Low-Dose Ketamine For Long Haul Covid, Post-Vaccine Syndrome, and ME/CFS

Low-Dose Ketamine For Long Haul Covid, Post-Vaccine Syndrome, and ME/CFS

by | Jan 13, 2026 | Long Haul Covid and Post-Vaccine Syndrome

Spike Protein and Brain Injury

Those suffering from spike protein  Post-Vaccine Syndrome and Long Haul Covid have found their brain to be profoundly impacted, and are seeking answers. Many patients talk of “brain fog”, which might include memory recall issues, word retrieval issues, unclear thinking, and difficulty focusing. However, the symptoms go well beyond brain fog.

In some corners of the internet, you may find discourse between patients dealing with anhedonia, depersonalization/derealization, depression, and anxiety. Additionally, you may even come across conversations about complete personality changes. You may be experiencing these things yourself. On the Side Effects with Dr. Josef podcast, Scott Marsland discusses why so many of the Post-Vaccine Syndrome injuries look like traumatic brain injuries.

Screenshot of play bar to Dr. Josef's

Even in the conventional medical system, there is now a significant body of research evidence demonstrating the various mechanisms by which the spike protein induces these brain-injury manifestations. If you peruse mainstream journals like Nature, you will find studies highlighting the ability of the spike protein’s S1 unit to cross the Blood Brain Barrier.

Here is a list of pathophysiological ways spike induces brain injury:

  1. Blood-Brain Barrier Disruption – binding to ACE2 receptors on endothelial cells, disrupting tight junctions and increases permeability; activating the RhoA signaling pathway, leading to the disassembly of the endothelial cell cytoskeleton and junction proteins; inducing the production of vascular endothelial growth factor (VEGF), a potent inducer of vascular permeability.
  2. Endothelial Damage – bind directly to fibrinogen, promoting the formation of proinflammatory blood clots (microthrombi) and contributing to systemic thromboinflammation, which can cause microvascular damage in the brain
  3. Neuroinflammation – directly activates glial cells (microglia and astrocytes), the brain’s resident immune cells, even without full viral replication in the brain parenchyma, which then release pro-inflammatory cytokines, especially interleukin-1β (IL-1β), which is neurotoxic and leads to bystander neuronal death
  4. Accumulation of Neurodegenerative Proteins – induce the aggregation and accumulation of proteins associated with neurodegenerative diseases, which are linked to synaptic dysfunction and neuronal loss
  5. Prion Formation – contains “prion-like” domains (PrDs) that can interact with amyloidogenic proteins in the brain, potentially accelerating their misfolding and contributing to neuroinflammation and neurodegenerative diseases
An illustration demonstrating spike proteins influence on Endothelial damage, BBB disruption, microglial and astrocyte activation, and neuronal damage

Foundations For Treating Spike Induced Injury

There is no shortage of avenues to attempt to treat the neurological symptoms of those suffering from Long Haul Covid and Post-Vaccine Syndrome. There are adaptogens, anti-inflammatory compounds, immunomodulatory compounds, and methods to support vascular health. A multi-pronged approach is key to addressing multiple pathophysiological mechanisms, as well as clearing the body and brain of spike protein.

When we look at therapeutic interventions, there are a couple things we consider:

  1. Efficacy
  2. Safety
  3. Degree of Impact
  4. Ability to address multiple issues at once.

One treatment checks all four boxes, and does so with gusto.

The History Of Low-Dose Ketamine

Ketamine was first synthesized in the 1960s as a general anesthetic and approved in 1970, by the FDA. In 2020, Brazilian researchers found a fungus called Pochonia chlamydosporia which produced ketamine naturally and found that it demonstrated potent anti-parasitic efficacy equivalent to Albendazole and Ivermectin.

