Addiction medications

DEFINITION: Addiction medications are drugs used to treat substance use disorders. The drugs are best used when combined with psychosocial treatment.

Introduction

Addiction is a brain disease. Once a person becomes addicted, changes typically occur in the body and the brain that make these systems function differently than before the development of the addiction. The functional (and perhaps structural) changes to the brain that occur with addiction can sometimes be treated with medications that allow the brain to function normally in the absence of the drug.

Medications are available for the treatment of opioid, alcohol, cocaine, and methamphetamine use disorders and for nicotine use. Each of these medications will be considered individually here.

Many of the medications used in the treatment of addiction are used “off-label.” In other words, the medications are used for addiction even though they have been approved by the US Food and Drug Administration (FDA) to treat other disorders, such as depression, muscle spasms, insomnia, and nausea. Only those medications currently legal to use in the United States (including those used off-label) are presented here. When available, both the clinical name and the more commonly used name will be included. The common name will appear in parentheses.

Many of the medications discussed fall under one of three categories: antagonist, full agonist, or partial agonist. An antagonist is a substance that binds to receptor cells so tightly that it will block any other substance from binding to that cell. Antagonists also bind to the cell without stimulating the cell or otherwise causing a response. Examples of antagonists include naltrexone and ondansetron.

A full agonist is similar to an antagonist in that it completely binds to a receptor cell. Unlike antagonists, however, full agonists will activate that receptor site. Examples of full agonists include morphine and topiramate (a gamma-aminobutyric acid, or GABA, agonist).

Partial agonists, like agonists, bind to receptor cells and activate them, but they cannot bind fully, so the receptor is only partially activated. Examples of partial agonists include varenicline and buprenorphine.

Medications are wonderful tools in the treatment of both physical and mental illnesses and disorders. It should be noted, however, that patients receiving medication also should receive psychosocial treatment.

Medications for Alcohol Addiction

Alcohol is a central nervous system depressant. It works by interfering with communication between nerve cells and by interacting with the receptors on some cells. Alcohol suppresses excitatory nerve pathway activity (for example, glutamine) and increases inhibitory nerve pathway activity (for example, GABA). Thus, alcohol lowers inhibitions, which is why it is often found to be a significant factor in violent and sexually motivated crimes. Medications used (or under study) to treat alcohol use disorders include baclofen, campral (Acamprosate), disulfiram (Antabuse), naltrexone (ReVia or Vivitrol), ondansetron (Zofran), and topiramate (Topamax).

Baclofen. Baclofen treats muscle tightness and cramping or spasms that are often associated with spinal cord injury, spinal cord disease, or multiple sclerosis. The drug is a derivative of GABA and works with alcohol dependence by decreasing withdrawal symptoms and cravings. These effects are achieved by inhibiting the activation of the receptors in the brain that become stimulated during withdrawal.

Campral. The FDA approved campral for the treatment of alcohol use disorder in 2004. Before this time, campral was used widely across Europe in the treatment of alcohol use disorders. Campral works by stimulating GABA receptors and thereby reducing the negative symptoms a person may experience when attempting to abstain from alcohol.

Disulfiram. Disulfiram has been used to treat alcohol use disorders since the 1950s. Originally thought to work well as a treatment for parasites, experts began to notice that persons who took the medication and who also drank alcohol became ill. The medication disrupts the metabolism of alcohol, resulting in a hangover type of physical illness. The physical effects caused by disulfiram in persons also ingesting alcohol include headache, flushing nausea, dizziness, and vomiting.

Naltrexone. Naltrexone is an antagonist; it binds to the mu (µ) opioid receptors in the brain, but it does not stimulate them. This is important because naltrexone is used to treat addictions but does so without causing euphoria, like some addiction medications. Naltrexone is available in two different administrations: oral and injection.

The oral version of naltrexone, ReVia, was approved for the treatment of alcohol use disorders in 1995. However, because it must be taken daily, its effectiveness varies for those who are not medication compliant or not committed to treatment. In addition, side effects may be substantial because the medication levels vary throughout the day. The injection form of naltrexone, Vivitrol, was approved in 2006. Vivitrol is a long acting, once-a-month, injection that works the same way as ReVia, but it has fewer side effects and better medication compliance.

Ondansetron. Ondansetron is an antiemetic that reduces the nausea and vomiting that often accompany chemotherapy treatment. Ondansetron is a serotonin receptor antagonist and works by reducing the activity of the vagus nerve, thereby blocking the sensation of the need to vomit. This medication also has been studied as a treatment for other disorders, including alcohol use disorder, and although it is not approved for this, it can be prescribed off-label.

