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About Ketamine
Ketamine is classified in the United States as a dissociative anesthetic because at high dosages, it allows a person to feel detached from their pain and environment. At lower dosages, it can induce hallucinogenic and consciousness-altering experiences.
As physicians, we believe in taking a legal, evidence-based approach to psychedelic psychotherapy. At this time, ketamine is the only legal psychedelic compound available for use in psychedelic psychotherapy. And while it has been extensively researched, and can be used legally in outpatient mental health settings, it has not received FDA approval for the treatment of depression or anxiety. This is due to a lack of funding for the specific types of studies required to receive FDA approval. Therefore, ketamine, currently approved for medical use as a safe, rapid-acting, outpatient anesthetic, is being used “off-label” in subanesthetic (low) dosages for the treatment of pain, anxiety and depression .
Esketamine, or Spravato, is an expensive, patented intranasal form of ketamine with FDA-approval for treatment-resistant depression. Spravato, as opposed to generic, inexpensive ketamine, is more lucrative for the pharmaceutic companies that funded the research studies that led to FDA approval for Spravato.
Ketamine has been found to have standalone anti-depressant activity through its effects on glutamate neurotransmission. This is a different neurotransmitter system than the serotonergic, dopaminergic and noradrenergic systems usually modulated by traditional antidepressants. However, studies also show that when combined with psychotherapy, the antidepressant effect is more durable, which is consistent with studies demonstrating the same effect when traditional antidepressant medication is combined with psychotherapy.
Because ketamine affects a different neurotransmitter system, it also has different effects on the brain than traditional antidepressants. Glutamate is thought to increase neural plasticity by increasing the number of connections between neurons . Increased glutamate transmission also appears to temporarily disconnect the default-mode network (DMN) in the brain where negative ruminations and self-referential thinking occur from the salience network in the prefrontal cortex (PFC), where we assign meaning to thoughts and other stimuli . The Increased neural plasticity and delinking of the DMN and PFC during and after ketamine administration, allow the person to pay less attention to self-critical thoughts and initiate new, healthy patterns more easily. Delinking the DMN and PFC is especially helpful for processing trauma, as the person is less likely to experience flashbacks and negative feelings when recalling traumatic events during and after ketamine administration.