All posts by yellowbeak

Schizophrenia and Toxoplasmosis

 

 

Parasite May Play Role in Some Schizophrenia Cases

A parasite responsible for toxoplasmosis – Toxoplasma gondii – may be involved in the cause of around a fifth of schizophrenia cases in the US. This is according to a new study published in the journal Preventive Veterinary Medicine.

Definition of schizophrenia

University of Pennsylvania researcher Greg Smith calculated that around a fifth of schizophrenia cases may be attributable toT. gondiiinfection.

The Centers for Disease Control and Prevention (CDC) estimate that around 60 million people in the US may be infected with T. gondii. Infection most commonly occurs through eating undercooked, contaminated meat, drinking contaminated water and coming into contact with cat feces that contain T. gondii.

Most people with T. gondii infection are unaware they have it; people with healthy immune systems are usually able to stop the parasite causing illness. But for those with weaker immune systems, such as older people, pregnant women and those with immune system disorders, the parasite can cause toxoplasmosis.

Toxoplasmosis a disease characterized by flu-like symptoms, including swollen lymph glands and muscle aches and pains. In severe cases, toxoplasmosis can cause damage to the eyes, brain and other organs.

Some studies, however, have linked T. gondii infection to mental health conditions. In 2012, for example, Medical News Today reported on a study linking T. gondi to increased risk of self-harm or suicide among new mothers.

More recently, studies have linked T. gondii infection to schizophrenia, and some have found that antipsychotic medication may even stop the parasite from replicating. But such research has been met with much criticism.

In this latest study, Gary Smith, of the School of Veterinary Medicine at the University of Pennsylvania, wanted to gain a better understanding of the link between T. gondii infection and schizophrenia.

Link between T. gondii and schizophrenia ‘should be considered, not ridiculed’

Smith wanted to determine the proportion of schizophrenia cases that could be attributable to T.gondii infection. He did this by calculating the population attributable fraction (PAF) – a measure used by epidemiologists to understand the importance of a risk factor.

“In other words,” explains Smith, “we ask, if you could stop infections with this parasite, how many [schizophrenia] cases could you prevent?”

Smith calculated the PAF fraction throughout an average lifetime to be 21.4%, meaning that a fifth of all schizophrenia cases over a lifetime could be prevented by stopping T. gondiiinfections from occurring. “That, to me, is significant,” says Smith.

He notes that many countries have a much higher prevalence of T. gondii infections than the US, and such countries also have a higher prevalence of schizophrenia.

Schizophrenia is one of the leading causes of disability in the US, affecting more than 3.5 million people.

Smith believes that his findings indicate the importance of gaining a better understanding of the link between T. gondii infection and schizophrenia. He adds:

By finding out how important a factor T. gondii infection is, this work might inform our attitude to researching the subject.

Instead of ridiculing the idea of a connection between T. gondiiand schizophrenia because it seems so extraordinary, we can sit down and consider the evidence. Perhaps then we might be persuaded to look for more ways to reduce the number of people infected with toxoplasma.”

Common food preservative may help to treat schizophrenia

A new randomized trial from Taiwan shows that a common food preservative could enhance the effect of a schizophrenia drug, even in the case of people normally resistant to treatment.
older man taking pillsNew research suggests that a common food preservative could be the answer for treatment-resistant people with schizophrenia.

Schizophrenia is a chronic, sometimes disabling mental disorder characterized by delusions, flat affect, agitated movements, and a difficulty in sustaining activities.

Treatments include antipsychotic medication — such as brexpiprazole, clozapine, or risperidone — and psychosocial treatments.

Studies have shown that “one fifth to one half of [people with schizophrenia] are classified as refractory to pharmacological treatment,” meaning that they do not respond to antipsychotics.

Researchers from China Medical University in Taiwan may now have found a way of boosting the effectiveness of certain drugs, which may help some people living with schizophrenia to respond better to treatment.

The answer, says the study’s lead investigator Dr. Hsien-Yuan Lane, may be found in a common food preservative: sodium benzoate. Dr. Lane and team conducted a randomized, double-blind, placebo-controlled trial showing that this preservative could enhance the effects of the antipsychotic drug clozapine.

“Clozapine,” he explains, “is considered the last-line antipsychotic agent for patients with refractory schizophrenia.” Despite this, a significant number of people living with schizophrenia are resistant to this drug.

The new trial seems to confirm for the first time that sodium benzoate — which has successfully been used as an add-on to other antipsychotics — can be added to clozapine to improve the symptoms of drug-resistant patients.

Dr. Lane and colleagues’ findings were recently published in the journal Biological Psychiatry. “If the finding can be confirmed, this approach may bring hope for treating patients with the most refractory schizophrenia,” he suggests.

Sodium Benzoate, a D-Amino Acid Oxidase Inhibitor, Added to Clozapine for the Treatment of Schizophrenia_ A Randomized, Double-Blind, Placebo-Controlled Trial

D-Amino Acid Oxidase Inhibition A New Glutamate Twist for Clozapine Augmentation in Schizophrenia

A series of clinical trials
found that currently available NMDA-enhancing agents
including glycine, D-cycloserine, D-serine, and sarcosine were
efficacious in improving the overall psychopathology of
schizophrenia without side effect or safety concern.

16. Lin CH, Lane HY, Tsai GE (2012): Glutamate signaling in the pathophysiology and therapy of schizophrenia. Pharmacol Biochem Behav 100:665–677.
17. Heresco-Levy U (2005): Glutamatergic neurotransmission modulators as emerging new drugs for schizophrenia. Expert Opin Emerg Drugs 10:827–844.
18. Coyle JT (2012): NMDA receptor and schizophrenia: A brief history. Schizophr Bull 38:920–926.
19. Javitt DC, Schoepp D, Kalivas PW, Volkow ND, Zarate C, Merchant K, et al. (2011): Translating glutamate: From pathophysiology to treatment.Sci Transl Med 3:102mr102.

Cat ownership in childhood linked to greater risk of later-life mental illness

They are cute, fluffy and have that wide-eyed glare that few of us can resist; it is no wonder more than 95 million of us own a cat. But there may be a darker side to our four-legged friends. New research claims the animals could increase our risk of mental illnesses, including schizophrenia and bipolar disorder.
Cat using litter boxHumans can become infected with Toxoplasma gondii by accidentally swallowing the parasite after coming into contact with a cat’s feces.

Two studies published in the journals Schizophrenia Research and Acta Psychiatrica Scandinavica attribute this association to Toxoplasma gondii – a parasite found in the intestines of cats. Humans can become infected with the parasite by accidentally swallowing it after coming into contact with the animal’s feces.

T. gondii is the cause of a disease known as toxoplasmosis. According to the Centers for Disease Control and Prevention (CDC), more than 60 million people in the US are infected with the parasite, though the majority of people are not aware of it.

People with a healthy immune system often stave off T. gondii infection, so it does not present any symptoms. However, pregnant women and people with weakened immune systems are more susceptible to infection and may experience flu-like symptoms – such as muscle aches and pains and swollen lymph nodes – as a result, while more severe infection may cause blindness and even death.

Previous studies have also linked T. gondii infection to greater risk of mental disorders. In November 2014, for example, Medical News Today reported on a study claiming the parasite is responsible for around a fifth of schizophrenia cases. Now, new research provides further evidence of this association.

Link between T. gondii and schizophrenia ‘should be considered, not ridiculed’

Smith wanted to determine the proportion of schizophrenia cases that could be attributable to T.gondii infection. He did this by calculating the population attributable fraction (PAF) – a measure used by epidemiologists to understand the importance of a risk factor.

“In other words,” explains Smith, “we ask, if you could stop infections with this parasite, how many [schizophrenia] cases could you prevent?”

Smith calculated the PAF fraction throughout an average lifetime to be 21.4%, meaning that a fifth of all schizophrenia cases over a lifetime could be prevented by stopping T. gondiiinfections from occurring. “That, to me, is significant,” says Smith.

He notes that many countries have a much higher prevalence of T. gondii infections than the US, and such countries also have a higher prevalence of schizophrenia.

Schizophrenia is one of the leading causes of disability in the US, affecting more than 3.5 million people.

Smith believes that his findings indicate the importance of gaining a better understanding of the link between T. gondii infection and schizophrenia. He adds:

By finding out how important a factor T. gondii infection is, this work might inform our attitude to researching the subject.

Instead of ridiculing the idea of a connection between T. gondiiand schizophrenia because it seems so extraordinary, we can sit down and consider the evidence. Perhaps then we might be persuaded to look for more ways to reduce the number of people infected with toxoplasma.”

People with ‘rage’ disorder twice as likely to have toxoplasmosis

A disorder that causes the individual to fly off the handle unexpectedly, as in road rage, has been significantly linked with toxoplasmosis, a parasite commonly associated with cat feces, according to the Journal of Clinical Psychiatry.

[road rage]

People with IED are prone to sudden anger.

Intermittent explosive disorder (IED) has been defined as “recurrent, impulsive, problematic outbursts of verbal or physical aggression that are disproportionate to the situations that trigger them.”

Up to 16 million Americans are thought to have IED, more than the total number for bipolar disorder and schizophrenia combined.

Toxoplasmosis is a common and generally harmless parasitic infection that is passed on through the feces of infected cats, contaminated water or undercooked meat.

 

It affects around 30% of all humans but is normally latent1.

Research has revealed that the parasite is found in brain tissue, and it has been linked to a number of psychiatric conditions, including schizophrenia, bipolar disorder and suicidal behavior.

Researchers from the University of Chicago, led by Dr. Emil Coccaro, have been looking for more effective ways to diagnose and treat IED and impulsive aggression.

 

This is a scanning electron micrograph of the protozoan parasite Toxoplasma gondii, tissue cyst in brain of an infected mouse.
Credit: David Ferguson

Individuals with a psychiatric disorder involving recurrent bouts of extreme, impulsive anger–road rage, for example–are more than twice as likely to have been exposed to a common parasite than healthy individuals with no psychiatric diagnosis.

In a study involving 358 adult subjects, a team led by researchers from the University of Chicago found that toxoplasmosis, a relatively harmless parasitic infection carried by an estimated 30 percent of all humans, is associated with intermittent explosive disorder and increased aggression.

The findings are published in the Journal of Clinical Psychiatry on March 23, 2016.

“Our work suggests that latent infection with the toxoplasma gondiiparasite may change brain chemistry in a fashion that increases the risk of aggressive behavior,” said senior study author Emil Coccaro, MD, Ellen. C. Manning Professor and Chair of Psychiatry and Behavioral Neuroscience at the University of Chicago.

“However, we do not know if this relationship is causal, and not everyone that tests positive for toxoplasmosis will have aggression issues,” Coccaro said, adding that additional studies are needed.

Intermittent explosive disorder (IED) is defined by the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, as recurrent, impulsive, problematic outbursts of verbal or physical aggression that are disproportionate to the situations that trigger them. IED is thought to affect as many as 16 million Americans, more than bipolar disorder and schizophrenia combined.

As part of their pioneering research to improve diagnosis and treatment for IED and impulsive aggression, Coccaro and his colleagues examined possible connections to toxoplasmosis, an extremely common parasitic infection. Transmitted through the feces of infected cats, undercooked meat or contaminated water, toxoplasmosis is typically latent and harmless for healthy adults. However, it is known to reside in brain tissue, and has been linked to several psychiatric diseases, including schizophrenia, bipolar disorder and suicidal behavior.

The research team recruited 358 adult subjects from the U.S., who were evaluated for IED, personality disorder, depression and other psychiatric disorders. Study participants were also scored on traits including anger, aggression and impulsivity. Participants fell into one of three groups. Roughly one third had IED. One third were healthy controls with no psychiatric history. The remaining third were individuals diagnosed with some psychiatric disorder, but not IED. This last group served as a control to distinguish IED from possible confounding psychiatric factors.

Hold your cats

The research team found that IED-diagnosed group was more than twice as likely to test positive for toxoplasmosis exposure (22 percent) as measured by a blood test, compared to the healthy control group (9 percent).

Around 16 percent of the psychiatric control group tested positive for toxoplasmosis, but had similar aggression and impulsivity scores to the healthy control group. IED-diagnosed subjects scored much higher on both measures than either control group.

Across all study subjects, toxoplasmosis-positive individuals scored significantly higher on scores of anger and aggression. The team noted a link between toxoplasmosis and increased impulsivity, but when adjusted for aggression scores, this link became non-significant. This finding suggests toxoplasmosis and aggression are most strongly correlated.

However, the authors caution that the study results do not address whether toxoplasmosis infection may cause increased aggression or IED.

“Correlation is not causation, and this is definitely not a sign that people should get rid of their cats,” said study co-author Royce Lee, MD, Associate Professor of Psychiatry and Behavioral Neuroscience at the University of Chicago. “We don’t yet understand the mechanisms involved–it could be an increased inflammatory response, direct brain modulation by the parasite, or even reverse causation where aggressive individuals tend to have more cats or eat more undercooked meat. Our study signals the need for more research and more evidence in humans.”

Coccaro and his team are now further examining the relationship between toxoplasmosis, aggression and IED. If better understood, this connection may inform new strategies to diagnose or treat IED in the future.

“It will take experimental studies to see if treating a latent toxoplasmosis infection with medication reduces aggressiveness,” Coccaro said. “If we can learn more, it could provide rational to treat IED in toxoplasmosis-positive patients by first treating the latent infection.”

People with rage disorder twice as likely to have latent toxoplasmosis parasite infection

Adjunctive Use of a Standardized Extract of Withania somnifera (Ashwagandha) to Treat Symptom Exacerbation in Schizophrenia

22% of subjects with IED tested positive for the parasite

In the current study, the authors evaluated 358 adult Americans for IED, personality disorderdepression and other psychiatric disorders and gave them scores for traits such as anger, aggression and impulsivity. They also screened for toxoplasmosis using blood tests.

Fast facts about toxoplasmosis

  • Around 60 million Americans are thought to have toxoplasmosis
  • If a woman catches it just before or during pregnancy, it can be dangerous for the baby
  • For those with a weakened immune system, there are medications to treat it.

They then classified the participants into three groups: approximately one third had IED, one third were healthy controls with no psychiatric history, and one third had received a diagnosis for a psychiatric disorder but not IED.

The purpose of the last group was to enable the team to distinguish IED from other psychiatric factors.

Findings showed that 22% of those with IED tested positive for toxoplasmosis exposure, compared with 9% of the healthy control group and 16% of the psychiatric control group.

The psychiatric group and the healthy group had similar scores for aggression and impulsivity, but the group with IED scored far higher on both counts than either of the other two groups.

An association emerged between toxoplasmosis and impulsivity. However, when the team adjusted for aggression scores, this association became non-significant, indicating a strong correlation between toxoplasmosis and aggression.

The authors point out that the findings do not mean that toxoplasmosis causes IED, or that people with cats are more likely to have the condition. It simply reveals a relationship.

T. gondii infection ‘may double schizophrenia risk’

For one study, Dr. Robert H. Yolken, of the Stanley Laboratory of Developmental Neurovirology at Johns Hopkins University School of Medicine in Baltimore, MD, and colleagues assessed the results of two previous studies.

These studies had identified a link between cat ownership in childhood and development of later-life schizophrenia and other mental disorders, comparing them with the results of a 1982 National Alliance for the Mentally Ill (NAMI) questionnaire.

The NAMI questionnaire – conducted around a decade before any data was published on cat ownership and mental illness – revealed that around 50% of individuals who had a cat as a family pet during childhood were diagnosed with schizophrenia or other mental illnesses later in life, compared with 42% who did not have a cat during childhood.

The questionnaire, the researchers say, produced similar results to those of the two previous studies, suggesting that “cat ownership in childhood is significantly more common in families in which the child later becomes seriously mentally ill.”

“If true,” the authors add, “an explanatory mechanism may be T. gondii. We urge our colleagues to try and replicate these findings to clarify whether childhood cat ownership is truly a risk factor for later schizophrenia.”

In another study, A. L. Sutterland, of the Academic Medical Centre in Amsterdam, the Netherlands, and colleagues conducted a meta-analysis of more than 50 studies that established a link between T. gondii and increased risk of schizophrenia.

They found that people infected with T. gondii are at more than double the risk of developing schizophrenia than those not infected with the parasite.

The team also identified a link between T. gondii infection and greater risk of bipolar disorderobsessive-compulsive disorder (OCD) and addiction.

“These findings suggest that T. gondii infection is associated with several psychiatric disorders and that in schizophrenia, reactivation of latent T. gondii infection may occur,” note the authors.

The CDC recommend changing a cat’s litter box every day to reduce the risk of T. gondii infection, noting that the parasite does not become infectious until 1-5 days after it has been shed in the animal’s feces.

They also recommend feeding cats only canned or dried commercial foods or well-cooked meats; feeding them raw or undercooked meats can increase the presence of T. gondii in a cat’s feces.

It is important to note that cat feces are not the only source of T. gondii infection. Humans can contract the parasite through consuming undercooked or contaminated meats and by drinking contaminated water.

How a cat parasite can change your personality

A new study suggests that infection with the cat-borne parasite Toxoplasma gondii could make people more risk-prone and likely to start their own business.
cute kitten

Your cute cat may host a parasite that could influence your behavior in surprising ways.

As humans who still inherit Enlightenment’s worship of rationality, we like to think that our decisions are autonomous and driven by reason alone.

However, science seems to contradict this popular belief. More and more research is showing that microorganisms such as bacteria and viruses influence our behavior and emotional states.

For instance, the bacteria in our guts may be responsible for states of anxiety and depression. Conversely, other studies have shown that some probiotic bacteria may relieve the effects of stress.

Now, a new study suggests that infection with the cat-borne parasite Toxoplasma gondii could make people change their behavior so that they become more prone to business and entrepreneurial ventures.

Stefanie K. Johnson, an associate professor at the University of Colorado (CU) Boulder’s Leeds School of Business, co-led the research in collaboration with Pieter Johnson, a professor in CU Boulder’s Department of Ecology and Evolutionary Biology.

The findings were published in the journal Proceedings of the Royal Society B.

Histamine intolerance | MCAS | Allergies | 703-844-0184 | Fairfax, Va NOVA Health Recovery

Call 703-844-0184 | email@novahealthrecovery | Fairfax, Va for a consultation | 

Multiple Chemical Sensitivity

Add multiple chemical sensitivity to the long list of chronic diseases that have been written off as psychosomatic for far too long. Chronic diseases are inherently complex and confusing for patients and doctors alike.

Fortunately, we live in a time where awareness for ‘invisible illnesses’ are on the rise. Hopefully, we can continue to spread awareness and get quality information into the hands of those that need it.

Today, I want to talk about multiple chemical sensitivity and dive deep into the science behind it.

 

What is Multiple Chemical Sensitivity?

Multiple chemical sensitivity is a condition that is activated by specific classes of chemicals which act along different pathways in the body and cause an increase in N-methyl-D-aspartate (NMDA) activity. NMDA receptors are critical in neuroplasticity, which affects your memory and brain function. NMDA is an amino acid that mimics glutamate, which is the neurotransmitter that normally binds to NMDA receptors.

Another way of saying this is: instead of glutamate acting on the NMDA receptors (which helps with normal brain function), multiple chemical sensitivity causes a higher level of NMDA to replace the glutamate, which can cause brain dysfunction.

These reactions in the body are lowered by NMDA antagonists, which suggests that it’s our body’s way of dealing with these toxic chemicals. But when that’s not enough and the body can’t properly detox, it can initiate multiple chemical sensitivity.

Genetically, there are certain genes that have been associated with the metabolism of these chemicals, and they can indicate whether or not a person will be susceptible to developing multiple chemical sensitivity.

 

Symptoms of Multiple Chemical Sensitivity

When the NO/ONOO (nitric oxide and peroxynitrite) cycle is thrown off due to the elevated NMDA activity, it can cause:

  • Energy metabolism dysfunction
  • Blood-brain barrier breakdown
  • Increased chemical sensitivity
  • Increased TRVP1 activity
  • Increased NMDA activity
  • Oxidative stress
  • Increased nitric oxide
  • Increased peroxynitrite
  • Increase inflammatory cytokines
  • Increased levels of intracellular calcium
  • Neurogenic inflammation
  • Airway sensitivity

These can cause a wide variety of symptoms in individuals and may include:

  • Headaches
  • Extreme
  • Nausea
  • Dizziness
  • Chest
  • Heart palpitations
  • Muscle pain
  • Brain fog
  • Constipation
  • Diarrhea
  • Memory problems
  • Mood changes
  • Congestion
  • Sneezing
  • Sore throat
  • Chest pain
  • Rashes
  • Breathing problems

 

What Types of Chemicals Trigger Multiple Chemical Sensitivity?

Because we are surrounded by tens of thousands of chemicals each day, it’s difficult to identify exactly where the chemicals that trigger multiple chemical sensitivity come from. The sheer number of chemicals combined with everybody’s unique body chemistry create an infinite number of combinations and potential reactions.

For a long time, researchers even argued that the diversity of chemicals made it unlikely that there would be a common response. So, defining multiple chemical sensitivity has been challenging.