Topiramate. Topiramate treats epilepsy; however, research also indicates that it may be useful as a treatment for alcohol, cocaine, and nicotine dependence. Topiramate is a glutamate antagonist and a GABA agonist. It works by blocking the glutamate receptors and by increasing the effects of GABA, which help to calm over-excited nerve cells. Topiramate has been shown useful in the treatment of alcohol dependence. Topiramate has a number of side effects, including weight loss, impaired memory and concentration, numbness and tingling of extremities (although this side effect is transient), and the development of kidney stones.

Medications for Cocaine Addiction

Cocaine is a stimulant of the central nervous system derived from the coca plant (not to be confused with the cocoa plant, which is used for chocolate). Cocaine is a serotonin-norepinephrine-dopamine reuptake inhibitor, which means that cocaine can increase alertness, euphoria, energy, motor activity, and feelings of competence. However, it also can result in anxiety, paranoia, restlessness, delusions, hallucinations, and tachycardia. Medications used (or under study) to treat cocaine use disorder include baclofen, disulfiram, gabapentin (Gabitrol), and modafinil (Provigil), bupropion (Wellbutrin), and the dietary supplement N-acetylcysteine (NAC).

Baclofen. Baclofen, which is used to treat muscle spasticity (found in persons with multiple sclerosis), also has been studied as a potential treatment for cocaine addiction. Baclofen is said to work by decreasing the effects of dopamine in the brain and, thereby, reducing cocaine-induced euphoria.

Disulfiram. Disulfiram, which is used to treat alcohol use disorders, also has been studied as a treatment for cocaine disorders. In one study conducted at Yale University, disulfiram was found to work well in decreasing cocaine use. Similar to its effect with alcohol users, the study showed that is caused cocaine users to become physically ill. This research has since been replicated.

Gabapentin. Gabapentin is an anticonvulsant medication used to treat seizure disorders, depression, and pain. The medication also has been studied as a treatment for cocaine use disorders. The medication works by making cravings less intense and by lessening the severity of any relapse to cocaine use. Because of these positive effects, however, some doctors are hesitant to prescribe gabapentin for cocaine use disorders; it is believed that the medication will reinforce cocaine use rather than discourage it.

Modafinil. Modafinil is FDA approved for the treatment of narcolepsy and other sleep disorders. It also has been studied in the treatment of cocaine use disorders. However, findings have proven inconclusive.

Bupropion. Bupropion is an antidepressant used to treat a variety of conditions, including depression, mental health and mood disorders, and smoking dependence. Bupropion is a norepinephrine-dopamine reuptake inhibitor (NDRI), which means it increases norepinephrine and dopamine in the brain, hormones that help regulate mood. Though it has a history of usage in fighting cocaine addiction and has been observed in multiple studies in attempts to alleviate the addiction of cocaine in patients, including with the combination of naltrexone, studies have shown that this drug does not demonstrate effectiveness when combatting cocaine use disorder.

N-acetylcysteine. N-acetylcysteine is an over-the-counter herbal supplement with purported antioxidant effects. It has been used to treat everything from carbon monoxide poisoning to acetaminophen overdose. Its effectiveness in treating cocaine use disorders has not been determined.

Medications for Methamphetamine Addiction

Methamphetamine is a synthetic drug. Although chemically similar to amphetamine, its effects are much longer lasting. Methamphetamine is a central nervous system stimulant with euphoric effects similar to those found with cocaine. Methamphetamine works by increasing the release of dopamine in the brain. No approved medications are on the market to treat methamphetamine addiction, and no medication is used off-label to treat methamphetamine addiction. However, a few drugs are under study, including paroxetine (Paxil), ondansetron, and gabapentin.

Paroxetine. Paroxetine is indicated for the treatment of mood disorders (depression and anxiety) and obsessive-compulsive disorder and panic disorder. It also is under study for the treatment of methamphetamine abuse.

Ondansetron. Ondansetron, used to treat alcohol use disorders, is FDA approved as an antinausea drug that may work to block specific binding sites for the neurotransmitter serotonin. Some preliminary studies have indicated that ondansetron may block the effects of methamphetamine.

Gabapentin. Gabapentin, in addition to being a potential medication for the treatment of cocaine use disorders, also may be a viable option for the treatment of methamphetamine use disorders.

A 2021 study published in the New England Journal of Medicine found that a combination of two medications helped some people combat methamphetamine addiction. The first was injectable naltrexone, which is better known by the brand name Vivitrol and used to treat opioid addiction and alcoholism. The second, oral bupropion, is an antidepressant. The twelve-week study found that 13.6 percent of patients who had taken the two drugs had repeated urine tests free of methamphetamine, compared to 2.5 percent of patients who had taken placebos.

