The neuron has a cell body that contains the nucleus. The nucleus is where DNA is stored and also where the cell processes of the neuron is regulated. The Neuron also contains other cell body: ribosomes-needed to make proteins like neurotransmitters and mitochondria-the miniature energy producing power plants of the cell.
Extending off the cell body of the neuron are axons. The axons are long extensions of the cell body that at its end junction communicate to other dendrites, extensions of other neurons, The communications is maintained by nerve electrical signals and neurotransmitters that transmit messages from one neuron to another. Dendrites also branch off at the other end of the neuron and form clusters of nerve fibers that send and receive messages from other cell bodies.
In the most developed part of the human brain, the cerebral cortex there are an estimated 14-16 neurons, making connections, firing signals, and forming pathways that are required in executive functioning, learning, memory, speech, and emotions etc.
Electric impulses, (Action Potentials) are transmitted from the axon of one neuron to the dendrites of another neuron. The junction where the neurons communicate is called the synapse. Neurotransmitters are brain chemicals, like serotonin, Nor-epinephrine, Dopamine and others. To transmit the nerve impulse neurotransmitters travel across the gap or synaptic cleft between neurons as chemical messengers to allow the impulse or signal to be propagated.
Neurotransmitters are made in the neurons and stored in tiny sacs, vesicles, at the ends of axons. The cell membrane or outer covering of the neurons are covered with receptors, which channel the neurotransmitters through to the next neuron. There receptors are specific for each type of neurotransmitter. The neurotransmitter fit like a key on the receptor which then opens the channel into the cell.
The nerve impulse at the end of the tip, also affect the opening of Calcium channels. These Calcium-charged elements then cause the vesicles to attach to the neuron cell membrane, which then allows for the pouring of Neurotransmitters to be secreted into the synapse. Neurotransmitters diffuse across the synapse gap and bind to their matching and specific receptors in the membrane of the postsynaptic neuron (the target neuron). The binding opens the channels leading into the cell interior and calcium, sodium, magnesium, and other ions flow in.
The flow of incoming ions such as calcium and sodium depolarizes( or changes the charge) the cell membrane, which gives the inside of the cell to be more negatively charges. When the depolarization threshold is reached the neuron fires an electrical signal. This impulse is then transmitted through the cell, down its axon, and on to the next neuron in the chain.
After the neurotransmitter has done its jobs in the synapse, it is taken back up or (reuptake) into the pre-synaptic cell membrane. From there the neurotransmitter is taken back into the cell and stored once again in the tiny sacs, vesicles. Neurotransmitters now repackaged await the signal of another cycle of impulses to repeat the actions as the messenger between neurons once again.
When the neurotransmitters are re-absorbed, the synapse turns off. The entire process of impulse and neurotransmitter communication back to reuptake into the cell occurs in milliseconds and happens billions of time a day, 24 hours a day!
In the brain, the neurotransmitters glutamate and dopamine are excitatory. The inhibitory neurotransmitters are GABA (gamma-aminobutyric acid), serotonin, and dopamine.
The release, removal, and reuptake of neurotransmitters is tightly regulated. If there is an effect on the reuptake of neurotransmitters, the concentration neurotransmitter or the sensitivity of neuron’s impulse, there can be a disruption in the brain’s communication, connectivity, and balance. This can lead to a dysregulated state of either too much excitation or inhibition in specific parts of the brain.
Glutamate is the most common excitatory neurotransmitter in the brain. It plays a particularly important role in neuroplasticity (the brain’s ability to form new synapses and neural connections over a lifetime), learning, and forming memories. When there’s too much glutamate in the brain, the postsynaptic neurons can become hyperexcited; when there’s way too much glutamate in the brain, it can damage neurons or even cause neuron death.
Toxic level and persistent stress affects the neurons of the cortex. Toxic stress puts the brain in an inflammatory and increases cortisol concentrations in the brain. Cortisol can cause neurons atrophy or early death and shrinkage of neurons. Dendrites also decrease in their ability to branch and spread, which leads to fewer connections between neurons. The axons are thinner and smaller. Glutamate signaling is also less effective and responsive.
