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NOVA Health Recovery | Alexandria, Va 22306 | Call for esketamine and nasal ketamine as well as IV Ketamine for depression, PTSD, anxiety  703-844-0184 < Link

Call NOVA Health Recovery at 703-844-0184 for a free consultation for a Ketamine infusion. No referral needed. We offer intranasal Ketamine follow up therapy as well. Alexandria, Va 22306.

Call NOVA Health Recovery at 703-844-0184 for a free consultation for a Ketamine infusion. No referral needed. We offer intranasal Ketamine follow up therapy as well. Alexandria, Va 22306.

From Popular Anesthetic to Antidepressant, Ketamine Isn’t the Drug You Think It Is

An hour before we spoke, Darragh O’Carroll, an emergency room physician from Hawaii, had just given an elderly patient a sedating shot of ketamine. The man had pneumonia and was acting confused and fidgety, making him hard to treat.

“Not only it was a pain control for him when I was putting needles into his neck, but it also kept him still,” O’Carroll says. “And with very minimal risk of lowering his blood pressure.”

Ketamine’s use as an anesthetic — and not as a party drug — is widespread, though not commonly known. In fact, the World Health Organizationestimates ketamine is the most widely used anesthetic in the world and keeps it on their list of essential medicines, a category of drugs that all developed countries should have on hand.

O’Carroll has described ketamine as his “favorite medicine of all time” in an article for Tonic, not only because the anesthetic is incredibly safe and effective, but also because of its versatility. It’s most widely used in surgery, but could also help treat severe asthma, chronic pain, and may even possess anti-tumor properties. In the last two decades, ketamine has also emerged as a potent antidepressant, able to treat symptoms of some mental illnesses in less than 72 hours.

“I think the more research that goes into ketamine, the more uses that we find for it,” O’Carroll says.

From PCP to Painkiller

Ketamine’s story begins with a drug called PCP. Yes, that PCP — phencyclidine or so-called “angel dust,” a drug that when smoked can cause a trance-like state, agitation and out-of-body hallucinations. After it was first synthesized by medicinal chemist Victor Maddox in 1956, the drug was briefly approved as an anesthetic by the FDA for its sedative properties. In tests with a wild rhesus monkey, for example, researchers put their fingers in the previously aggressive animal’s mouth and watched its jaw remain slack.

But while it was safe and effective for pain relief, the side effects of PCP soon became too obvious to ignore.

Some patients under the influence of PCP would feel like they lost their arms or legs or that they were floating in space. It could also cause seizures and delirium. Scientists began seeking a shorter-acting anesthetic without convulsant properties. In 1962, chemistry professor Calvin Stevens discovered a PCP analogue that fit the bill: ketamine.

Ketamine is a potent, sedating painkiller that can cause amnesia and is mostly used in surgery and veterinary medicine. During the Vietnam Invasion, ketamine saw widespread use in the U.S. military because it has several advantages over opioids. First, unlike morphine, ketamine doesn’t suppress blood pressure or breathing. It also doesn’t need to be refrigerated, making it useful in the field or in rural areas that don’t have access to electricity.

Ketamine’s benefits extend beyond use as an anesthetic, though — in some cases it can serve as a balm for the mind as well. A 2008 analysis found that burn victims who were given ketamine were less likely to develop symptoms of post-traumatic stress disorder, even if their injuries were more severe. Those findings have been replicated, such as a 2014 clinical trial of 41 patients, who saw their PTSD symptoms diminish within 24 hours, an effect that lasted for two weeks.

“When somebody gets one of their limbs dramatically blown off or is shot in the face, it’s a very traumatic event,” O’Carroll says. In such a situation, giving ketamine not only provides instant pain relief, it could prevent long-lasting trauma.

Because its chemical structure is so similar to PCP, ketamine can still give lucid hallucinations, such as feeling that your mind has separated from the body — a dissociative state users sometimes call a “K-hole.” One recent study based on users’ written reports even indicated that this kind of experience might be a close analogue to a near-death experience. However, these dissociative states only happen at high doses — the amount of ketamine used to for surgery and to treat depression is typically much lower.