Medications for Nicotine Addiction

Nicotine is a stimulant found in tobacco and tobacco products. The American Heart Association reports that nicotine dependence is one of the most difficult addictions to break. Some medications, including bupropion (Wellbutrin) and varenicline (Chantix), and other products, such as nicotine replacements, are available to assist persons addicted to nicotine. The use of bupropion and varenicline in nicotine addiction treatment, however, has been linked to serious side effects, including depression and suicidal ideation. Nicotine replacement products (such as patches and gum) provide the user with nicotine, but they do not have the harmful carcinogens that accompany many of the delivery systems (such as smoking or tobacco chewing).

Bupropion. Bupropion is a well-known antidepressant that has been used in the treatment of nicotine dependence. The drug works by reducing the urge to smoke.

Varenicline. Varenicline is a nicotine receptor partial agonist. It works by decreasing the cravings for nicotine and by decreasing the pleasurable effects of nicotine consumption.

Medications for Opioid Addiction

Opioids are narcotic analgesics (painkillers) that are derived naturally from the poppy plant (these are called opiates, such as morphine and codeine) and from artificial synthesis. Opioids work by binding to opioid receptors in the brain. The receptors where opioids bind typically control movement, digestion, mood, the experience of pain, and, most problematic, body temperature and respiration.

Opioid use disorder varies and can include addiction to heroin and painkillers (such as vicodin and oxycodone). In the 2010s, the powerful opioid fentanyl also became a serious problem, as opioid abuse reached epidemic proportions in the United States; fentanyl is often mixed into heroin or cocaine and is responsible for thousands of overdose deaths per year. The main medications used to treat opioid use disorder include buprenorphine, methadone, and naltrexone. However, the opioid epidemic stimulated a flurry of research into new medications, such as lofexidine (Lucemyra), approved by the FDA in 2018 to alleviate the symptoms of opioid withdrawal; it was the first non-opioid treatment approved for such purposes but is not by itself a treatment for opioid use disorder.

Buprenorphine. The FDA approved buprenorphine in 2002 as a treatment for opioid use disorder. The drug works by binding to the same receptors as opioids, but because it is a partial agonist it does not completely fill the receptor; therefore, little euphoria is achieved when taken as prescribed. A doctor prescribes buprenorphine, and induction (introduction of buprenorphine into the system) can be done in a doctor’s office rather than at a substance abuse treatment facility. The effects of buprenorphine can last up to three days, so unlike the common drug methadone, daily doses are not required.

The two most common formulations of buprenorphine are Subutex and Suboxone. Subutex contains only buprenorphine and is the formulation used during the first few days of induction. Suboxone includes both buprenorphine and naloxone. Naloxone is a powerful substance that blocks the effects of opioids and is often used to treat opioid overdose. When combined with buprenorphine, it greatly reduces the abuse potential of this medication. In 2018, the FDA approved a new formulation of buprenorphine called Sublocade, which can be administered in once-a-month injections; this is an advantage for recovering addicts who often have difficulty with medication adherence when the medication must be administered daily.

Methadone. Methadone, perhaps the best-known medication to treat opioid use disorder, is a synthetic opioid and a narcotic pain reliever similar to morphine. It has been used in the treatment of opioid addiction since the 1960s. Methadone is a full mu (µ) opioid agonist and works by binding to this receptor and by preventing other opioids from binding to that same receptor. However, methadone, if given in the incorrect dosage or through certain routes, can result in euphoria similar to that of illicit opioids.

Withdrawal from methadone can take several weeks to several months and has been described as more difficult to withdraw from than other opioids. Methadone is taken orally and is typically taken daily.

Naltrexone. Naltrexone, in addition to treating alcohol use disorders, also has been shown to be effective in the treatment of opioid use disorder. When used for opioid use disorder, naltrexone works as it does for alcohol: It binds tightly to the mu (µ) opioid receptors and prevents any other drug from binding to those same receptors. The binding action reduces cravings for the substance and also prevents the high that is normally experienced from opioid use. Because naltrexone is an antagonist, it is powerful enough to push the opioids out of the receptors to bind to them. This is important because naltrexone will place a patient into precipitated withdrawal from opioids if the patient has not abstained from opioids before receiving naltrexone.

There are two main ways to administer naltrexone: orally (ReVia) and through an intramuscular injection (Vivitrol). Both forms, as well as versions sold under other trade names, are FDA-approved for the treatment of opioid use disorder.

Buvidal (a form of Buprenorphine) is a medication used to treat opioid addiction. The medication was tentatively approved for use in the United States in 2018. It is an injection that is given once a month. This is an advantage for those in treatment because they do not have to frequently go to the pharmacy, where they risk coming into contact with others users.

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