In 2000 to present day, a number of studies have demonstrated the effect of Ketamine on psychiatric disorders:

  • In 2000, psychiatrists at Yale figured out that sub-anesthetic doses of ketamine produced rapid anti-depressant effects. That discovery initiated the practice of using IV ketamine to treat depression
  • In 2013, Brazilian researchers discovered that a low dose of sublingual ketamine (10 mg every 2- 7 days) led to full or clear responses in 77% of patients with treatment-resistant unipolar and bipolar depression.
  • In this series of hundreds of patients, the patients received six treatments of 300mg rapidly dissolving tablets of ketamine. 48% of patients demonstrated a significant reduction in depression scores after three treatments and after 6 treatments, 72.4% demonstrated improvements in anxiety and depression scores.
  • In another case series, 17 patients received 0.5mg/kg or 1mg/kg SLK every 7 or 14 days with 76% (13) of the subjects classified as responders.

Our Introduction To Low Dose Ketamine

Our clinical team is fortunate to have become colleagues with (and students of) two of the most clinically experienced psychiatrists at the leading edge of using Ketamine in clinical practice – Dr. Rachel Wilkenson and Dr. Mitch Leister. They have now been using sublingual low-dose Ketamine in the treatment of numerous mental illness conditions for 5 and 3 years respectively.

In both published and unpublished case reports and series, the results they have achieved in their patients is nothing short of revolutionary. For the first time in their 20 and 40 year careers, they have seen dramatic recoveries in mood disorders, including:

Here are a few pieces of their clinical and research work:

  • In an abstract they presented at the World Congress of Psychiatry in Vienna in 2023 they reported that an incredible 96% of patients’ depression scores improved (27% in full remission, 37% with an over 50% improvement, and 32% with improvements between 7-49%) over an average of just 3.4 months.
  • Another trial gave 5 days of SL ketamine to 329 patients and found 168 had achieved a significant response by Day 8. These patients then received 12 weeks of treatment at various dose levels or placebo. At 13 weeks, the highest dose (180mg) met the primary outcome of a large reduction in score on a depression scale, while 70.6% of the placebo group relapsed compared to only 42.9% of ketamine patients during the trial.

Largely because of Dr. Wilkinson, Dr. Leister, and others’ research and clinical work, Ketamine is now on all updated protocols for depression and bipolar disorder as of Fall of 2023, according to continuing medical education articles (FOCUS journal sponsored by the American Psychiatric Association). There is no set limitation on the duration that patients are able to be treated with Ketamine, and recently there have been articles released that indicate long-term use results in cognitive improvement over at least the duration of two years – longer studies are ongoing.

Psychoplastogen... We Say Neuroplastogen

The importance of Ketamine is that it is a “paradigm shifter” given that it modulates a neurotransmitter called glutamate, rather than the neurotransmitters traditionally thought to be involved in and targeted by drugs for depression (i.e. deficiencies of serotonin, norepinephrine and/or dopamine).

Beyond its recognized glutamate modulating properties, Ketamine was found to be the prototype for a new class of medicines identified and named by a chemist in 2018 as “psychoplastogens” because of their ability to induce both structural and functional changes to the brain. However, for reasons you are about to see, we think Ketamine belongs under the name “neuroplastogen”.

At its simplest, ketamine can induce “brain growth” because at low doses (not at high doses):

  • Stimulates the release of brain-derived neurotrophic factor (BDNF).
  • Reduces excitotoxicity,
  • Increases cerebral blood flow
  • Up-regulates BDNF
  • Increases nerve growth, dendritic spine density, and synapses
  • Reduces neuroinflammation, apoptosis, cell death, and superoxide production.

As a result of up-regulated and stimulated release of BDNF, low-dose Ketamine also:

Here’s a picture taken with an electron microscope showing the effects of ketamine on a rat neuron. You can see all the extra bulbs or spikes that develop (yellow arrows) following treatment with ketamine. Each of these forms a new synapse.

Image shows neuronal growth in a rat that underwent ketamine tratment, versus the lack of neuronal growth in a control group

Low-Dose Ketamine and Long Haul Covid, Post-Vaccine Syndrome, and ME/CFS

Under the tutelage of Dr. Wilkinson and Dr. Leister, we have confidently combined their findings on Low-Dose Ketamine, to our clinical findings with Long Haul Covid, Post-Vaccine Syndrome, and ME/CFS patients. In a year of implementing Low-Dose Ketamine treatments, we have seen promising results. Scott Marsland has written a few case studies on neurodegenerative disease, typical Long Haul ME/CFS related neurological presentation, and a variety of other patient cases.

