Ketamine and Brain Plasticity

By Kristen R. Dagenais, BSN RN SCRN

The term plasticity, when referring to the brain, means the ability to form new connections and/or structures in the brain. Through a multitude of imaging studies, such as MRI, it is now known that chronic stress, trauma, and depression cause “atrophy of neurons in limbic brain regions implicated in depression, including the prefrontal cortex and hippocampus” (Duman et al., 2012). In other words, the cells (neurons) in your brain shrink and die causing structural damage to your brain. A study done by the neuropharmacology division at Yale discovered that “ketamine rapidly increases synaptogenesis” (Duman et al., 2021).

Synaptogenesis is brain plasticity… ketamine causes new neurons (brain cells) to be formed rapidly! As a result, the beneficial effects of ketamine are close to immediate. Rather than waiting two to four weeks for an antidepressant medication like an SSRI to be of any help, ketamine acts rapidly to decrease depressive symptoms while also repairing the brain damage caused by chronic stress! “Together these studies indicate that ketamine rapidly reverses the [shrinking] of [neurons] in the [brain] and thereby causes a functional reconnection of neurons that underlies the rapid behavioral responses” (Duman et al., 2012).

Because of this amazing discovery, ketamine can be used in crisis situations (like when someone is experiencing suicidal thoughts). You feel the effects within minutes of starting the infusion and the results from one infusion last at least two weeks! This window of efficacy allows for the space and time to confront your issues in a manner that comes from a healthy head space. Clinical evidence shows that exposure to ketamine produced rapid and persistent antidepressant effects in a significant portion of treatment-resistant depression subjects (Colo et al., 2019). Ketamine helps your brain to rewire its own circuits to repair years of structural damage. And it has also been shown to be extremely effective for alcohol and substance abuse recovery.

If you have been battling depression, anxiety, and/or PTSD without relief from conventional antidepressant treatments, do some research on your own about ketamine. Major breakthroughs are being made by the world’s top scientists and researchers about the effects of ketamine and other psychoactive medicines. The studies are showing amazing results in the field of mental wellness.

References
Collo, G., Cavalleri, L., & Pich, E. M. (2019). Structural plasticity induced by ketamine in human dopaminergic neurons as mechanism relevant for treatment-resistant depression. Chronic Stress, 3, 1-6. https://doi.org/10.1177%2F2470547019842545

Duman, R. S., Li, N., Liu, R. J., Duric, V., & Aghajanian, G. (2012). Signaling pathways underlying the rapid antidepressant actions of ketamine. Neuropharmacology. 62(1): 35–41. doi:10.1016/j.neuropharm.2011.08.044

Interview with the Ketamine Academy

Watch to learn about Shelley’s personal Ketamine journey in her interview with the Ketamine Academy!

 

 

Ketamine Room Walkthrough

Welcome to Hope for Healing! Listen to one of our owners give a brief walkthrough of a ketamine treatment room.

What is Ketamine?

Hope for Healing Behavioral Health Center offers Ketamine treatments for treatment resistant depression.  Once ordered by a prescriber, ketamine is infused by licensed ICU nurses and nurse anesthetists.

WHAT IS KETAMINE

Ketamine is a dissociative anesthetic that has been around since the 1960’s.   It has proven very safe.  It distorts perceptions of sight and sound and makes a person feel disconnected from their pain, anxiety, depression, and their environment while it is being administered.  Low dose Ketamine can induce a state of sedation (feeling calm and relaxed).  Its lasts a short time approximately 30 to 60 minutes.

Here is what some people have said:

“It was spiritual for me.  I felt that I was with God and I felt an overwhelming sense of peace and love.  This made me feel like everything was going to be OK.”  -Jaime 4/8/2021

“While I was under the influence of ketamine, I felt like I resolved a bad break up with someone who had hurt me in the past.  I saw the person in my mind and began to cry, we made up and forgave each other.  It was beautiful.  I didn’t even realize this broken relationship was bothering me until this happened.  I felt so at peace.” -Anne 1/13/2020

“I saw myself as a toddler- wearing torn and dirty clothing, crying and all alone.  My adult self -picked up my child self and hugged her and told her everything would be OK.  I felt loved after the infusion was over.” Caitlyn 3/2/2021

TREATMENT FOR DEPRESSION

People usually take antidepressants for weeks before they might see an effect.  Ketamine is different.  Its effects on depression happen as it leaves your body.  The former director of the National Institute of Mental Health states, “recent data suggest that ketamine, given intravenously, might be the most important breakthrough in antidepressant treatment in decades.” (Insel, 2014).   If a person responds to ketamine, it can rapidly reduce suicidality and relieve other serious symptoms of depression. Ketamine also can be effective for treating depression combined with anxiety.