But ketamine’s side effects are less common and easier to manage than PCP. In fact, ketamine is one of the safest drugs used in medicine today and can even be given to young children. For example, ketamine was used to sedatethe boys’ soccer team trapped in a cave in Thailand last year. Putting the kids in a tranquilized state made it easier to rescue them, and ketamine is safer than the opioids or benzodiazepines that are also commonly used as sedatives.  

Ketamine as Antidepressant

But it wasn’t until the 1990s that what could turn out to be ketamine’s most important function was discovered. A team from Yale University School of Medicine was examining the role of glutamate, a common neurotransmitter, in depression, and discovered something remarkable: ketamine could rapidly relieve depression symptoms.

“To our surprise, the patients started saying, they were better in a few hours,” Dennis Charney, one of the researchers, told Bloomberg. This rapid relief was unheard of in psychiatry.

Glutamate is associated with neural plasticity, our brain’s ability to adapt and change at the level of the neuron. Ketamine blocks certain glutamate receptors, but not others, and the end effect could be to promote the growth of new neurons while protecting old ones. This could explain how ketamine can help reset the brain, though the theory hasn’t yet been definitively proven.

The prescription meds currently on the market for depression have some major drawbacks. Drugs like Prozac or Wellbutrin can take a few weeks or months to kick in while worsening symptoms in the short term — not a good combination, especially for someone who is extremely depressed, or even suicidal.

It took around a decade for mainstream science to take notice of these early ketamine-depression studies. But once it did, ketamine clinics began popping up all across North America, offering fast relief for depression, anxiety and other mental illnesses. Patients are given an infusion — an IV drip that lasts about an hour — and many people, but not everyone, have seen rapid relief of their symptoms.

Suddenly, ketamine infusions became trendy, though the science to back up some of the medical claims is still inconclusive, according to STAT. However, ketamine infusions are rarely covered by insurance, although that is changing. A typical session can run $700, with many patients taking six sessions or more. But many of these patients have so-called treatment-resistant depression. They’ve tried other medications or therapies without success and some see ketamine as a last resort.

Steven Mandel, a clinical psychologist and anesthesiologist, has used ketamine on patients since it first came on the market around 50 years ago. In 2014, he began using it for patients with depression and opened Ketamine Clinics of Los Angeles, one of the oldest and largest clinics in the country. They’ve done over 8,000 infusions so far.

“Our success rate is better than 83 percent,” Mandel says. For his clinic, success means a 50 percent improvement of depression symptoms for longer than three months.

Ketamine’s success as an antidepressant couldn’t help but attract the attention of major pharmaceutical companies as well. In 2009, Johnson & Johnson began developing their own version of the drug they called esketamine. Rather than an infusion through a vein, it’s dispensed through a nasal spray. The FDA approved their formulation in early March. It was thefirst drug in 35 years to fight depression using a different approach than traditional drugs.

“Esketamine is a giant step forward,” Mandel says. “It means we’re not going to be demonizing mind-altering substances used for therapeutic purposes. It opens the door to research on LSD, on psilocybin, on MDMA and many other agents that could possibly relieve a great deal of suffering.”

But many clinicians have raised concerns about long-term side effects, such as heart and bladder toxicity. Others have been critical of esketamine, saying there isn’t enough data yet to suggest the drug is safe or effective. Husseini Manji, a neuroscientist who helped develop the drug for Johnson & Johnson at their subsidiary Janssen, has pushed back against these claims.

“When you line up the totality of the studies, it was really an overwhelming amount of data that was all in the same direction,” Manji says in a call. Though just two of the five late-state clinical trials showed significant results, the changes in mood in the three that fell short were “almost identical in magnitude” to the others, Manji says. It was enough for the drug to meet standards for FDA approval.

We can probably expect other ketamine-related drugs to come to market soon. ATAI Life Sciences, a company funding research on the use of magic mushrooms for depression, is developing their own ketamine depression drug. The pharmaceutical company Allergan also developed rapastinel, another ketamine-like drug, though it failed to show any real benefits for patients in later trials. Manji says this is unfortunate for people who could be helped by these kinds of drugs.

“From a patient standpoint, we were hoping it would work,” he says, even though he was not involved in rapastinel’s development. “But sometimes if you really haven’t got the mechanism right and you haven’t really threaded the needle, then sometimes you don’t see these results.”