If you recall, early in this piece, we highlighted a number of neurodegenerative pathways, neuronal destruction, and other neuroinflammatory pathways of spike protein. Then, we introduced the mechanisms of action of Low-Dose Ketamine. Mainly, these mechanisms of action reflected an uncanny ability to rebuild neuronal connections, reduce neuroinflammation, re-myelinate neurons, and develop new synapses.

So, how does this translate to our patients? We have seen any combination of the following:

  • Improvement or cessation of dysautonomia
  • Improvement or return to baseline energy levels and reduction or cessation of Post-Exertional Malaise (PEM)
  • Improvement or return to executive functioning and cognition
  • Improved GI symptoms, or return to normal GI function
  • Improvement in mood, and/or reduction or cessation of depression, anxiety, and anhedonia
  • Improvement or cessation of neuropathy
  • Return of smell and/or taste

This is an incomplete list of clinical observations. But, it highlights some of the most significant types of improvements we see. We have witnessed patients go from disabled, to able-bodied. Furthermore, patients who are not quite disabled, report significant improvements allowing them to live more meaningful and full lives.

Conclusion

We have been extremely pleased with the results we have seen at Leading Edge Clinic. Of course, it is not as simple as just spoon-feeding Low-Dose Ketamine. Some patients with significant glutamate in the brain must first address these levels. While some patients see results immediately, others require time, patience, and careful titration.

Another significant factor that needs to be addressed is clearing the inflammatory, disruptive, and toxic spike protein. Low-Dose Ketamine does not do this. Of course, all of the information on the use of Low-Dose Ketamine in Long Haul Covid, Post-Vaccine Syndrome, ME/CFS, and neurodenerative diseases are purely clinical. Every case is different.

Nothing from this article should be construed as medical advice. Do not self treat. Find a capable and experienced clinician that can safely advise on the use of these therapies. Furthermore, ensure the clinician can deal with the full picture. Low-Dose Ketamine is a great therapy that helps on multiple layers of spike pathology. But, it is not a panacea. There is no panacea for multi-system complex illness.

Stay tuned as we expect more case studies from the front lines on patients treated with Low-Dose Ketamine.

8 Questions To Ask A Potential Long Covid or Post-Vaccine Syndrome Clinic

8 Questions To Ask A Potential Long Covid or Post-Vaccine Syndrome Clinic

by | Jan 6, 2026 | Long Haul Covid and Post-Vaccine Syndrome

Long Covid (Post-Acute Sequelae of Covid-19) and Post-Vaccine Syndrome (or “PVS”) are some of the most complex, idiosyncratic diseases of our time. However, they are nothing new. For decades, a small subset of patients have suffered immensely from a disease called Myalgic Encephalomyelitis. This is also known as Chronic Fatigue Syndrome. Historically, those diagnosed with ME/CFS found their disease began after a viral infection (ie: EBV, HPV, Lymes, etc…), or after prolonged exposure to environmental toxins (ie: mycotoxins/mold toxicity).

With the introduction of Long Haul Covid and Post-Vaccine Syndrome, the reports of ME/CFS have exploded. NIH studies and data suggests a 15-fold increase in ME/CFS diagnoses since 2020. Furthermore, 4.5% of study participants who had a SARS-CoV-2 infection met the ME/CFS diagnostic criteria six months later, compared to just 0.6% of uninfected participants. This is further supported by data coming from the insurance industry. Actuaries reported an increase in disability filings from typically healthy cohorts (not just elderly populations) since 2020, with a particular explosion in the second half of 2021.

