New Understanding of Addiction: The Role of DNA in Withdrawal
Addiction is a complicated concept that continues to be studied and better understood. Part of the complication is that addiction takes place in the brain as part of a complex chemical messaging system. The brain, of course, is responsible for all thoughts and functions, so there is definitely a lot going on up there.
Our understanding of brain chemistry has seen major advances in recent years. Scientists are breaking down the compound functions of neurotransmitters, for example, and mapping the individual regions of the brain. Genetics are a major contributing component to brain function, and those are being broken down as well.
Getting specific in our understanding of the connection between addiction and genetics is moving us closer to more effective treatments, especially for those who seem to struggle the most with addiction. A better understanding of why some people are more prone to develop an addiction and find it much harder to avoid relapse in recovery will ultimately lead to reduced suffering.
The Basics of DNA and Addiction
There is no question that addiction runs in families. This has been clear to even the casual observer for decades. There is nothing unusual about a father with substance abuse problems raising a son who eventually develops the same addiction issues.
However, with awareness and proper precautions, you do not have to develop an addiction just because one of your parents was prone to substance abuse. Having the genetic predisposition for addiction is not a guarantee of the same outcome. There are plenty of cases to show that genetics can be counter-acted with favorable results.
The question about addiction that remains is how much of it is genetics and what role environment plays in its development. For any habit, genetics are only one component. It is possible that a person who suffered with addiction their whole life does not transmit that addiction gene to their offspring and yet raises a child who ends up suffering from addiction as well.
Scientists have never been able to isolate a single gene that carries addiction, so they are more certain that the disease includes a number of genes — a gene combination. At the same time, behavioral scientists cannot rule out the ability of environment to produce habits such as addiction that are not genetically preprogrammed.
So the nature versus nurture battle rages on in the addiction realm. In the absence of a specific genetic predisposition for addiction, an addiction can still develop. Yet even with a proven genetic track record for addiction that could span multiple generations, abstinence can be maintained.
The question now is how the genetic factors come into play when abstinence is not maintained. DNA is permanent while environment can be changed. In many cases of addiction, though, changing the environment is not enough to avoid relapse. There needs to be a way to alter genetics, and scientists may have found it.
D2, DNA and Epigenetic Tags
Recent research results put medical science closer to understanding the specifics of the genetic connection to addiction. But, like everything else in the brain, it is not a simple situation. Current wisdom is that not only do you have genes that produce certain characteristics and personality traits, but, although your DNA is permanent, genes can be activated at different levels.
The understanding is that genes are always there but not always expressing themselves. They are activated like lights with switches. They can be turned on or turned off in different combinations. In addition, they can be “dimmed,” or turned off partially, to different levels. This switching increases the number of combinations of gene expression exponentially.
Genetics are responsible for the number of D2 receptors in your brain. The D2 receptors accept signals from dopamine, a feel-good brain chemical. These same receptors are the ones affected by cocaine. Various studies have revealed that lower levels of D2 receptors are associated with a pre-disposition to addiction.
Research on rat brains has centered around the D2 pleasure receptor to try to better understand the genetic role in addiction. Lower levels of D2 were found in the brains of addiction-prone rats. These rats also had an epigenetic tag, a genetic marker, that prevented their brains from reading the gene for D2 receptors, further reducing their availability.
This means a brain that is predisposed to addiction starts out with fewer pleasure receptors than others. It has the capacity, therefore, to take in lesser amounts of feel-good chemicals. In addition, it also has a genetic marker that prohibits the use of these receptors.
With the use of their minimal D2 receptors diminished, rats, monkeys and presumably people, experience a greater reward from substances like cocaine. The theory is that since there are fewer D2 receptors available for the drug to bind with, they take in less of the feel-good chemicals. That intake, however, represents a larger percentage increase in the overall amount of feel-good chemicals in the brain.
If a brain with the average amount of D2 receptors suddenly gets an additional 5 mg of dopamine, its overall good feeling increases by a small percentage, say 10%. When there are fewer D2 receptors, though, and the same 5 mg of dopamine comes in, the overall increase in feel-good chemicals is a higher percentage, say 45%. The same amount of cocaine, therefore, has a greater effect on a brain with fewer available D2 receptors. The larger reward brings a greater craving, and addiction is born.
