Summary: Ketamine is an anesthetic and can also reduce pain sensation. However, its use to treat depression is new. Studies show that few ketamine infusions can provide prolonged relief from depression. However, some doctors have raised concerns regarding the risk of ketamine abuse. Fortunately, a new study in rodents shows that ketamine is not addictive. It does cause an increase in dopamine. However, any such upsurge is short-lived and thus does not appear to be enough to cause addiction.
Ketamine is an anesthetic, and it is also known to help with pain. However, its use in managing depression is new. There is significant interest in ketamine treatment for depression as the studies show that it may help provide prolonged relief, unlike traditional antidepressants. However, on the other hand, it is no secret that ketamine is also a club drug, a substance of abuse. It causes euphoria at higher dosages. Therefore, doctors worry that its frequent use may put their patients at risk, and many might become addicted to it. But some experts think that though it is psychotropic, it does not appear addictive. After all, it has been available for a long time, and there are not many people addicted to ketamine. Now, a new study shows that though it may stimulate the reward pathway, it also affects some other brain pathways that help prevent ketamine abuse.
Addiction vs. Dependence
Before discussing the risk of addiction further, it is vital to understand that addiction and dependence are two different things. Addiction is when one seeks a substance despite its negative health consequences. Addiction is a kind of behavioral disorder. For instance, opioid addiction treatment is carried out when abuse of opioids begins to produce negative effects on the body. Dependence, on the other hand, causes withdrawal syndrome on discontinuation of the use of the substance. In addition, dependence often causes severe physical signs. Drugs that cause dependence may affect most people who use them regularly.
Although most people may become dependent on some substances after their prolonged use, the same is not true for addiction. Studies show that only some people become addicted. Moreover, addiction only affects a small number of people.For example, studies show that only one-fifth of cocaine users are really addicted to it. And for opiates, this rate is about 30%. In a recent study, researchers tried to understand the risk of addiction to ketamine.
Ketamine Has A Short-lived Impact On The Reward Pathway
Generally, people get addicted to substances as they increase the levels of the pleasure molecule dopamine. For example, cocaine can boost the brain’s dopamine level for a long time. However, after some time, it would start falling, and thus a person would seek the drug to increase dopamine level again. In the new study, researchers used a special device that allowed mice to self-administer ketamine. They found that it increased dopamine levels in mice, so they repeated the self-administration. However, they found dopamine levels elevated due to ketamine also fell quite quickly, unlike many other drugs of abuse.
Ketamine Also Seems To Have The Effect That Prevents Reward Pathway Stimulation
Researchers wanted to know why unlike other drugs of abuse, ketamine treatment for depression causes such a short-lived increase in dopamine levels. They found that ketamine increased dopamine by inhibiting NMDA receptors. However, it also modulated other receptors, called the D2 receptors, that act as a brake on the rapidly increasing dopamine1. Hence, they found that it is this dual mechanism that helps prevent permanent changes in the brain, unlike other drugs. Therefore, ketamine does not cause long-term behavioral changes. The increase in dopamine levels is for such a short time that it is not enough to cause addiction. The researchers concluded that there is almost zero addiction risk of ketamine in rodents.
Of course, these are still early findings. Nonetheless, it provides the basis for further studies. There is a need to find out if this is also true for humans. Considering that quite often, what works in rodents also works in humans, it is pretty likely that it does not cause addiction. Even if it does cause, any such effect is probably quite low.
By Gurpreet Singh Padda, MD, MBA, MHP