That being said there are number of chemicals and toxins that have been identified in multiple chemical sensitivity, including:

  • Organic solvents
  • Organophosphorus pesticide (like glyphosate)
  • Carbamate pesticides
  • Organochlorine pesticides
  • Pyrethroid Pesticides
  • Mercury
  • Hydrogen sulfide
  • Carbon monoxide

You might look at this list and think, “what the heck are these?”

Unfortunately, most of these are pesticides and herbicides that end up in our food and water. These chemicals produce common toxic responses in the body and cause an elevation of NMDA activity, which result in perplexing symptoms.

Finally, there are lawsuits being waged against Monsanto for it’s misleading claims about glyphosate, hopefully something will come of it. I recently wrote about this and glyphosate, you can read that here:  We Can No Longer Ignore Glyphosate.

 

Diagnosing and Treating Multiple Chemical Sensitivity

Similar to other chronic diseases, multiple chemical sensitivity causes widespread systemic responses that vary from person to person – therefore it’s not an obvious diagnosis.

There are 5 principles of multiple chemical sensitivity that set it apart from other chronic toxin related illnesses.

  1. Short-term stressors trigger multi-system responses by raising nitric oxide and other cycles.
  2. This trigger is converted into a chronic illness through long-term elevation of peroxynitrite and other cycle elements.
  3. Symptoms and signs of these illnesses include other mechanisms. Such as elevated levels of peroxynitrite, inflammatory cytokines, oxidative stress, elevated NMDA, TRPV1 receptor activity, ATP depletion, and BH4 depletion.
  4. The influence of these mechanisms occur on a local level via individual cells and biological tissues.
  5.  Therapy should focus on down-regulating NO/ONOO (nitric oxide and peroxynitrite) cycle biochemistry.

 

When MCS is Mistaken for CFS/ME and Fibromyalgia

Multiple chemical sensitivity differs from chronic fatigue syndrome/myalgic encephalomyelitis and fibromyalgia because it’s specifically triggered by the chemicals listed above. Though multiple chemical sensitivity might be mistaken for these conditions. Especially since they are also associated with increased nitric acid level oxide levels. The important distinction here is the mechanism that causes increased nitric acid level oxide levels in multiple chemical sensitivity is the increased NMDA activity.

So, if you’ve ever received a chronic fatigue syndrome/myalgic encephalomyelitis or fibromyalgia diagnosis, it’s important that you make sure your doctor is aware of the growing research on multiple chemical sensitivity. These conditions are often mistaken for one another.

 

Work to Reduce Your Toxic Burden

I realize this is one of my more technical articles, but I wanted to include as much information as possible since there is a general lack of quality articles on multiple chemical sensitivity available online.

If you suspect you have multiple chemical sensitivity, remember you are your best advocate. It is possible that your doctor is not aware of this condition because it is a very complex illness involving multiple systems in the body. Researchers are still working to define its parameters and diagnostic procedures.

Just like so many other chronic illnesses, when it comes to multiple chemical sensitivity the name of the game is to reduce your overall toxic burden.

I have written extensively on reducing toxic burden and you can find my blog on this here as well as my free guide on how to reduce your daily toxin exposure here.

 

Resources:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3181613/  NMDA receptor function, memory, and brain aging

https://www.ncbi.nlm.nih.gov/pubmed/15256524 Case-control study of genotypes in multiple chemical sensitivity CYP2D6, NAT1, NAT2, PON 1, MTHFR

http://emerge.org.au/wp-content/uploads/2015/02/Pall-M.-L.-2009.-Multiple-chemical-sensitivity-toxicological-questions-and-mechanisms-John-Wiley-Sons-Ltd.pdf

Toxic Burden

I believe environmental toxicity is one of the biggest contributors to the rise in chronic illness today. And yet, because doctors don’t really learn about chronic toxic burden in medical school,  it’s now become somewhat of an elephant in the room.

The fact of the matter is when it comes to toxicity we mostly understand when it’s acute – when it causes sudden and definitive symptoms. However, most toxin exposures are chronic, involve more than one toxin, and happen after years, even decades of accumulation. This accumulation overloads the body’s detox mechanisms and causes symptoms such as:

  • Fatigue
  • Memory disturbance
  • Sleep issues
  • Headaches

Over time, if the environmental toxicity and detox pathways aren’t addressed, the toxic burden can lead to conditions like:

  • Cancer
  • Autoimmune disease
  • Neurodegenerative diseases

In a 2015 review in the prestigious journal Carcinogenesis, researchers found that lifestyle factors are responsible for a considerable portion of cancers worldwide. Concluding that 7-19% of all cancers are attributable to toxic environmental exposures. On top of this, they examined 85 chemicals and found 59% of them exerted low-dose effects.

In my personal practice, I’ve seen the devastating effects of environmental toxin exposure.  Because the symptoms are chronic and multisystem it can lead to a perplexing situation for both the patient and the practitioner. I found the best method for helping a patient with a chronic condition is to reduce their levels of toxin exposure and improve detoxification to bring down their toxic burden.

So today I want to talk about different types of toxins, other factors that add to your burden, symptoms and conditions of suspected environmental toxicity, and detoxification.

 

17 Possible Environmental Toxins

Toxins can either be introduced to the body through external exposure or internal exposure.  I break different exposures down into exotoxins (external) and endotoxins (internal). A huge part of reducing your toxic burden is being aware of different sources of toxins so that you can avoid potential exposures. With that in mind the list below is meant to be a resource for different areas of your life that should be considered when you work to reduce your toxic burden.

Exotoxins:

  1. Heavy metals – Can come from cookware, tap water, personal care products, and home furnishings.
  2. Solvents/VOCs – Can come from cleaning products or off gas from new furniture or carpet. Oftentimes are indoor air is more toxic than the air outside.
  3. Pesticides – As an exotoxin, pesticides affect people when they work with them either at their job or in their personal garden or lawn.
  4. BPA – BPA is an endocrine disruptor and also found in plastics.
  5. Phthalates – Can be found in personal care products, home cleaning products, and makeup.
  6. Parabens – Also found in personal care products, home cleaning products, and makeup.
  7. EMF radiation – This comes from electronics and Wi-Fi sources, so cell phones, smart TVs, microwaves, fitness trackers, routers, cell phone towers, and airplanes.
  8. Heterocyclic amines – These are chemicals that are released from animal products when they are cooked at high temperatures.
  9. Mold – Look Below

 

Endotoxins:

  1. Intestinal bacteria – Such as endotoxemia from LPS.
  2. Yeast/candida – Candida produce the toxin acetaldehyde.
  3. Other infectious diseases – Common ones include Epstein-Barr and Lyme disease.
  4. Food – Standard American Diet contributes to total toxic burden. Chemicals, food additives, and glyphosate all cause problems. When it comes to food your best bet is to eat as organic as possible.
  5. Insulin resistance – When insulin resistance climbs in your body it causes stress. Work to promote insulin sensitivity instead.
  6. Medications – Medications generally contribute to overall toxic burden.
  7. Stress – Stress is an extremely powerful influence in your overall health and yet it’s often not taken into consideration.
  8. Emotions – Emotions cause biochemical reactions in the body and are often overlooked.

 

What Else Can Add to Your Total Toxic Burden?

Besides toxins there are other things that can contribute to your total toxic burden that you might not have considered. This is because your total toxic burden includes all stressors on the body, which means things like emotional and psychological stress.

I mentioned stress and emotions above but it’s worth taking the time to dig a little deeper on each because they are all too commonly overlooked. They don’t fit our traditional idea of a toxin. A few potential stressors that are outright “toxins” include:

  • Age
  • Sex
  • Financial stress
  • Sedentary lifestyle
  • Career stress
  • Toxic personal relationships
  • Significant life events, such as a death in the family or divorce
  • Unresolved emotional trauma

 

25 Symptoms of Environmental Toxicity

Over the years I’ve noticed there are some symptoms that are more commonly seen in patients with environmental toxicity. If someone comes into my office with a few of any of the following symptoms I immediately start checking for sources of toxins and for ways to reduce their overall toxic burden.

Here are 25 symptoms of environmental toxicity:

  1. Fatigue
  2. Muscle aches
  3. Joint pain
  4. Sinus congestion
  5. Postnasal drip
  6. Headaches
  7. Gas/Bloating
  8. Constipation
  9. Diarrhea
  10. Foul-smelling stools
  11. Heartburn
  12. Insomnia
  13. Difficulty concentrating
  14. Food cravings
  15. Water retention
  16. Trouble losing weight
  17. Rashes
  18. Skin problems
  19. Eczema
  20. Psoriasis
  21. Acne
  22. Canker sores
  23. Dark circles under the eyes
  24. Premenstrual syndrome
  25. Bad breath

In addition to these symptoms there are a few conditions that are major red flags to me. These include:

  • Immune system dysfunction
  • Chronic infection
  • Autoimmune diseases
  • Endocrine disorders
  • Multiple chemical sensitivity
  • Infertility
  • Adverse reactions to medications
  • Allergies and asthma
  • Obvious industrial or agricultural exposure
  • Poor caffeine tolerance

 

5 Methods of Detoxification Support

Here’s the deal, we all need detoxification support. This is because we live in a time when we are constantly bombarded with toxins unlike any other point in human history. Tens of thousands of chemicals are introduced via our products each day and there’s very little oversight. Basically, we’re all human guinea pigs and we need to take steps to reduce our routes of exposure and support our detoxification organs.

  • Glutathione – A master antioxidant which can be taken orally or intravenously. Glutathione reduces oxidative stress, is an intracellular antioxidant, and helps with detoxification of environmental toxins.
  • Reducing medication use – Genexa Health has come up with a line of natural products for various ailments. I recommend most of my patients do what they can to address the root causes of their conditions so they can limit the amount of medications they’re on. Genexa Health is a great way to get people off of over-the-counter medications such as Advil, which only contribute to leaky gut and inflammation.
  • Make sure you’re going to the bathroom regularly – To properly eliminate toxins in the body you need to be sure you are not constipated. Consider using an Elimination Diet to find any food sensitivities.
  • Use detox binders – I recommend using detox binders like activated charcoal and GI detox. These bind to toxins and help your body eliminate them more readily.
  • Take detox supporting nutrients:
    • Chlorophyll
    • Green Tea
    • Quercetin
    • Active B complex
    • Milk Thistle
    • Calcium D-glucarate
    • Curcumin
    • Probiotics 50 billion CFUs

I’ve put together a thorough guideline with more detail to help you through the process of reducing your toxin exposure. You can find that here: Reduce Your Daily Toxin Exposure.

 

Resources:

https://www.ncbi.nlm.nih.gov/pubmed/26106142 Overview of air pollution and endocrine disorders  |  Assessing the carcinogenic potential of low-dose exposures to chemical mixtures in the environment

______________________________________________

detox binders

You might be wondering, why would you want to detox in the first place?

Our bodies are exposed to more chemicals now than ever before. Every day new chemicals are added to our personal environments via food, pollution, plastics, furniture, food containers, cookware, carpets, electronics, personal care products, and more.

Some of these chemicals are newly created and their effects on the human body are entirely unknown. Others are only a few decades or even a couple of years old and we are still learning about their impacts.

Possibly the most concerning factor behind all these chemicals is that there are few to no barriers in the process which allows chemicals to be used in everyday items. Meaning your body is slowly taking in small amounts of new chemicals and toxic buildup over time.

It’s a war of attrition.

This constant chemical bombardment your body is fighting each day just to keep you healthy is why you should be interested in detox.

I’m not talking about a harsh detox that can sometimes put the body under more pressure and stress than necessary. Juice cleanses and powerful liver detoxes can backfire because they deprive your body of nutrients or place overwhelming stress on detox pathways.

We need to reduce our toxic burden wherever possible, support our body’s natural detox pathways, and incorporate detox binders into our health routine.

I want to focus on this last strategy – using binders for detox – because I’ve seen binders work well in my personal practice and I want to share them with you. Binders work by:

 

Detoxing to support your health

There are some toxins we should be worried about more than others. Some of the worst offenders are mold toxins, heavy metals, and bisphenol-A (BPA). When it comes to ridding our bodies of these chemicals, I’ve found there are two binders work particularly well:

GI Detox and Upgraded Coconut Charcoal are two effective binders that help you with daily detox from mold, heavy metals, and other toxins. They are also strong enough to use in more targeted therapies such as mold exposure treatments.

 

GI Detox

GI Detox is made from two binders – it consists of 75 percent Pyrophyllite clay and 25 percent activated charcoal.

Pyrophyllite clay a very rare clay that has been used medicinally for thousands of years. It’s richer in silica and quartz than other clays (such as bentonite) and works through both adsorbing (to bind to) and absorbing (to ‘swallow’ up) chemicals.

Phyrophyllite clay is negatively charged and binds readily to endotoxins from Gram negative bacteria, by-products of yeast and bacteria, and heavy metals. This process assists in restoring gut microbial balance and is recommended as an effective detox strategy that is also gentle enough to use daily.

Activated charcoal is one of the most effective binders known to man. Considered more effective than stomach pumping in poisoned patients, charcoal effectively rids the body of unwanted toxins. This is why I recommend using is on its own as well as in the GI Detox.

For normal use, I recommend taking one to two capsule of GI Detox once a day on an empty stomach – an hour before eating or two hours after.

 

Upgraded Coconut Charcoal

Activated charcoal works by binding to toxins through adsorption. Adsorption is different from absorption because the chemicals are trapped in the little holes of this porous substance rather than being soaked up. The charcoal isn’t absorbable by your body so it passes through the GI tract while taking unwanted toxins with it.

You can order Upgraded Coconut Charcoal here. For normal use, take Upgraded Coconut Charcoal with other binders on an empty stomach. You can also take your activated charcoal with food you know to be low quality.

 

Using Binders for Mold Detox

You can use both GI Detox and Upgraded Coconut Charcoal to fight daily toxins or in a mold treatment protocol. The toxins produced by toxic mold are called mycotoxins and ridding your body of these takes a comprehensive plan that lasts between six months to a year.

GI Detox – Take one to two capsules twice daily with Upgraded Coconut Charcoal.

Upgraded Coconut Charcoal – Take 1000 to 1500 mg (2-3 capsules) twice daily with water, GI Detox, and on an empty stomach.

For more specifics on mold detox protocol, you can read a Mold Exposure Treatment Guide.  Your_Complete_Mold_Exposure_Guide and SURVIVING MOLD LINK

 and Do binders interfere with nutrient absorption?

Because of the effectiveness of binders in their absorption and adsorption of chemicals, it’s a completely logical concern to think they would also bind with beneficial nutrients. In general, we need more research on this subject but preliminary animal studies have found that adding charcoal to sheep’s diets did not decrease their nutrient levels. Also, toxins are predominantly positively charged, which is how the negatively charged binders are readily attracted to them.

You can reduce the chance your binders will work on the wrong particles through taking them on an empty stomach. All binders should be taken at the same time and either one hour before or two hours after medications and supplements.

 

Other Detox Strategies Worth Considering

We live in a time where we are exposed to more chemicals than ever before. Learning about detox strategies is now as important as learning to eat a healthy and balanced diet. Other detox strategies worth learning more about include:

  1. Infrared saunas ( See Below)
  2. Exercise
  3. Glutathione – Love this brand…. Bulletproof Liposomal Gluathione Force
  4. Calcium D-Glucarate

Each of these can be used on their own or together for a compounding effect. Also, each of these are included in  A Mold Exposure Treatment Guide. Your_Complete_Mold_Exposure_Guide

 

Add Detox to Your Daily Routine

Toxins are a part of our daily lives. Fortunately, there steps you can take to reduce their overall impact on your health. I recommend incorporating GI Detox and activated charcoal into your daily health routine.

If you’re healthy, take both the GI Detox and Upgraded Coconut Charcoal to deal with daily toxins.

If you’ve been exposed to mold, you can take GI Detox and Upgraded Coconut Charcoal to help with a comprehensive Mold Exposure Treatment. Remember, these two binders are only part of a mold treatment protocol.

I recommend adding detox strategies to your daily routine to combat the unprecedented number of chemicals that bombard us each day.

 

Resources:

http://www.cnn.com/2016/07/01/health/everyday-chemicals-we-need-to-reduce-exposure-to/index.html

https://www.ncbi.nlm.nih.gov/pubmed/3521259

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1676641/pdf/bmj00002-0006.pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1306980/

https://www.ncbi.nlm.nih.gov/pubmed/6499964

____________________________________________________________________________________________________

Infrared Saunas

The term sauna is typically used to refer to a Finnish sauna, which is a deeply ingrained part of the culture in Finland. In the United States very few people use saunas, though they are making somewhat of a stir in the health and wellness community due to their benefits. Infrared saunas have numerous health benefits including helping your body rid itself of toxins, reduce inflammation, and increase blood flow.

Plus, infrared saunas feel pretty amazing.

 

Infrared saunas versus saunas – what’s the difference?

In all saunas your body temperature is raised which induces sweating. With traditional wet or dry saunas the air is heated and you warm from the outside in. Infrared saunas cause your body temperature to rise, but the surrounding air remains the same – your body temperature rises from the inside out.

Two major benefits of infrared saunas are their cost and portability – they can be used in most homes and there are even some that pack down very small for easy storage. Infrared saunas also allow people to withstand the heating effects longer than a traditional sauna would and are therefore a good option for people sensitive to excess heat.

Infrared heat penetrates the body more deeply than heated air, which results in a more vigorous sweating at a lower temperature. The way your body sweats in infrared saunas compared to traditional saunas is believed to be more effective for delivering benefits to your body.

 

7 Benefits of Infrared Saunas

1. Flushes toxins

If you do a quick Google search you’ll find a lot of people knocking the ability of saunas to flush toxins, but we’ve known for a long time that sweating helps the body rid itself of toxins.

Studies have found that increased sweating, as experienced in a sauna, can help you excrete toxic metals like arsenic, cadmium, lead, and mercury. One study found “that body stores of trace metals may be depleted during prolonged exposure to heat.”

Another study found that “induced sweating in saunas can mobilize BPA in adipose tissue thus leading to enhanced excretion in sweat.” The science is there – sweating helps you eliminate toxins and infrared saunas can help you sweat at a much faster rate.

2. Fights dementia & Alzheimer’s disease

Saunas have been shown to improve vascular function, blood pressure, reduce inflammation, and boost cognition. One study found that Finnish men who frequently used saunas had a significant reduction in dementia and Alzheimer’s risk. With Alzheimer’s now clocking in as the third most common cause of death in the United States, any technique that can help resist the impacts of dementia onset adds hope.

3. Burns calories

The calorie burning effect of infrared saunas is one of the most sought after benefits. Infrared saunas are able to increase your body’s core temperature in a manner similar to working out. You can burn between 400 to 600 calories in a 30-minute session, which has led to the use of infrared saunas in weight loss programs.

4. Speeds up recovery

Studies have found that infrared saunas help your neuromuscular system recover faster. Athletes have found they are able to recover from endurance training more quickly while enjoying the pleasurable effects of an infrared sauna.

In most infrared sauna studies, researchers comment on the enjoyable and relaxing effects which are experienced on top of the healing outcomes.

5. Improves athletic performance

On top of the added recovery benefits infrared saunas can help improve overall athletic performance. Athletes who used saunas post-workout saw an improvement in plasma, red blood cell volumes, and an improvement in overall performance.

One study found that post-exercise sauna use produced a “worthwhile enhancement of endurance running performance” and researchers suggested it was due to an overall increase in blood volume.

6. Improves cardiovascular function

Using a sauna is often compared to working out because of the raised body temperature, sweating, released endorphins, and other similarities. Studies on the effects of infrared saunas on cardiovascular health typically find similar benefits.

One study that examined heart health and sauna use found that saunas reduce the risk of sudden cardiac death, coronary heart disease, fatal cardiovascular disease, and all-cause mortality.

7. Pain reduction

This is one of my favorite benefits of the infrared sauna.

Though it may sound counterintuitive, infrared saunas appear to help with inflammation and pain. Numerous studies have found that infrared saunas reduce pain caused by inflammation.

One study found infrared saunas reduced the pain experienced by fibromyalgia patients by half. Another study examining the impacts of infrared saunas on cardiovascular health found they were effective in reducing chronic pain. Infrared saunas have shown to be an effective treatment for those suffering from chronic lower back pain.

With the opioid crisis claiming more and more lives, it’s important that we explore all non-pharmaceutical pain relief options seriously. Though infrared saunas may require a steep initial investment, if used regularly they could quickly become a very worthwhile purchase. This is especially true for those suffering with chronic pain because infrared saunas are a potential pain solution that prevents the need for addictive substances such as opioids.

 

Why quality matters with infrared saunas

Infrared saunas are generally seen as a more convenient option for consumers. They are typically cheaper and easier to move than their wet and dry Finnish counterparts. You can even find one on Amazon for around $200, but I have concerns surrounding these cheaper models.

Electromagnetic fields are often radiated directly from electrical infrared saunas and can literally bathe you in harmful electromagnetic radiation. This is why I recommend High Tech Health International’s infrared saunas. They’ve addressed the EMF concern and more.

Next week, we will be digging deeper into the concerns behind EMF and why you should consider unplugging your Wi-Fi at night.

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Thinking of getting your own sauna?!  