It has been shown that in chronically depressed people, the size of the prefrontal cortex is smaller and connections to other key components of the brain, are restricted and become dysfunctional in the emotional (limbic) and memory centers (hippocampus) of the brain.
The toxic and inflammatory state of the brain, in trauma, depression, anxiety limits effectiveness of the glutamate neuronal pathways.
Ketamine, which is an anesthetic works by activating glutamate release into the synapse. Researchers studying depression discovered that glutamate receptors can be “dysfunctional” in people with depression. -this is focus of ketamines effect on the glutamate system in treating depression.
Ketamine when used as an anesthetic, was also found to lift symptoms of depression. Since the 1990s more research has shown that small doses of ketamine when given to severely depressed patients, who did not respond to standard antidepressants like SSRI’s had remarkable results.
We know that ketamine does affect other receptors but it most important receptor it activates are glutamate receptors.
Neurons have many binding sites for glutamate, but when it comes to ketamine, two are of particular interest: the NMDA (N-methyl-D-aspartate) receptor and the AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptor.
Glutamate activates the ion channels in both NMDA (N-methyl-D-aspartate) and AMPA α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid) receptors.
At the very low dose, Ketamine increases release of glutamate from presynaptic cleft into the synapse, which has an antidepressant effect. However, Ketamine then preferentially blocks glutamate at the NMDA receptors of the postsynaptic cell but not at the adjacent AMPA receptors. This causes a net effect to increase AMPA activation. In addition, Ketamine triggers the neuron to make more AMPA receptors, moving them into the membrane of the synapse area.
Not only does Ketamine increase glutamate transmission and a net increase in AMPA activation, it also allows for quick up-regulation of neuronal production and release of BDNF (brain-derived neurotrophic factor). BDNF is a growth factor in the brain that promotes neuronal growth and enhances survival it leads to restoration and neuroplasticity of neurons and their connectivity.
In addition, Ketamine works on another important pathway called mTOR(mammalian target of rapamycin) which is involved in regulation of cell growth and synthesis of proteins necessary for long-term memory. The combination of mTOR and BDNF also improve connectivity in the synpses of the prefrontal cortex and hippocapmus- areas involved in processing emotional regulation, memory. Research has shown that within a hours of treatment doses of Ketamine, there is repair, regrowth, and enhanced connectivity in areas of the brain, PFC and hippocampus, damaged by toxic and or persistent stress. When this type of neuroplasticity occurs, symptoms of trauma, anxiety, and depression are diminished.
It is also, important to realize that at higher doses(Anesthetic level doses) of Ketamine, neuroplasticity and increase in BDNF does not occur.
Further research has uncovered the effect of Ketamine on other receptors, NMDA and parvalumin interneurons. Ketamine blocks one part of the NMDA receptors, and in these parvalbumin interneurons, the effect is and increase activity of brain circuitry which awakens the brain. Ketamine can trigger increased release of the neuromodulators dopamine and noradrenaline; it also binds weakly to nicotinic and opioid receptors. More actions of Ketamine are also known to effect on organelles (structures) in the neuron that are involved in signaling, protein and lipid synthesis, and transport proteins.
Toxic level stress impacts the brain at both micro-cellular and macro-structural level on the brain. Chronic depression, anxiety, and PTSD lead to decreased size, response, and connectivity in the key parts of the brain. The prefrontal cortex is where a significant portion of executive functioning occurs, planning, organizing, self regulation, problem solving. Ketamine enhances global connectivity within the prefrontal cortex and the pathways in other sub-regions of the brain.
Before you undergo Ketamine therapy we first interview you carefully to find out if you’re eligible to receive this medication.
You may not undergo the treatment if you belong in one (or more) of these categories:
(There are specific criteria that would make you ineligible for Ketamine depression therapy.)
