Inside the drug that’s taking on the opioid crisis

If you’ve been affected by the opioid crisis, you have probably heard of an anti-overdose drug called naloxone. The Food and Drug Administration backs it, and in recent years, its use has spread rapidly in North America. Naloxone is now sold over-the-counter, without a prescription, in 43 U.S. states. In Ontario, pharmacies have even begun distributing it for no cost.

So what is naloxone? What does it do? Is it really a solution for North America’s opioid crisis? Here are some questions and answers.

How does naloxone work, exactly?

To understand how naloxone works in the body, it’s important to understand how opioids work. Like most drugs, opioids operate by activating certain cellular proteins called receptors. Receptors are a key part of how the trillions of cells in a human body communicate. When a receptor is activated, its cell will either carry out a task or release chemicals that go on to activate receptors in other cells.

Just as there are many sorts of cells in the body, there are many different types of receptors. Like a lock that will only accept very specific keys, a receptor will only activate if it comes into contact with the specific chemicals that match it.

Opioid receptors are no exception. They’re typically found in the brain, spinal cord and digestive system. When an opioid enters the body and activates those receptors, the affected cells begin transmitting chemical signals, telling other cells to block pain, constrict pupils, tighten airways, induce drowsiness and cause opioids’ other effects.

Naloxone binds to some of the very same opioid receptors. Essentially, if opioid receptors are locks, then naloxone is like putty that fills those locks and prevents them from being used — thereby preventing the opioids from having an effect and actually reversing ongoing effects by, for instance, instructing cells to dilate pupils and free up airways.

Is naloxone easy to take?

Very.

It comes in multiple forms, too. The most common is naloxone hydrochloride, a white powder that can be dissolved in water to create a liquid solution. Either the powder or the solution can be used as medication.

If the solution is injected directly into the bloodstream, naloxone can begin acting in less than two minutes. If only a smaller needle is available, then it’s also possible to inject naloxone under the skin. Some opioid pills now come combined with naloxone powder, so that the naloxone can help prevent dependency from that same opioid.

Following the lead of paramedics who used improvised aerosol nasal sprays, the FDA recently approved naloxone as both a nasal spray and as an auto-injector. First responders now usually carry naloxone in one of these forms.

The chief barrier to even more widespread use of naloxone is that some people still aren’t fully aware of its benefits and ease of use, according to Thom Duddy of Emergent BioSolutions, which manufactures the naloxone nasal spray Narcan. “The real issue we see with naloxone is not access to the reversal agent but rather awareness of it,” he says.

So, it must be new, then?

Actually, no. Although naloxone has had a high profile lately, it’s not a novel drug. It’s been around since the early 1960s, and the FDA actually first approved it in 1971 — long before the outbreak of America’s current prescription-fueled opioid epidemic.

One positive result of naloxone’s age is that generic versions are very readily available, especially in developing countries. The World Health Organization lists naloxone on its Model List of Essential Medicines.

In the U.S., access to naloxone has expanded in the last several years: the annual number of naloxone prescriptions more than doubled between 2017 and 2018, going from 270,000 to 556,000, according to the Centers for Disease Control and Prevention (CDC). Nine states — Arizona, California, Florida, New Mexico, Ohio, Rhode Island, Vermont, Virginia and Washington — now mandate co-prescribing naloxone with some or all opioid prescriptions.

Still, actual distribution lags behind: of the 13.5 million Americans prescribed large daily doses of opioids in 2018, less than 1% received naloxone, according to the CDC.

Is that because there are side effects?

Not necessarily. One of the reasons naloxone’s proponents are so enthusiastic is that it has little effect unless opioids are already present in the body. This allows naloxone to be safely used “not only in emergency treatment of known opioid overdose cases, but also in suspected opioid overdose,” explains Wasantha Jayawardene, a public health researcher at Indiana University.

While side effects are rare, there have been cases of hypersensitivity or allergic reactions to naloxone. Jayawardene also says the drug is less effective the more opioids the patient has taken.

Another concern: naloxone is only effective for 30-45 minutes, shorter than the time of action of most opioids — and multiple doses are often needed.

It’s even possible that administering naloxone to an opioid-dependent person and rapidly reversing the opioids’ effects could trigger a severe, potentially life-threatening withdrawal. That is why proper training with naloxone is so important, says Jayawardene.

Why isn’t naloxone being used more widely, then?

For one, naloxone’s availability can vary wildly from region to region, often driven by state or province government policies. The CDC found that, in the U.S., pharmacies in urban areas were far more likely to have naloxone than pharmacies in rural areas that often are badly affected by the opioid crisis.

Even though generic naloxone is readily available worldwide, cost is another factor in the U.S. In 2018, more than 30% of U.S. naloxone prescriptions required out-of-pocket payments of greater than $50, according to the CDC. Kaleo, the manufacturer of a naloxone auto-injector called Evizo, has come under fire by a U.S. Senate subcommittee for raising the price of Evizo sixfold, from an average of under $600 in 2014 to more than $3300 in 2018.

Amongst pharmacists and medical staff, attitudes and lack of knowledge are also slowing naloxone’s spread, according to Jayawardene. The CDC also found that certain types of health care providers, including addiction specialists, psychiatrists and pediatricians are more likely to prescribe naloxone than others, such as primary care doctors, surgeons and nurse practitioners.

So is naloxone really a permanent solution to opioid addiction?

Only in part: it can keep overdosing patients alive long enough to get them into a treatment program. While naloxone can treat an overdose, it cannot treat addiction — only comprehensive treatment programs, including detox that addresses both a patient’s medical and social factors, can do that. Naloxone isn’t a long-term solution, says Jayawardene, but rather a “useful tool that gives another chance to live.”

Correction: Wasantha Jayawardene is affiliated with Indiana University, rather than the University of Indiana.