The Initial Mental health Evaluation/Preparation Session Will Include: 

• A review of prior medications or procedures used to treat your condition 
• Review of Allergies 
• Review of Medical conditions, such as diabetes or hypertension 

• A discussion of mental health treatments you may have been involved with, such as EMDR (Eye Movement Desensitization and Reprocessing), CBT (Cognitive Behavioral Therapy), IFS (Internal Family Systems), or other treatments 
• A review of any eating disorders  
• Substance use discussion and treatment options 
• Exercise and movement to improve outcomes
• Structured time and lifestyle evaluation 

• Current stresses such as legal, financial, divorce, or workplace issues. 
• A discussion of expectations of outcomes with ketamine therapies: not everyone responds, and relapse can occur and may require booster infusions for maintenance. We also discuss why some people do not respond well to ketamine therapy or only partially.
• Consideration of further lab investigations of etiologies of mood disorders: Mold testing, Lyme disease, heavy metals, bacterial and yeast overgrowth, organic acid testing, environmental pollutants, obesity-related testing, iron, Ferritin, CRP, testosterone, estrogen, SHBG, prolactin, hemoglobin A1C, thyroid panels, cortisol, Vitamin D, Vitamin B12, homocysteine, advanced lipid panel, erythrocyte sedimentation rate, C-reactive protein, kryptopyrroles, Serum copper, Vitamin levels, and hormonal testing (DUTCH) testing. 
• Recognize that the treatment is non-linear. In other words, you will have ups and downs. For those who are depressed, any feeling less than better feels catastrophic. Depression causes the negative side of our brain (amygdala and lateral habenula) to overestimate anti-rewards and sense failure when things are actually getting better. We lose self-awareness and the ability to recognize improvement when we are depressed. This improves over time, but frequently it is the family that notices improvements in mood and behavior before the patient does. 
• Improvement can be seen around the fourth infusion or even later in some cases. Improvement may materialize as improvements of various components of mental health such as better mood, more hope, less ruminations, less brain fog, less fatigue, less negative self-talk, more motivation, or other components. These improve at variable rates just like the modem lights turn back on one by one after a power outage. Each returning light represents a different component of your mental health. That is the way components of your mental health may return as well – piece by piece over time. 

• This is an ongoing treatment. Know that depression and mood disorders are neurodegenerative and will return over time. There is no cure for this cognitively scarring condition that frequently causes loss of self-awareness of mood and functioning. It is important to monitor your improvement and maintenance using journaling, therapy, self-report, family observations, and medically validated monitoring as with the OSMIND app to track depression, anxiety, ADHD, and other mental health parameters. These are mental health vital signs.  
• Recognize that you may achieve remission in symptoms, but this may take time. At-home ketamine therapy with lozenges and ketamine nasal spray may be needed to help the treatment process after the initial series. Know that 6 infusions are not ‘set in stone.’ Some patients require several more infusions in rapid succession. Treatment is not ‘done’ at 6 infusions. Recurrence of symptoms may occur within weeks if some maintenance infusions, home treatments, therapy, and lifestyle changes are not included. 
• Do not let more than 5-7 days go between initial ketamine infusions. This may affect results. 
• This treatment is about neuroplasticity – it will reconnect neural networks that have been damaged by stress, medical issues, genetics, and environmental concerns. This will not change your personality. If you like the color pink, we cannot make you like blue. 
• Ketamine therapy can treat your mood and associated features of wellness. It cannot change your behavior. Altered and low mood can result in behavioral changes to cope with the mood. These behaviors get translated into habits by the brain. These habits are treated with psychotherapy. Medications cannot change behaviors.  