Here are two brands I highly recommend:

1. TR2 Infrared Detox Sauna from High Tech Health in Boulder, CO

  • Lowest total EMF from our in-house designed, patent-pending heaters
  • Healthy materials, very low-toxicity

2.  Sunlighten M-Pulse 3 in 1 Sauna –

  • Full-spectrum IR technology
  • Customizable heaters
  • Preset health programs
  • LCD touch-screen control panel
  • Five mPulse Infrared Sauna Models Available

 

Resources:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2718593/

https://www.hindawi.com/journals/jeph/2012/184745/

https://pdfs.semanticscholar.org/6b45/e199b8720aa23b09d1537e6bd7d8469a601d.pdf

https://www.hindawi.com/journals/jeph/2012/185731/

https://www.ncbi.nlm.nih.gov/pubmed/27932366

https://jamanetwork.com/journals/jama/article-abstract/360118

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4493260/

https://www.ncbi.nlm.nih.gov/pubmed/25705824

https://www.ncbi.nlm.nih.gov/pubmed/16877041

https://www.jstage.jst.go.jp/article/internalmedicine/47/16/47_16_1473/_pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2718593/

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2539004/

https://www.jstage.jst.go.jp/article/internalmedicine/47/16/47_16_1473/_pdf

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2539004/

_____________________________________________________________________________________________________________

Is Toxic Mold Exposure the Cause of Your Symptoms?

Is Toxic Mold Exposure the Cause of Your Symptoms?

Are you one of the many people unknowingly living or working in water damaged building?  Did you know it may be dramatically affecting your health?  It’s estimated that indoor air pollutants, including mold and mycotoxins may be contributing to more than 50% of our patient’s illnesses.  Typically we think of smog, smoke, and outdoor pollution as detrimental to our health but indoor air quality may be an even bigger risk to your health.  Many patients are unaware that a toxic home or workplace is contributing to their symptoms.

Exposure to water-damaged indoor environments is associated with exposure to molds.  The most common types of mold that are found indoors include CladosporiumPenicilliumAlternaria, and AspergillusStachybotrys chartarum (sometimes referred to as “toxic black mold”) is a greenish-black mold, which grows on household surfaces that have high cellulose content, such as wood, fiberboard, gypsum board, paper, dust, and lint and is usually an indicator that there has been elevated moisture present or previous water damage.

Some molds secrete mycotoxins, that can be measured in the urine, such as ochratoxin, aflatoxin, and trichothecenes.  Exposure to mold and mold components is well known to trigger inflammation, allergies and asthma, oxidative stress, and immune dysfunction in both human and animal studies.  Mold spores, fungal fragments, and mycotoxins can be measured in the indoor environments of moldy buildings and in humans who are exposed to these environments.  Most of the time, we are exposed to molds, like stachybotrys, through the skin contact, through ingestion, and by inhalation.  Most common are reports of exposure involve water-damaged homes, schools, office buildings, court houses, hospitals, and hotels.  It’s estimated that as many as 25% of buildings in the US have had some sort of water damage.  Molds have the ability to produce various symptoms, such as skin rashes, respiratory distress, various types of inflammation,  cognitive issues, neurological symptoms, and immune suppression. The most common symptoms associated with mold exposure are allergic rhinitis and new onset asthma.

How do you know if you’ve been exposed to mold or a water damaged building?

Top Symptoms Associated with Mold-Associated Illness:

  1. Fatigue and weakness
  2. Headache, light sensitivity
  3. Poor memory, difficult word finding
  4. Difficulty concentration
  5. Morning stiffness, joint pain
  6. Unusual skin sensations, tingling and numbness
  7. Shortness of breath, sinus congestion or chronic cough
  8. Appetite swings, body temperature regulation,
  9. Increased urinary frequency or increased thirst
  10. Red eyes, blurred vision, sweats, mood swings, sharp pains
  11. Abdominal pain, diarrhea, bloating
  12. Tearing, disorientation, metallic taste in mouth
  13. Static shocks
  14. Vertigo, feeling lightheaded

Checklist that might indicate mold exposure or mold sensitivity (from ECH website)

  • Do musty odors bother you?
  • Have you worked or lived in a building where the air vents or ceiling tiles were discolored?
  • Have you noticed water damage or discoloration elsewhere?
  • Has your home been flooded?
  • Have you had leaks in the roof?
  • Do you experience unusual shortness of breath?
  • Do you experience recurring sinus infections?
  • Do you experience recurring respiratory infections and coughing?
  • Do you have frequent flu-like symptoms?
  • Do your symptoms worsen on rainy days?
  • Do you have frequent headaches?
  • Are you fatigued and have a skin rash?

How do I Treat Mold/mycotoxin Exposure?

  1. Remove yourself from the contaminated environment first. (don’t even think about going on to other treatments until you get out of the contaminated environment)
  2. Avoid exposure to porous items (paper, clothing, etc) from the moldy environment.
  3. Use clay, charcoal, cholestyramine or other binders to bind internal mycotoxins
    1. The Shoemaker protocol has proven effectiveness for cholestyramine powder or prescription Welchol as off-label bile sequestering agents to decrease total toxic load of mold and other toxins from water damaged buildings.
    2. I also recommend Upgraded Coconut Charcoal or GI Detox to bind toxins in the gastrointestinal tract and Glutathione Force to support glutathione, which is often depleted in toxin-related illness.
  4. While you are using binders, you must maintain normal bowel function and avoid constipation.  You can add magnesium citrate, buffered C powder, or even gentle laxatives if needed but constipation is the enemy of detoxification!
  5. Treat colonizing molds/fungal or bacterial infections in the body
    • Common locations of colonization include sinuses, gut, bladder, vagina, lungs
    • Test and treat for candida overgrowth – living in an environment with mold leads to immune dysregulation that allows candida to overgrow in the body in some immunocompromised patients
  6. Enhance detoxification support
    • Some common supplements used to aid detox are liposomal glutathione, milk thistle, n-acetylcysteine, alpha lipoid acid, glycine, glutamine, and taurine.  Methylation support is also key and involves optimal levels of methylcobalamin (B12), methyl-folate, B6, riboflavin, and minerals
  7. Invest in a high quality air filter and home and at work, like Austin Air Healthmate Plus
  8. Avoid common mycotoxin containing foods:
    • Corn, wheat, barley, rye, peanuts, sorghum, cottonseed, some cheeses, and alcoholic beverages such as wine and beer.  Others include oats, rice, tree nuts pistachios, brazil nuts, chiles, oil seeds, spices, black pepper, dried fruits, figs, coffee, cocoa, beans, bread.

Other Treatment Options

  • Follow A Low Mold Diet – many patients to well on a paleo, grain-free diet since grains are often contaminated with mycotoxins and molds
  • The Low Mold Diet

    THE LOW MOLD DIET

    The Low Mold Diet. Use this guide to shift your diet away from high sugar and starchy foods to more fresh, whole foods.  If you suspect you’ve been exposed to mold or mycotoxins,  read on below.

    Foods that must be avoided

    Avoid sugar  and sugar containing foods: Table sugar and all other simple, fast releasing sugars such as fructose, lactose, maltose, glucose, mannitol and sorbitol.  This includes honey and natural sugar syrup type products such as maple syrup and molasses. This also includes all candies, sweets, cakes, cookies, and baked goods.

    Sweetleaf whole leaf stevia concentrate may be used in moderation

    High sugar fruits:

    • Avoid pineapple, mango, banana, melons, oranges, and grapes
    • Organic berries, apples and lemon/lime are ok

    Packaged and processed foods:

    • Avoid canned, bottled, boxed and otherwise processed and pre-packaged foods as they more often than not contain sugar of one type or another.
    • Canned – Baked beans, soups, ready-made sauces.
    • Bottled – Soft drinks, fruit juices, all condiments and sauces.
    • Boxed/Packaged – Ready-made meals, breakfast cereals, chocolate/candy, ice cream, frozen foods.

    Mold and yeast containing foods:

    • Cheeses: all cheese, especially moldy cheeses like stilton are the worst, buttermilk, sour cream               and sour milk products.
    • Alcoholic drinks: beer, wine, cider, whiskey, brandy, gin and rum.
    • Condiments: vinegar and foods containing vinegar, mayonnaise, pickles, soy sauce, mustard, relishes.
    • Edible fungi: including all types of mushrooms and truffles.
    • Processed and smoked meats: sausages, hot dogs, corned beef, pastrami, smoked fish, ham, bacon.
    • Fruit juices: All packaged fruit juices may potentially contain molds.
    • Dried fruits: raisins, apricots, prunes, figs, dates, etc.

    Foods ok to be eaten in small amounts

    1. Gluten-free grains: brown rice, quinoa, buckwheat, millet, teff, certified gluten-free oats
    2. High starch vegetables and legumes: sweet corn, potatoes, beans and peas, lentils, sweet potatoes, squashes, turnips, parsnips.
    3. Fruits: low sugar types such as berries, apples, pears and peaches.

    Foods to be eaten freely

    1. Organic pastured animal products: beef, bison, veal, lamb buffalo, wild-caught seafood, poultry, pastured eggs
    2. Low carbohydrate vegetables: broccoli, spinach, cauliflower, kale, cabbage, arugula, chard, cucumber, peppers, tomato (fresh only), onion, leek, asparagus, garlic, artichokes,
    3. Raw nuts and seeds: sunflower seeds, pumpkin seeds, flax seeds, chia seeds, almonds, low mold nuts (No peanuts, walnuts, pecans,cashews, brazil nuts, )
    4. Healthy Fats: Extra virgin olive oil, coconut oil, coconut milk, ghee, avocado, organic butter
    5. Other: Tempeh, Miso, Apple Cider Vinegar
    6. Beverages: Filtered Water, non-fruity herbal teas, mineral water, fresh veggie juice
  • Sublingual immunotherapy (SLIT)
  • Anti-fungal herbs and medications
  • Infared sauna
  • Detoxification support – oral and IV
  • Remediation procedures for environment and belongings
  • Create a “safe” place, with little potential for mold/allergens and great filtration system – this could be a bedroom or other room that is mold and chemical free
  • Some patients benefit from IV immunoglobulin therapy (IVIg)

Here is a chart from article in Townsend Letter July 2014 that explains sources and binders for common mycotoxins: Townsend-Letter-Mold-Article-1

Screen Shot 2015-02-07 at 8.45.26 PM

 

PODCASTS:

More Helpful Resources:

__________________________________________________________

BROCCOLI SPROUT BEVERAGE HELPS DETOXIFY AIR POLLUTANTS

antioxidant-green-drink John Groopman, Ph.D.
Johns Hopkins Bloomberg School of Public Health
NIEHS Grant P01ES006052, P30ES003819

Research funded in part by NIEHS has shown that drinking a broccoli sprout beverage daily can enhance the detoxification of some airborne pollutants. This inexpensive food-based intervention may provide a way to decrease the long-term health risks of air pollution.

The researchers conducted a clinical trial that included 291 men and women living in a rural farming community in Jiangsu Province, China, an area that experiences high levels of air pollution due to its proximity to Shanghai. Broccoli sprouts provide a good source of glucoraphanin, which is converted to sulforaphane when consumed. Sulforaphane has been shown to increase levels of enzymes involved in detoxification. During the 12-week trial, the researchers asked one group of study participants to drink a broccoli sprout-derived beverage that provided daily doses of 600 micromol glucoraphanin and 40 micromol sulforaphane while a control group of participants consumed a drink that did not contain broccoli sprouts.

For participants receiving the broccoli sprout beverage, the rate of excretion of the carcinogen benzene increased 61 percent on the first day and was maintained throughout the 12 weeks. The rate of excretion of the irritant acrolein rapidly increased 23 percent during the 12-week trial. Additional analyses indicated that sulforaphane might activate the signaling molecule NRF2, which increases the capacity to adapt to and survive a broad range of environmental toxins.

Citation: Egner PA, Chen JG, Zarth AT, Ng D, Wang J, Kensler KH, Jacobson LP, Munoz A, Johnson JL, Groopman JD, Fahey JW, Talalay P, Zhu J, Chen TY, Qian GS, Carmella SG, Hecht SS, Kensler TW. 2014. Rapid and Sustainable Detoxication of Airborne Pollutants by Broccoli Sprout Beverage: Results of a Randomized Clinical Trial in China. Cancer Prev Res (Phila); doi: 10.1158/1940-6207.CAPR-14-0103 [Online 9 June 2014].

The Mastocytosis Society, Inc.
www.tmsforacure.org

______________________________________________________________

Mold and Biotixins Resources – Local and California

*Inclusion on this list does not necessarily mean that we endorse the organization, group, or business. Before making any changes in your treatment, always be sure to consult your physician.

Mold and Biotixins Resources – National

*Inclusion on this list does not necessarily mean that we endorse the organization, group, or business. Before making any changes in your treatment, always be sure to consult your physician.

  • Mast

    WAIT! Before you get started, make sure to access your FREE guide to mold exposure HERE.

    Mast cells are an important part of your immune system, without them you would never heal from an injury. However, there is a condition where they become overactive and cause serious problems in the body – this condition is called mast cell activation syndrome (MCAS).

    Mast cell activation syndrome is different from mastocytosis because mast cells aren’t accumulating in various organs. With mastocytosis, there is a proliferation or growth of mast cells, like a cancer. Mastocytosis is also very rare and not usually triggered by an irritant.

    On the other hand, MCAS is characterized by overactive mast cells. MCAS can be imagined as though something rubbed up against your mast cells wrong, causing them to become aggravated. Another important difference between MCAS and mastocytosis is that MCAS patients will often come up normal during lab work.

    Many things can trigger MCAS, including:

    • Mold
    • Chemicals
    • Allergens
    • Viruses
    • Heavy metals
    • Toxins

    From what I’ve seen in my practice and have heard from my colleagues, mold is probably the number one trigger of MCAS, followed by infections. Once these cells are activated they start pouring out all sorts of inflammatory agents, such as histamine, and cytokines.

     

    Beyond Histamine

    Up until recently, when anything to do with mast cells where mentioned, histamine was the main inflammatory mediator that came to mind. However, we’ve come to realize that histamine is a very small part of the story.

    Hundreds of chemicals have been associated with mast cells and they all have different actions in the body. Mediators include:

    • Histamine
    • Cytokines
    • Interleukins
    • Prostaglandins
    • Chemokines

     

    Symptoms of MCAS

    Currently, the most common illness associated with mold is chronic inflammatory response syndrome (CIRS) but we are finding MCAS is another disease often triggered by mold exposure. Similar to CIRS, MCAS has widespread symptoms that affect nearly every system of the body. This adds to the difficult nature of diagnosing MCAS properly.

    Here some of the most common symptoms of MCAS:

    • Fatigue
    • Poor memory
    • Brain fog
    • Inability to focus
    • Mood disorders
    • Migraines
    • Rashes
    • Hives
    • Low blood pressure
    • Heart racing
    • Becomes lightheaded when they stand up quickly
    • Diarrhea
    • Abdominal pain
    • Constipation
    • Nausea
    • Bloating
    • Strong PMS symptoms
    • Allergy-like symptoms
    • Asthma
    • Wheezing
    • Shortness of breath

    It’s a common misconception that patients with MCAS have skin problems as the primary symptom. The number one sign of MCAS are neurological symptoms. However, they may also have skin reactions especially if there are a mold patient. Most of my mold patients have hives, flushing, and other skin reactions. This is especially true if they are coming in direct contact with mold or if they are detoxing from mold.

    It is possible for a patient with CIRS to also have MCAS. You can tell this is happening when CIRS is correctly and systematically treated, yet the patient doesn’t get well. This is when doctors tend to notice things like flushing and rashes, which are all signs of classical histamine reactions.

    Histamine is problematic because it causes blood-brain barrier permeability and gut permeability. Usually, this is accompanied by food allergies and sensitivities. Chronic conditions such as MCAS are inherently complex, this makes diagnosis a process of elimination.

    When I see suspected MCAS patients, we have to systematically work through multiple potential diagnoses until we rule out each disease individually. Ultimately, we come to the conclusion that they are struggling with MCAS by ruling out other possibilities.

     

    My Personal Experience with Mold and Mast Cells

    In 2014, my office flooded and we had massive mold issues which I didn’t realize for several months. When I realized, I implemented the Shoemaker Protocol immediately. I started taking binders, used other detox methods, and removed myself from the mold exposure.

    Shortly after, my body broke out in very severe hives. I took an anti-histamine to deal with the hives but realized what was happening was a massive mast cell activation in detox. My body was detoxing from mold through my treatments and by removing myself from the exposure, but it was causing mast cell activation symptoms. I experiences brain fog, respiratory issues, gastrointestinal distress, and my skin was covered in hives.

    I’ve experienced firsthand mast cell activation – it can be very scary. What this means for me is that my body is going to continue to be more sensitive to environmental changes and toxin exposures than the average person. I am more prone to getting hives to exposures like VOCs and other triggers. While this is somewhat unfortunate, there is a lot that can be done for MCAS. Though MCAS treatment does require vigilance, it is possible to live a relatively normal life.

     

    Biomarkers for MCAS

    Though there is no definitive test for MCAS there are numerous tests you can combine to  support your diagnosis. In the figure below, you’ll find the most common biomarker testing recommended for those suspected of having MCAS. There’s no one lab that does all of these tests, you’ll need to use both LabCorp and Quest.

    When it comes to MCAS that’s triggered by mold, there are few biomarkers that are more common than others. These include:

    • MMP – 9
    • C4a (C4b is usually seen  bacterial trigger)
    • TGF beta
    • VEGF

    Also, you need to be sure that your doctor and the lab both know how to carefully handle samples for accurate results. Ultimately, blood test can’t really confirm or deny the presence of an illness. The best way to know if you have MCAS or not, is by ruling out other illnesses through a comprehensive process of elimination. Lab testing helps this process but it’s not the full solution.

    Slide credit to Dr. Sandeep Gupta with Mold Illness Made Simple

     

    MTHFR status and MCAS

    When people have MTHFR, A1298C and C677T, They have impaired methylation.  If they don’t have enough active methylfolate or active methyl B12 or P5P or Riboflavin they’re prone to have problems with methylation. This is especially important with anyone suspected of having MCAS,

    Because methylation is one of the most important pathways our body uses to break down histamine.

    In the situation where a patient has impaired methylation, deficiencies and B vitamins, and the MTHFR genetic mutation,  this can complicate problems with excess histamine in the body. This is because the body is unable to break down histamine  well. If I find a patient is positive for the MTHFR status, we can add methyl B12 and methylfolate.

    Other ways the body breaks down histamine include the DAO and  MAO enzymes.

     

    Reducing mold exposure is the name of the game

    If you suspect you have CIRS or MCAS,  it’s important to check for mold exposure.  without identifying mold exposure symptoms will only continue to get worse and treatments will be ineffective.  this may mean removing yourself from the water damage building.

    However, even when you fully remove yourself from a mold exposure your mass cells still might remain active. This is because they need assistance to detox and to return to a stable state.

     

    Treating MCAS

    When it comes to treating MCAS  that’s been triggered by mold, you must eliminate mold exposure. Imagine your MCAS like a bucket, the more factors you have contributing to your activated mast cells, the worse your symptoms are.

    You need to reduce the number of factors contributing to your MCAS. This is what I mean when I say you need to reduce your toxin burden. You might be surprised at how big of a difference it can make to get yourself into clean air and eating clean food. I always recommend eating as organic as possible, using a water filter, and an air purifier.

    At first I can feel overwhelming, but if you change a little at a time, eventually you can make the overhaul necessary to live a full and healthy life. My patients often asked me if everything needs to be done with a hundred percent accuracy. When it comes to mold you really do need to remove yourself completely from the mold filled environment. In other areas of your life you might not necessarily need to be as strict after a while. However, it pays to be as strict as possible when you’re working to stabilize your mast cells initially.

    There are a number of supplements you can take to help MCAS, these include natural antihistamines and mast cell stabilizers.

      • Ascorbic acid
      • Quercetin
      • Omega 3s
      • Vitamin B6
      • Vitamin B12
      • Vitamin C
      • Glutathione
      • Turmeric
      • P5P
      • Diamine Oxidase enzymes (DAO)
      • Resveratrol
      • Methylfolate
      • Umbrellux DAO
      • Lactobacillus rhamnosus
      • Bifidobacterium spp

    If you suspect you have mast cell activation syndrome, I recommend you find an experiences functional medicine doctor who you like working with and trust. Because working to get a chronic condition under control takes time and patience. The good news is – it is possible to live a full and healthy live with MCAS.