Drug of Abuse?

Even though ketamine’s medical uses are well-established, most people have only heard of ketamine in the context of a party drug. Because of this bad reputation — and what’s perceived as growing misuse of the drug — several countries, such as China and the UK, have tried to place greater restrictions on ketamine. This would make it harder to study and more expensive in clinical use.

“If it was to ever be rescheduled, places that would be first affected would be you know places that need it most,” O’Carroll says. The WHO has asked at least four times for countries to keep access to ketamine open. “The medical benefits of ketamine far outweigh potential harm from recreational use,” Marie-Paule Kieny, assistant director general for Health Systems and Innovation at WHO, said in 2015.

So far, no countries have put greater restrictions on ketamine, and that’s probably a good thing. Ketamine has a rich history, but its future is still being written.



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NOVA Health Recovery | Alexandria, Va 22306 | Call for esketamine and nasal ketamine as well as IV Ketamine for depression, PTSD, anxiety  703-844-0184 < Link

Ketamine Virginia Link

NOVA Health Recovery | Alexandria, Va 22306 | Call for esketamine and nasal ketamine as well as IV Ketamine for depression, PTSD, anxiety  703-844-0184 < Link

Ketamine Virginia Link

Ketamine-like depression treatment on track for FDA approval

CNN)A ketamine-like drug for treatment-resistant depression was backed by a US Food and Drug Administration advisory committee on Tuesday. If it is then approved by the FDA, the drug — called esketamine — may provide a new option for patients with major depressive disorder who have tried at least two other antidepressants without success.A panel of experts voted to endorse the drug, which is made in nasal spray form by the pharmaceutical company Janssen, a division of Johnson & Johnson. Fourteen members voted that the benefits outweighed the risk, with two opposed and one abstaining.

Ketamine offers lifeline for people with severe depression, suicidal thoughts
703-844-0184 | NOVA Health Recovery | Alexandria, Va 22306

Ketamine offers lifeline for people with severe depression, suicidal thoughtsThe drug is a close relative of ketamine, a powerful medication used in hospitals primarily as an anesthetic; recent scientific studies have also shown its potential with treatment-resistant depression and suicidal ideation. Ketamine is also used recreationally — and illegally — as a club drug known as Special K. It generates an intense high and dissociative effects.Esketamine, which is not FDA-approved for any conditions, targets a different brain pathway than approved antidepressants, many of which have been around for decades. It is expected to be used in combination with antidepressants, but the latter can take a month or two to take effect. Esketamine, on the other hand, might have an effect within hours or days, according to an FDA briefing document.The drug was designated as a breakthrough therapy in 2013, intending to “expedite the development and review of drugs for serious or life-threatening conditions,” the FDA says. First-line treatments don’t work for roughly 30% to 40% of patients with major depressive disorder, according to the briefing document.The FDA does not have to follow the recommendation of advisory committees, though it often does.

ERs 'flooded' with mentally ill patients with no place else to turn

ERs ‘flooded’ with mentally ill patients with no place else to turnHowever, the research behind esketamine has come under some criticism, with two of five key studies failing to meet their primary endpoints. Only one of these studies is a positive short-term trial, whereas most FDA-approved antidepressants are backed by at least two, according to the briefing document. But Janssen has maintained that the overall picture is positive.Adverse events tended to occur in the first two hours patients received the drug, including sedation, blood pressure increases and dissociation. For this reason, patients wouldn’t be able to pick it up at a local pharmacy; it would be given under the supervision of health care professionals who can keep an eye on the person during those first two hours.Because of the drug’s close relationship to ketamine, experts have also raised concerns about its potential for misuse and abuse. The clinical trials have not seen evidence of this risk, according to presentations made during the meeting.Advisory panelists also expressed concern that not enough long-term data was available to characterize the drug’s cognitive effects and other health impacts down the line.Get CNN Health’s weekly newsletter

There were six deaths of patients taking esketamine in trials, including three suicides, but FDA materials concluded “it is difficult to consider these deaths as drug-related.”The only current FDA-approved medication for treatment-resistant depression combines two other drugs already on the market. Other non-pharmaceutical treatments exist, such as electroconvulsive therapy.Janssen spokesman Greg Panico said no information about pricing would be available at this time. An FDA decision is expected in early March, he added.