Nursing Mothers and Pregnant Women – Ketamine may have potentially unwanted effects on the nursing child or the fetus. Data from the study published in Nature suggests that prenatal exposure to Ketamine impairs the neuronal development of the prefrontal cortex.
Untreated Cardiovascular Problem–Hypertension, especially if it’s untreated, is a contraindication to the use of Ketamine. The drug causes a rise in blood pressure. Individuals with a history of heart problem, therefore, may not be eligible to take this treatment.
Untreated Hyperthyroidism – People with this condition should not take Ketamine. The drug increases the risk of tachycardia and hypertension.
Conditions that are Excluded in Ketamine therapy
Absolute Exclusions to KAP
Relative Exclusions
People undergoing ketamine therapy can take the drug in various ways. Ketamine can be administered by medical professionals:
When used in a supervised setting at appropriate dosing, Ketamine therapy is quite safe. You will have fully trained health professionals at your side throughout your treatment journey. As with any treatment, there are potential risks and side effects. Before beginning your treatment with us, you will meet with our medical team to ensure it’s a good fit for you.
Ketamine is listed as a schedule III drug by the Drug Enforcement Agency or DEA. It can only be administered by licensed providers who are trained and have experience with its responsible use. In this setting, Ketamine is safe and well tolerated therapy and benefits many people. The use outside of a clinically prescribed setting is considered illegal. When used or abused in this manner, people have experienced extreme effects that include not only extremely distressing disassociation but also, uncontrolled blood pressure, dizziness and fast heart rates. Any side effects or dosage adjustments that can occur, will be monitored by licensed medical doctors and professionals.
The largest study ever done on depression called NIMH(National Institute of Mental Health) STAR*D Medical Trial in 2006, Rush et al. Read more
This study was unique because it measured outcomes of depression treatment in real people in real medical practices.
They were looking to see if antidepressants could result in remission of depression, not just suppression of symptoms. What they found was that most people did not significantly improve or achieve remission on conventional medication. Furthermore, the more sequential antidepressants prescribed to achieve symptom improvement or remission the even more lower likelihood of improvement. In the meanwhile, studies were emerging that ketamine had greater and more immediate effects in depression remission.
Ketamine Assisted Psychotherapy or KAP is considered to be a game changer. Data has shown that KAP can alter the course of depression in about 70% of people.
People stay better longer and can actually experience complete resolution of their symptoms. For many of us in medicine, we have not seen this kind of response ever.
Unlike antidepressants, that “suppress” symptoms, KAP experiences tend to be “evocative”- activating your own ability and inner healing to take place with the support of the medicine and our treatment team.
Each person’s response can vary by dose and depth of the ketamine’s effect. The experience has been described as “euphoric,” “calming,” and “mystical. You may experience a sense of disassociation—that you are observing your mind and body from outside rather than within.
The experience can also feel “empathogenic”- where one’s typical defense mind mechanisms are relaxed.
Higher doses of ketamine can provide a profoundly transcendental experience- that can result in amenable ways to self exploration and deeper therapeutic insights.
The effects of improving mood, depression, anxiety, and inner knowing can extend for weeks to months.
Ketamine interacts with some of your brain’s neurotransmitters. Its effects can include relieving anxiety and pain relief, and acting as an antidepressant.
Under medical supervision, lower doses of Ketamine can relax your mind and allow you to temporarily disengage from your routine thought patterns.
Ketamine can raise blood pressure temporarily. Your blood pressure, heart rate, and breathing are also monitored to ensure your safety.
If any effects of Ketamine effect you during the session, such as nausea, this is monitored and treated.
The antidepressant effects of ketamine were first described over two decades ago. Many prominent researchers and institutes have studied the neuroscience of ketamine and the neural basis of stress-related and trauma in many psychiatric conditions. There is a the physical effect of persistent toxic stress leads to neuronal changes, reduced synaptic connectivity between neurons and communication. This is especially prominent in the prefrontal cortex and the hippocampus of the brain.
