on the risk of addiction, new treatments may emerge that will work by directly removing the neurochemical rewards associated with an addictive substance. As our knowledge deepens, we may also find better ways to design fully personalized treatment regimens through combinations of drugs specifically designed to target an individual’s unique addiction pathway.
Addiction is often a progressively destructive disease. The more treatment options we have at our disposal, the greater our chances of reducing its devastating toll.