Ketamine causes little addiction, according to the University of Geneva
The results of a Geneva study show that the therapeutic use of this substance prescribed in psychiatry is relatively safe.
The researchers used a device that allowed mice to self-administer doses of ketamine.
UNIGE
Increasingly prescribed against depression resistant to common drugs, ketamine is not very addictive, according to a Geneva study. Its therapeutic use is relatively safe, say the researchers in the journal Nature.
Discovered in 1962 by American chemist Calvin Lee Stevens, ketamine is a synthetic drug with powerful anesthetic properties. It is commonly used in human and veterinary medicine, in particular to relieve pain and operate short sedations.
This substance is also illegally consumed for recreational purposes, its dissociative effect inducing an altered perception of reality, the University of Geneva (UNIGE) said in a press release on Wednesday. For the past ten years, ketamine has also been prescribed to relieve depressive symptoms in people who are resistant to conventional treatments.
Its action also has the advantage of being very fast: it is felt a few hours after the first intake, whereas traditional antidepressants take several weeks to act. But although its prescription is increasing, this substance is still widely debated within the scientific community.
Addictive risk
“Some believe that ketamine presents a high addictive risk in the event of prolonged intake, others do not. The whole challenge of our research was to try to provide some answers, ”says Christian Lüscher, full professor in the Department of Basic Neurosciences at UNIGE, quoted in the press release.
Addiction is defined as the compulsive consumption of a substance despite its negative consequences (behavioral disorder). Dependence is characterized by the appearance of one or more withdrawal symptoms when consumption is suddenly stopped (physiological disorder).
Addiction affects everyone. Addiction, on the other hand, affects only a minority of people and is not caused by all drugs. For example, in the case of cocaine, only 20% of users become addicted, even after prolonged exposure. For opiates, only 30%.
Brief stimulation
It is precisely the addictive risk that the Geneva team sought to assess. To do this, she used a device allowing mice to self-administer doses of ketamine.
“The drugs intensely stimulate the reward system in the brain, which leads to an increase in dopamine levels. The first step consisted in observing whether this mechanism was also at work when taking ketamine”, explains Yue Li, post-doctoral researcher in the Department of Basic Neurosciences at UNIGE.
The scientists found that the level of dopamine, also called the “pleasure molecule”, increased well with each dose and induced positive reinforcement in the mice, which motivated them to repeat the self-administration. “However, unlike cocaine for example, we found that the dopamine level decreased very quickly after taking it,” notes Yue Li.
The drug does not leave its mark
The team found that ketamine triggered an increase in dopamine by inhibiting a molecule in the reward center of rodent brains called the NMDA receptor. She then observed that this dopamine binds to a second receptor, called the D2 receptor, which quickly slows down its increase.
The researchers also confirmed that the action of the NMDA receptor was necessary to alter the communication between nerve cells that underlies the behavioral change leading to addiction. When taking ketamine, its inhibition makes this change impossible.
“The consequence of this dual action of ketamine is that it does not induce the synaptic plasticity that addictive drugs cause and which persists in the brain after the substance has disappeared. It is this ‘memorization’ of the product in the reward system – absent in the case of ketamine, therefore – which leads to repeated consumption”, concludes Christian Lüscher.
Therefore, the addictive risk of ketamine seems zero, at least in rodents, writes UNIGE. This study now provides a solid framework for discussing access to its therapeutic use, according to the authors.
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