• Returning to psychotherapy is important. Ketamine therapy can lubricate therapy results, especially if you are ‘stuck in therapy’ with hamster-wheel thoughts.  
• Ketamine therapy decreases cognitive rigidity and increases psychological flexibility so you can think outside of the box. This increases your mental foundation to deal with daily stresses in a more effective way.  
• Ketamine therapy is a piece of the treatment process, but you have to play an active role in the healing process. It is important for you to remain compliant with your medications, engage in therapy, structure your day schedule to stay active, exercise (if medically clear), eat healthily, consider appropriate supplements, avoid substances such as alcohol and marijuana, and consider intermittent fasting. 
• If you are in a toxic environment, such as a bad relationship, undesirable job, or other situation, recognize that ketamine therapy will not change that. This continued stress will be harmful over time, but ketamine therapy may allow you to have increased resilience to handle such problems. 
• Also keep in mind that you are receiving ketamine therapy, not those around you. People will still be driving the same way and behaving the same way despite your treatment. You may have more resilience and understanding with this therapy. 

• Cognition is one of the most affected aspects in depression, anxiety, and suicidal ideation. Tracking neurocognitive deficits is important. NOVA Health Recovery utilizes Creyos testing to assess working memory, visuospatial processing, verbal recall, and other parameters that, when affected, result in ‘brain fog’ and ADHD symptoms associated with depression. 

What is Ketamine? 

Ketamine is a dissociative anesthetic developed as a relative to PCP (phencyclidine) for the purposes of medical and veterinarian use. Dissociative anesthesia is the state of “lights on but nobody home,” in which the patient maintains airway reflexes while seemingly awake, yet they are completely unresponsive. The safety profile is such that it is one of the safest medications for the medical use and even the World Health Organization lists it as a ‘must have’ medication. In fact, per the W.H.O. worksheet, it (ketamine) does not require reliable electricity supply, oxygen, highly trained staff or monitoring systems to administer. That makes it critical in surgery in low- and middle-income countries.”  

It was first synthesized in 1962, patented for use in 1966, and FDA approved for anesthesia in 1970. Ketamine could rapidly produce profound analgesia with a unique state of altered consciousness and a limited duration of effect that could be safely prolonged with repeated administration. A European Monitoring Centre for Drugs and Drug Addiction report identified 12 deaths in which ketamine was identified between 1987 and 2000, with three involving ketamine as the sole substance. 

How does ketamine work? 

Ketamine works in very complex ways in the brain and there is a lot of debate and unknown mechanisms that are at play. The details of its mechanisms of action are esoteric at best, but effectively Ketamine impacts numerous systems in the brain. Ketamine is an antagonist at the NMDA receptor site, which is involved with the neurotransmitter, glutamine, an excitatory neurotransmitter. Ketamine effectively binds to an area inside the receptor and blocks it from letting in excitatory ions, thus quieting the neuron. Ketamine works, in part, by activating certain neurons in a network and thereby shutting down other networks, resulting in an antidepressant effect. It also has a relaxant effect on airway smooth muscle that has been attributed to its inhibition of L-type voltage-dependent Ca2+ channels, which also may produce the altered perceptions and impaired verbal fluency during an infusion. It also blocks other systems in the brain such as preventing serotonin uptake and reducing pain perception. Ketamine’s block of large-conductance KCa channels (BK channels) preferentially suppresses spinal microglia hyperactivation after nerve injury and may explain its potent effects on neuropathic pain. Estrogen and progesterone may also potentiate the rapidity and potency of ketamine’s antidepressant effects, and hence there are sex differences  in the response to ketamine. 

Chronic stress, medical illness, alcohol, drugs, genetics, medications, toxins, and numerous other external traumatic interactions result in changes in the neurons of the brain with reduced synaptic connectivity. This occurs in the prefrontal cortex (involved with decision making and executive functioning) as well as in the hippocampus (the memory center). This can be seen on functional MRI’s as decreased activity and connectivity, and in fact, depression and mental illness can shrink these areas in size. That is where brain fog, decreased processing speed, and poor memory stem from. Cognitive tests demonstrate these phenomena, which results in poorer performance in the work and school environment as the individual is not fully able to think clearly due to these poorly connected memory and cognitive circuits. PTSD, anxiety, depression, and bipolar disorder all decrease functional connectivity in the brain. 

Ketamine therapy has been shown to increase connectivity and repair nerves in the brain, and in fact the degree of clinical response is comparable to the degree of connectivity. 