There are some theories as to how it works:

  • It prompts connections to regrow between brain cells that are involved in mood.  These effects can be profound and works faster than antidepressants (Collins, 2018).
  • Ketamine targets NMDA receptors in the brain. By binding to these receptors, ketamine appears to increase the amount of a neurotransmitter called glutamate in the spaces between neurons. Glutamate then activates connections in another receptor, called the AMPA receptor. Together, the initial blockade of NMDA receptors and activation of AMPA receptors lead to the release of other molecules that help neurons communicate with each other along new pathways. Known as synaptogenesis, this process likely affects mood, thought patterns, and cognition (Aleksandrova et al., 2017).
  • Ketamine may reduce signals involved in inflammation, which has been linked to mood disorders, or facilitate communication within specific areas in the brain (Meisner, 2019).
  • Increased levels of brain derived neurotrophic factor (BDNF), a protein that plays a role in the growth and maintenance of neurons, is involved (Bathina and Das, 2015).
  • A recent study suggests that HDAC5, an enzyme, regulates the antidepressant effects of ketamine through a process called phosphorylation, which regulates protein function. Ketamine increases BDNF levels in the central nervous system which prompts the growth and connections of dendrites on the neurons in the brain (Ketamine, 2019).
  • Research suggests that repeated trauma reduces levels of BDNF in the amygdala, hippocampus, and nucleus accumbens.   Ketamine reverses this damage in the amygdala and nucleus accumbens. This is important because the amygdala plays a critical response in fear and strong emotions, while the nucleus accumbens is essential in motivation, aversion, reward, and learning (Yu and Chen, 2011).

All of these may play a role in decreasing depression, anxiety, and helping people through their traumatic pasts.

HOW IS IT ADMINISTERED

A much lower dose of ketamine is given for depression compared with the dose necessary for anesthesia.  Ketamine is given intravenously, twice per week for three weeks for a total of six treatments.  Each infusion lasts 40 minutes but you will be in the clinic for about 1.5 hours to allow for preparation time and recovery.

SIDE EFFECTS

All drugs have side effects. When someone is suicidal or severely depressed, possible benefits may outweigh the possible risks.

Ketamine given by infusion may cause:

  • high blood pressure
  • nausea and vomiting (although Zofran is given to prevent this)

 

References:

Aleksandrova, Lily R, et al. “Antidepressant Effects of Ketamine and the Roles of AMPA Glutamate Receptors and Other Mechanisms beyond NMDA Receptor Antagonism.” Journal of Psychiatry & Neuroscience : JPN, Joule Inc., June 2017.

Bathina, Siresha, and Undurti N Das. “Brain-Derived Neurotrophic Factor and Its Clinical Implications.” Archives of Medical Science : AMS, Termedia Publishing House, 10 Dec. 2015.

Choi, Miyeon, et al. “Ketamine Induces Brain-Derived Neurotrophic Factor Expression via Phosphorylation of Histone Deacetylase 5 in Rats.” Biochemical and Biophysical Research Communications, vol. 489, no. 4, 2017, pp. 420–425., doi:10.1016/j.bbrc.2017.05.157.

Collins, Sonya. “What Is Ketamine? How It Works and Helps Severe Depression.” WebMD, WebMD, 27 Feb. 2018.

Insel, Thomas. “Post by Former NIMH Director Thomas Insel: Ketamine.” National Institute of Mental Health, U.S. Department of Health and Human Services, 1 Oct. 2014.

Ketamine, Reset. “Ketamine’s Impact on Brain-Derived Neurotrophic Factor (BDNF).” Reset Ketamine – Ketamine Infusion Clinic in Palm Springs, California, Reset Ketamine – Ketamine Infusion Clinic in Palm Springs, California, 1 Nov. 2020.

Lepack, A. E., et al. “BDNF Release Is Required for the Behavioral Actions of Ketamine.” International Journal of Neuropsychopharmacology, vol. 18, no. 1, 2014, doi:10.1093/ijnp/pyu033.