     

    Resources:

    https://www.ncbi.nlm.nih.gov/pubmed/24784142

    https://www.ncbi.nlm.nih.gov/pubmed/28262205

    https://www.ncbi.nlm.nih.gov/pubmed/23179866

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3753019/

    https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3069946/

Ketamine for OCD | 703-844-0184 | Fairfax, Va 22306 | Ketamine Clinic | Ketamine doctors | IV Ketamine | Ketamine near me | Ketamine for obsessive compulsive disorder | 22308 | 22314 | Dr. Sendi

NOVA Health Recovery  <<< Ketamine Treatment Center Fairfax, Virginia

CAll 703-844-0184 for an immediate appointment to evaluate you for a Ketamine infusion:

Ketaminealexandria.com    703-844-0184 Call for an infusion to treat your depression. PTSD, Anxiety, CRPS, or other pain disorder today.

email@novahealthrecovery.com  << Email for questions to the doctor

Ketamine center in Fairfax, Virginia    << Ketamine infusions

Ketamine – NOVA Ketamine facebook page – ketamine treatment for depression

facebook Ketamine page

NOVA Health Recovery  << Ketamine clinic Fairfax, Va  – Call 703-844-0184 for an appointment – Fairfax, Virginia

Ketamine Consultants Blog

Ketamine Virginia = Ketamine IV Drip Doctors

The IV Medical Center - IV Vitamin Drips for wellness and recovery

The pros and cons of ketamine

Geuris “Jerry” Rivas, a native of New York, was diagnosed with severe obsessive-compulsive disorder when he was 15. Obsessions with organizing and reorganizing the belongings in his bedroom — posters, comic books, videos — took over most of his life.

Forced by germ obsessions to compulsively wash and rewash his hands, he started wearing gloves all day to both protect him from the germs and stop him from washing his hands raw. Now, at 36, OCD symptoms continue to cost him jobs and relationships. He’s managed to turn his organizational skills into a profession — he’s a home organizer and house cleaner — but still he struggles daily with his obsessions.

“It’s caused me a great deal of suffering,” Rivas says. “I’ve tried many, many medications. I’ve wasted so much of my life.”

In 2012, running out of answers, Rivas took part in the first clinical trial to test ketamine as a treatment for OCD. While ketamine is approved by the U.S. Food and Drug Administration as an anesthetic, it is also an illicit party drug known as “Special K,” with hallucinogenic effects and the potential for abuse. Over the past 10 years, dozens of small studies of ketamine’s ability to treat a variety of mood and anxiety disorders have reported remarkable results — including the sudden alleviation of treatment-resistant depression, bipolar disorder and post-traumatic stress disorder. And these effects lasted days, sometimes weeks, after the hallucinogenic effects of the drug wore off.

With a single infusion of the drug, Rivas experienced for two weeks what it was like to live without the compulsions and obsessions that had for years controlled his life.

“I felt like, for the first time, I was able to function like a regular person,” he says.

Illustration of a giant K being painted by a man in a white coat

Pros and cons

Ketamine has brought hope to a psychiatric field desperate to find new treatments for severe OCD, a chronic condition marked by debilitating obsessions and repetitive behaviors. Current treatments, which include antidepressants such as Prozac, can take months to have any effect on the disease, if they work at all.

“Severe OCD takes such a toll on patients,” says Carolyn Rodriguez, MD, PhD, who as a researcher at Columbia University ran the OCD trial. Now an assistant professor of psychiatry and behavioral sciences at Stanford, she has continued to explore the pros and cons of using ketamine to treat OCD. “The constant, intrusive thoughts that something is contaminated, the checking and rechecking, the repetitive behaviors. It interferes with your life, your jobs, your relationships.”

Ketamine was developed in the 1960s and has been used for decades as an anesthetic during surgery. It remains a mystery just how the drug works in the brain, and there are safety concerns. There is evidence from people who take the drug routinely — in much higher doses — that chronic, high-frequency ketamine use may be associated with increased risk of bladder inflammation and cognitive impairment, Rodriguez says. And if taken regularly, it can lead to dependence.

But researchers like Rodriguez are intrigued about the drug’s potential to help them identify a whole new line of medicines for fast-acting treatment of mental health disorders.

“What most excites me about ketamine is that it works in a different way than traditional antidepressants,” Rodriguez says. “Using ketamine, we hope to understand the neurobiology that could lead to safe, fast-acting treatments. I feel that is part of my mission as a physician and researcher.”

‘Right out of a movie’

Rodriguez’s interest in ketamine as a treatment for OCD was sparked about a decade ago when she was starting out as a research scientist at Columbia. A small, placebo-controlled study published in 2006 by a mentor of hers, Carlos Zarate, MD, now chief of the section on neurobiology and treatment of mood disorders at the National Institute of Mental Health, had shown that ketamine induced dramatic improvement in treatment-resistant depression within two hours of infusion. It was a landmark study, drawing attention among the psychiatric community and launching a new field of research into the use of ketamine to treat various mood and anxiety disorders.

“What most excites me about ketamine is that it works in a different way than traditional antidepressants.”

Rodriguez, intent on searching for better, faster treatments for her patients like Rivas with OCD, took note. There was an emerging theory that ketamine affects the levels of the neurotransmitter glutamate in the brain and increasing evidence that glutamate plays a role in OCD symptoms, she says. Perhaps ketamine could help regulate OCD symptoms as well as depression.

In 2013, Rodriguez and colleagues published their results from that first clinical trial of ketamine in OCD patients. The trial randomized 15 patients with OCD to ketamine or placebo.

In those patients who were given ketamine, the effect was immediate. Patients reported dramatic decreases in their obsessive-compulsive symptoms midway through the 40-minute infusion, according to the study. The diminished symptoms lasted throughout the following week in half of the patients. Most striking were comments by the patients quoted in the study: “I tried to have OCD thoughts, but I couldn’t,” said one. Another said, “I feel as if the weight of OCD has been lifted.” A third said, “I don’t have any intrusive thoughts. … This is amazing, unbelievable. This is right out of a movie.” And while nearly all initially had dissociative effects like feelings of unreality, distortions of time or hallucinations, they were gone within two hours after the start of the infusion.

“Carolyn’s study was quite exciting,” Zarate says, adding that there were a number of similar, small but rigorous studies following his 2006 study that found fast-acting results using ketamine to treat bipolar disorder and post-traumatic stress disorder.

“We had no reason to believe that ketamine could wipe out any symptoms of these disorders within hours or days,” he says.

So how does it work?

Virtually all of the antidepressants used in the past 60 years work the same way: by raising levels of serotonin or one or two other neurotransmitters. Ketamine, however, doesn’t affect serotonin levels. Exactly what it does remains unclear.

“There’s a recognition that people like me and others are using the drug to treat patients now. There’s an incredible need for something.”

Since coming to Stanford in 2015, Rodriguez has been funded by the National Institute of Mental Health for a large clinical trial of ketamine’s effects on OCD. This five-year trial aims to follow 90 OCD patients for as long as six months after they’ve been given a dose of ketamine or an alternative drug. Rodriguez and her research team want to observe how ketamine changes participants’ brains, as well as test for side effects.

Ultimately, Rodriguez says, she hopes the study will lead to the discovery of other fast-acting drugs that work in the brain like ketamine but without its addictive potential.

Recent research in the field indicates that the glutamate hypothesis that triggered her pilot study might be further refined.

“Ketamine is a complicated drug that works on many different receptor sites,” she says. “Researchers have fixated on the NMDA receptor, one of the glutamate-type receptors, but it might not be the only receptor bringing benefit.”

In May 2016, researchers from NIMH and the University of Maryland — Zarate among them — published a study conducted in mice showing that a chemical byproduct, or metabolite, created as the body breaks down ketamine might hold the secret to its rapid antidepressant actions. This metabolite, hydroxynorketamine, reversed depressionlike symptoms in mice without triggering any of the anesthetic, dissociative or addictive side effects associated with ketamine, Zarate says.

“Ideally, we’d like to test hydroxynorketamine and possibly other drugs that act on glutamate pathways without ketamine-like side effects as possible alternatives to ketamine in OCD,” Rodriguez says.

Beyond the clubs

Meanwhile, dozens of commercial ketamine clinics have popped up across the country, making treatments available to patients who are searching for help to stop their suffering now. Medical insurance companies usually cover ketamine’s FDA-approved use as an anesthetic but won’t cover its use for other purposes, such as mental health disorders. So patients who have run out of treatment options are paying hundreds of dollars a dose for repeated ketamine infusions.

“The fact that these clinics exist is due to the desperation of patients,” says Rodriguez.

She and other researchers are calling for guidelines to protect patients and more research to learn how to use the drug safely.

“I think it’s a game changer, and it’s here to stay,” says David Feifel, MD, PhD, professor emeritus of psychiatry at UC-San Diego, who studies the effect of ketamine on clinical depression. Feifel began prescribing the drug for patients with treatment-resistant depression in 2010.

“I’ve found it to be very safe,” Feifel says, adding that the American Psychiatric Association this year issued safety guidelines on how to use ketamine clinically for treatment of depression.

“There’s a recognition that people like me and others are using the drug to treat patients now,” he says. “There’s an incredible need for something.”

The drug hasn’t worked for everyone he’s treated, Feifel says, but for many it’s been “life-changing.”

Rodriguez says she understands what motivates the clinicians to prescribe the drug now to patients in dire straits — those who are suicidal or who have tried every possible medication and therapeutic option and continue to suffer each day.

“I see it as a way to treat people whose OCD is very, very severe,” she says. “People who can’t come out of the house, who are suicidal, who have no other options.

“I just don’t like the idea of people being in pain,” Rodriguez adds. “I want to see science translated into treatments now.”

Meanwhile, researchers are learning more about the drug. Janssen Pharmaceutical is testing the efficacy of a version of ketamine, known as esketamine, as a therapy for treatment-resistant depression and for major depressive disorder with imminent risk for suicide. The FDA has fast-tracked both investigations. At Stanford, Alan Schatzberg, MD, a professor of psychiatry and behavioral sciences, along with other faculty including Rodriguez, is studying the mechanism of action for ketamine in treating depression.

Rodriguez is also interested in using ketamine to kick-start a type of cognitive behavioral therapy called exposure and response prevention, an evidence-based psychological treatment designed to help patients overcome OCD. The therapy involves teaching patients with OCD to face anxieties by refraining from ritualizing behaviors, then progressing to more challenging anxieties as they experience success.

Relaxation and other techniques also help patients tolerate their anxiety — for example, postponing the compulsion to wash their hands for at least 30 minutes, then extending that time period.

“My goal isn’t to have people taking ketamine for long periods of time,” Rodriguez says. But perhaps a short-term course of ketamine could provide its own kind of exposure and response prevention by allowing patients to experience that it is possible not to be controlled by their OCD, she says.

Rivas well remembers that infusion of ketamine he received during Rodriguez’s first clinical trial to test the drug. The rush made him feel “like Superman.”

“I felt like my body was bigger, that I was more muscular, that I could tackle anything,” he says. But that feeling only lasted the duration of the 40-minute infusion. His OCD symptoms disappeared immediately and were still gone for two weeks after.

“I was amazed that something like that would work and work so fast,” he says. His OCD symptoms today are still intrusive, but he manages to keep them under control by taking antidepressants and seeing a therapist. Still, each day when he comes home from work, he has to put gloves on before he enters his apartment building, and as soon as he enters his apartment, he must wash his hands.

“It’s a ritual now,” he says. “There has never been a time that I haven’t done that, except those two weeks after the ketamine.”

When he heard that certain private ketamine clinics are now offering the drug as treatment for OCD, he said he understands why patients take the risks and pay the high prices. As more research has become available, he’s begun considering it himself.

“I’ve been suffering through my OCD for so long, I’ve gotten to the point where I’d try anything,” he says.

USING KETAMINE TO TREAT SEVERE MENTAL ILLNESSA conversation with Stanford psychiatrist Carolyn Rodriguez, MD, PhD, about how she got interested in the use of ketamine to treat obsessive-compulsive disorder and how she is determined to find out why, in studies, the drug has provided relief from symptoms.

AUDIO Interview

Addiction Domain LINK

Strategies for Depression | Ketamine for Depression | 703-844-0184 | Alexandria, Va | 22306 | Ketamine therapy | IV Ketamine center | Ketamine doctor | Springfield, Va

NOVA Health Recovery  <<< Ketamine Treatment Center Fairfax, Virginia

CAll 703-844-0184 for an immediate appointment to evaluate you for a Ketamine infusion:

Ketaminealexandria.com    703-844-0184 Call for an infusion to treat your depression. PTSD, Anxiety, CRPS, or other pain disorder today.

email@novahealthrecovery.com  << Email for questions to the doctor

Ketamine center in Fairfax, Virginia    << Ketamine infusions

Ketamine – NOVA Ketamine facebook page – ketamine treatment for depression

facebook Ketamine page

NOVA Health Recovery  << Ketamine clinic Fairfax, Va  – Call 703-844-0184 for an appointment – Fairfax, Virginia

Ketamine Consultants Blog

Ketamine Virginia = Ketamine IV Drip Doctors

The IV Medical Center - IV Vitamin Drips for wellness and recovery

The Psychopharmacology of Depression: Strategies, Formulations, and Future Implications

 

With well over two dozen traditional antidepressants available in the US, and an ever-growing list of other psychotropic compounds with apparent antidepressant properties, pharmacological options for treating clinical depression today are broad and vast. However, recent findings suggest that the magnitude of efficacy for most antidepressants compared with placebo may be more modest than previously thought.1Most depressed patients do not respond fully to a first antidepressant trial, and with each consequent trial, there is less chance of symptom remission.2 About one-third of patients receiving long-term treatment report persistent moderate-to-severe depression.3 Hence, there remains more than a little room for improvement.

Since the late 1950s, the traditional view of treating depression has focused on the role of monoamines (serotonin, norepinephrine, and dopamine) as the main targets for medications. Newer treatments are looking beyond effects on monoamines as potential strategies to leverage depressive symptoms.

A major challenge for progress in novel pharmacotherapies has been our lack of a full understanding about the causes of depression. Advances in functional neuroimaging and genetic markers have begun to shed new light on brain regions and pathways associated with aberrant neural functioning in depression, but not in ways that have led to treatments aimed at remedying its pathogenesis. This makes it hard to think of antidepressant medications as “treating” the pathophysiology of depression (as when antibiotics eliminate the cause of an infection); rather, antidepressant relieve symptoms by counteracting or compensating for depression’s consequences (as when diuretics alleviate peripheral edema regardless of its etiology).

Gone are the days of oversimplified theories that depression is caused by a “chemical imbalance.” More likely, depression involves changes in brain architecture and the interplay of complex circuits in which chemicals, or neurotransmitters, are the messengers of information, rather than the causes of faulty functioning. Table 1 summarizes some of the major conceptual shifts that have occurred in thinking about the probable causes of depression (or at least its neurobiological context), which sets the stage for new ways to consider innovative treatment strategies. Looking beyond the role of monoamines as treatment targets in depression, a number of novel therapeutic strategies have begun to receive growing interest in preclinical and clinical trials. Key points about emerging novel depression pharmacotherapies are summarized in Table 2, and described more fully below.

Subanesthetically dosed intravenous (IV) ketamine currently represents perhaps the most dramatic and innovative antidepressant pharmacotherapy to emerge in decades.4,5 It is pharmacodynamically unique in its rapid onset (hours rather than days to weeks) and its potential ability to reduce suicidal ideation after a single dose, independent of its antidepressant properties.6 (While both lithium and clozapine have been shown to reduce suicidal behaviors, neither has been shown to reduce ideation, much less in the same day after a single dose.) Meta-analyses suggest that 0.5 mg/kg IV ketamine produces nearly a 10-fold greater likelihood of response than placebo at day 1 and a 4- to 5-fold likelihood of sustained response after one week.7

The exact psychotropic mechanism of action of ketamine remains elusive. Initial work focused on blockade of ionotropic N-methyl-D-aspartate (NMDA) receptors as accounting broadly for its antidepressant effects. However, subsequent negative randomized trials with other NMDA receptor antagonists (such as riluzole8) redirected interest toward ketamine’s other, non-NMDA receptor-related mechanisms, such as sigma receptor agonism, mu opioid receptor antagonism, or midbrain monoaminergic inhibition. Other authors have suggested that at low doses, ketamine’s antidepressant effects may derive from an increase in glutamate transmission with increased α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor expression, leading to increased release of brain-derived neurotrophic factor (BDNF).9Murrough and colleagues10 recently observed the necessity of AMPA receptor activation for the antidepressant effects of ketamine. They reported that “directly targeting the NMDA [receptor] may not be required.” As noted by the American Psychiatric Association Council on Research Task Force on Novel Biomarkers and Treatments,11 future advances will depend on a better understanding of the many mechanisms of action relative to the antidepressant properties of ketamine.

Ketamine is currently not approved by the FDA as a treatment for depression. Uncertainty remains as to whether repeated dosing is safe, effective, and necessary to avoid relapse and, if so, when, at what frequency, and for how long. The aforementioned APA Council on Research Consensus Statement on ketamine treatment for depression11 stated that while some clinics already offer 2- to 3-week courses of ketamine delivered 2 to 3 times per week, “there remain no published data that clearly supports this practice, and . . . the relative benefit of each ketamine infusion [should] be considered in light of the potential risks associated with longer term exposure to ketamine and the lack of published evidence for prolonged efficacy with ongoing administration.” 11 Thus far, studies of other pharmacotherapies to sustain an initial ketamine response (such as riluzole or lithium) have proven no better than placebo.

Enantiomeric esketamine remains investigational as a possible easier-to-administer intranasal (IN) antidepressant, although IN bioavailability is only about half that of IV ketamine’s 100%. Two randomized multi-site trials of IN esketamine added to antidepressants showed dose-related better efficacy than placebo: Daly and colleagues12 found that 28 mg to 84 mg of IN ketamine twice weekly over two weeks produced significant improvement in depressive symptoms as compared to placebo beginning after 1 week and continuing through week 9 for the majority of responders. A study by Canuso and colleagues13 demonstrated a significant reduction in depressive symptoms within 4 hours of administration (56 mg to 84 mg insufflated over 15 minutes) and a medium to large effect size, sustained after 25 days; suicidal ideation reduced significantly at 4 hours but not beyond that time. Another recent randomized pilot trial of IN racemic ketamine (the mixture of S- and R-ketamine) was prematurely discontinued due to poor tolerability (including cardiovascular and neurological adverse effects) and highly variable absorption across subjects.14

Modulation of the endogenous opioid system has long been a target of interest in the treatment of mood disorders, but it is limited by safety risks, tolerance, and addiction potential. Recent work has focused on a proprietary combination of the μ-opioid partial agonist/kappa antagonist buprenorphine plus the μ-opioid receptor antagonist samidorphan (ALKS 5461). The potent blockade of μ-opioid receptors in samidorphan, which prevents buprenorphine access to these receptors, effectively renders buprenorphine a selective kappa opiate receptor (KOR) antagonist, which is its putative antidepressant mechanism. After initial favorable Phase II trials, in 2013 the FDA granted ALKS 5461 fast track status for accelerated regulatory review as an antidepressant adjunct. Subsequent randomized trials in treatment-resistant major depression revealed statistically significant differences from placebo on some, but not all, depressive symptom outcome measures and at some, but not all, doses studied.15,16 The FDA initially refused to review the new drug application for ALKS 5461 as an adjunctive therapy for depression because of concerns about bioavailability and lack of evidence, but then reversed its position. ALKS 5461 is currently under regulatory review and a decision regarding its possible approval is expected by early 2019.

Antiinflammatories and immunomodulators

There has been growing recognition of complex interrelationships between depression and inflammation. Some but not all patients with clinically significant depression appear to have elevated serum markers of systemic inflammation, such as high sensitivity C-reactive protein (hs-CRP) and inflammatory cytokines. While causal relationships between depression and inflammation are poorly understood and questions remain whether depression causes inflammation or vice versa, randomized trial data suggest potential antidepressant value of nonsteroidal anti-inflammatory drugs (NSAIDs), particularly the COX-2 inhibitor celecoxib. A pooled meta-analysis of 5447 participants from 10 NSAID trials and 4 cytokine inhibitors (as mono- or add-on therapy for depression) revealed statistically significant advantages over placebo, with small to medium effect sizes, for response (odds ratio = 6.6; 95% confidence interval=2.2-19.4) or remission (odds ratio = 7.9; 95% confidence interval=2.9-21.1)17It has not been established whether adding celecoxib or other NSAIDs to an antidepressant may be more useful only in the setting of elevated serum markers of inflammation. Elsewhere, preliminary studies reveal that inflammatory depressive subtypes (ie, high baseline hs-CRP) may respond better to a tricyclic than SSRI,18 adjunctive L-methylfolate,19 or the tumor necrosis factor (TNF) antagonist infliximab (admnistered IV at 5 mg/kg over 3 doses).20

The antimicrobial minocycline exerts anti-inflammatory and anti-oxidative properties and has been preliminarily studied mostly in small or open/nonrandomized trials. A meta-analysis of 3 randomized controlled trials found an overall significantly greater effect than placebo with a medium to large effect size and good tolerability, although the small number of well-designed studies and samples sizes (total N = 158) limits their generalizability.21

Anticholinergic muscarinic agents

Harkening back to the 1970s hypothesis that depression could reflect cholinergic-adrenergic dysregulation, interest has turned to the possible antidepressant effects of the muscarinic cholinergic antagonist scopolamine. Preliminary studies of intravenous scopolamine dosed at 4 µg/kg in both unipolar and bipolar depression have produced remission rates from 45% to 56% (Cohen’s d ranged from 1.2-3.4) typically within several days of administration, with persistence for 10 to 14 days.22Antimuscarinic adverse effects such as sedation, dry mouth, and blurry vision are common but transient. Neurocognitive measures reaction time during selective attention tasks reveal no significant delays following IV scopolamine infusion.23 Analogous to IV ketamine, questions remain about the optimal number of infusions to minimize relapse as well as the use of nonparenteral formulations.

