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Ketamine Shows Promise in Treatment of Mental Health, Chronic Pain, Addiction

April 12, 2021

A report published by CDC in August 2020 showed huge increases in mental health issues during the time period April-June 2020 compared with the same time period the previous year. Instances of suicidal conditions increased 200%, anxiety disorders 300%, and depression 400%. The report indicates this increase in mental health challenges has been associated with the morbidity, mortality and mitigation activities resulting from the COVID-19 pandemic.=

As the population continues to struggle with mental health issues, many related to the pandemic, an increasing number of people are turning to ketamine infusion therapy as an alternative to traditional medications and forms of treatment. Used for decades as an anesthetic, ketamine is being widely used as a highly effective off-label treatment for a variety of mood disorders including depression, suicidality, anxiety, PTSD, obsessive-compulsive disorder, postpartum depression and bipolar depression. It has also proven to be very effective in the treatment of chronic pain.

Dozens of peer-reviewed studies and clinical trials conducted during the past two decades have demonstrated ketamine to be effective in treating mental health disorders and chronic pain, particularly among patients who have treatment-resistant conditions. Ketamine infusion therapy, in particular, has been shown to work faster, better and more safely than many conventional mental health disorder treatments and medications.

How ketamine works

The simplest way to explain how ketamine works is that it causes physical growth in the prefrontal cortex and other areas of the brain associated with these conditions. It also establishes new connections among neurons while repairing damaged cells. It builds new pathways in the brain which improve function in the areas of mood and sleep, among others.

Ketamine acts by modulating glutamate, one of the brain’s key neurotransmitters, an amino acid found in 80% 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 disorders. Evidence suggests ketamine helps rebalance the glutamate system by acting as a receptor antagonist, and this increase in glutamate is believed to be one key factor in enabling the antidepressant effect of ketamine.


Ketamine can be administered to patients in a variety of ways, including intravenously, intramuscularly, orally, sublingually, dermally and through insufflation (nasal passages). Recently there has been much talk about esketamine, a derivative of ketamine that was approved by FDA on March 5, 2019, for use as a treatment for mental health disorders. Esketamine is only available to patients as a nasal spray. It can be self-administered, but this must be done in a doctor’s office. Preliminary results show esketamine nasal spray to be significantly less effective than intravenously administered ketamine; in some cases, less than half as effective. This is primarily due to the bioavailability differentials between nasal and intravenous absorption as well as the inherent differences between ketamine and esketamine. There have also been discussions about the higher likelihood of misuse and abuse of a self-administered nasal spray compared to an infusion controlled and administered by medical professionals.

IV ketamine vs. antidepressants

Ketamine infusion therapy can provide many benefits over other antidepressants. While antidepressants can be effective, there are several downsides to their use. Generally speaking, relief from symptoms can often take months to achieve. There can be side effects, such as weight gain, loss of libido, insomnia and dry mouth. Drug interactions are a concern, as are withdrawal reactions and loss of effectiveness over time. Antidepressants are generally effective around 40% of the time. Ketamine, on the other hand, is non-habit forming, has minimal short-term side effects, and does not have any known long-term side effects when used in a clinical setting. Ketamine also offers patients almost instant relief, with the benefits of ketamine often occurring within hours or days, instead of the weeks to months other antidepressants take. IV ketamine is effective around 70-83% of the time, depending upon the protocol used.

Treatment for addiction

Ketamine has also been shown to be effective in the treatment of alcoholism and other forms of addiction. A 2019 study published in The American Journal of Psychiatry tested the effects of ketamine treatment for addiction. The study showed that participants who received ketamine infusion therapy had a significantly lower relapse rate. Ketamine helps treat addiction by obstructing the NMDA receptor in the brain, which enables the creation of new memories. Studies suggest that this obstruction can help with disrupting the negative behavior that results from addiction. By addressing the underlying issues that contribute to substance abuse, ketamine can help stop cravings at their source.

As the use of ketamine and psychedelics continue to be studied and used as effective treatments for a variety of mood disorders, the medical and psychotherapy communities are developing ways in which to collaborate in offering patients faster, safer, and more effective solutions to improve their quality of life.

Steven L. Mandel, MD, the founder and first president of the American Society of Ketamine Physicians, Psychotherapists, and Practitioners. He is also the founder and president of Ketamine Clinics Los Angeles, a ketamine infusion therapy clinic in Southern California.

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