Opiate-blocking drugs, or opioid antagonists, stop narcotics from binding to the opioid receptors in the brain.
Naltrexone and naloxone are the most familiar opioid blockers.
What are Opiate-Blocking Drugs?
Opioid blockers, or opioid antagonists, stop opioid substances from attaching to the delta, kappa, or mu receptors on neurons in the brain. Opioid antagonists bind to these receptors on neurons, and they sometimes kick opioids off those receptors and replace them. This prevents the action of the opioid drug for the length of time it takes for the opioid antagonist to be metabolized through the body.
Because opioid blockers attach to the opioid receptors that are on neurons, there have been some reported analgesic effects, leading to reduced pain sensations. There is little or no breath depression, heartbeat irregularity, or changes to digestion — all issues that are present for narcotic painkillers.
While there are several drugs considered opioid blockers, only two are given as prescription substances in the United States: naloxone and naltrexone. Both of these medications block exogenously administered opioids or narcotic substances that are not directly produced by the brain, like morphine, heroin, oxycodone, hydrocodone, meperidine, codeine, and methadone. These medications may also block endogenously released endorphins or enkephalins, like the brain’s natural opioids.
How Do Some Drugs Block Opioids From Neuron Receptors?
There are three basic types of chemicals that affect the opioid receptors in the brain.
These are opioid drugs like codeine, methadone, or fentanyl that bind to the opioid receptors found on neurons. They activate these receptors to produce analgesia, relaxation, tiredness and suppressed breathing. While feelings of euphoria, intoxication, and pain relief may not last more than a few minutes or hours, many of the other effects can continue for much of the day.
The most famous and important partial agonist is buprenorphine, which binds to opioid receptors in the brain to relieve pain. In people who have struggled with high-dose opioid abuse, buprenorphine relieves withdrawal symptoms like anxiety and cravings. These drugs do not produce any feeling of intoxication unless the person is opioid-naïve.
While these drugs bind to opioid receptors and may paradoxically produce some analgesia, antagonists are mainly used to stop opioids from binding to these receptor sites on neurons or to kick them off if they are present.
Antagonists force the body to react differently to agonists and partial agonists, which can be very helpful when treating opioid addiction or overdose. There are about a dozen chemicals considered opioid antagonists, including:
- Those that relieve moderate to severe pain, such as pentazocine, nalbuphine, buprenorphine, butorphanol, and dezocine.
- Those that treat opioid-induced constipation or bowel issues, such as methylnaltrexone, naloxegol, eluxadoline, and naldemedine.
- Those that reverse overdose effects, such as naloxone, levallorphan, nalorphine, and diprenorphine (specifically works for carfentanil, a potent fentanyl analog).
- Those that block opioids from binding to neurons, such as naltrexone and nalmefene.
While some medical studies are examining the use of low doses of opioid antagonists to treat pain, there are two drugs used in opioid addiction treatment in the U.S. Few others are used at all.
Naloxone And Naltrexone: The Main Opioid Blockers
Naloxone and naltrexone are the most famous opioid antagonists in the U.S. and the most widely used.
This drug is notorious for “reversing” opioid overdoses. While this effect does not last forever since naloxone has a shorter half-life than most opioid drugs, the substance does push opioids off the brain’s opioid receptors, which can block the toxic effects of an opiate overdose long enough for medical help to arrive.
While naloxone has been available to emergency medical personnel and hospitals for several years, the U.S. Food and Drug Administration (FDA) approved the nasal spray for more general use in 2015.
Naloxone can be administered either as an intranasal spray, an intramuscular injection, a subcutaneous (under the skin) injection, or intravenous injection. Many states are expanding access to naloxone through pharmacies. Instead of requiring someone to have an opiate prescription or be a caregiver to someone who takes opiates to manage pain, Good Samaritan laws have allowed expanded naloxone access.
Anyone who sees someone experiencing an opiate overdose can administer the drug. This is typically in the form of the nasal spray since it is the easiest to administer.
This chemical has also been added to buprenorphine as one approach to managing withdrawal symptoms during opioid detox. Suboxone is the brand name for the medication that combines these two drugs. Buprenorphine, as a partial opioid agonist, eases physical and psychological discomfort associated with opioid withdrawal by binding to the opioid receptors in the brain without causing euphoria.
The naloxone in Suboxone does not take effect unless the person tries to abuse the substance by destroying the time-release aspects of the medication. At that point, naloxone is released instead and stops buprenorphine or any other opioids from binding to the brain and causing a high. This sends the individual into withdrawal, and they will likely require further medical treatment.
People who may benefit from naloxone treatment during detox include those who:
- Receive rotating opioid medication regimens, as directed by their doctor. These drugs may overlap accidentally necessitating naloxone intervention.
- Have been discharged from emergency opioid overdose treatment.
- Are completing mandatory opioid detox or abstinence programs.
Unlike many medications, there are no known problems with naloxone like dependence or tolerance. It is possible to have an allergic reaction to the drug, which would cause symptoms like swelling in the face, lips, or throat. This reaction requires emergency medical treatment.
This medication started as a treatment to manage cravings and reduce the risk of relapse after alcohol use disorder (AUD) treatment; however, it was found to be effective at reducing the risk of relapse after opioid detox as well.
It was approved in 2010 by the FDA for this use under the prescription brands Vivitrol, ReVia, and Depade. Both ReVia and Depade are pills that should be taken once per day, while Vivitrol is a once-per-month injection administered by a physician.
Unlike naloxone, naltrexone binds long term to the opioid receptors in the brain and prevents opioid agonists from binding to these receptor sites at all, which limits or stops the sedative, euphoric, and breath-suppressing effects of opioid drugs like morphine, heroin, and oxycodone.
While the person is taking naltrexone, especially if they have received the month-long shot, they will feel fewer cravings for substances like opioids. If they do relapse back into opiate abuse, they will not feel intoxicated from the drugs. This helps the person examine their actions and, subconsciously, unlearn the association between taking opioids and feeling good.
Naltrexone may lead to reduced tolerance for opioid medications in the future, but it is not an intoxicating substance, has few side effects, and will not lead to diversion or abuse. There are some potential side effects.
- Upset stomach, nausea, and vomiting
- Tiredness or trouble sleeping
- Muscle or joint pain
Rarely, there may be complications associated with taking naltrexone, including liver injury, especially after alcohol abuse; infection or reactions at the injection site; and allergic reactions, including allergic pneumonia.
Using Opiate Blockers Effectively in Addiction Treatment
While both naltrexone and naloxone are important medications, they are not the main forms of medication-assisted treatment (MAT). Buprenorphine is the primary substance currently used in the U.S. to manage opioid detox by tapering the body off physical dependence on opioids. Methadone is also used for this purpose, although it is not used as often as buprenorphine.
Naloxone, by itself, is specifically used to temporarily stop opioid overdoses, while naltrexone is prescribed to some people after they have detoxed from opioids if they have struggled to remain sober after treatment. These opiate-blocking drugs are essential medications in the overall treatment of the opioid epidemic in the U.S.