Before we begin, I wanted to make sure everyone knows that this is a very special and important post, above and beyond what I normally write about. The topic’s importance cannot be understated. Most of you reading this know someone or have been personally affected by addiction. If you are currently suffering from addiction, regardless of the source, I hope that you take this opportunity to learn and seek help. Life is far too short and precious.
This week’s question comes from Briana, who asks, “I recently lost my boyfriend to an overdose due to an opiate addiction. In order to be at peace with what happened, I’ve been searching for information about addiction and how specifically it affects a person’s brain. How does a person develop an addiction to opiates? What changes occur in the brain after an addiction sets in?”
Well Briana, sadly you are not alone in experiencing this kind of tragedy. Prescription drug overdoses, for example, kill tens of thousands of people a year and leave thousands more with permanent disability, organ damage, and/or contracted infectious diseases. Likewise, more socially acceptable drugs like tobacco and alcohol bring these numbers well into the six figure range. In total, according to the NIH’s National Institute on Drug Abuse, nearly $600 billion in lost productivity and healthcare costs are associated with addiction to alcohol, tobacco, and drugs. This makes addiction not just a pressing personal matter but also a national catastrophe both in terms of the physical harm and associated healthcare costs.
Further compounding this issue, many people still do not see addiction as a disease. Instead, addicts are labeled as maladjusted, unpredictable people seconds away from committing a crime or unspeakable violence to protect their habit. They are seen as simply out of control, that the drug takes ahold of them and they are lost forever. However, this view is dangerously incorrect. By making addiction such a stigma, addicts are pushed to the darkest corners of society; instead of helping people, we may be unwittingly contributing to their injury by forcing them into the shadows out of shame or fear.
Before we get into the specifics of opiate addiction, we should first explore how the brain becomes addicted to anything in the first place. The term “addiction” is colloquially used to describe both behavioral and chemical dependency; these are not necessarily discrete elements however addiction need not be of chemical origin. One can become addicted to basically any activity because the activity itself triggers a change in the brain over time. Many people have heard of gambling and sex addiction, which fall into this category. The brain effectively associates the given activity with being a positive and gives you a sense of reward and pleasure for accomplishing it. When competitors say they are “addicted to winning,” they are not entirely off base with their word choice, since winning in competition is a very deeply rooted trigger of this neurological process. The variation then comes with how socially acceptable it is — a person who is addicted to winning basketball games gets showered in adulation, while a gambling addict is labeled socially unacceptable for doing the same.
It is in this pleasure providing activity that we find the neurological basis for addiction. We have discussed before the role of dopamine in the brain (see here for past posts), but not yet in any particular detail. As those articles have described, dopamine is an integral neurotransmitter for, among other things, the reward-pleasure centers of the brain. This system has evolved over millions of years to make us seek out things that are beneficial to survival. We like sex, caloric foods, being active, winning, and not feeling pain because all of these things allowed us to survive longer and produce more successful offspring. Unfortunately for us, this system can be easily tricked. Drugs like amphetamines and cocaine cause a large release of dopamine in the brain directly, while drugs like alcohol and heroin indirectly cause dopamine levels to increase.
To be more specific, the area of the brain in question is known as the nucleus accumbens. Dopamine producing neurons from the ventral tegmental area of the brain terminate in the nucleus accumbens, depositing dopamine into it directly. Drugs and behaviors that affect this area can do so by multiple pathways. The nucleus accumbens is directly capable of being influenced by an increase in dopamine from these dopamine producing neurons. Drugs that cause abnormal dopamine rise can cause an actual physiological change that reinforces the value of their behavior to the brain. Over time, this modulation can cause a behavioral addiction to the act of taking drugs (“drug taking behavior”). This provides the basis for not only becoming addicted to the drug itself but also the act of taking them.
Along with reinforced behavior, the body can simply become addicted to feeling pleasure and reward stimulation. This is the basis upon which one can become addicted to behaviors that do not cause an externally sourced dopamine increase. Instead, we can look at these elements as internally sourced dopamine releases. In simpler terms, the body is rewarding you for what it believes you should be doing. This system is hard wired into all of us, but some people are more susceptible to addiction than others. There is evidence that this has a genetic basis, however the specifics of this are still undefined. Still, it remains a fact that hundreds of thousands if not millions of people in the US alone are actively addicted to something. It is in our best interest as a society to more fully understand the basis for this disease so that we can better and more comprehensively treat it.