 

NOVA Health Recovery | Alexandria, Va 22306 | Call for esketamine and nasal ketamine as well as IV Ketamine for depression, PTSD, anxiety  703-844-0184 < Link

Ketamine Virginia Link

Ketamine-like depression treatment on track for FDA approval

CNN)A ketamine-like drug for treatment-resistant depression was backed by a US Food and Drug Administration advisory committee on Tuesday. If it is then approved by the FDA, the drug — called esketamine — may provide a new option for patients with major depressive disorder who have tried at least two other antidepressants without success.A panel of experts voted to endorse the drug, which is made in nasal spray form by the pharmaceutical company Janssen, a division of Johnson & Johnson. Fourteen members voted that the benefits outweighed the risk, with two opposed and one abstaining.

Ketamine offers lifeline for people with severe depression, suicidal thoughts
703-844-0184 | NOVA Health Recovery | Alexandria, Va 22306

Ketamine offers lifeline for people with severe depression, suicidal thoughtsThe drug is a close relative of ketamine, a powerful medication used in hospitals primarily as an anesthetic; recent scientific studies have also shown its potential with treatment-resistant depression and suicidal ideation. Ketamine is also used recreationally — and illegally — as a club drug known as Special K. It generates an intense high and dissociative effects.Esketamine, which is not FDA-approved for any conditions, targets a different brain pathway than approved antidepressants, many of which have been around for decades. It is expected to be used in combination with antidepressants, but the latter can take a month or two to take effect. Esketamine, on the other hand, might have an effect within hours or days, according to an FDA briefing document.The drug was designated as a breakthrough therapy in 2013, intending to “expedite the development and review of drugs for serious or life-threatening conditions,” the FDA says. First-line treatments don’t work for roughly 30% to 40% of patients with major depressive disorder, according to the briefing document.The FDA does not have to follow the recommendation of advisory committees, though it often does.

ERs 'flooded' with mentally ill patients with no place else to turn

ERs ‘flooded’ with mentally ill patients with no place else to turnHowever, the research behind esketamine has come under some criticism, with two of five key studies failing to meet their primary endpoints. Only one of these studies is a positive short-term trial, whereas most FDA-approved antidepressants are backed by at least two, according to the briefing document. But Janssen has maintained that the overall picture is positive.Adverse events tended to occur in the first two hours patients received the drug, including sedation, blood pressure increases and dissociation. For this reason, patients wouldn’t be able to pick it up at a local pharmacy; it would be given under the supervision of health care professionals who can keep an eye on the person during those first two hours.Because of the drug’s close relationship to ketamine, experts have also raised concerns about its potential for misuse and abuse. The clinical trials have not seen evidence of this risk, according to presentations made during the meeting.Advisory panelists also expressed concern that not enough long-term data was available to characterize the drug’s cognitive effects and other health impacts down the line.Get CNN Health’s weekly newsletter

There were six deaths of patients taking esketamine in trials, including three suicides, but FDA materials concluded “it is difficult to consider these deaths as drug-related.”The only current FDA-approved medication for treatment-resistant depression combines two other drugs already on the market. Other non-pharmaceutical treatments exist, such as electroconvulsive therapy.Janssen spokesman Greg Panico said no information about pricing would be available at this time. An FDA decision is expected in early March, he added.



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NOVA Health Recovery Ketamine Infusion Center | 703-844-0184 – call for a Ketamine infusion or Ketamine nasal spray to treat your depression Alexandria, Va 22306 EMAIL is email@novahealthrecovery.com

NEW VARIATION OF KETAMINE TO BE APPROVED BY FDA FOR TREATMENT OF DEPRESSION

“The biggest breakthrough in depression treatment since Prozac”

  • 6 FEBRUARY 2019
New variation of ketamine to be approved by FDA for treatment of depression

Back in July of 2017, the world’s first ketamine trial for depression proved to be “incredibly effective” in curing elderly patients. The drug, often referred to as Special K, is a popular substance found clubland culture, but recent breakthrough studies and the development of chemical variations of ketamine has shown that the drug is a powerful tool that can help save lives and allow people to live life to the fullest potential.