Brexanolone (SAGE-547), also known as allopregnanolone, is a positive allosteric modulator of GABA-A receptors. It is a progesterone metabolite that exerts neuroprotective, pro-cognitive, and possible antidepressant/anxiolytic properties. Precipitous drops in progesterone and allopregnanolone after childbirth prompted interest in the use of allopregnanolone specifically in postpartum depression. A small (N = 21) initial trial of brexanolone (administered intravenously because of its short half-life and poor oral bioavailability) or placebo for severe postpartum depression yielded a substantial reduction in depressive symptom severity within 60 hours (effect size = 1.2).24 Further data remain pending. SAGE-217 is reformulated brexanolone that has good oral bioavailability, allowing for oral administration, as well as a longer half-life allowing once-a-day dosing. It is currently being studied as an adjunctive agent for treatment resistant depression.

PPAR-γ agonists and incretins

Thiazolidinediones are insulin sensitizers that also demonstrate antidepressant properties in animal studies and appear to possess anti-inflammatory, neuroprotective, antioxidant and anti-excitatory properties. Pioglitazone, a PPAR-γ agonist thiazolidinedione, has been studied versus placebo or metformin in major depression, both as monotherapy and in combination with antidepressants or lithium. A meta-analysis of 4 trials revealed significantly higher remission rates than controls (27% versus 10%, respectively; odds ratio of remission in major depression = 5.9 (95% confidence interval=1.6-22.4), p = .009), with an NNT = 6.25 Even though PPAR-γ agonists can decrease insulin resistance, weight gain can be an undesired adverse effect that is possibly a result of a combination of fat cell proliferation, fluid retention, and increased appetite. Pioglitazone also carries serious adverse risks for congestive heart failure and bladder cancer.

Glucagon-like peptide 1

Another class of antidiabetic drugs known as glucagon-like peptide 1 (GLP-1) agonists mimic the action of insulin (so-called incretins) and are of interest as a potential target for depression. GLP-1 agonists such as liraglutide possess neuroprotective and antiapoptotic properties, and animal studies suggest it has antidepressant and pro-cognitive effects, particularly involving reward and motivation. Human studies have thus far focused more on weight-reducing and possible cognitive benefits of liraglutide more than its potential antidepressant efficacy, but its mechanism represents a promising direction for further study.

Future directions

This brief overview has focused on emerging novel pharmacotherapies for depression. While the provisional nature of proof-of-concept studies may be encouraging, they are far from definitive. The aforementioned findings are largely preliminary and meant more to prompt larger randomized trials to establish efficacy, safety, and generalizability rather than inspire premature immediate uptake into clinical practice.

Given the focus on neuroprotection and enhanced neuroplasticity as proposed targets of treatment, it would seem remiss not to at least mention the neurobiological impact of depression-specific psychotherapies, mindfulness meditation, and related psychosocial interventions. Psychotherapy is, among other things, a behavioral learning paradigm, presumably rendering alterations in cognitive functions (memory, attention, and decision-making), fear extinction, and emotional processing. Evidence-based psychotherapies for depression have been shown to produce changes in brain network connectivity26 (recapitulating the idea of Hebbian synapses, where “neurons that fire together wire together”) and upregulation of intracellular transcription factors involved in neuronal plasticity.27Enhanced neuroplasticity may represent a common denominator target for effective biological or psychosocial treatments for depression.

Increasingly, drugs we call antidepressants are diversifying to include broader classes of molecules. A more neuroscience-based nomenclature for psychotropic drugs has already been proposed28 and will no doubt invoke more novel drug mechanisms, supplanting older concepts about depression as a chemical imbalance as perspectives continue to evolve about how antidepressants impact neuronal viability and brain microarchitecture.

References:

1. Cipriani A, Furukawa TA, Salanti G,et al.Comparative efficacy and acceptability of 21 antidepressant drugs for the acute treatment of adults with major depressive disorder: a systematic review and network meta-analysis. Lancet 2018; S0140-6736:32802-7. [Epub ahead of print]

2. Trivedi MH, Rush AJ, Wisniewski SR, et al. Evaluation of outcomes with citalopram for depression using measurement-based care in STAR*D: implications for clinical practice. Am J Psychiatry. 2006;163:28-40.

3. Cartwright C, Gibson K, Read J, et al. Long-term antidepressant use: patient perspectives of benefits and adverse effects. Patient Prefer Adher. 2016;10:1401-1407.

4. Zarate CA Jr., Singh JB, Carlson PJ, et al. A randomized trial of an N-methyl-D-aspartate antagonist in treatment-resistant major depression. Arch Gen Psychiatry. 2006;63:856-864.

5. Murrough JW, Iosifescu DV, Chang LC, et al. Antidepressant efficacy of ketamine in treatment-resistant major depression: a two-site randomized controlled trial. Am J Psychiatry. 2013;170:1134-1142.

6. Wilkinson ST, Ballard ED, Bloch MH, et al. The effect of a single dose of intravenous ketamine on suicidal ideation: a systematic review and individual participant data meta-analysis. Am J Psychiatry. 2018;175:150-158.

7. Newport DJ, Carpenter LL, McDonald WM, et al. Ketamine and other NMDA antagonists: early clinical trials and possible mechanisms in depression. Am J Psychiatry. 2015;172:950-966.

8. Mathew SJ, Gueorguieva R, Brandt C, et al. A randomized, double-blind, placebo-controlled, sequential parallel comparison design trial of adjunctive riluzole for treatment-resistant major depressive disorder. Neuropsychopharmacol 2017;42: 2567-2574.

9. Duman RS, Li N, Liu RJ, et al. Signaling pathways underlying the rapid antidepressant actions of ketamine. Neuropharmacol. 2012;62:35-41.

10. Murrough JW, Abdallah CG, Mathew SJ. Targeting glutamate signalling in depression: progress and prospects. Nat Rev Drug Discov. 2017;16:472-486.

11. Sanacora G, Frye MA, McDonald W, et al. A consensus statement on the use of ketamine in the treatment of mood disorders. JAMA Psychiatry. 2017;74:399-405.

12. Daly EJ, Singh JB, Fedgchin M, et al. Efficacy and safety of intranasal esketamine adjunctive to oral antidepressant therapy in treatment-resistant depression: a randomized clinical trial. JAMA Psychiatry. 2018;75:139-148.

13. Canuso CM, Singh JB, Fedgchin M, et al. Efficacy and safety of intranasal esketamine for the rapid reduction of symptoms of depression and suicidality in patients at imminent risk for suicide: results of a double-blind, randomized, placebo-controlled study. Am J Psychiatry. April 2018; Epub ahead of print.

14. Gálvez V, Li A, Huggins C, et al. Repeated intranasal ketamine for treatment-resistant depression – the way to go? Results from a pilot randomised controlled trial. J Clin Psychopharmacol. 2018;32:397-407.

15. Ehrich E, Turncliff R, Du Y, et al. Evaluation of opioid modulation in major depressive disorder. Neuropsychopharmacol. 2015;40:1448-1455.

16. Fava M, Memisoglu A, Thase ME, et al. Opioid modulation with buprenorphine/samidorphan as adjunctive treatment for inadequate response to antidepressants: a randomized double-blind placebo-controlled trial. Am J Psychiatry. 2016;173:499-508.

17. Köhler O, Benros ME, Nordentoft M, et al. Effect of anti-inflammatory treatment on depression, depressive symptoms, and adverse effects: a systematic review and meta-analysis of randomized clinical trials. JAMA Psychiatry. 2014;71:1381-1391.

18. Uher R, Tansey KE, Dew T, et al. An inflammatory biomarker as a differential predictor of outcome of depression treatment with escitalopram and nortriptyline. Am J Psychiatry. 2014;171:1278-1286.

19. Papakostas GI, Shelton RC, Zajecka JM, et al. Effect of adjunctive L-methylfolate 15 mg among inadequate responders to SSRIs in depressed patients who were stratified by biomarker levels and genotype: results from a randomized clinical trial. J Clin Psychiatry. 2014;75:855-863.

20. Raison CL, Rutheford RE, Woolwine BJ, et al. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry. 2013;70:31-41.

21. Rosenblat JD, McIntyre RS. Efficacy and tolerability of minocycline for depression: a systematic review and meta-analysis of clinical trials. J Affect Disord. 2018;227:219-225.

22. Drevets WC, Zarate CA Jr, Furey ML. Antidepressant effects of the muscarinic cholinergic antagonist scopolamine: a review. Biol Psychiatry. 2013;73:1156-1163.

23. Furey ML Pietrini P, Haxby JV, et al. Selective effects of cholinergic modulation on task performance during selective attention. Neuropsychopharmacol 2008; 33:913-923.

24. Kanes S, Colquohoun H, Grunduz-Bruce H, et al. Brexanolone (SAGE-547 injection) in post-partum depression: a randomised controlled trial. Lancet. 2017;390:480-489.

25. Colle R, de Larminat D, Rotenberg S, et al. Pioglitazone could induce remission in major depression: a meta-analysis. Neuropsychiatr Dis Treat 2016;13: 9-16.

26.Yang CC, Barrós-Loscertales A, Pinazo D, et al. State and training effects of mindfulness meditation on brain networks reflect neuronal mechanisms of its antidepressant effect. Neural Plast. 2016;2016:9504642.

27. Koch JM, Hinze-Selch D, Stingele K, et al. Changes in CREB phosphorylation and BDNF plasma levels during psychotherapy of depression. Psychother Psychosom. 2009;78:187-192.

28. ECNP Neuroscience Applied. Neuroscience-based Nomenclature. https://www.ecnp.eu/research-innovation/nomenclature.aspx. Accessed June 6, 2018.

Ketamine for Depression | Articles and Links | 703-844-0184 | Springfield, Virginia |22306 | IV Ketamine Center | Ketamine Clinic | 22304| Ketamine Virginia

NOVA Health Recovery  <<< Ketamine Treatment Center Fairfax, Virginia CAll 703-844-0184 for an immediate appointment to evaluate you for a Ketamine infusion:

Ketaminealexandria.com    703-844-0184 Call for an infusion to treat your depression. PTSD, Anxiety, CRPS, or other pain disorder today.

email@novahealthrecovery.com  << Email for questions to the doctor

Ketamine center in Fairfax, Virginia    << Ketamine infusions

Ketamine – NOVA Ketamine facebook page – ketamine treatment for depression

facebook Ketamine page

NOVA Health Recovery  << Ketamine clinic Fairfax, Va  – Call 703-844-0184 for an appointment – Fairfax, Virginia

Ketamine Consultants Blog

Ketamine Virginia = Ketamine IV Drip Doctors

The IV Medical Center – IV Vitamin Drips for wellness and recovery

____________________________________________________________________________________________

Ketamine for Chronic Pain & Depression

Intravenous Ketamine is proving to be a tremendous treatment for intractable depression as well as chronic pain.  About half the patients treated respond positively with results lasting up to a week in most of the responders.

It has emerged as a treatment option for a variety of chronic pain conditions including fibromyalgia, small fiber neuropathy, Complex Regional Pain Syndrome (CRPS), Reflex Sympathetic Dystrophy (RSD) and psychiatric conditions including depression, Post Traumatic Stress Disorder (PTSD), suicidal ideation, and Obsessive-Compulsive Disorder (OCD).

Ketamine in the News

Remarkable secrets of ketamine’s antidepressant effect unlocked by scientists

Could Party Drug Ketamine Be a Treatment for Depression?

‘The fog is gone’: How ketamine could help lift hard-to-treat depression

Ketamine Research

Ketamine for Depression, 1: Clinical Summary of Issues Related to Efficacy, Adverse Effects, and Mechanism of Action.

Ketamine safety and tolerability in clinical trials for treatment-resistant depression.

Low-dose ketamine for treatment resistant depression in an academic clinical practice setting.

Symptomatology and predictors of antidepressant efficacy in extended responders to a single ketamine infusion.

How does ketamine elicit a rapid antidepressant response?

The use of ketamine as an antidepressant: a systematic review and meta-analysis.

Ketamine for rapid reduction of suicidal ideation: a randomized controlled trial.

Do the dissociative side effects of ketamine mediate its antidepressant effects?

Rapid and longer-term antidepressant effects of repeated ketamine infusions in treatment-resistant major depression.

SUBLOCADE | SUBOXONE TREATMENT | Buprenorphine for Kratom Dependence | ADDICTION TREATMENT DOCTOR | FAIRFAX, VA | ALEXANDRIA | 703-844-0184 | DR. SENDI | 22304 | 22314 |BUPRENORPHINE TREATMENT for KRATOM| ZUBSOLV | ADDICTION TREATMENT FACILITY | DEPRESSION |

NOVA Addiction Specialists website – Suboxone and telemedicine treatment in Alexandria, Virginia 703-844-0184

Dr. Sendi – at NOVA Addiction Specialists can evaluate you to see if Sublocade will work for you.

NOVA Health Recovery    <<, Suboxone treatment and Ketamine treatment

NOVA Addiction facebook page

Suboxone treatment in Alexandria, Virginia 703-844-0184

Suboxone treatment in Fairfax, Virginia 703-844-0184

http://www.suboxonewoodbridge.com

Suboxone, buprenorphine telemedicine treatment in Alexandria  << Link here

http://addictiondomain.com/ Addiction Blog

https://www.facebook.com/novaddiction – Facebook page

http://www.suboxonealexandria.com

http://www.suboxonecenter.org/ Suboxone treatment – telemedicine also – 703-844-0184 24/7


Case Report Details Use of Buprenorphine for Treatment of Kratom Dependence

 

Kratom is an herbal supplement that shares structural similarities with opioid analgesics

Kratom is an herbal supplement that shares structural similarities with opioid analgesics

Opioid-like dependence due to chronic kratom use can be successfully treated with buprenorphine, according to a recent case report published in the Journal of Addiction Medicine.

Kratom, an herbal supplement that shares structural similarities with opioid analgesics, has recently grown in popularity as an unapproved opioid replacement therapy. The drug is easily obtained via the Internet (as it does not require a prescription), but oftentimes contains higher than typical doses and may be mixed with adulterants, increasing the risk of toxicity.

In their article, the authors report on two patients who used kratom to self-treat their chronic pain after they could no longer receive opioid analgesics from healthcare providers. Both patients presented to the clinic with evidence of kratom dependence and withdrawal and underwent home initiation of sublingual buprenorphine-naloxone therapy. In each case, transitioning to buprenorphine-naloxone maintenance led to control of both their chronic pain and opioid withdrawal symptoms.

RELATED ARTICLES

“Although some debate whether kratom is a true opioid or not, this case series shows that opioid agonist treatment with buprenorphine-naloxone is effective for some patients with kratom dependence and demonstrates 2 safe home initiations of buprenorphine,” concluded the authors.

 

Treatment of Kratom Dependence With Buprenorphine

KETAMINE FOR DEPRESSION | 703-844-0184 | FAIRFAX, VA | LOUDON, VA| LORTON, VA | |Ketamine For Geriatric Depression| 22308 |22304

NOVA Health Recovery  <<< Ketamine Treatment Center Fairfax, Virginia

CAll 703-844-0184 for an immediate appointment to evaluate you for a Ketamine infusion:

Ketaminealexandria.com    703-844-0184 Call for an infusion to treat your depression. PTSD, Anxiety, CRPS, or other pain disorder today.

email@novahealthrecovery.com  << Email for questions to the doctor

Ketamine center in Fairfax, Virginia    << Ketamine infusions

Ketamine – NOVA Ketamine facebook page – ketamine treatment for depression

facebook Ketamine page

NOVA Health Recovery  << Ketamine clinic Fairfax, Va  – Call 703-844-0184 for an appointment – Fairfax, Virginia

Ketamine Consultants Blog

 

Ketamine has ‘truly remarkable’ effect on depression and is effective in elderly patients, scientists say

Ketamine Infusions | 703-844-0184 | Fairfax, Va | 22304 | ketamine for depression

Ketamine can have a “truly remarkable” effect on people with depression, researchers have said after a new study showed promising results among elderly patients.

Colleen Loo, a professor at the University of New South Wales in Australia, led the world’s first randomised control trial into the drug’s effect on people over 60 with treatment-resistant depression.

“This trial has shown ketamine can be used safely in the elderly and it tends to be effective,” she told The Independent, adding that a similar effect was observed in this age group as in younger patients.

It is important to test how people of different ages respond to a new treatment before it can be offered by doctors, she said: “Sometimes depression in the elderly can be harder to treat, especially with medication.

“Also, they tend to have more medical problems, which can interfere with medication.”

Ketamine was discovered in 1962 and is licenced for medical use in the UK as an anaesthetic, but is also used illegally as a recreational drug.

Of the study’s 16 participants, 11 reported an improvement in their condition while being treated with the drug, according to the research published in the American Journal of Geriatric Psychiatry.

After six months, 43 per cent of the subjects said they had no significant symptoms of depression – a high rate given that the participants had not responded to previous treatment, said Professor Loo.

“It is truly remarkable the way ketamine can work,” she said. “Other people have also found you get a rapid and powerful effect after a single dose of ketamine.”

“Some people mistakenly think we are inducing a temporary, drug-induced euphoria and people are ‘out of it’, which is why they’re not depressed.

“But the effects take place in the first hour, and they’re not euphoric at all. In fact, all of our research participants disliked them. They considered them adverse effects.

“The antidepressant effect kicks in a few hours later and are maximised about 20 hours later, when you’re fully alert and in your usual state of mind.”

While research into the use of ketamine to treat mental health problems is still in its early stages, scientists at Oxford University have said their studies show the drug can provide relief to patients with severe depression “where nothing has helped before”.

Rupert McShane, the consultant psychiatrist who is leading Oxford’s ketamine treatment programme, told The Independent it was “good to see that, contrary to some reports, some older people do respond to ketamine.”

“This study highlights that ketamine can be given in a variety of ways (not just intravenous), that it’s a good idea to adjust the dose, and that the more resistant someone’s depression is, the higher the dose that they are likely to need,” he said.

Professor Loo and her colleagues delivered ketamine to the patients using a small injection under the skin – similar to the insulin jabs given to diabetes patients.

This makes the drug easier and quicker to administer than the intravenous infusions used in other trials, which require a machine pump to regulate the dose and takes up to an hour to complete.

Participants received increasing doses of ketamine over a period of five weeks, with the dose personalised for each patient.

However, she warned that while the research is one step closer to providing a model for how doctors could prescribe ketamine as a treatment for depression in future, it would still be “premature to jump into clinical practice”.

“There are ‘super-responders’, who after a single treatment can be well for several months,” said Professor Loo, giving the example of a subject who, in 2014, remained free of depressive symptoms for five months after just one dose of ketamine.

But “most people are well but then they relapse over around three to seven days,” she said. “That’s where repeated dosing comes in.”

Ketamine Injections May Help Older Adults With Depression

Repeated subcutaneous injections of ketamine significantly improved symptoms in a small group of older adults with treatment-resistant depression, researchers found in a pilot study published online in The American Journal of Geriatric Psychiatry.

The randomized controlled trial is the first to assess the efficacy and safety of ketamine in the geriatric patient population.

“These findings take us a big step forward as we begin to fully understand the potential and limitations of ketamine’s antidepressant qualities,” said lead author Colleen Loo, MD, a professor in the School of Psychiatry at the University of New South Wales, Sydney, Australia.

Psychiatrists Issue ‘Much-needed’ Consensus on Ketamine for Mood Disorders

“Not only was ketamine well-tolerated by participants, with none experiencing severe or problematic side effects, but giving the treatment by a simple subcutaneous injection (a small injection under the skin) was also shown to be an acceptable method for administering the drug in a safe and effective way.”

Overall, the response and remission rate for older adults receiving ketamine was 68.8%.

Australian researchers tested individualized dosing of ketamine using a dose-titration method in 16 adults age 60 and older. Participants received increasing doses over 5 weeks. The double-blind, placebo-controlled trial included 1 session in which participants received an active treatment substitute that, similar to ketamine, caused sedation.

Why Not Make Ketamine a First-line Treatment?

After the randomized controlled trial, participants received 12 ketamine doses in an open-label phase.

At a 6-month follow-up, 7 of 14 older adults who had completed the randomized controlled trial had depression remission — 5 of whom remitted at doses below the common ketamine dose of 0.5 mg/kg, researchers reported. Repeated treatments, they added, resulted in a higher likelihood of remission or a longer time to relapse.

“Elderly patients with severe depression face additional barriers when seeking treatment for the condition. Many medications may cause more side effects or have lower efficacy as the brain ages,” said researcher Duncan George, MBBS, School of Psychiatry, University of New South Wales. “Older people are also more likely to have comorbidities like neurodegenerative disorders and chronic pain, which can cause further complications due to ketamine’s reported side effects.

“Our results indicate a dose-titration method may be particularly useful for older patients, as the best dose was selected for each individual person to maximize ketamine’s benefits while minimizing its adverse side effects.”