If your brain does not have the genetic markers that inhibit D2 receptors, you still get a high from cocaine, but your high is not as significant as that of someone who has the epigenetic tag. You can still develop an addiction, but it will take longer and a greater exposure to the drug for addiction to really set in. You may get away with using cocaine once or twice and still have the ability to stop on your own, while the person with the epigenetic tag will almost certainly become addicted right away.
Recent Breakthrough in DNA Research
In more recent studies that support this model of D2 and epigenetic tag’s involvement in addiction development, another genetic marker was discovered. A comparison of the brains of addiction-prone rats to those who did not become addicted in the experiment isolated another genetic difference. This difference can be used to better understand why some people are prone to addiction and relapse more easily in recovery.
The new findings center on the FGF2 gene, another one known to be involved in addiction. The rats who did not become addicted carried a genetic marker that turned their FGF2 gene off, or at least dimmed it. This epigenetic tag is believed to have protected the rats from becoming addicted, so when the drug was withheld from them, they did not relapse to addictive behaviors.
The implications of these research results are that the genes for addiction are just as important as the genes for non-addiction. In our complicated brains, there are combinations that promote addiction and those that prohibit addiction. Similar to the nature versus nurture argument, the balance of two opposing forces determines the outcome, which exists in shades of variation.
Brain Changes During Addiction Withdrawal
It is a well-known fact that drugs cause changes in the brain, some of which can be long-lasting. In addition to the chemical changes in the brain that produce the euphoric effect, there are also structural changes that take place over time.
In the last decade, scientists have revised their theories on brain development. It was once believed that each person had a certain number of brain cells. When cells died as a result of injury or trauma, they did not grow back. The understanding was that we don’t use all of our brain cells, so the death of cells was not noticeable until it reached a certain threshold.
No one seemed to know what that magic number was. However, the belief was that if you killed too many brain cells with drugs, for instance, you would no longer be able to function normally, and you would not be able to recover those normal brain functions. This theory has been replaced by evidence that brain cells, like other cells in the body, spontaneously regenerate.
Drug abuse is still a danger to the brain and brain development, though. Brain cells die and regenerate, but they are not replaced in a one-for-one fashion. When you lose a receptor in the pleasure-center of your brain, for instance, you may not gain a new one. Instead, your brain uses the growth cycle to develop different thought pathways. The brain structures that create a positive outlook, when they die one cell at a time, may be replaced with more negative thought pathways.
DNA Changes During Withdrawal
Recent research suggests that brain changes during active drug abuse are eclipsed by changes in the brain that take place during withdrawal. When drugs are withheld from the brain, it cannot support its altered structure. Without the routine flood of feel-good chemicals, negative thought pathways can develop in abundance. Eventually, there may be too few receptors available to feel pleasure at all.
The DNA changes in the brain during withdrawal affect the addiction and relapse process. The reduced number of D2 receptors available that make the euphoric effect of cocaine more intense also create a stronger craving for the drug when it is withheld. Those thought pathways become hard-wired and outnumber others. It is possible that withdrawal actually increases a person’s pre-disposition to addiction, making it nearly impossible to avoid relapse.
Recent research reveals that during withdrawal, the brain shows an increased level of a certain protein referred to as BDNF, which is linked with increased drug cravings. The elevated levels of BDNF make it much more difficult to avoid relapse. These BDNF levels are believed to spontaneously increase during withdrawal.
Testing Addiction Treatments at the DNA Level
Understanding the role epigenetic tags play, not only in addiction predisposition but also in protecting against addiction, brings us closer to new methods of treatment for addiction. If we could replicate the DNA markers that result in a protection from addiction and figure out when and how to administer it, we might be able to stop addiction before it starts.
A more plausible short-term goal is to intervene during withdrawal to reduce the risk of relapse. By stopping the increase in BDNF in the brain that is triggered during relapse, or blocking its effects of regulating thought pathways in critical areas of the brain, cravings could be reduced and relapse curtailed significantly.
The existence of increased levels of BDNF points to changes happening in the brain at the genetic level. Since genes are permanent, the only chance of affecting a different outcome is to use epigenetic tags to dim or turn off the certain genes associated with addiction. Now that we have isolated some of the genes central to the addiction process, turning them off during withdrawal becomes more feasible.