In depression and other psychiatric disorders resulting from toxic stress, a reduction in prefrontal and hippocampal connectivity has been observed in functional MRI imaging studies. Other chronic stress mental states (e.g., PTSD, generalized anxiety disorder, OCD) have similar patterns of decreased connectivity and maladaptive effect brain architecture.
Ketamine and soon to be approved other psychedelics has demonstrated:
As part of the approach to holism and wellness, ShaMynds offers another source to improve your physical and mental health. This includes intravenous therapies for a wide variety of conditions.
CONDITIONS FOR INTRAVENOUS NUTRITION
Prior to receiving any of these therapies, a physical history will need to be completed to determine if intravenous vitamin/nutrient replenishment is safe for you.
This history will include a risk assessment, medications you are currently taking, and certain disease states that would need consideration prior to infusion therapy.
Safety is of utmost importance always. We take your vitals before and after the infusion, use only staff trained in intravenous infusions and monitor you during your session. Sometimes, we may make a recommendation for blood work or other testing prior to an infusion.
After an IV therapy, it is usually a good idea to:
If you are familiar with intermittent fasting, it’s a good thing to try to let your digestive system take a break and do the fast. Alternatively, consider going on a bone broth day. The fat and protein in the broth should keep you satiated. If you would like to do a juice fast instead, do include lots of vegetables in it as a fruit only juice can make you feel worse (due to its effect on insulin). Add some organic coconut oil to it to slow down absorption of glucose.
You can continue with the various cocktails and make sure that you inform the center if you experience side effects, if any.
Transcranial magnetic stimulation or TMS is a non-invasive, diagnostic and therapeutic technique that uses small magnetic fields to stimulate or inhibit regions of the brain by electromagnetic induction through a small generator coil (Figure-8 or H-coil), placed over the patient’s head. It can be used for the treatment of conditions such as depression and obsessive-compulsive disorder (OCD).
Every patient is different. Most large TMS research studies provided treatment five days a week for 4-6wks up to 36 sessions for a figure of 8 coil treatment. H-coil treatments have been studied for 5 days a week of treatment followed by 12 weeks of treatment 2 times a week for a total of 44 sessions. There is no demonstrated toxicity from treatment beyond this amount of sessions and, in some situations, it may be reasonable to continue treatments beyond this number. Some people may require a schedule of maintenance treatments to maintain their treatment results.
TMS delivers magnetic pulses to certain brain regions, producing changes in the activity of the brain cells. The frequency of pulse delivery influences whether brain activity is increased or decreased in the affected cells. This means that the effects of TMS treatment can be long lasting because it changes the patterns by which nerve cells and brain networks connect and communicate with each other.
Your doctor will discuss with you the best way to administer TMS. The session lasts between three and 37 minutes depending on the protocol used.
Both TMS and ECT are forms of neuromodulation used to treat depression. Electro-convulsive therapy (ECT) involves passing an electric current through the brain. This causes a generalized (grand mal) seizure. It therefore requires a general anesthetic. While having ECT, patients may require inpatient care or require someone to drive them to and from ECT treatments. ECT can cause short term memory loss for the period before and after each treatment session. Patients usually have 6-12 treatment sessions over three to six weeks and few patients have memory loss for this whole time period.
TMS uses an electromagnetic coil to create an alternating magnetic field over the scalp and this magnetic field induces small currents in the brain.
TMS is an outpatient procedure that does not require an anesthetic and patients can resume their normal life activity after the session.
Both TMS and ECT can lead to a rapid improvement in symptoms. Up to 70% of depressed patients who fail to respond to antidepressants respond to ECT and about 60% of patients who fail to respond to antidepressants respond to TMS.
Some patients who fail to respond to ECT will respond to TMS and some patients who fail to respond to TMS will respond to ECT. ECT is still considered the best treatment for some patients with very severe depression, psychotic depression or catatonia. Your doctor will advise you about which is the best treatment for you.