Chemical dependency, unlike behavior based addiction, is a more complicated matter. One can only become chemically dependent on drugs, be they legal or illegal, because only drugs are capable of altering the normal physiology to the point of functional dependency. The drug alters the brain in some way that over time causes a replacement of normal function by the drug itself. For example, alcohol increases GABA receptor function (GABA reduces nerve activity) and depresses NMDA receptor sensitivity to the neurotransmitter glutamate (glutamate makes nerves more excitable). This is what is thought to cause the sedative effects. Chronic abuse of alcohol can cause these receptors to function abnormally: NMDA receptors become hypersensitive and GABA receptors become less responsive. With NMDA receptors going wild and no GABA activity to stop them, alcohol withdrawal symptoms such as the condition delirium tremens and seizures can result. Severe, untreated alcohol withdrawal can lead to death from prolonged seizures. Other drugs, such as benzodiazapines, can also cause similar withdrawal symptoms and different, non-sedative drugs, can have a variety of other withdrawal effects. In short, addiction to certain drugs isn’t just dangerous due to overdose potential but can also cause significant damage if the habit is improperly or suddenly stopped. The brain, quite literally, cannot function without them.
Specifically discussing opiates, drugs like hydrocodone (Vicodin), oxycodone (Oxycontin, Percocet), hydromorphone (Dilaudid), diacetylmorphine (heroin), and morphine are some of the most commonly prescribed drugs on the planet to treat acute and chronic severe pain. They also happen to be some of the most addictive substances available. While extremely useful in select circumstances, by and large these drugs are taken inappropriately. Many people take them to mask less than severe pain or avoid treating the underlying pathology or behavior. For example, a high school football player could either rest a sprained ankle and miss two games or take a Vicodin and play through it. For many people, these drugs are what keep them doing what they want to do when their bodies otherwise say no.
Likewise, these drugs are often over-prescribed and under-supervised. After surgery, for example, patients can be given upwards of 120 pills at a time. While the reason, to prevent unnecessary pain and suffering, is noble, ultimately it is a very sharp double edged sword. Even common pain killers like Vicodin can initiate a terrible cascade of dependency. One not need be a junkie or rebellious youth to become addicted to drugs. Sometimes something as innocuous as a broken bone or outpatient surgery can lead to a lifetime of addiction. Despite their utility in treating pain, these drugs unfortunately come at a terrible price.
Opiates can cause chemical and behavioral dependency very rapidly and this effect can grow more serious over time as the brain becomes tolerant of the drugs. Opiates operate by attaching to receptors in the brain known as opioid receptors. The body has three types of receptors (delta, kappa, and mu) and makes four of its own types of opiates, of which the well known endorphin is one (the other three are enkephalins, endomorphins, and dynorphins). Their job is to reduce the body’s response to pain signals as well as a few other functions around the body such as helping to regulate hunger and thirst. By binding to these receptors, opiate drugs take the place of these endogenous (internally sourced) opioids. However, these receptors never normally receive such a large influx of stimulation. Because of this, continuous use can cause the receptors to lose sensitivity, both reducing the value of internal opioids and forcing an ever increasing amount and strength of external opiates to keep up.
Many of the other effects, such as euphoria and sedation, are side effects related to their effect on the central nervous system, especially related to GABA receptors (the effect on which also causes the spike in dopamine that results in euphoria). Thus, opiates hit on all aspects of addiction, from dopamine release in the nucleus accumbens to opioid and GABA receptor chemical dependency. However, like with other sedative drugs, opiates can have terrible, even deadly, withdrawal symptoms as a result of their abnormal interaction with GABA.
Also, as was mentioned earlier, the dependency related to ever decreasing receptor sensitivity can cause opiate addicts to seek stronger and stronger opiates as weaker ones lose their effectiveness. This involuntary seeking behavior can and often does place them on a razor’s edge between satisfying their addiction and accidentally overdosing. Opiate overdoses are deadly serious business, often resulting in cardiopulmonary (heart and lung) emergencies such as severely depressed breathing, slowed heart rate, and low blood pressure, as well as lethargy, seizures, and loss of consciousness. If left untreated, these symptoms can become deadly in a short period of time. Sadly, it is relatively easy to overdose on opiates; so easy, in fact, that some cities around the world to distribute free overdose kits containing naloxone, a potent drug that can rapidly reverse these deadly symptoms.
In sum, we as a society must re-imagine our concept of addiction. Addiction is a very complex disease that involves multiple different areas of human behavior and biology. Clearly, the neurobiological elements involved with both the behavioral and chemical dependencies make addiction involuntary on multiple fronts. In particular, drugs, especially opiates, are tremendously difficult to leave because they take advantage of some of our most deeply seeded and essential neurobehavioral elements. Further complicating this is a genetic component of addiction that makes some much more susceptible than average. With better training, treatment, and understanding, we may be able to reclaim some of the tens of thousands of lives and billions of dollars we lose every year by pushing the problem under the rug.
Thank you for your question and for sharing your story, Briana. As always, if you want to ask a question, feel free to submit it at the link above.
Till next time,
Written in memory of Blake Norvell and the hundreds of thousands of others like him.