How Ketamine Cures Depression: The Science Behind It

Source: Albert Dahan

Like many other drugs, ketamine has multiple effects rendering it suitable for various indications including anesthesia, sedation, acute and chronic pain relief and treatment of therapy-resistant depression.

Ketamine is a complex drug with a high affinity for various receptor systems including the NMDA receptor, opioid receptor system and cytokine receptors such as the Innate Repair Receptor system (IRR). The activation of multiple receptor systems is translated into a variety of wanted effects that are useful in clinical practice.

Clinical effects include anesthesia due to a dissociation between thalamus and limbic system (ie. Ketamine is a dissociative anesthetic), relief of acute pain due to inhibition of excitatory NMDA receptors at spinal and supraspinal sites, relief of chronic pain due to activity at NMDA, opioid and cytokine receptors (e.g. the IRR), rapid antidepressant effects, due to enhancement of synaptogenesis at prefrontal cortical areas.

Notorious are ketamine’s side effects including addiction, psychedelic or schizotypical effects (hallucinations, paranoia, anxiety/panic attacks), cardiovascular, liver and urogenital toxicity.

In clinical practice the occurrence of psychedelic effect is worrisome and various approaches are being developed to counteract these effects. As a recreational drug or drug of abuse, ketamine is prone to addiction and development of damage to various organs (liver, the urogenital system). Research in volunteers and patients in the LUMC has led to a wealth of information on ketamine’s analgesic and antidepressant behavior which will be discussed.

Dr. Dahan is Full Professor of Anesthesiology at Leiden University Medical Center. He graduated from the Free University (VU) in Amsterdam (MD) and Leiden University (PhD). He is head of Research at the Department of Anesthesiology. He founded and heads the Anesthesia & Pain Research Unit since 1995, a non-profit academic institute that performs outcome research in anesthesia and pain management aimed at improvement of care in anesthesia and pain treatment and the wide distribution of gained knowledge, in close cooperation with non-academic partners. The research on opioids and ketamine are among the major research topics of the Anesthesia & Pain Research Unit. With respect to ketamine these studies focus on wanted effects (eg in depression and pain) and (psychedelic) side effects. Prof. Dahan has published over 300 papers in peer-review journals.

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