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Ketamine and the Treatment of Mental Health Conditions

Revolutionizing the way we treat mood disorders.

Key points

  • Ketamine infusion therapy is a clinically proven, effective, fast-acting, and safe treatment for mental health conditions.
  • IV infusions of ketamine are the gold-standard route of administration and are the most effective.
  • Combining psychotherapy with ketamine can be valuable, and doing both on separate occasions may prove most effective.

There has been much written recently about ketamine and, more broadly, psychedelics and their use in treating mental health disorders. Ketamine is in a different bucket than other psychedelics such as MDMA and psilocybin because it has more than 50 years of clinical use, research, and significant patient safety and efficacy data behind it. Ketamine has been a widely used anesthetic for decades. From potential side effects to dosage, it is safe to say that the medical community knows almost everything there is to know about ketamine, though it continues to be understood better and better as its use cases expand.

During the past 20 years, ketamine has been proven to be effective as an off-label treatment for a variety of mental health disorders, including depression, anxiety, PTSD, and suicidality. It has been shown to be particularly effective for people suffering from treatment-resistant mental health disorders—those patients who have tried many medications and treatments and still do not get well.

Ketamine works by causing physical growth in the prefrontal cortex and other areas of the brain associated with emotion regulation and mental health disorders. It also establishes new connections among neurons while repairing damaged cells. It builds new pathways in the brain that improve function in the areas of mood, function, sleep, and others.

Ketamine acts by modulating glutamate, one of the brain’s key neurotransmitters, an amino acid found in 80 percent of neurons. Glutamate is the most plentiful of all the neurotransmitters and it influences the formation of, and the number of, brain synapses—the vital connections between neurons. Glutamate also acts with another important neurotransmitter, GABA, to maintain a healthy and well-functioning nervous system. An imbalance between GABA and glutamate can cause problems, including anxiety, difficulty sleeping, overstimulation, and other mental conditions. Evidence suggests ketamine helps rebalance the glutamate system by acting as an NMDA-receptor antagonist and this increase in glutamate is believed to be one key factor in enabling the antidepressant effect of ketamine.

For the past 20 years, researchers at top scientific institutions and universities have researched the efficacy of ketamine in the treatment of mental health disorders and shown positive results. Institutions such as Yale, Stanford, Harvard, UCLA, USC, NYU, the National Institute of Mental Health, and the Cleveland Clinic have found that 70 percent of patients treated with ketamine showed a significant decrease in depressive symptoms; virtually all of these patients failed to respond to traditional forms of treatment including medications.

Now, enter psychotherapy.

Psychotherapy, broadly speaking, is an effort to use communication and the skills of the therapist to help the person suffering from incompletions or dislocations in their development to become more internally whole, so they can move forward with consistency and with less conflict. One of the things that makes this process so difficult is when the patient cannot participate or is resistant to authentically participating. Ketamine has been shown to be a great asset in removing a patient’s resistance to psychotherapy and allowing them to recall past events and relate to their innermost feelings without the mask of ego.

There are essentially three ways in which ketamine and psychotherapy can be used together for the benefit of the patient. Ketamine-assisted psychotherapy (KAP) is an extensive process whereby ketamine is administered to the patient during psychotherapy. KAP has very specific protocols and the process is predetermined. Ketamine-enhanced psychotherapy (KEP) is a process by which ketamine is also administered to the patient during psychotherapy; however, it is less rigid than KAP in that the mental health provider can move in different directions more easily and not have to adhere to a specific format of prep, session, and integration afterward.

Finally, you have a process by which the patient receives ketamine first and then, usually within a few days, has a session with their psychotherapist. In this instance, the ketamine has enabled the patient to have moments of realization independently and then discuss them with a mental health professional when not under the influence of the medication. All three can be beneficial, though most of the clinical research proving ketamine’s effectiveness for mental health conditions has been conducted with IV infusions of ketamine without psychotherapy at the same time.

There has been evidence showing the later method—receiving a ketamine treatment separate from psychotherapy—as more effective for several reasons. The first is that ketamine is administered intravenously as opposed to routes like intramuscular injections, sublingually, or intranasally. The bioavailability of ketamine and the body’s absorption is 100 percent via the IV route, much greater than when delivered by any of the other methods. Secondly, to have true, transformative breakthroughs with ketamine, it needs to be given in dosages that often do not allow the patient to immediately communicate or have meaningful conversations with a psychotherapist.

Patients generally need to have some “downtime” to return from their ketamine experience and process their thoughts and realizations in solitude and without outside influence. Trying to talk with a patient during their ketamine experience can be a somewhat futile effort. To find optimal benefit and transformation from ketamine, a conversation is usually best had at a later date.

Ketamine treats depression, suicidality, and PTSD effectively. If that remains the case, derailing its use to treat mental health disorders will be difficult. As mindsets and stigmas around alternative medicines continue to shift, there is hope that other agents will evolve in comparison to ketamine that are equally effective, safe, and can be widely accessible.


NIH: The Role of Ketamine in Treatment-Resistant Depression: A Systematic Review

NIH: Efficacy of ketamine therapy in the treatment of depression