by Mary May
figures by Neal Akatsuka
An estimated 59,000 to 65,000 Americans died due to drug overdoses last year, which is more than the number of deaths from HIV/AIDS at the peak of the epidemic in 1995 and more than the total number of American deaths in the Vietnam War. The over-prescription of pain-relieving opioid drugs like morphine and oxycodone has created another epidemic that is currently sweeping across low-income and rural areas in the United States, so much so that the Trump administration has declared a “public health emergency.” Opioids were so accessible from 1999 to 2010 that the number of prescriptions for opioids quadrupled in that span. Merely halting the rise in opioid prescriptions, however, has not been enough to combat the crisis; once prescription opioids became more difficult to obtain, patients often sought illicit alternatives like heroin.
The stigma attached to opioid addiction is significant and poses a barrier to treatments that are essential for combating the epidemic. Scientists and health officials are pursuing multiple approaches to help addicts, including managing opioid addiction with a drug called methadone and exploring how vaccines might be able to dampen the effects of certain opioids. Even so, some are left wondering: will we ever be able to “cure” addicts, and how can we more effectively combat this epidemic?
How do opioids work?
Controversy over the amount of control an individual has over their addiction has existed for decades. Patients seeking medication-assisted therapy experience significant prejudice and discrimination from healthcare workers, friends, and family. However, more people are beginning to embrace the view that addiction is a disease that we can treat using medication.
To understand how such medication might work, we need to understand how opioids behave on the molecular level. Psychoactive substances like opioids alter the ways in which brain cells called neurons communicate with each other, changing the way we think, feel, and control our bodies. Normally, chemicals called neurotransmitters are released by one neuron and taken up by its neighbor, allowing a message to be transmitted throughout the brain one neuron at a time. These chemicals attach to receptors on the neighboring neuron like a key fits into a lock: when a neurotransmitter binds the correct receptor, it opens the metaphorical door to propagate the signal to the next neuron (Figure 1).
The brain naturally produces chemicals that bind opioid receptors, which are normally involved in stress response, mood, learning, memory, and immune functions. Any substance that interacts with these receptors is called an opioid, such as the class of neurotransmitters known as endorphins. These natural opioids are produced to block pain from stress or harm. They are also generated during intense exercise and contribute to the brief feeling of euphoria known as “runner’s high.”
Humans have been able to find and create chemicals (like heroin and OxyContin) that closely resemble the chemical “keys” that unlock opioid receptors. As a result, many of these opioid drugs elicit pain relief, but they also produce the euphoric effects that drug abusers crave.
How does addiction develop?
When neurons are exposed to opioid drugs over long periods of time (e.g. when prescription drugs are used to treat chronic pain or are abused continuously to get high), the brain makes changes to the neurons that contain these receptors. The number of receptors on the surface of the neuron decreases, resulting in fewer receptors to signal between neurons. This means that the same amount of drug will have less of an effect on neural activity. Moreover, neurons can release other chemicals that deactivate the receptors and counteract the effects of the drug, which also contributes to tolerance (Figure 2).
In addition to relieving pain, opioids also signal the brain to release a chemical called dopamine. Dopamine is involved in reward pathways that make people want to repeat behaviors that increase dopamine levels—a positive feedback loop that contributes to addiction.
These changes to individual neurons spread throughout the brain, fundamentally altering an addict’s brain chemistry in areas involved in learning and stress, causing withdrawal when opioids are not present. Changes in the production of many different neurotransmitters during withdrawal cause intense physical symptoms like nausea, anxiety, insomnia, and itching. So not only do addicts need more of the drug to feel the same positive effects, but they also experience symptoms that make it difficult to function normally.
Using methadone to manage opioid addiction
Methadone is a highly regulated opioid used to both treat chronic pain and help wean opioid addicts off of illicit drugs. At low doses, methadone binds enough opioid receptors to prevent withdrawal but not cause a high. Because methadone is taken orally rather than injected, the risk of spreading diseases like HIV and hepatitis via dirty needles is drastically reduced.
Controversially, patients can become addicted to and dependent upon methadone itself, so some view it as replacing one addiction with another. Unlike recreational drug users, however, patients taking methadone are supervised by a doctor and frequently go through behavioral therapy that has also been shown to help manage the symptoms of addiction. Many professionals believe that the positive benefits of methadone treatment far outweigh the risks of using it for treatment.
Opioid Vaccines: Progress towards a cure?
The public’s reluctance to accept and fund opioid substitution treatments (such as methadone) to address opioid addiction is reflected in the current administration’s handling of the opioid crisis. During his brief tenure as Secretary of Health and Human Services, Tom Price suggested that scientists were on their way to producing a vaccine that could prevent addiction to opioids. This attention has gotten people excited about the prospect of an actual cure for opioid addiction.
All vaccines work by priming your own immune system to attack foreign invaders in the body. The vaccine stimulates your immune system to produce substances called antibodies. Antibodies are similar to receptors in that they also bind very specific molecules—such as those carried by bacteria, viruses, and other things that make use sick—using a lock-and-key fit.
Scientists have been experimenting with methods for making antibodies that bind chemicals like heroin instead of molecules from bacteria or viruses. For example, vaccines for heroin would stimulate the body to produce antibodies that recognize and neutralize heroin molecules before they reach the brain. This would prevent the drug from binding opioid receptors and prevent the signaling that causes users to get high (Figure 3).
While vaccines for heroin and other opioids show real promise, they do come with some caveats. Taking the vaccine wouldn’t be able to prevent any of the debilitating withdrawal symptoms that patients experience. It’s also possible that patients could take dangerously high doses of the drug to overwhelm the immune system’s defenses and still manage to get high. Furthermore, one vaccine is unlikely to be effective against the broad spectrum of opioid drugs because antibodies are so specific; in other words, someone who has gotten the heroin vaccine could still get high by taking a different opioid, such as fentanyl. Scientists are optimistic that an opioid vaccine could be a helpful supplement to current methods of treatment, but they stress the need to continue to support current treatment methods.
Combating this public health emergency
The first step of addressing the opioid crisis is to acknowledge that people who are addicted need help and that we have the resources to help them. Continued research into vaccines that would help addicts and other medications that would reduce the effects of withdrawal and dependence is an essential step that should be a priority for the current administration. Although there doesn’t appear to be a miracle drug that cures addiction (at the moment), the benefits of opioid substitution treatment and behavioral therapy can drastically improve the lives of opioid addicts, their families, and their friends.
Mary May is a third-year Ph.D. student in the Chemical Biology program at Harvard University where she studies novel antibiotic targets in bacteria.