—Jolynn Tumolo

References

George D, Gálvez V, Martin D, et al. Pilot randomized controlled trial of titrated subcutaneous ketamine in older patients with treatment-resistant depression. The American Journal of Geriatric Psychiatry. 2017 June 13;[Epub ahead of print].

World-first ketamine trial shows promise for geriatric depression [press release]. Sydney, Australia: University of New South Wales; July 24, 2017.

__________________________________________________________________

Poster Number: EI 5
Ketamine in Late Life Treatment-Resistant Depression
Erika Heard, MD1
; Yousuf Sohail, MD1
; Anusuiya Nagar, MD1
; Oliver M. Glass, MD2
; Adriana P. Hermida, MD1

Introduction: Ketamine is a dissociative anesthetic, which provides antagonism on the N-methyl-D-aspartate (NMDA)
receptor. Several studies have demonstrated rapid anti-depressant and anti-suicidal effects from the administration of ketamine
in adult patients but studies in late life patients are lacking. While ketamine may increase sympathetic stimulation and cause
decreased respiratory rate in geriatric patients, it is still nonetheless considered a safe agent. Low-dose intravenous infusion of
ketamine is gaining popularity in the treatment for treatment-resistant depression (TRD) in late life patients. We provide a case
report on a patient in late life who suffered from TRD and was treated with ketamine.
Methods: A case report of the use of intravenous ketamine to treat a geriatric patient with TRD along with a literature review
of the subject.
Results: A 76-year-old female with a history of hypertension and arthritis presented with worsening depressive symptoms for the
past two years. She endorsed neuro-vegetative symptoms of depressed mood, poor appetite, unintentional 25-pound weight loss,
and conflicted feelings about wanting to live. She also reported difficulties with concentration and memory, feelings of
worthlessness, and psychomotor retardation. Her daughter stated she was more vegetative and had a strong desire not to live alone.
QIDS (Quick Inventory of Depressive Symptomatology) baseline was 23. She had previous trials of multiple medications including
paroxetine, fluoxetine, sertraline, escitalopram, buproprion, and venlafaxine. This patient showed poor tolerance to all the
medications and at the time of assessment was taking mirtazapine 7.5 mg and duloxetine 60 mg. Electroconvulsive therapy (ECT)
was recommended; however, the patient was found to be not a good candidate as per anesthesiology due to multiple comorbidities.
As a result, mirtazapine was titrated to 15 mg nightly while duloxentine was continued at 60 mg daily. Patient was started on
intravenous ketamine infusions of 20 mg (0.5 mg/kg) over 40 minutes. Patient tolerated the acute course of ketamine, which was
administered twice per week. Patient and daughter reported clinicial improvement after the first infusion with noticeable
improvement in QIDS (23 to 12) after 6 acute sessions without adverse effects. Improved symptoms included brighter affect,
increased energy, decreased anhedonia, increased daily activity, improved appetite (gained 40lbs), and being more engaged in the
community. Additionally, she began to take care of herself again. She has received 17 ketamine treatments with latest QIDS score of
1. After 6 acute infusion sessions, she was tapered to once per week, then once per 10 days, once per 2 weeks and then to a once
every three week schedule before discontinuing. The patient continued to report improvements. The literature on intravenous
ketamine infusions has shown effectiveness in reducing depressive symptoms in cases of TRD. The patient presented in this study
demonstrates promise of the use of ketamine in late life depression patients. This case also highlights that ketamine can be an
alternative option for elderly patients with TRD who do not qualify for ECT. Within the geriatric population, comorbid medical
conditions and polypharmacy may increase the chance of morbidity and mortality. Ketamine infusions at a low dose must be
monitored closely over a course of time. Therefore, ketamine infusions should only be administered to TRD patients in facilities
where appropriate medical monitoring can occur. Geriatric patients who are given ketamine infusions should be assessed for the
development of dependency, and addiction given its abuse potential. Further research on this novel therapy will yield greater
knowledge of how to best utilize ketamine infusions in geriatric patients.
Conclusions: The literature on intravenous ketamine infusions has shown effectiveness in reducing depressive symptoms in cases of
TRD. Similarly, our patient had a decline in depressive symptoms and a positive outcome. The case highlights that ketamine can be
used as an alternative for the TRD population that may not qualify for ECT. Within the geriatric population, comorbid pathology
and poly-pharmacy increase the chance of morbidity and mortality. Ketamine infusions at a low dose can be a potential treatment if
monitored closely over a course of time. Therefore, ketamine infusions offer a safe and effective alternative option for TRD patients
in psychiatric facilities where close monitoring can occur. Patients on ketamine treatments should be continually monitored for
addiction potential and adverse effects to ketamine infusions, none of which were seen with our current patient. Further research on
this novel therapy will yield greater knowledge of how to best utilize ketamine infusions for the general population and more
specifically for the geriatric subset that encompasses the majority of TRD patients.

___________________________________________________________________________________

Exploring Ketamine Use in Geriatric Patients Suffering From Treatment-Resistant Depression

Introduction: Ketamine is a glutamate NMDA receptor antagonist and is commonly used as an anesthetic. Low-dose
subanesthetic intravenous ketamine is fairly new and an increasingly popular treatment for treatment-resistant depression
(TRD) in the adult population; however, there is a scarcity of evidence of ketamine’s use among geriatric patients. Previously,
psychotropics and electroconvulsive therapy (ECT) have been used in the geriatric TRD population. Ketamine provides a
possible new treatment modality for those patients concerned with ECT-induced cognitive effects and may also allow for use in
patients with significant cardiovascular co-morbidities, who would likely not quality for ECT.
Methods: We provide a literature review on the use of ketamine for TRD in the geriatric population.
Results: Studies and case series have shown the use of ketamine as a monotherapy and augmented therapy with
electroconvulsive therapy in the adult and geriatric population. Literature supports efficacy with monotherapy and questionable
benefit from augmentative therapy. Dosing ranges from 0.2 mg/kg to 0.5 mg/kg, with evidence showing remittance with
ketamine dosing less than 0.5 mg/kg. Some studies have shown cognitive protection as compared to other TRD treatment
modalities, while the majority of studies have not thoroughly analyzed systemic adverse risk profiles including cognitive and
cardiovascular effects.

Conclusions: There is evidence in the literature for the use of intravenous ketamine in the TRD geriatric population. Larger
randomized control trials are needed to provided guidance regarding dosing, cognitive and systemic effects, and treatment
response.

USe of Ketamine in agitated delirium in the ELderly:

Treatment of Behavior Disturbances with Ketamine in a Patient Diagnosed with Major Neurocognitive Disorder

Ketamine has been shown to be beneficial for some
depressed patients, but it is not known whether it could
be beneficial for agitated demented patients who are
not depressed.

_____________________________________________________

Augmentation of response and remission to serial intravenous ketamine in TRD

Background: Ketamine has been showing high efficacy and rapid antidepressant effect. However, studies of ketamine infusion wash subjects out from prior antidepressants, which may be impractical in routine practice. In this study, we determined antidepressant response and remission to six consecutive ketamine infusions while maintaining stable doses of antidepressant regimen. We also examined thetrajectory of response and remission, and the time to relapse among responders.

Methods: TRD subjects had at least 2-month period of stable dose of antidepressants. Subjects completed
six IV infusions of 0.5 mg/kg ketamine over 40 min on a Monday–Wednesday–Friday schedule during a
12-day period participants meeting response criteria were monitored for relapse for 4 weeks

.
Results: Fourteen subjects were enrolled. Out of twelve subjects who completed all six infusions, eleven(91.6%) achieved response criterion while eight (66.6%) remitted. After the first infusion, only three andone out of twelve subjects responded and remitted, respectively. Four achieved response and sixremitted after 3 or more infusions. Five out of eleven subjects remain in response status throughout the 4weeks of follow-up. The mean time for six subjects who relapsed was 16 days.Limitations: Small sample and lack of a placebo group limits the interpretation of efficacy.

Conclusions: Safety and efficacy of repeated ketamine infusions were attained without medication-free state in patients with TRD. Repeated infusions achieved superior antidepressant outcomes as compared to a single infusion with different trajectories of response and remission. Future studies are needed to elucidate neural circuits involved in treatment response to ketamine.

 

_____________________________________________________

Why Treat Depression besides feeling better? It is associated with increased risk of DEATH:

Anxiety, Depression Linked With Higher Cardiovascular Risk

Adults with mood disorders like anxiety and depression may be more likely to have a heart attack or stroke than people without mental illness, a new study suggests.

Researchers enrolled 221,677 people age 45 and older without any history of heart attack or stroke and tracked them for an average of nearly five years.

More than 90% of participants were ages 45 to 79. In this age group, compared to men without mental health issues at the start, men with moderate psychological distress were 28% more likely to have a heart attack during the study and 20% more likely to have a stroke. Men in this age group with high levels of distress were 60% more likely to have a heart attack and 44% more likely to have a stroke.

Women ages 45 to 79 with moderate psychological problems were 12% more likely to have a heart attack and 28% more likely to have a stroke than women without any mental distress. Women with high psychological distress were 24% more likely to have a heart attack and 68% more likely to have a stroke.

“The stronger association between psychological distress and heart attack in men compared to women could be due to women being more likely than men to seek primary care for mental and physical health problems, thus partly negating the possible physical effects of mental health problems,” said lead study author Caroline Jackson of the University of Edinburgh in the U.K.

“Alternatively, it could reflect the known hormonal protection against heart disease in women since the study population included a large number of younger women,” Jackson said by email. “We did however find a strong association between psychological distress and stroke in women, perhaps suggesting different mechanisms exist between psychological distress and different types of cardiovascular disease in women.”

Overall, the study participants suffered 4,573 heart attacks and 2,421 strokes.

The study wasn’t designed to prove whether or how depression or anxiety might directly cause heart attacks or strokes, researchers note in Circulation: Cardiovascular Quality Outcomes.

Another limitation is that researchers assessed psychological factors at a single point in time, making it impossible to know if worsening cardiovascular health contributed to mood disorders or if mental illness caused heart problems.

However, it’s possible that lifestyle factors like poor eating and exercise habits, smoking, or inactivity might independently influence both the risk of mental health problems and heart issues, the study authors note.

“It is also possible that symptoms of depression or anxiety directly affect the body’s physiology through mechanisms such as hormonal pathways, inflammatory processes in arteries and increased risk of blood clotting,” Jackson said. “It is vital that further research seeks to identify the underlying mechanisms so that we can better understand the link between mental health and subsequent physical health and inform intervention strategies.”

Researchers assessed psychological distress using a standard set of questions designed to reveal symptoms of mood disorders. The questions asked, for example, how often people felt tired for no reason, how often they felt restless or fidgety, and how frequently they felt so sad that nothing could cheer them up.

Overall, about 16% of the study participants had moderate psychological distress and roughly 7% had high or very high levels of mental distress.

SOURCE: http://bit.ly/2PfAJjd    Psychological Distress and Risk of Myocardial Infarction and Stroke in the 45 and Up Study

Psychological Distress and Risk of MI and stroke in the 45 and up study

 

Circulation: Cardiovascular Quality and Outcomes 2018.

________________________________________________

Psychological distress, physical illness, and risk of coronary heart disease 2005

depressed-patients-likely-experience-mi-stroke

 

Resistance Training Reduces Depressive Symptoms

Weightlifting and muscle training significantly reduced depressive symptoms among adults regardless of their age and health status, the amount of training, and whether they grew stronger, researchers found in a meta-analysis.

The study, published online in JAMA Psychiatry, spanned 33 randomized clinical trials with more than 1800 participants.

The best improvement appeared to be in participants with mild or moderate depression, suggesting resistance training could be an alternative or add-on treatment option.

Trivia: How Much Exercise Is Needed to Prevent Depression?

“For general feelings of depression and the beginning phases of major depression, antidepressants and medications may not be very effective. There also is a shift toward finding options that do not require someone to start a drug regimen they may be on for the rest of their lives,” said researcher Jacob Meyer, PhD, assistant professor of kinesiology at Iowa State University in Ames.

“Understanding that resistance training appears to have similar benefits to aerobic exercise may help those wading through daunting traditional medication treatment options.”

The meta-analysis did identify smaller reductions in depressive symptoms in randomized clinical trials with blinded allocation or assessment. Better quality trials that compare resistance training with other proven treatments for depression are needed, researchers advised.

—Jolynn Tumolo

References

Gordon BR, McDowell CP, Hallgren M, Meyer JD, Lyons M, Herring MP. Association of efficacy of resistance exercise training with depressive symptoms. JAMA Psychiatry. 2018 May 9;[Epub ahead of print].

Motivation to move may start with being mindful [press release]. Ames, Iowa: Iowa State University; May 14, 2018.

Resistance exercise training may reduce symptoms of depression. Psychiatric News Alert. May 15, 2018.

__________________________________

Neurologic Changes and Depression

KEY POINTS
 The assessment of late-life depression with comorbid cognitive impairment can be challenging and requires a clear clinical history and a thorough medical and cognitive assessment.

 There are several neuropsychological changes associated with late-life depression, ranging from subjective cognitive complaints to mild cognitive impairment to dementia.

 Changes on neuroimaging and in several biomarkers (eg, apolipoprotein E e4 allele, beta amyloid, tau, neurotrophins, and so forth) have been associated with late-life depression.

 Multiple psychotherapeutic techniques have been found effective in the treatment of late life depression as well as holistic/nontraditional, pharmacologic, and brain-stimulation
approaches.

______________________________________________________

Why Does Ketamine Work?

Ketamine and Ketamine Metabolite Pharmacology Insights into Therapeutic Mechanisms.

Abstract

Ketamine, a racemic mixture consisting of (S)- and (R)-ketamine, has been in clinical use since 1970. Although best characterized for its dissociative anesthetic properties, ketamine also exerts analgesic, anti-inflammatory, and antidepressant actions. We provide a comprehensive review of these therapeutic uses, emphasizing drug dose, route of administration, and the time course of these effects. Dissociative, psychotomimetic, cognitive, and peripheral side effects associated with short-term or prolonged exposure, as well as recreational ketamine use, are also discussed. We further describe ketamine’s pharmacokinetics, including its rapid and extensive metabolism to norketamine, dehydronorketamine, hydroxyketamine, and hydroxynorketamine (HNK) metabolites. Whereas the anesthetic and analgesic properties of ketamine are generally attributed to direct ketamine-induced inhibition of N-methyl-D-aspartate receptors, other putative lower-affinity pharmacological targets of ketamine include, but are not limited to, γ-amynobutyric acid (GABA), dopamine, serotonin, sigma, opioid, and cholinergic receptors, as well as voltage-gated sodium and hyperpolarization-activated cyclic nucleotide-gated channels. We examine the evidence supporting the relevance of these targets of ketamine and its metabolites to the clinical effects of the drug. Ketamine metabolites may have broader clinical relevance than was previously considered, given that HNK metabolites have antidepressant efficacy in preclinical studies. Overall, pharmacological target deconvolution of ketamine and its metabolites will provide insight critical to the development of new pharmacotherapies that possess the desirable clinical effects of ketamine, but limit undesirable side effects.

Mechanisms of ketamine action as an antidepressant.

Ketamine administration during a critical period after forced ethanol abstinence inhibits the development of time-dependent affective disturbances.

Article Link::

Ketamine administration during a critical period after forced ethanol abstinence inhibits the development of time-dependent affective disturbances

We find
that ketamine prevents the development of affective disturbances
when administered at the onset of forced abstinence, and not
shortly thereafter (2–6 days).Studies suggest that the GluN2B subunit of the N- methyl- Daspartate
(NMDA) receptor participates in regulating affect and in
the antidepressant actions of ketamine [9, 14, 16]. Chronic ethanol
administration and early withdrawal increase expression of
GluN2B in several brain areas, particularly within the central
nucleus of the amygdala and bed nucleus of the stria terminalis
(BNST) [17], both of which are heavily involved in regulating affect
[18–21]. Previously, we found that knockdown of GluN2B-within
the BNST produces antidepressant-like actions similar to ketamine
[22] and that GluN2B is necessary for long-term potentiation (LTP) within the BNST [23]. Furthermore, we have previously shown that
non-contingent chronic intermittent ethanol enhances LTP within
the BNST which is dependent on the GluN2B subunit [23].
However, no studies have looked at LTP within the BNST during
withdrawal after contingent 2-bottle choice ethanol drinking. Here
we show that withdrawal from 2BC ethanol drinking decreases the
early component of LTP within the BNST. Further, administration
of ketamine at the onset of forced abstinence, but not shortly
thereafter (2–6 days) facilitated later LTP induction.

Ketamine administered at the onset of
abstinence, but not 6 days later rescued the STP deficit and overall increased the capacity for plasticity within the BNST. Our results suggest, for the first time to our knowledge, that ketamine may need to be administered at a specific time point during abstinence in order to effectively treat and manage alcohol use dependent affective disturbances. These data thus suggest a “critical period” during which ketamine is effective in preventing the development of alcohol abstinence induced affective
disturbances.

_____________________________________________________________

Ketamine and MAG Lipase Inhibitor-Dependent Reversal of Evolving Depressive-Like Behavior During Forced Abstinence From Alcohol Drinking

Introduction: Ketamine has emerged as a safe and effective treatment option for treatment refractory depression (TRD) and
suicidal ideation. Electroconvulsive therapy (ECT) is a well established treatment for refractory depression, but this treatment is often deferred or terminated before response due tolerability or medical concerns.
Methods: We present a case series of TRD patients who were unable to receive ECT and offered intravenous ketamine at a dose
of 0.5 mg/kg infused over the course of forty minutes for up 3 treatment sessions within two weeks. Most of these patients
were hospitalized older patients with sufficient medical conditions that increased ECT risks.

Results: Ketamine appears to be a safe and effective alternative for these patients, leading to resolution of suicidality, adherence
to antidepressant treatment, and prompt hospital discharge.

Conclusions: In conclusion, for TRD patients unable to undergo ECT, availability of intravenous ketamine, as an adjunct to
an ECT service, can not only avert the prospect of a prolonged and costly course of hospitalization, but also quickly improve
patients’ quality of life.

___________________________________________

Why magnesium is important in treating depression:

Magnesium for treatment-resistant depression A review and hypothesis

Sixty percent of cases of clinical depression are considered to be treatment-resistant depression (TRD). Magnesium-deficiency causes N-methyl-D-aspartate (NMDA) coupled calcium channels to be biased towards opening, causing neuronal injury and neurological dysfunction, which may appear to humans as major depression. Oral administration of magnesium to animals led to anti-depressant-like effects that were comparable to those of strong anti-depressant drugs. Cerebral spinal fluid (CSF) magnesium has been found low in treatment-resistant suicidal depression and in patients that have attempted suicide. Brain magnesium has been found low in TRD using phosphorous nuclear magnetic resonance spectroscopy, an accurate means for measuring brain magnesium. Blood and CSF magnesium do not appear well correlated with major depression. Although the first report of magnesium treatment for agitated depression was published in 1921 showing success in 220 out of 250 cases, and there are modern case reports showing rapid terminating of TRD, only a few modern clinical trials were found. A 2008 randomized clinical trial showed that magnesium was as effective as the tricyclic anti-depressant imipramine in treating depression in diabetics and without any of the side effects of imipramine. Intravenous and oral magnesium in specific protocols have been reported to rapidly terminate TRD safely and without side effects. Magnesium has been largely removed from processed foods, potentially harming the brain. Calcium, glutamate and aspartate are common food additives that may worsen affective disorders. We hypothesize that – when taken together – there is more than sufficient evidence to implicate inadequate dietary magnesium as the main cause of TRD, and that physicians should prescribe magnesium for TRD. Since inadequate brain magnesium appears to reduce serotonin levels, and since anti-depressants have been shown to have the action of raising brain magnesium, we further hypothesize that magnesium treatment will be found beneficial for nearly all depressives, not only TRD.

___________________________________________________________________

Does oral administration of ketamine accelerate response to treatment in MDD

Conclusion:

Altogether, our results suggest that oral ketamine may be considered as suitable adjuvant to sertraline
in relieving depressive symptoms.

Patients received sertraline (150 mg a day). As an adjuvant, they
received either 50 mg/day ketamine or placebo. Formulation of ketamine capsules used in this study is delineated elsewhere. Different doses of oral ketamine have been used in previous studies; a number of studies have used a fixed dose 0.5 mg/kg or 150 mg/day (Irwin et al., 2013; Jafarinia et al., 2016) whereas others titrated the drug in a rangefrom 0.5 mg/kg to 0.7 mg/kg or 25–300 mg/day (Al Shirawi et al., 2017; Hartberg et al., 2017). The frequency of administration also varies from once daily usage to three times a day (Irwin et al., 2013;
Jafarinia et al., 2016). For IV administration, previous trials recommendan injection once every two or three days (Andrade, 2017).
Here, we used ketamine as an adjuvant and thus a fixed low dose was chosen to minimize adverse effects. Sertraline was initiated at 25 mg/day and increased by 25 mg every three days. The maximum dose reached 150 mg. Ketamine prescription started with initial dose ofsertraline and was prescribed at 25 mg twice daily. During the course of the trial, patients were not allowed to participate in psychotherapeutic sessions or receive any other medication, such as other antidepressants, anxiolytics or hypnotics. They were followed for six weeks and were asked to inform their therapist in case they experienced any adverse effects. Vital signs were recorded and physical examination was performed at the screening session and at each of the post-baseline visits. Upon high clinical suspicion for cardiovascular disease, electrocardiogram monitoring was performed and positive findings were excluded.