Antidepressants work by modifying the actions of neurotransmitters (brain chemicals) or modifying neurotransmitter receptors. TMS induces small electrical currents in the brain which improve the connections between brain cells and increase the growth of brain cells. Treatment with antidepressants involves taking medications which are absorbed through the mouth, stomach and small intestine with possible side effects throughout the body. They can cause adverse effects such as gastrointestinal side effects weight gain and can have an effect on sexual function (reduced sex drive and delayed ejaculation). Patients can also be allergic to antidepressants or other chemicals contained in the medication.
TMS does not involve the ingestion of chemicals, therefore, there are no systemic adverse effects. There is no impact on the digestive system, on sexual function, cognition and there are no allergic responses. The only side effect with TMS that is greater than 5% is transient site pain, headache which abates typically within the first week as patients desensitize to the treatment.
Antidepressants modify brain chemicals and receptors via an effect on protein synthesis, they can take between three to six weeks to work, while TMS has a faster onset of action. Studies show that in patients who have not responded to two or three antidepressants the response rate the next antidepressant is 10-15%. If such patients are given TMS, the response rate is about 60%.
TMS can be very effective in the treatment of depression. For over 20 years it has demonstrated the ability to improve depression symptoms in patients in research studies as well as under more real-world conditions. In one of the largest studies of patients treated with TMS for depression, around 60% of participants reduced their symptoms by at least 50% (responded) and around 30% of participants no longer met criteria for depression (remitted). This study did include some participants who have been treated with ECT to manage their symptoms and they had equal chances to achieve improvement compared to people who had not had ECT in the past. TMS is effective in the treatment of obsessive-compulsive disorder (OCD) as well. Around 40% of participants in the landmark study for FDA (Food and Drug Administration) clearance achieved remission and around 60% of participants responded to treatment. This is just a sample of some of the illnesses that TMS has been demonstrated to effectively treat but there are other illnesses that are under investigation or approved in countries outside of the United States including PTSD, stroke rehabilitation, and chronic pain.
TMS has been tried as a treatment for different mental health and neurological conditions such as, depression, obsessive compulsive disorder (OCD), post traumatic stress disorder (PTSD), anxiety, addiction, eating disorders, dementia, autism, migraine, neuropathic pain, fibromyalgia, post stroke conditions … etc. However, the current evidence to support the use of TMS in treating different conditions vary significantly. At the present time there is very strong evidence to support the use of TMS as a treatment for depression. This led to TMS being used in the treatment of depression in many countries around the world. For example, in 2008 the FDA approved the first TMS machine for the treatment of depression and in 2015 NICE (National Institute for Health and Care Excellence) in the UK recommended TMS as a treatment for depression. The FDA also approved some TMS devices to be used for the treatment of OCD and Migraine. The evidence supporting the use of TMS as a treatment for different mental health and neurological conditions is growing very quickly. Therefore, we advise you to check with your treating doctor if TMS could be a possible treatment option for your condition. You can find a TMS clinician in your local area by checking find a provider page on our website.
The most common side effects of TMS are discomfort at the site of treatment during the treatment sessions and a mild headache for a few hours following the sessions. Occasionally patients experience discomfort in the eye, teeth or jaw and typically alleviated with over the counter analgesics.
Some patients may experience increased anxiety and sleep difficulties. All of these usually decrease following the first week of treatment.
TMS is a loud treatment, wearing appropriate ear plugs during sessions protects hearing. There is a very small risk that some patients will develop seizures during treatment sessions. The probability of a patient without a history of epilepsy developing seizures is 1 per 60,000 treatment sessions. This is less than the risk of seizures developing in patients who take antidepressants.