ME/CFS and Spike Protein Disease

 

The hallmarks of ME/CFS are: 1) cognitive dysfunction; 2) Post-Exertional Malaise; and 3) profound and unrelenting fatigue. First, cognitive function may be experienced or described as memory issues, difficulty concentrating, and “brain fog”. Second, Post-Exertional Malaise (PEM) is described as severe exhaustion and symptom exacerbation after minimal exertion, sometimes lasting for days or weeks. Third, fatigue is not just a word to describe feeling tired after running errands all day. It is a profound fatigue that leaves patients feeling unable to carry out activities of daily life (ADLs). Aside from the three hallmark symptoms, there are a myriad of other pathologies and symptoms experienced by Long Covid, PVS, and ME/CFS patients. These include orthostatic intolerance or dysautonomia (ie: POTS), chronic pain, lymphadenopathy, flu-like symptoms, sensory intolerance and nervous system dysregulation, GI issues, neuropathy, and more.

ME/CFS exists on a spectrum. Some patients are so severe they find themselves only able to lay in a dark room all day with no stimulation. These patients are completely disabled. Others experience a less severe form of illness. They can work a low-stress job, and they can function. However, they must carefully budget and plan their  mental and physical exertion. Many land somewhere in-between. However, all report being unable to live a “normal” life prior to the onset of disease.

A silver lining in the explosion of ME/CFS in Long Haul Covid and Post-Vaccine Syndrome patients is a reallocation of resources. Specifically, more research and more support for these patients who have historically been written off by a modern medical apparatus that struggles to classify and serve complex, chronically ill patients.

Existing research highlights complex, multi-system involvement. Some studies point to viral persistence intracellularly (in blood cells, in tissue, in endothelial cells). Other research points towards immune dysfunction and autoimmunity. Much of the research is inconclusive. A major shortfall of the research and healthcare apparatus is the need to pinpoint and isolate causes, then treat these specific issues. When you look at the complex interplay of body systems, and existing research, you start to see how this becomes problematic very fast. A chicken and egg debate can occur very quickly – did the spike protein, EBV virus, mycotoxin, etc… invade the cell, which then set off a chronic immune response? Did the chronic immune response exist beneath the surface due to a genetic or epigenetic factor, which was then amplified by the presence of the external stimuli?

You may also start to perhaps notice why there was an explosion of ME/CFS diagnoses after the spike protein was introduced to our environment. Spike protein has an affinity for ACE-2 receptors. These receptors are abundant in endothelial tissue, and organ tissue (see: viral persistence in endothelial cells). Furthermore, spike protein has been demonstrated to induce IgG4 class switching, in which the body learns to “tolerate” the spike protein instead of fight it (see: immune dysfunction). This is hardly scraping the surface. Spike protein also up-regulates Mast Cell activity. Mast-Cell Activation Syndrome can manifest as chronic pain, dysautonomia, shortness of breath, GI pain, and so much more. For Long Covid and Post-Vaccine Syndrome (both spike protein diseases), you can begin to see, even with these few examples, just how complex and idiosyncratic these conditions can be. And, we haven’t even touched on clotting issues, other inflammatory cascades, blood-brain barrier issues, etc… But, that is for another day.

Patient and Doctor sit down together to discuss care

Finding The Right Kind Of help

When you are seeking care for multi-system, complex, chronic illness – especially Long Haul Covid and Post-Vaccine Syndrome – here are some questions to ask potential clinics you are interviewing…

