Medical ketamine is unlikely to be addictive, a new study in rodents suggests. Ketamine raised dopamine, but the rise was brief and too small to cause addiction. That matters. A few ketamine infusions can bring lasting relief from depression, and some doctors had worried about abuse.
Summary: Ketamine is an anesthetic. It also dulls pain. Its use to treat depression is new. Studies show that a few ketamine infusions can bring long relief from depression. But some doctors have raised concerns about the risk of ketamine abuse. Good news: a new study in rodents shows that ketamine is not addictive. It does raise dopamine. But the rise is brief, so it does not seem to be enough to cause addiction.
Ketamine is an anesthetic, and it also helps with pain. Its use for depression is new. There is strong interest in ketamine treatment for depression. Studies show it may bring long relief, unlike standard antidepressants.
On the other hand, everyone knows ketamine is also a club drug. People abuse it. At higher doses it causes euphoria (a strong high). So doctors worry that frequent use may put patients at risk. Many might become addicted to it.
But some experts think ketamine does not seem addictive, even though it changes the mind. After all, it has been around a long time, and few people are addicted to it. Now a new study shows that it may turn on the reward pathway. But it also acts on other brain pathways that help prevent ketamine abuse.
What is the difference between addiction and dependence?
Before going further, you need to know that addiction and dependence are two different things. Addiction is when a person keeps seeking a drug even though it hurts their health. Addiction is a kind of behavior disorder. For instance, opioid addiction treatment starts when opioid abuse begins to harm the body.
Dependence is different. When a person stops the drug, they go into withdrawal. Dependence often causes severe physical signs too. Drugs that cause dependence may affect most people who use them often.
Most people may become dependent on some drugs after long use. That is not true for addiction. Studies show that only some people become addicted. Addiction affects only a small number of people.
For example, studies show that only one-fifth of cocaine users are truly addicted to it. For opiates, the rate is about 30%. In a recent study, researchers looked at the risk of addiction to ketamine.
How does ketamine affect dopamine compared with other drugs?
In general, people get addicted to drugs that raise dopamine, the brain’s pleasure chemical. For example, cocaine can keep the brain’s dopamine high for a long time. But after a while, it starts to fall. Then the person seeks the drug to push dopamine back up.
In the new study, researchers used a special device that let mice give themselves ketamine. Ketamine raised dopamine in the mice, so they kept dosing. But the dopamine rise from ketamine also fell fast. Most other drugs of abuse do not act this way.
Why is the addiction risk of ketamine so low?
Researchers wanted to know why ketamine treatment for depression gives such a brief dopamine rise when other drugs of abuse do not. They found that ketamine raises dopamine by blocking NMDA receptors. But it also acts on other receptors, called D2 receptors. These work like a brake on the fast dopamine rise.
So this two-way action helps prevent lasting changes in the brain, unlike other drugs. Ketamine does not cause long-term behavior changes. The dopamine rise lasts such a short time that it is not enough to cause addiction. The researchers concluded that ketamine carries almost zero addiction risk in rodents.
Of course, these are still early findings. But they lay the groundwork for more studies. We need to find out if this also holds true in humans. What works in rodents often works in humans. So ketamine likely does not cause addiction. Even if it does, the risk is probably quite low.
Frequently asked questions
Is ketamine addictive?
A new study in rodents shows ketamine is not addictive. It raises dopamine, but the rise is brief and too small to cause addiction. The researchers found almost zero addiction risk in rodents. Ketamine has also been around a long time, and few people are addicted to it. What works in rodents often holds in humans.
Why is ketamine used for depression?
Ketamine began as an anesthetic. It also reduces pain. Its use for depression is newer. Studies show that a few ketamine infusions can bring long relief from depression, unlike standard antidepressants. That is why there is so much interest in it. It is also why the question of addiction risk matters to patients and doctors.
Why do doctors worry about ketamine abuse?
Ketamine is also a club drug. At higher doses it causes euphoria (a strong high). So some doctors worry that frequent medical use could put patients at risk of addiction. The new study answers that concern. Ketamine turns on the reward pathway only briefly. It also acts on other brain pathways that help prevent abuse.
How does ketamine compare with cocaine and opioids?
Cocaine keeps dopamine high for a long time. When it falls, the person seeks the drug again. Ketamine’s dopamine rise fades fast. Addiction rates differ too. Only about one-fifth of cocaine users are truly addicted, and about 30% of opiate users. For ketamine in rodents, researchers found almost zero addiction risk.
Related reading
Ketamine for Cocaine Addiction · Ketamine for Fentanyl Withdrawal · Digital Addiction and Dopamine · Drug Addiction Treatment, St. Louis
Sources
- Simmler LD, Li Y, Hadjas LC, et al. Dual action of ketamine confines addiction liability. Nature. 2022;608(7922):368-373. PMID 35896744 · DOI 10.1038/s41586-022-04993-7.