What are Neurons? 

Neurons are the fundamental cells of the brain. The nerve cell body sends signals elsewhere through the axons and receives information through the dendrites. Dendrites are a bushy-like area of the nerve body that connects with other nerve cells, much like a cluster of ivy on a wall. These connections form the basis of learning and memory. When they are over-pruned, depression and other mental illnesses can result. 

Health state – represented by a full ‘wall of ivy’ (neurons) 

Over-pruned and depressed – fewer neurons and synapses – results in depression 

The brain’s neural network is like a wall of ivy as in the first photo, where neurons are all interconnected. This pattern is lost and over pruned in depression, as in the lower photo. This results in vegetative, sickness behaviors such as low motivation, slow processing speed, poor memory, and no interest in otherwise rewarding events. 

The brain keeps a balance between excitement and ‘rest’ through its neurotransmitters. 

Neurotransmitters are small molecules that cross from one nerve cell to another. It is a way of communications, and the molecule type can help determine the message. Molecules such as dopamine, serotonin, norepinephrine, GABA, and Glutamate are examples of these neurotransmitters. The actions of these neurotransmitters are very regulated and too much excitatory or inhibitory transmitters can disrupt a balanced brain. 

Glutamate is the most common excitatory neurotransmitter and is a key molecule in learning and neuroplasticity. Neuroplasticity is the ability of the brain to form new connections as in learning and forming new memories. Excess glutamate can damage nerve cells and this is associated with inflammation and depression.  

Stress and neuronal damage 

Stress with elevated cortisol levels results in damage to nerve endings as axons thin and dendrites disappear. Constant glutamate transmission from a brain on fire results in damage and loss of neurons. This is seen on MRI’s as measurable loss of brain volume. This is seen clinically as depression and anxiety. Depression is being recognized as more of a glutamate receptor issue. Ketamine can reverse this by replacing damaged neuronal spines and rapidly increasing connectivity in the brain. 

Ketamine rapidly allows neurons to form new spines 

Ketamine and glutamate 

Ketamine affects multiple receptors in the brain in complex manners. There are many different receptor types in the brain, some excitatory and others inhibitory, and ketamine interacts with many. In the case of glutamate, ketamine affects the NMDA receptor (N-methyl-D aspartate) receptor and the AMPA receptor., activating both.  

Glutamate binds to NMDA receptors and activates the receptor to let calcium into the neuron, whereas when glutamate interacts with AMPA, it lets in sodium and lets out potassium from the neuron.  This causes the activation of the nerve. Ketamine blocks the glutamate binding at the NMDA receptors of the postsynaptic cell (the neuron that receives the signal) but doesn’t block AMPA binding, with glutamate thus AMPA gets activated, which turns on the neuroplasticity machinery. 

Brain-Derived Neurotrophic Factor (BDNF) is brain fertilizer 

In summary, ketamine shifts activation by glutamate from the NMDA receptors to the AMPA receptors resulting in the production of BDNF, which promotes growth and survival of neurons and thereby produces neuroplasticity. In these same neurons, mTor (mammalian target of rapamycin) is activated, which synthesizes proteins involved in memory formation, particularly in the prefrontal cortex (the CEO of the brain) and the hippocampus (involved in memory). Thus, BDNF reverses the damage produced by chronic stress. This is what produces the new dendritic spines of learning and connection in the brain to reverse depression. This occurs within hours of an infusion.  

Depression relief is all about the connectivity 

Depression and other mood disorders disrupt connectivity in the brain. This can be seen as decreased activity on functional MRI’s as well as ‘brain shrinkage’ in key areas of the brain, such as the prefrontal cortex and hippocampus. This is seen at a microscopic level as decreased dendritic spines and retracted smaller neurons or even loss of neurons the results are brain fog, slow processing speed, weak memory, and symptoms of depression, such as hopelessness, lack of motivation, sadness, and many body-related symptoms. Ketamine represents a significant step forward in the rapid treatment and resolution of the damage to the brain caused by stress. 

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