Ketamine Therapy | Ketamine Doctors | 703-844-0184 | Fairfax, Virginia | Depression causes RAPID AGING due to Oxidative stress | NOVA Health Recovery, Alexandria, Va 22306

NOVA Health Recovery  <<< Ketamine Treatment Center Fairfax, Virginia

CAll 703-844-0184 for an immediate appointment to evaluate you for a Ketamine infusion:

Ketaminealexandria.com    703-844-0184 Call for an infusion to treat your depression. PTSD, Anxiety, CRPS, or other pain disorder today.

email@novahealthrecovery.com  << Email for questions to the doctor

Ketamine center in Fairfax, Virginia    << Ketamine infusions

Ketamine – NOVA Ketamine facebook page – ketamine treatment for depression

facebook Ketamine page

NOVA Health Recovery  << Ketamine clinic Fairfax, Va  – Call 703-844-0184 for an appointment – Fairfax, Virginia

Ketamine Consultants Blog
________________________________

Reasons to treat depression rapidly – Depression causes rapid aging> Consider using a rapid – acting antidepressant!

Depression ‘makes us biologically older’  BBC Article

Major depressive disorder and accelerated cellular aging

Patients with major depressive disorder (MDD) have an increased onset risk of aging-related somatic diseases such as heart disease,
diabetes, obesity and cancer. This suggests mechanisms of accelerated biological aging among the depressed, which can be
indicated by a shorter length of telomeres. We examine whether MDD is associated with accelerated biological aging, and whether
depression characteristics such as severity, duration, and psychoactive medication do further impact on biological aging. Data are
from the Netherlands Study of Depression and Anxiety, including 1095 current MDD patients, 802 remitted MDD patients and 510
control subjects. Telomere length (TL) was assessed as the telomere sequence copy number (T) compared to a single-copy gene
copy number (S) using quantitative polymerase chain reaction. This resulted in a T/S ratio and was converted to base pairs (bp).
MDD diagnosis and MDD characteristics were determined by self-report questionnaires and structured psychiatric interviews.
Compared with control subjects (mean bp = 5541), sociodemographic-adjusted TL was shorter among remitted MDD patients
(mean bp = 5459; P = 0.014) and current MDD patients (mean bp = 5461; P = 0.012). Adjustment for health and lifestyle variables did
not reduce the associations. Within the current MDD patients, separate analyses showed that both higher depression severity
(P<0.01) and longer symptom duration in the past 4 years (P = 0.01) were associated with shorter TL. Our results demonstrate that
depressed patients show accelerated cellular aging according to a ‘dose–response’ gradient: those with the most severe and
chronic MDD showed the shortest TL. We also confirmed the imprint of past exposure to depression, as those with remitted MDD
had shorter TL than controls

In this large cohort study we demonstrated that currently
depressed persons had shorter TL than never-depressed controls.
Based on an estimated mean telomere shortening rate of 14–20
bp per year as found in this and other studies,20,23,26 the
differences observed indicate 4–6 years of accelerated aging for
the current MDD sample as compared to controls. We also showed
evidence for the imprint of past exposure to depression since
those with remitted MDD also had shorter TL than control
subjects. These observed associations remained significant after
controlling for lifestyle and somatic health variables, suggesting that the shortened telomeres were not simply due to unhealthylifestyle or poorer somatic health among depressed persons.
Finally, the association between MDD and TL showed a ‘dose–
response’ gradient, since the most severely and chronically
depressed patients had the shortest telomeres.

MDD is thus associated with shortened TL, which resembles
accelerated biological aging. The disorder has previously also been
associated with dysregulations of the hypothalamus–pituitary–
adrenal (HPA) axis,43,45 the immune system,46,47 the autonomic
nervous system (ANS)48,49 and increased oxidative stress.50
Shortened telomeres, in turn, are suggested to be a consequence
or a concomitant of these dysregulated biological stress systems.
In line with this, several in vitro and in vivo studies found increased
cortisol,51 oxidative stress52 and pro-inflammatory cytokines53
to be associated with shorter TL. Dysregulations of these stress systems could contribute to telomere shortening in MDD patients.9,12
However, the exact biological mechanisms that mediate the relation
between depression and telomere shortening, as well as the
direction of the link, remain to be further explored.

Oxidative stress shortens telomeres

Elevated DNA Oxidation and DNA Repair Enzyme Expression in Brain White Matter in Major Depressive Disorder.

The Role of Oxidative Stress in Depressive Disorders

Abstract:

Studies of the World Health Organization suggest that in the year 2020, depressive disorder will be the illness with the highest
burden of disease. Especially unipolar depression is the psychiatric disorder with the highest prevalence and incidence, it is cost-intensive and has a relatively high morbidity. Lately, the biological process involved in the aetiology of depression has been the focus of research.
Since its emergence, the monoamine hypothesis has been adjusted and extended considerably. An increasing body of evidence points to
alterations not only in brain function, but also in neuronal plasticity. The clinical presentations demonstrate these dysfunctions by accompanying cognitive symptoms such as problems with memory and concentration. Modern imaging techniques show volume reduction of the hippocampus and the frontal cortex. These findings are in line with post-mortem studies of patients with depressive disorder and they point to a significant decrease of neuronal and glial cells in cortico-limbic regions which can be seen as a consequence of alterations in
neuronal plasticity in this disorder. This could be triggered by an increase of free radicals which in turn eventually leads to cell death and consequently atrophy of vulnerable neuronal and glial cell population in these regions. Therefore, research on increased oxidative stress in unipolar depressive disorder, mediated by elevated concentrations of free radicals, has been undertaken. This review gives a comprehensive overview over the current literature discussing the involvement of oxidative stress and free radicals in depression.

Membrane damage in blood of patients with depression has
been shown by elevated of omega 3- fatty-acids [45] and by increased
lipid peroxidation products in patients with DD [42, 45,
[46, 47]. Furthermore, DNA-strand brakes have been reported in
the blood of these patients [48]. DD has been linked to increased
serum levels of malondialdehyde (MDA), a breakdown product of
oxidized apolipoprotein B-containing lipoproteins, and thus a
marker of the rate of peroxide breakdown [49, 50].

In patients with DD (Depressive Disorders), elevated levels of MDA adversely affect
the efficiency of visual-spatial and auditory-verbal working memory,
short-term declarative memory and delayed recall declarative
memory [51]. Higher concentration of plasma MDA in patients
with recurrent depression is associated with the severity of depressive
symptoms, both at the beginning of antidepressant pharmacotherapy,
and after 8 weeks of treatment. Statistically significant
differences were found in the intensity of depressive symptoms,
measured on therapy onset versus the examination results after
8 weeks of treatment [51]. Although this is used as a marker of lipid peroxidation, it is considered to be less stable than 8-iso-PGF2a, and more susceptible to confounding factors such as antioxidants from diet [52]. Therefore, the best way to investigate oxidative disruptions to lipids in humans is via assessing levels of F2-
isoprostanes [52-54]. These are stable compounds produced in the
process of lipid peroxidation [52, 54]. 8-iso-PGF2a are specific F2-
isoprostane molecules produced during the peroxidation of arachnidonic acid. However, the mean serum level of 8-iso-PGF2a was shown to be significantly higher in a group of patients with DD,
controlling for lifestyle variables such as body mass index, alcohol
consumption, and physical activity [55, 56]. Cerebral membrane
abnormalities and altered membrane phospholipids have been suggested by an increased choline-containing compound seen in the
putamen of patients with DD [57] which has been interpreted as a
result of increased oxidative stress in patients with DD.

A Meta-Analysis of Oxidative Stress Markers in Depression

Results
115 articles met the inclusion criteria. Lower TAC was noted in acute episodes (AEs) of depressed patients (p<0.05). Antioxidants, including serum paraoxonase, uric acid, albumin,
high-density lipoprotein cholesterol and zinc levels were lower than controls (p<0.05); the serum uric acid, albumin and vitamin C levels were increased after antidepressant therapy
(p<0.05). Oxidative damage products, including red blood cell (RBC) malondialdehyde (MDA), serum MDA and 8-F2-isoprostanes levels were higher than controls (p<0.05). After
antidepressant medication, RBC and serum MDA levels were decreased (p<0.05). Moreover, serum peroxide in free radicals levels were higher than controls (p<0.05). There were
no difference

Conclusion
This meta-analysis supports the facts that the serum TAC, paraoxonase and antioxidant levels are lower, and the serum free radical and oxidative damage product levels are higher
than controls in depressed patients. Meanwhile, the antioxidant levels are increased and the oxidative damage product levels are decreased after antidepressant medication. The
pathophysiological relationships between oxidative stress and depression, and the potential benefits of antioxidant supplementation deserve further research.

Some studies have demonstrated that depressed patients’ oxidative product levels in their peripheral blood [3, 4], red blood cells (RBC) [4], mononuclear cells [5], urine [6], cerebrospinal
fluid [7] and postmortem brains [8] were abnormal. Antioxidant system disturbance in peripheral blood has also been reported [9]. Autoimmune responses against neoepitopes
induced by oxidative damage of fatty acid and protein membranes have been reported [10, 11].
Lower glutathione (GSH) levels [12] and a negative relationship between anhedonia severity
and occipital GSH levels [13] were found through magnetic resonance spectroscopy (MRS).

Oxidative stress is defined as a persistent imbalance between oxidation and anti-oxidation, which leads to the damage of cellular macromolecules [14, 15]. The free radicals consist of reactive
oxygen species (ROS) and reactive nitrogen species (RNS). The main ROS includes superoxide anion, hydroxy radical and hydrogen peroxide, and the RNS consists of nitric oxide
(NO), nitrogen dioxide and peroxynitrite. Nitrite is often used as a marker of NO activity. Interestingly, the brain appears to be more susceptible to the ROS/RNS because of the high
content of unsaturated fatty acids, high oxygen consumption per unit weight, high content of key ingredients of lipid peroxidation (LP) and scarcity of antioxidant defence systems [16].
The oxidative products include products of oxidative damage of LP, protein and DNA in depression. As a product of LP, abnormal malondialdehyde (MDA) levels in depression have
been reported [17]. 8-F2-isoprostane (8-iso-PGF2α) is another product of LP [18] that is considered
to be a marker of LP because of its chemical stability [19]. The protein carbonyl (PC), 8-hydroxy-2-deoxyguanosine (8-OHdG) and 8-oxo-7, 8-dihydroguanosine (8-oxoGuo) are
the markers of protein, DNA and RNA oxidative damage, respectively [3, 20, 21]. The oxidative damage to cellular macromolecules changes the structure of original epitopes, which leads to the generation of new epitopes modified (neoepitopes). The antibodies against oxidative neoepitopes
in depression have been found [10, 11, 22–24]. On the other hand, the antioxidant defence systems can be divided into enzymatic and non-enzymatic antioxidants. The nonenzymatic
antioxidants include vitamins C and E, albumin, uric acid, high-density lipoprotein cholesterol (HDL-C), GSH, coenzyme Q10 (CoQ10), ceruloplasmin, zinc, selenium, and so on.
The enzymatic antioxidants include superoxide dismutase (SOD), glutathione peroxidase (GPX), catalase (CAT), glutathione reductase (GR), paraoxonase 1 (PON1), and so on.

Discussion
The present findings support oxidative stress may be disordered in depressed patients, which is demonstrated by abnormal oxidative stress marker levels. In this meta-analysis, at first we
found in depressed patients: 1) the serum TAC, PON, uric acid, albumin, HDL-C and zinc levels were lower than controls; 2) the serum peroxide, MDA, 8-iso-PGF2α and RBC MDA levels
were higher than controls. To explore the effect of the antidepressant therapy to oxidative stress
markers, we reviewed the studies which had changes. And it came to the conclusions: 1) the serum uric acid, albumin, and vitamin C levels were increased; 2) the serum nitrite, RBC and
serum MDA levels were decreased.

The serum antioxidant levels are significantly lower in depression in our study and previous
reports, including PON, albumin, zinc, uric acid HDL-C, CoQ10 [146] and GSH [4, 38].
Meanwhile, the oxidative damage product levels are significantly higher. The body couldn’t
scavenge the excess free radicals (peroxide), leading to damages of main parts of cellular macromolecules
such as fatty acids, protein, DNA, RNA and mitochondria. The longitudinal antidepressant
therapy can reverse these abnormal oxidative stress parameters. It has proved
these phenomena occur in depression, such as increased levels of MDA, 8-iso-PGF2α, 8-oxoGuo
and 8-OHdG [3, 21]. Oxidative stress plays a crucial role in the pathophysiology of
depression. Some genes may be a potential factor. Lawlor et al (2007) reported the R allele of
PON1Q192R was associated with depression [147]. In addition, poor appetite, psychological
stressors, obesity, metabolic syndrome, sleep disorders, cigarette smoking and unhealthy lifestyle
may also contribute to it [148]. Furthermore, oxidative stress activates the immuneinflammatory
pathways [148]. But some studies supported decrease in albumin, zinc and
HDL-C levels was probably related to increased levels of pro-inflammatory cytokines (such as
interleukin-1 (IL-1) and IL-6) [59, 70–72, 117] during an acute phase response, which illustrated the activated immune-inflammatory pathways also activates the oxidative stress. These two mechanisms influence each other. On the other hand, the oxidative damage to cellular macromolecules changes the structure of original epitopes, which leads to generation of newepitopes modified (neoepitopes). Oxidative neoepitopes reported up to now include the conjugated oleic and azelaic acid, MDA, phosphatidyl inositol (Pi), NO-modified adducts and oxidized low density lipoprotein (oxLDL) [11, 22–24]. Maes et al reported the levels of serum IgG antibody against the oxLDL and IgM antibodies against the conjugated oleic and azelaic acid, MDA, Pi and NO-modified adducts were increased in depression [11, 22–24]. Depleted antioxidant defence in depression suggests that antioxidant supplements may be useful in clinical management. Preliminary evidence has indicated that patients treated with CoQ10 showed improvement in depressive symptoms and decrease in hippocampal oxidative DNA damage [149]. In our analyses, vitamin C and E levels did not differ between depressed patients and controls, but many studies have reported that vitamin C and E supplements could improve depressive moods [150, 151].

Malondialdehyde plasma concentration correlates with declarative and working memory in patients with recurrent depressive disorder

Abstract

Oxidative stress has been implicated in the cognitive decline, especially in memory impairment. The purpose of this study was to determine the concentration of malondialdehyde (MDA) in patients with recurrent depressive disorders (rDD) and to define relationship between plasma levels of MDA and the cognitive performance. The study comprised 46 patients meeting criteria for rDD. Cognitive function assessment was based on: The Trail Making Test , The Stroop Test, Verbal Fluency Test and Auditory-Verbal Learning Test. The severity of depression symptoms was assessed using the Hamilton Depression Rating Scale (HDRS). Statistically significant differences were found in the intensity of depression symptoms, measured by the HDRS on therapy onset versus the examination results after 8 weeks of treatment (P < 0.001). Considering the 8-week pharmacotherapy period, rDD patients presented better outcomes in cognitive function tests. There was no statistically significant correlation between plasma MDA levels, and the age, disease duration, number of previous depressive episodes and the results in HDRS applied on admission and on discharge. Elevated levels of MDA adversely affected the efficiency of visual-spatial and auditory-verbal working memory, short-term declarative memory and the delayed recall declarative memory. 1. Higher concentration of plasma MDA in rDD patients is associated with the severity of depressive symptoms, both at the beginning of antidepressants pharmacotherapy, and after 8 weeks of its duration. 2. Elevated levels of plasma MDA are related to the impairment of visual-spatial and auditory-verbal working memory and short-term and delayed declarative memory.

Antioxidant /Antidepressant-like Effect of Ascorbic acid (Vitamine
C) and Fluoxetine
Another study investigated the influence of ascorbic acid
(which is an antioxidant with antidepressant-like effects in animals)
on both depressive-like behaviour induced by a chronic unpredictable
stress (CUS) paradigm and on serum markers of oxidative
stress and in cerebral cortex and hippocampus of mice [120]. The
CUS-model is an animal model for induced depression-like behaviour
in animals. Depressive-like behaviour induced by CUS was
accompanied by significantly increased lipid peroxidation (cerebral
cortex and hippocampus), decreased catalase (CAT) (cerebral cortex
and hippocampus) and glutathione reductase (GR) (hippocampus)
activities and reduced levels of glutathione (cerebral cortex).
Repeated ascorbic acid as well as fluoxetine administration significantly
reversed CUS-induced depressive-like behaviour as well as
oxidative damage. No alterations were observed in locomotor activity
and glutathione peroxidase (GPx) activity in the same sample.
These findings pointed to a rapid and robust effect of ascorbic acid
in reversing behavioural and biochemical alterations induced in an
animal model [120].  Ascorbic acid treatment, similarly to fluoxetine, reverses depressive-like behavior and brain oxidative damage induced by chronic unpredictable stress.

 

Ketamine Therapy | Ketamine Doctors | 703-844-0184 | Fairfax, Virginia | Ketamine and Psychedelic drugs – for depression and neuroplasticity | NOVA Health Recovery, Alexandria, Va 22306

NOVA Health Recovery  <<< Ketamine Treatment Center Fairfax, Virginia

CAll 703-844-0184 for an immediate appointment to evaluate you for a Ketamine infusion:

Ketaminealexandria.com    703-844-0184 Call for an infusion to treat your depression. PTSD, Anxiety, CRPS, or other pain disorder today.

email@novahealthrecovery.com  << Email for questions to the doctor

Ketamine center in Fairfax, Virginia    << Ketamine infusions

Ketamine – NOVA Ketamine facebook page – ketamine treatment for depression

facebook Ketamine page

NOVA Health Recovery  << Ketamine clinic Fairfax, Va  – Call 703-844-0184 for an appointment – Fairfax, Virginia

Ketamine Consultants Blog
_______________________________________________________________________________________________


Ketamine and Psychedelic Drugs Change Structure of Neurons

ummary: A new study reveals psychedelics increase dendrites, dendritic spines and synapses, while ketamine may promote neuroplasticity. The findings could help develop new treatments for anxiety, depression and other related disorders.

Source: UC Davis.

A team of scientists at the University of California, Davis is exploring how hallucinogenic drugs impact the structure and function of neurons — research that could lead to new treatments for depression, anxiety, and related disorders. In a paper published on June 12 in the journal Cell Reports, they demonstrate that a wide range of psychedelic drugs, including well-known compounds such as LSD and MDMA, increase the number of neuronal branches (dendrites), the density of small protrusions on these branches (dendritic spines), and the number of connections between neurons (synapses). These structural changes suggest that psychedelics are capable of repairing the circuits that are malfunctioning in mood and anxiety disorders.

“People have long assumed that psychedelics are capable of altering neuronal structure, but this is the first study that clearly and unambiguously supports that hypothesis. What is really exciting is that psychedelics seem to mirror the effects produced by ketamine,” said David Olson, assistant professor in the Departments of Chemistry and of Biochemistry and Molecular Medicine, who leads the research team.

Ketamine, an anesthetic, has been receiving a lot of attention lately because it produces rapid antidepressant effects in treatment-resistant populations, leading the U.S. Food and Drug Administration to fast-track clinical trials of two antidepressant drugs based on ketamine. The antidepressant properties of ketamine may stem from its tendency to promote neural plasticity — the ability of neurons to rewire their connections.

“The rapid effects of ketamine on mood and plasticity are truly astounding. The big question we were trying to answer was whether or not other compounds are capable of doing what ketamine does,” Olson said.

Psychedelics show similar effects to ketamine

Olson’s group has demonstrated that psychedelics mimic the effects of ketamine on neurons grown in a dish, and that these results extend to structural and electrical properties of neurons in animals. Rats treated with a single dose of DMT — a psychedelic compound found in the Amazonian herbal tea known as ayahuasca — showed an increase in the number of dendritic spines, similar to that seen with ketamine treatment. DMT itself is very short-lived in the rat: Most of the drug is eliminated within an hour. But the “rewiring” effects on the brain could be seen 24 hours later, demonstrating that these effects last for some time.

Fairfax | NOVA Ketamine IV Ketamine for depression | Fairfax, Va 22306 | 703-844-0184
Fairfax | NOVA Ketamine IV Ketamine for depression | Fairfax, Va 22306 | 703-844-0184

Ketamine and Psychedelic Drugs Change Structure of Neurons

Summary: A new study reveals psychedelics increase dendrites, dendritic spines and synapses, while ketamine may promote neuroplasticity. The findings could help develop new treatments for anxiety, depression and other related disorders.

Source: UC Davis.

A team of scientists at the University of California, Davis is exploring how hallucinogenic drugs impact the structure and function of neurons — research that could lead to new treatments for depression, anxiety, and related disorders. In a paper published on June 12 in the journal Cell Reports, they demonstrate that a wide range of psychedelic drugs, including well-known compounds such as LSD and MDMA, increase the number of neuronal branches (dendrites), the density of small protrusions on these branches (dendritic spines), and the number of connections between neurons (synapses). These structural changes suggest that psychedelics are capable of repairing the circuits that are malfunctioning in mood and anxiety disorders.