It is advisable that you have regular follow-ups with your treating clinician after you respond to TMS. This should help to consolidate your recovery and in order to agree on a treatment plan if you start having depressive symptoms again. A lot of patients who respond to TMS maintain their improvement without having additional treatments for at least a year. However, there is a group of patients who might re-experience depressive symptoms after responding to TMS. For this group of patients, the treating clinician might decide to reintroduce TMS. These are sometimes called booster or rescue TMS and if you responded to your initial course of TMS it is highly likely you will respond to TMS again. In addition, if TMS is reintroduced sooner in the onset of depression, typically patients require fewer TMS booster sessions to stabilize their mood. Some patients might need to have what we call maintenance TMS sessions. This involves the patient having regularly scheduled TMS sessions once every few weeks in order to maintain mood stability. The frequency of these maintenance TMS sessions is usually decided after a discussion between the patient and their treating clinician while taking different factors into account. Your treating clinician might also suggest prescribing you medication (such as an antidepressant) to consolidate your recovery, deal with recurrence of symptoms or to protect you against relapsing.
In summary, a good proportion of patients who respond to TMS maintain their improvement without further interventions and for patients who re-experience depressive symptoms TMS can still help them to overcome these symptoms.
Around 60% of people treated with TMS respond to treatment. If people do not respond to TMS they should be evaluated by their treating psychiatrist and other treatments should be considered. This should include medication review, ECT and psychotherapy. Some patients will improve using different TMS sequences or treatment locations.
TMS is a well-tolerated treatment, the vast majority of patients can have TMS. People with non-removable metallic, ferromagnetic objects which is less than 30 cm from the treatment coil might not be suitable for TMS and should consult with their TMS prescriber if they have any of these items:
TMS can still be given to people with certain types of stents and implants. People with implanted cardiac defibrillators cannot have TMS. Dental work including fillings/implants and piercings are not a contraindication for TMS.
The time needed for a patient to start seeing positive results differs from one patient to the other and it is quite difficult to predict. Assuming that patients have daily sessions for five days every week the majority of patients who respond to TMS start seeing positive results after a few weeks of receiving the treatment. However, some patients report positive results sooner than this and other patients can have a delayed response that at times happens towards the end of the 6th week of TMS treatment.
Transcranial magnetic stimulation (TMS) is a non-invasive form of brain stimulation that uses electromagnetic induction to create electrical current in specific brain areas. This technology is used in research as well as in clinical care. It can be used for many purposes including providing real-time information about the state of the brain and providing treatment for various health conditions.
As this technology has multiple uses, we would like to clarify the definition of terms to help ensure that society members, trainees, and the general public have a clear understanding of transcranial magnetic stimulation.
Repetitive TMS (rTMS)
rTMS is currently the most widespread form of TMS for clinical applications. In rTMS, magnetic pulses are delivered in a rapid series or “train.” When rTMS is used, multiple single-pulse stimuli are presented at a specific frequency, intensity, and time duration. Repetitive TMS also includes Deep TMS™ (dTMS), a trademarked term from a TMS device company.
Single Pulse TMS (spTMS)
One electromagnetic pulse is applied no faster than once every few seconds. SpTMS is most commonly used to examine connections in the motor areas of the brain.
Paired pulse TMS (ppTMS)
As a tool in research, paired pulse TMS uses 2 pulses applied out of phase to inhibit or excite brain cells within the same hemisphere or to inhibit brain cells in one hemisphere while exciting them in the other hemisphere.
Ketamine therapy may cost more than traditional treatments due to a lack of insurance coverage. We’ll walk you through the steps to figure out how to pay for alternative depression treatments so you can get the help you need.
However, you could actually save money in long run, as ketamine treatment is given in 3 month course and short courses have been shown to be effective, in comparison to chronic use of other antidepressants and the costs associated with this model of care.
Do you offer financial support?
We also work with you and your financial concerns to:
Don’t let mental health challenges or uncertainty hold you back from living the life you deserve. At ShaMynds, we’re here to provide you with compassionate care, advanced treatments, and unwavering support every step of the way. Whether you’re ready to start a new chapter or simply want to explore your options, we’re here to guide you.
Take that first step toward balance and well-being today.