An epigenetic drug called RG108 has been developed and tested on rats. The rats were first taught to self-administer cocaine when a certain light came on. After their addiction was established, the cocaine was withheld for 30 days while the rats went through withdrawal. After their withdrawal, when they were exposed to the light cue, the rats showed addictive behaviors. However, when RG108 was administered after withdrawal, the rats did not display any strong drug-seeking behavior.
The addiction of the rats in this experiment was heightened by the withdrawal period, presumably by the same DNA mechanism that increases BDNF levels. The drug they were given, RG108, acted as an epigenetic tag and blocked that DNA activity. The BDNF levels did not increase, and, therefore, the drug-seeking behavior was lessened. The results of the single dose of RG108 that was administered lasted for several days.
Although RG108 therapy has only been tested on rats, it shows promise for the advancement of addiction treatment in humans. It could represent a way to greatly reduce the relapse rate for people trying to recover from addiction. The relapse rate for cocaine addiction can be as high as 80%, making recovery a long, tough battle.
Implications for Addiction Treatment
These recent discoveries in the connections between DNA and withdrawal are very promising for the future of addiction treatment. It will be a long time, however, before new treatments are available and safe for human consumption. For right now, relapse remains a serious concern in recovery and requires behavioral therapy including specific strategies to maintain abstinence.
There are some implications of this latest research, though, that we can apply to our approach to addiction recovery today:
• Addiction is actually accelerated during withdrawal. While this might seem like a reason to give up on the idea of recovery, in fact it is a tool to help develop more effective treatment programs. Beginning with detox and lasting through the withdrawal period, it is important to have an intense recovery program that emphasizes strategies for maintaining abstinence.
• Relapse will always be a part of the recovery journey, but recent findings illuminate the role of relapse. It is a learning experience, of course, and points out that the recovery program needs to be adjusted. But relapse also means another trip through withdrawal, where we now know the cravings can be genetically enhanced. We can use this information to strengthen the use of relapse-avoidance strategies and emphasize the importance of recognizing triggers before relapse occurs.
• For those who display a genetically pre-disposed tendency toward addiction, this new research shows how intense those connections can be, giving a greater importance to abstinence in recovery. There are those who dispute the idea of addiction as a chronic disease because a chronic disease is never cured but only managed. In the case of addiction with a clear genetic component, we now have further evidence to suggest the chronic nature of addiction. It can be managed, but DNA is permanent. Given the right conditions, addiction can develop again with drug use.
• The genetic basis of addiction, although more complicated than previously understood, can still be overcome with the correct environmental conditions. Good habits are an important part of a healthy lifestyle, so avoiding exposure to addictive behaviors is key. Now that we have a better idea of the how the DNA forces work to create and prolong addiction, we know how important it is to try to overcome addiction before it starts.
Drug addiction is a growing problem in the U.S. with 23.5 million Americans suffering from addiction. The latest medical research into the connection between DNA and addiction is promising, but it’s still a long way from a cure. We need to continue to use the methods we already have available to treat this growing disease.
While current relapse rates for all drug addiction are similar to those of other chronic diseases, recovery is possible and within reach for many of the people suffering from addiction today. The future holds even more promise for ending the suffering, so we have to continue in our diligence to treat addiction on all levels.
If you would like to learn more about the latest research in addiction recovery, contact 12 Keys. We can answer all of your questions about the science of rehabilitation, as well as the behavioral and social implications. Our compassionate staff continuously follows developments in the field of addiction recovery, so we can implement the most effective, scientifically proven method of recovery for our clients.
At 12 Keys, we take an individualized approach to recovery programs. We understand that no two addictions are the same. Like your genetics, your addiction is specific to you, and therefore, the most effective treatment program must be unique to you as well. Our individualized treatment programs are supported by a variety of treatment modalities that are all science-based and proven to be effective means of overcoming addiction.
We treat the whole person at 12 Keys — not just the addiction. We offer a multi-track, multi-disciplinary method of treatment that includes behavioral therapy, group and family counseling, addiction education, nutrition and exercise. We recognize that treating your body well is integral to your mental and behavioral health.
If you are concerned that your genetics are causing additional complications for you with addiction, we can help. Contact 12 Keys today to begin your journey to addiction recovery. Let us guide you from where you are to a healthy, happy, substance-free life. You deserve the best treatment we can provide.