  1. How do you ensure patients are properly supported while undergoing treatment? Due to the idiosyncratic, complex nature of Long Haul Covid, Post-Vaccine Syndrome, ME/CFS, and other complex chronic conditions, patients can often ill afford to set off on treatment plans without close followup. Ask potential providers how they ensure you are properly monitored in-between appointments. If there is no support between appointments, consider how that may impact your health and healing should you experience herxheimer reactions, treatment intolerances, symptom flares, etc… Also ask what kind of continuity patients experience in care. Are you seen by the same clinician? Are you followed up with by the same RN staff? Or, are you seen and speaking with a different person every time you interact with the clinic?
  2. What kind of expertise do you have in treating these conditions? Between 2021 and current day, many have claimed expertise in the realm of treating spike protein diseases. While there are certainly way more options for treatment now than in 2021, there is still a considerable range of expertise for those treating these conditions. How many patients have they seen? What is their approach? What kind of results have they seen?
  3. Do you have examples of patient success? How about difficult patient cases? Due to patient privacy law, the answer will typically be broad. Check clinic websites for patient reviews, case studies, etc… Asking about difficult cases gives an opportunity for a clinic or clinician to demonstrate honesty and integrity. No one has a 100% success record. Furthermore, success doesn’t always look the same. When you begin to consider that every patient is different, you start to realize why a strong support network (see question #1) is important.
  4. Am I going to get better, fast? This is a way to gauge the honesty of a potential clinic or clinician. Again, spike protein disease, ME/CFS, and other complex conditions are idiosyncratic. They are not kind to one-size-fits-all approaches. If a clinic or clinician is quick to tout a rapid and easy path to health, you should reflect on how they have answered some of these other questions. Does their confidence match their competence? Are they telling you what you want to hear? The truth is, these conditions often require iterative approaches, and foundational health measures that take time to see impact. Often, healing is not a linear experience, and there is no quick fix.
  5. How has your approach evolved over the time you have been treating patients for these conditions? In 2021, a lot of treatment for spike protein disease was based on hypotheses and limited research on pathophysiological mechanisms of the spike protein. As time has progressed, there has been massive evolution in avenues for treatment. There should be some underlying principles that remain the same – these principles drive the evolution of treatment. Again, consider the idiosyncratic nature of spike protein disease. An iterative treatment process involving trials of various therapies is an example of a foundational approach. No one patient may respond to the same treatment as another patient. However, the various therapies should change over time as clinical observation demonstrates more effective and safer ways to approach treatment. Is the clinic or clinician willing to throw away treatments they believed in early on, if they have found them not as effective as they hoped?
  6. How do you evolve over time? How do you innovate? How a clinic has evolved its approach is almost equally as important as whether or not they evolved at all. What research are they following? How do they collaborate internally? How do they collaborate outside of their organization? How do they use clinical observations to improve patient outcomes?
  7. How do you demonstrate outside-of-the-box thinking to help patients heal and regain quality of life? Conventional medicine has rightfully received a reputation for treating symptoms. You may have directly experienced this in your illness? For example, the spike protein causes cellular dysfunction and blood vessel damage. Both of these things are catalysts for cholesterol being released into the bloodstream. Cholesterol in the bloodstream is not an issue. It is a symptom of the issue. However, when you got to your primary doctor, the first thing they do is look to lower your cholesterol through dietary changes, and statins. The liver produces 80% of cholesterol, so dietary changes are of little importance, even if cholesterol was “bad”. Now, let’s take this about ten steps further. Multiple modalities are often employed to successfully treat spike protein disease. If you’re interviewing a naturopath, are they willing to recommend a therapy that falls outside of herbs? If you’re interviewing an allopathic MD, are they able to think outside of their med school programming? What does that look like? Can they give an example?
  8. How reliably can you help me with broad access to off-label medications? Unfortunately, after all these years, the politicization of post-pandemic healthcare has turned some pharmacists, into misguided activists. Whether it be Long Haul Covid, Post-Vaccine Syndrome, or even Adjunctive Cancer Care, off-label drugs have been life-changing and, in some cases, life-saving for many. However, access to these medications has been inconsistent, due to gatekeeping behavior and prioritizing compliance over patient care. Make sure your provider has been able to successfully get patients access to off-label medications.
Patient and Doctor shake hands after establishing trust

Conclusion

 

Due to the complexity of Long Haul Covid, Post-Vaccine Syndrome, and ME/CFS, patients should do their due diligence when selecting a clinician or clinic. The questions from this guide can be tweaked to your own personal situation. However, the most important things to consider are the support systems in place at prospective clinics, and expertise in treatment. Remember, there is no one-size-fits-all approach to multi-system, complex illness. It can not be taken off an AI system. Nor can it be solved with a magic pill. A good relationship with a supportive and knowledgeable team is a great foundation for healing and health.

 

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