How Does Narcan Work: The Secret Life of a “Miracle Drug”

Written By Detoxes - February 19th, 2017
How Does Narcan Work: The Secret Life of a “Miracle Drug”

No one denies that Narcan can—literally—raise the dead. Both those who have suffered an overdose from an opioid drug as well as the first responders who resuscitated them can agree: Narcan is both fast and effective at reversing the effect of opioid drugs.

It only takes minutes for an opioid overdose to have permanent—if not fatal—consequences. So it’s no surprise many EMTs and police who have administered Narcan praise the fast-acting drug as nothing short of “miraculous.” Yet, the very people Narcan rescued have described the experience as “jarring,” even “painful.”

This may seem contradictory, but with an understanding what is Narcan and how Narcan works, both reactions make sense and provide insight into the nature of—and treatment for— opioid addiction.

Narcan is the brand name of the prescription, non-schedule (a.k.a., non-addictive) drug Naloxone, used to rapidly reverse the effects of an overdose from opioid drugs such as heroin as well as prescription pain medications like morphine, codeine, oxycodone, methadone and Vicodin.

Most often released as a nasal spray, signs of recovery are typically observed within 30 seconds to 2 minutes. The victim’s heart rate and breathing will increase, offsetting the most obvious imminent threat during an overdose: severe respiratory depression.

As heart rate and breathing stabilize, the victim regains consciousness and will appear responsive. Upon waking, however, euphoric feelings associated with an opioid high will be noticeably absent in the victim. Likewise, if Narcan is given to a person who has not taken an opioid drug, it has no effect.

This is because Narcan works as an “opioid antagonist,” meaning it competes with—and quickly overcomes—an opioid’s ability to bind to cell receptors, which are specialized proteins found on the surface of a cell. These receptors function like “biochemical gatekeepers” by controlling various biological processes.

When—and only when—molecules with a unique shape and configuration attach to a cell receptor it “activates” whatever biological process that receptor regulates. This is how opioid drugs get users high: the molecules that make up opioid drugs bind to mu opioid receptors found on brain cells.

This activates a process in brain that produces the pleasure non-drug users feel when eating delicious food and having amazing sex. The mu opioid receptors control a “reward mechanism” in the brain that uses pleasurable feelings as a “bribe” for completing basic life functions. Also, activation helps relieve severe physical pain and so opioids are often prescribed after traumatic injury.

When the mu opioid receptors are activated in the absence of pain and without reason for reward (i.e., when ingesting or injecting an opioid), a “conditioned association” to the drug develops, making repeated use likely. Each subsequent exposure further reinforces this conditioned association, often leading to habitual drug use.

The user then plunges into a downward spiral of escalating dose and duration. Tolerance to the drug increases along with the user’s dependence on it. Addiction becomes all but inevitable as the user’s brain function inverts: to feel “normal” requires opioid in the user’s system.

In fact, long-time users feel so abnormal when not on drugs that avoiding withdrawal symptoms becomes one of—if not the most—powerful driving forces to their addition. Tragically, this makes the risk of an overdose not a question of if, but when.

It’s at this point Narcan is often used to intervene.

By the time first responders are called, the overdose victim usually has already become unresponsive or unconscious. Opioid depress the central nervous system so much that the victim can actually “forget” to breathe. This cuts oxygen off to the brain, which can result in brain damage or death if not reversed immediately.

Narcan is able to intervene almost instantaneously because it disrupts the contact point between the opioid molecule and mu opioid receptor. No matter how much of the drug is circulating in the user’s system, potency always depends on the availability of the mu opioid receptors. If the receptor is blocked or occupied, the drug is rendered useless.

It’s similar to a fingerprint scanner built into an iPhone. The phone will only unlock when the fingerprint it’s programmed to recognize makes contact with the scanner. If you were to stick a thick, black strip of masking tape over the scanner, the phone will be impossible to unlock.

Antagonist drugs like Narcan “block” cell receptors in the same way. Like a sticky piece of tape, Narcan has an affinity for the mu opioid receptor 100 times that of opioid molecules. Better yet, while Narcan will bind, it doesn’t activate the reception and “unlock” the process that produces a high. Narcan simply knocks the opioid molecule off the receptor, takes it place, thereby blocking access and further contact and activation.

Narcan will monopolize the receptor anywhere between 30 minutes to 2 hours. Due to this relatively short half-life, another dose of Narcan is sometimes necessary for preventing relapse. If opioids remain in the user’s system when Narcan wears off, as in cases of extremely high dosages or opioids with a prolonged half-life (e.g., methadone), the user will again be at risk once Narcan wears off.

Broader challenges also surface when treating long-term opioid addicts with Narcan. While these are often the users most at risk of overdosing, there are the most vulnerable to the deliberating aftereffects felt when abruptly “coming down” from an opioid high.

Ironically, Narcan’s “miraculous” ability to quickly avert the crisis of an overdose is also why so many users say they’re left intensely craving the same drug that almost just took their life. If users are kept trapped in this cycle of addition, Narcan is only a temporary, “Band-Aid” solution. Doctors now are even prescribing individuals Naltrexone implants to avoid overdoses.

Instead, the addition must be treated with the same life-and-death severity as the overdose or else Narcan is giving addicts another chance to live without another chance at life.