“People have long assumed that psychedelics are capable of altering neuronal structure, but this is the first study that clearly and unambiguously supports that hypothesis. What is really exciting is that psychedelics seem to mirror the effects produced by ketamine,” said David Olson, assistant professor in the Departments of Chemistry and of Biochemistry and Molecular Medicine, who leads the research team.

Ketamine, an anesthetic, has been receiving a lot of attention lately because it produces rapid antidepressant effects in treatment-resistant populations, leading the U.S. Food and Drug Administration to fast-track clinical trials of two antidepressant drugs based on ketamine. The antidepressant properties of ketamine may stem from its tendency to promote neural plasticity — the ability of neurons to rewire their connections.

“The rapid effects of ketamine on mood and plasticity are truly astounding. The big question we were trying to answer was whether or not other compounds are capable of doing what ketamine does,” Olson said.

Psychedelics show similar effects to ketamine

Olson’s group has demonstrated that psychedelics mimic the effects of ketamine on neurons grown in a dish, and that these results extend to structural and electrical properties of neurons in animals. Rats treated with a single dose of DMT — a psychedelic compound found in the Amazonian herbal tea known as ayahuasca — showed an increase in the number of dendritic spines, similar to that seen with ketamine treatment. DMT itself is very short-lived in the rat: Most of the drug is eliminated within an hour. But the “rewiring” effects on the brain could be seen 24 hours later, demonstrating that these effects last for some time.

image shows neurons under psychedelics and ketamine

Psychedelic drugs such as LSD and ayahuasca change the structure of nerve cells, causing them to sprout more branches and spines, UC Davis researchers have found. This could help in “rewiring” the brain to treat depression and other disorders. In this false-colored image, the rainbow-colored cell was treated with LSD compared to a control cell in blue. NeuroscienceNews.com image is credited to Calvin and Joanne Ly.

Behavioral studies also hint at the similarities between psychedelics and ketamine. In another recent paper published in ACS Chemical Neuroscience, Olson’s group showed that DMT treatment enabled rats to overcome a “fear response” to the memory of a mild electric shock. This test is considered to be a model of post-traumatic stress disorder (PTSD), and interestingly, ketamine produces the same effect. Recent clinical trials have shown that like ketamine, DMT-containing ayahuasca might have fast-acting effects in people with recurrent depression, Olson said.

These discoveries potentially open doors for the development of novel drugs to treat mood and anxiety disorders, Olson said. His team has proposed the term “psychoplastogen” to describe this new class of “plasticity-promoting” compounds.

“Ketamine is no longer our only option. Our work demonstrates that there are a number of distinct chemical scaffolds capable of promoting plasticity like ketamine, providing additional opportunities for medicinal chemists to develop safer and more effective alternatives,” Olson said.

 

Psychedelic drugs, ketamine change structure of neurons

Psychedelic drugs, ketamine change structure of neurons

Psychedelics as Possible Treatments for Depression and PTSD

A team of scientists at the University of California, Davis, is exploring how hallucinogenic drugs impact the structure and function of neurons — research that could lead to new treatments for depression, anxiety and related disorders.

In a paper published on June 12 in the journal Cell Reports, they demonstrate that a wide range of psychedelic drugs, including well-known compounds such as LSD and MDMA, increase the number of neuronal branches (dendrites), the density of small protrusions on these branches (dendritic spines) and the number of connections between neurons (synapses). These structural changes could suggest that psychedelics are capable of repairing the circuits that are malfunctioning in mood and anxiety disorders.

“People have long assumed that psychedelics are capable of altering neuronal structure, but this is the first study that clearly and unambiguously supports that hypothesis. What is really exciting is that psychedelics seem to mirror the effects produced by ketamine,” said David Olson, assistant professor in the departments of Chemistry and of Biochemistry and Molecular Medicine, who leads the research team.

Ketamine, an anesthetic, has been receiving a lot of attention lately because it produces rapid antidepressant effects in treatment-resistant populations, leading the U.S. Food and Drug Administration to fast-track clinical trials of two antidepressant drugs based on ketamine. The antidepressant properties of ketamine may stem from its tendency to promote neural plasticity — the ability of neurons to rewire their connections.

“The rapid effects of ketamine on mood and plasticity are truly astounding. The big question we were trying to answer was whether or not other compounds are capable of doing what ketamine does,” Olson said.

Psychedelics show similar effects to ketamine

Olson’s group has demonstrated that psychedelics mimic the effects of ketamine on neurons grown in a dish, and that these results extend to structural and electrical properties of neurons in animals. Rats treated with a single dose of DMT — a psychedelic compound found in the Amazonian herbal tea known as ayahuasca — showed an increase in the number of dendritic spines, similar to that seen with ketamine treatment. DMT itself is very short-lived in the rat: Most of the drug is eliminated within an hour. But the “rewiring” effects on the brain could be seen 24 hours later, demonstrating that these effects last for some time.

Behavioral studies also hint at the similarities between psychedelics and ketamine. In another recent paper published in ACS Chemical Neuroscience, Olson’s group showed that DMT treatment enabled rats to overcome a “fear response” to the memory of a mild electric shock. This test is considered to be a model of post-traumatic stress disorder, or PTSD, and interestingly, ketamine produces the same effect. Recent clinical trials have shown that like ketamine, DMT-containing ayahuasca might have fast-acting effects in people with recurrent depression, Olson said.

These discoveries potentially open doors for the development of novel drugs to treat mood and anxiety disorders, Olson said. His team has proposed the term “psychoplastogen” to describe this new class of “plasticity-promoting” compounds.

“Ketamine is no longer our only option. Our work demonstrates that there are a number of distinct chemical scaffolds capable of promoting plasticity like ketamine, providing additional opportunities for medicinal chemists to develop safer and more effective alternatives,” Olson said.

Additional co-authors on the Cell Reports “Psychedelics Promote Structural and Functional Neural Plasticity.” study are Calvin Ly, Alexandra Greb, Sina Soltanzadeh Zarandi, Lindsay Cameron, Jonathon Wong, Eden Barragan, Paige Wilson, Michael Paddy, Kassandra Ori-McKinney, Kyle Burbach, Megan Dennis, Alexander Sood, Whitney Duim, Kimberley McAllister and John Gray.

Olson and Cameron were co-authors on the ACS Chemical Neuroscience paper along with Charlie Benson and Lee Dunlap.

The work was partly supported by grants from the National Institutes of Health.

Psychedelics Promote Structural and Functional
Neural Plasticity

Below is the Intro and Discussion for the article:

Psychedelics Promote Structural and Functional neural Plasticity

Authors:

Calvin Ly, Alexandra C. Greb,
Lindsay P. Cameron, …,
Kassandra M. Ori-McKenney,
John A. Gray, David E. Olson
Correspondence
deolson@ucdavis.edu

In Brief
Ly et al. demonstrate that psychedelic
compounds such as LSD, DMT, and DOI
increase dendritic arbor complexity,
promote dendritic spine growth, and
stimulate synapse formation. These
cellular effects are similar to those
produced by the fast-acting
antidepressant ketamine and highlight
the potential of psychedelics for treating
depression and related disorders.

  • Highlights
     Serotonergic psychedelics increase neuritogenesis,
    spinogenesis, and synaptogenesis
  •  Psychedelics promote plasticity via an evolutionarily
    conserved mechanism
  •  TrkB, mTOR, and 5-HT2A signaling underlie psychedelicinduced
    plasticity
  •  Noribogaine, but not ibogaine, is capable of promoting
    structural neural plasticity

SUMMARY
Atrophy of neurons in the prefrontal cortex (PFC)
plays a key role in the pathophysiology of depression
and related disorders. The ability to promote
both structural and functional plasticity in the PFC
has been hypothesized to underlie the fast-acting
antidepressant properties of the dissociative anesthetic
ketamine. Here, we report that, like ketamine,
serotonergic psychedelics are capable of robustly
increasing neuritogenesis and/or spinogenesis both
in vitro and in vivo. These changes in neuronal structure
are accompanied by increased synapse number
and function, as measured by fluorescence microscopy
and electrophysiology. The structural changes
induced by psychedelics appear to result from stimulation
of the TrkB, mTOR, and 5-HT2A signaling
pathways and could possibly explain the clinical
effectiveness of these compounds. Our results underscore
the therapeutic potential of psychedelics
and, importantly, identify several lead scaffolds for
medicinal chemistry efforts focused on developing
plasticity-promoting compounds as safe, effective,
and fast-acting treatments for depression and
related disorders.

INTRODUCTION
Neuropsychiatric diseases, including mood and anxiety disorders,
are some of the leading causes of disability worldwide
and place an enormous economic burden on society (Gustavsson
et al., 2011; Whiteford et al., 2013). Approximately
one-third of patients will not respond to current antidepressant
drugs, and those who do will usually require at least 2–4 weeks
of treatment before they experience any beneficial effects
(Rush et al., 2006). Depression, post-traumatic stress disorder
(PTSD), and addiction share common neural circuitry (Arnsten,
2009; Russo et al., 2009; Peters et al., 2010; Russo and
Nestler, 2013) and have high comorbidity (Kelly and Daley,
2013). A preponderance of evidence from a combination of
human imaging, postmortem studies, and animal models suggests
that atrophy of neurons in the prefrontal cortex (PFC)
plays a key role in the pathophysiology of depression and
related disorders and is precipitated and/or exacerbated by
stress (Arnsten, 2009; Autry and Monteggia, 2012; Christoffel
et al., 2011; Duman and Aghajanian, 2012; Duman et al.,
2016; Izquierdo et al., 2006; Pittenger and Duman, 2008;
Qiao et al., 2016; Russo and Nestler, 2013). These structural
changes, such as the retraction of neurites, loss of dendritic
spines, and elimination of synapses, can potentially be counteracted
by compounds capable of promoting structural and
functional neural plasticity in the PFC (Castre´ n and Antila,
2017; Cramer et al., 2011; Duman, 2002; Hayley and Litteljohn,
2013; Kolb and Muhammad, 2014; Krystal et al., 2009;
Mathew et al., 2008), providing a general solution to treating
all of these related diseases. However, only a relatively small
number of compounds capable of promoting plasticity in the
PFC have been identified so far, each with significant drawbacks
(Castre´ n and Antila, 2017). Of these, the dissociative
anesthetic ketamine has shown the most promise, revitalizing
the field of molecular psychiatry in recent years.
Ketamine has demonstrated remarkable clinical potential as a
fast-acting antidepressant (Berman et al., 2000; Ionescu et al.,
2016; Zarate et al., 2012), even exhibiting efficacy in treatmentresistant
populations (DiazGranados et al., 2010; Murrough
et al., 2013; Zarate et al., 2006). Additionally, it has shown promise
for treating PTSD (Feder et al., 2014) and heroin addiction
(Krupitsky et al., 2002). Animal models suggest that its therapeutic
effects stem from its ability to promote the growth of dendritic
spines, increase the synthesis of synaptic proteins, and
strengthen synaptic responses (Autry et al., 2011; Browne and
Lucki, 2013; Li et al., 2010).

Like ketamine, serotonergic psychedelics and entactogens
have demonstrated rapid and long-lasting antidepressant and
anxiolytic effects in the clinic after a single dose (Bouso et al.,
2008; Carhart-Harris and Goodwin, 2017; Grob et al., 2011;
Mithoefer et al., 2013, 2016; Nichols et al., 2017; Sanches
et al., 2016; Oso´ rio et al., 2015), including in treatment-resistant
populations (Carhart-Harris et al., 2016, 2017; Mithoefer et al.,
2011; Oehen et al., 2013; Rucker et al., 2016). In fact, there
have been numerous clinical trials in the past 30 years examining
the therapeutic effects of these drugs (Dos Santos et al., 2016),
with 3,4-methylenedioxymethamphetamine (MDMA) recently
receiving the ‘‘breakthrough therapy’’ designation by the Food
and Drug Administration for treating PTSD. Furthermore, classical
psychedelics and entactogens produce antidepressant
and anxiolytic responses in rodent behavioral tests, such as
the forced swim test (Cameron et al., 2018) and fear extinction
learning (Cameron et al., 2018; Catlow et al., 2013; Young
et al., 2015), paradigms for which ketamine has also been shown
to be effective (Autry et al., 2011; Girgenti et al., 2017; Li et al.,
2010). Despite the promising antidepressant, anxiolytic, and
anti-addictive properties of serotonergic psychedelics, their
therapeutic mechanism of action remains poorly understood,
and concerns about safety have severely limited their clinical
usefulness.
Because of the similarities between classical serotonergic
psychedelics and ketamine in both preclinical models and clinical
studies, we reasoned that their therapeutic effects might
result from a shared ability to promote structural and functional
neural plasticity in cortical neurons. Here, we report that serotonergic
psychedelics and entactogens from a variety of chemical
classes (e.g., amphetamine, tryptamine, and ergoline) display
plasticity-promoting properties comparable to or greater than
ketamine. Like ketamine, these compounds stimulate structural
plasticity by activating the mammalian target of rapamycin
(mTOR). To classify the growing number of compounds capable
of rapidly promoting induced plasticity (Castre´ n and Antila,
2017), we introduce the term ‘‘psychoplastogen,’’ from the
Greek roots psych- (mind), -plast (molded), and -gen (producing).
Our work strengthens the growing body of literature indicating
that psychoplastogens capable of promoting plasticity
in the PFC might have value as fast-acting antidepressants
and anxiolytics with efficacy in treatment-resistant populations
and suggests that it may be possible to use classical psychedelics
as lead structures for identifying safer alternatives.

DISCUSSION
Classical serotonergic psychedelics are known to cause
changes in mood (Griffiths et al., 2006, 2008, 2011) and brain
function (Carhart-Harris et al., 2017) that persist long after the
acute effects of the drugs have subsided. Moreover, several
psychedelics elevate glutamate levels in the cortex (Nichols,
2004, 2016) and increase gene expression in vivo of the neurotrophin
BDNF as well as immediate-early genes associated with
plasticity (Martin et al., 2014; Nichols and Sanders-Bush, 2002;
Vaidya et al., 1997). This indirect evidence has led to the
reasonable hypothesis that psychedelics promote structural
and functional neural plasticity, although this assumption had
never been rigorously tested (Bogenschutz and Pommy,
2012; Vollenweider and Kometer, 2010). The data presented
here provide direct evidence for this hypothesis, demonstrating
that psychedelics cause both structural and functional changes
in cortical neurons.

Prior to this study, two reports suggested
that psychedelics might be able
to produce changes in neuronal structure.
Jones et al. (2009) demonstrated that DOI
was capable of transiently increasing the
size of dendritic spines on cortical neurons,
but no change in spine density was
observed. The second study showed
that DOI promoted neurite extension in a
cell line of neuronal lineage (Marinova
et al., 2017). Both of these reports utilized
DOI, a psychedelic of the amphetamine
class. Here we demonstrate that the ability
to change neuronal structure is not a
unique property of amphetamines like
DOI because psychedelics from the ergoline,
tryptamine, and iboga classes of compounds also promote
structural plasticity. Additionally, D-amphetamine does not increase
the complexity of cortical dendritic arbors in culture,
and therefore, these morphological changes cannot be simply
attributed to an increase in monoamine neurotransmission.
The identification of psychoplastogens belonging to distinct
chemical families is an important aspect of this work because
it suggests that ketamine is not unique in its ability to promote
structural and functional plasticity. In addition to ketamine, the
prototypical psychoplastogen, only a relatively small number of
plasticity-promoting small molecules have been identified previously.
Such compounds include the N-methyl-D-aspartate
(NMDA) receptor ligand GLYX-13 (i.e., rapastinel), the mGlu2/3
antagonist LY341495, the TrkB agonist 7,8-DHF, and the muscarinic
receptor antagonist scopolamine (Lepack et al., 2016; Castello
et al., 2014; Zeng et al., 2012; Voleti et al., 2013). We
observe that hallucinogens from four distinct structural classes
(i.e., tryptamine, amphetamine, ergoline, and iboga) are also
potent psychoplastogens, providing additional lead scaffolds
for medicinal chemistry efforts aimed at identifying neurotherapeutics.
Furthermore, our cellular assays revealed that several
of these compounds were more efficacious (e.g., MDMA) or more potent (e.g., LSD) than ketamine. In fact, the plasticity-promoting
properties of psychedelics and entactogens rivaled that
of BDNF (Figures 3A–3C and S3). The extreme potency of LSD
in particular might be due to slow off kinetics, as recently proposed
following the disclosure of the LSD-bound 5-HT2B crystal
structure (Wacker et al., 2017).
Importantly, the psychoplastogenic effects of psychedelics in
cortical cultures were also observed in vivo using both vertebrate
and invertebrate models, demonstrating that they act through an
evolutionarily conserved mechanism. Furthermore, the concentrations
of psychedelics utilized in our in vitro cell culture assays
were consistent with those reached in the brain following systemic
administration of therapeutic doses in rodents (Yang
et al., 2018; Cohen and Vogel, 1972). This suggests that neuritogenesis,
spinogenesis, and/or synaptogenesis assays performed
using cortical cultures might have value for identifying
psychoplastogens and fast-acting antidepressants. It should
be noted that our structural plasticity studies performed in vitro
utilized neurons exposed to psychedelics for extended periods
of time. Because brain exposure to these compounds is often
of short duration due to rapid metabolism, it will be interesting
to assess the kinetics of psychedelic-induced plasticity.
A key question in the field of psychedelic medicine has been
whether or not psychedelics promote changes in the density of
dendritic spines (Kyzar et al., 2017). Using super-resolution
SIM, we clearly demonstrate that psychedelics do, in fact, increase
the density of dendritic spines on cortical neurons, an effect
that is not restricted to a particular structural class of compounds.
Using DMT, we verified that cortical neuron spine
density increases in vivo and that these changes in structural
plasticity are accompanied by functional effects such as
increased amplitude and frequency of spontaneous EPSCs.

We specifically designed these experiments
to mimic previous studies of ketamine
(Li et al., 2010) so that we might
directly compare these two compounds,
and, to a first approximation, they appear
to be remarkably similar. Not only do they
both increase spine density and neuronal
excitability in the cortex, they seem to
have similar behavioral effects. We have
shown previously that, like ketamine,
DMT promotes fear extinction learning
and has antidepressant effects in the
forced swim test (Cameron et al., 2018). These results, coupled
with the fact that ayahuasca, a DMT-containing concoction, has
potent antidepressant effects in humans (Oso´ rio et al., 2015;
Sanches et al., 2016; Santos et al., 2007), suggests that classical
psychedelics and ketamine might share a related therapeutic
mechanism.
Although the molecular targets of ketamine and psychedelics
are different (NMDA and 5-HT2A receptors, respectively), they
appear to cause similar downstream effects on structural plasticity
by activating mTOR. This finding is significant because ketamine is
known to be addictive whereas many classical psychedelics are
not (Nutt et al., 2007, 2010). The exact mechanisms by which these
compounds stimulate mTOR is still not entirely understood, but
our data suggest that, at least for classical psychedelics, TrkB
and 5-HT2A receptors are involved. Although most classical psychedelics
are not considered to be addictive, there are still significant
safety concerns with their use in medicine because they
cause profound perceptual disturbances and still have the potential
to be abused. Therefore, the identification of non-hallucinogenic
analogs capable of promoting plasticity in the PFC could
facilitate a paradigm shift in our approach to treating neuropsychiatric
diseases. Moreover, such compounds could be critical to
resolving the long-standing debate in the field concerning whether
the subjective effects of psychedelics are necessary for their therapeutic
effects (Majic et al., 2015  ). Although our group is actively
investigating the psychoplastogenic properties of non-hallucinogenic
analogs of psychedelics, others have reported the therapeutic
potential of safer structural and functional analogs of ketamine
(Moskal et al., 2017; Yang et al., 2015; Zanos et al., 2016).
Our data demonstrate that classical psychedelics from several
distinct chemical classes are capable of robustly promoting the
growth of both neurites and dendritic spines in vitro, in vivo, and across species. Importantly, our studies highlight the similarities
between the effects of ketamine and those of classical serotonergic
psychedelics, supporting the hypothesis that the clinical
antidepressant and anxiolytic effects of these molecules might
result from their ability to promote structural and functional plasticity
in prefrontal cortical neurons. We have demonstrated that
the plasticity-promoting properties of psychedelics require
TrkB, mTOR, and 5-HT2A signaling, suggesting that these key
signaling hubs may serve as potential targets for the development
of psychoplastogens, fast-acting antidepressants, and anxiolytics.
Taken together, our results suggest that psychedelics
may be used as lead structures to identify next-generation neurotherapeutics
with improved efficacy and safety profiles.

Also below is a great article on DMT and neuroplasticity:

 

Dark Classics in Chemical Neuroscience N,N-Dimethyltryptamine DMT

Zika Virus, Aging, nutrition, diseases and discussions regarding healthy life choices and physical activity. Alternative medicine and mainstream medicine included!