Réus, Gislaine, et al. “Ketamine Treatment Partly Reverses Alterations in Brain Derived- Neurotrophic Factor, Oxidative Stress and Energy Metabolism Parameters Induced by an Animal Model of Depression.” Current Neurovascular Research, vol. 12, no. 1, 2015, pp. 73–84., doi:10.2174/1567202612666150122122924.

Robert C. Meisner, MD. “Ketamine for Major Depression: New Tool, New Questions.” Harvard Health Blog, 20 May 2019.

Yu, Hui, and Zhe-yu Chen. “The Role of BDNF in Depression on the Basis of Its Location in the Neural Circuitry.” Acta Pharmacologica Sinica, Nature Publishing Group, Jan. 2011.

What to Expect During a Ketamine Infusion Session

We provide it as a mental health treatment option for only those clients who would benefit from its short-term and lasting effects.

During treatment, Ketamine is administered as an intravenous infusion at a much lower dose than given for anesthesia. Clients who experience relief from depressive symptoms within one to three ketamine treatments will most likely extend these positive and regenerative effects with additional ketamine treatments. While every plan is individualized, clients typically receive 6 doses over a 2-3 week period.

Our Ketamine program is designed to be completed within 7-8 weeks. Successive sessions, as part of an on-going mental health plan, may help prolong the effectiveness of ketamine treatment. This option is available on a case-by-case basis.

Hope for People with PTSD:  Six Ketamine Infusions

The American Journal of Psychiatry (January 5, 2021) presented the results of a study that showed ketamine infusions rapidly reduced the symptoms of post traumatic stress disorder (PTSD).  This research was conducted at the Icahn School of Medicine at Mount Sinai in New York.  Repeated IV ketamine infusions were well tolerated and safe.

Individuals participating in this study were diagnosed with chronic PTSD with symptoms lasting an average of 14 years.  There are three symptom clusters associated with PTSD (Scher et al., 2008).

Intrusive Cluster:  This cluster of symptoms includes nightmares and flashbacks.   These are disturbing, involuntary thoughts or images that may become obsessive and distressing.  People often feel as though they cannot control these thoughts and images (Scher, et al., 2008).

Avoidance Cluster: This cluster of symptoms includes emotional numbing, dissociation, and avoiding situations that bring up memories.  These are actions are an attempt to alleviate the distress of symptoms and includes dissociation and substance use/abuse.  These while helpful temporarily end up causing more harm (Scher, et al., 2008).

Hyperarousal Cluster: This cluster of symptoms includes insomnia, poor attention, hypervigilance, and paranoia.  This is a disturbing inability to relax, experience peace, and leads to overaction of the sympathetic nervous system (i.e., rapid heart rate, rapid breathing, “fight or flight”) (Scher, et al., 2008).

The study separated participants into 2 groups:  one group received 6 low dose ketamine infusions (3x per week for 2 weeks) and the other group received midazolam (an antianxiety medication) at the same frequency.

Results showed that the ketamine group experienced a decrease in symptoms leading to less distress, in fact, 67% of participants in this group had a 30% reduction of symptoms.  Interestingly, the ketamine group also had a reduction in co-existing depressive symptoms.

Symptom reduction was experienced as quickly as 24 hours following the infusions and this improvement continued to be experienced for up to 4 weeks after the infusion.

“The data presented in our current study not only replicate, but also builds on our initial findings about ketamine for PTSD, indicating that in addition to being rapid, ketamine’s effect can be maintained over several weeks,” Dennis S. Charney, MD, and colleagues said (Feder, et al., 2021).

References

Feder, A, Costi, S, Rutter, S, Collins, Abigail B, Govindarajulu, Usha, Jha,  Manish K, Horn, Sarah R, Kautz, Marin, Corniquel, Morgan, Collins, Katherine A, Bevilacqua, Laura, Glasgow, Andrew M, Brallier, Jess, Pietrzak, Robert H, Murrough, James W, Charney, Dennis S.  A randomized controlled trial of repeated Ketamine administration for chronic posttraumatic stress disorder.  The American Journal of Psychiatry:  2021 January 5. 

Scher, Christine D, McCreary, Donald R., Asmundson, Gordon J.G, Resick, Patricia A. “The Structure of Post-Traumatic Stress Disorder Symptoms in Three Female Trauma Samples: a Comparison of Interview and Self-Report Measures.” Journal of Anxiety Disorders, U.S. National Library of Medicine, Oct. 2008