According to Bloomberg, the Food and Drug Administration (FDA) has cleared the way for the first drug based on ketamine, from Johnson & Johnson, to gain approval as soon as March 2019. The ketamine variant, called esketamine, may very well become the first-ever rapid-acting antidepressant for suicidal patients and “treatment-resistant depression”. While physicians are still unsure about the long term effects of the drug and more trials need to be conducted in order to get to the root of its effectiveness, many doctors think esketamine may be “the biggest breakthrough in depression treatment since Prozac”.

The long-form story published in Bloomberg tells the stories of multiple people who have benefited from ketamine treatment and how the rapid development of this new miracle drug is being used to combat the skyrocketing rate of suicide in the United States (up 33 per cent in the last 20 years).

The drug esketamine provides “a quick molecular reset button for brains impaired by stress or depression”. Initially developed as an intravenous drug, Johnson & Johnson has developed a nasal solution that has the same effect. The initial study of the drug involved 68 people at high risk that were all antidepressants and other treatment – no placebos were used on actively suicidal patients. Of those who were given esketamine, 40 per cent were deemed “no longer at risk of killing themselves within 24 hours”.

As physicians and investors race to find out more about this supposed miracle drug, concerns remain that a new abuse crisis – similar to that of the current opioid crisis – may arise following federal approval of the substance.

Check out the captivating story behind these successful studies here

Learn more about ketamine’s colorful clubland history here.

Find out how we survived an unconventional, silly, hilarious and definitely brilliant musical about ketamine here.

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VA uses ketamine to treat PTSD effectively

The San Francisco Veterans Affairs Medical Center is administering ketamine to veterans with post-traumatic stress disorder and depression.

Tobias Marton, the director of the ketamine infusion program at the center, said that since the program first launched two years ago, they have treated about 40 patients who had virtually exhausted all other options.

“They’ve done everything we’ve asked them to do and they remain with very severe symptoms and with a poor or impaired quality of life,” he said. “Despite (past treatments), there remains a high risk of suicide (with some veterans).”

While it was not clear where the 40 patients are from, the option is something that is available to Humboldt County veterans who are suffering from PTSD or depression.

Marton said that in general, about a third of people diagnosed with depression don’t respond to first, second and third lines of treatment.

In contrast, ketamine infusion has yielded “impressive outcomes.”

Many people know of ketamine as a party drug, often referred to as Special K, but it is mainly used medically for anesthesia or pain treatment.

Miracle of medicine

“We know ketamine has rapid and powerful anti-suicide properties,” he said. “To have another tool, a potentially powerful tool to have an impact on suicide rates is really exciting.”

While Marton is proceeding with “cautious optimism,” Boris Nikolov, the CEO of Neurosciences Medical Clinic in Miami, Florida, which has a ketamine clinic, believes the application might be a medical breakthrough.

It’s one of the greatest discoveries in the field of depression,” he said. “This is one of the miracles in medicine.

Nikolov’s clinic has treated 120 patients with ketamine, including his wife who has PTSD as a result of severe child abuse.

“Ketamine really helped her,” he said. “That was a really big part of her recovery.”

Nikolov said most medicines that treat depression take from two to four weeks to start working. Ketamine begins working within hours after it is administered, a process which usually involves an IV infusion over the course of about an hour.

“What’s most important is the strong and fast effect of ketamine in patients who are very seriously depressed, or want to hurt themselves,” he said. “When they finish treatment, they’re totally different people. There is no other medication that does that.”

Brad Burge, the director of strategic communication at the Multidisciplinary Association for Psychedelic Studies, or MAPS, said there has been “an explosion of treatment that’s outpaced research.”

“It means that people are going to have another option, an alternative to conventional medications,” he said.

According to Burge, MAPS believes the best form of ketamine infusion involves pairing with other forms of psychotherapy such as group or individual counseling.

Ketamine availability

While ketamine is an FDA-approved drug which has been used as an anesthetic as well as a pain reliever, it isn’t officially sanctioned by the FDA to be used for treating mental health disorders. However, Marton said that ketamine has been administered in this fashion for over 18 years now.

A company is currently in the process of trying to get an intranasal product approved by the FDA which would administer ketamine through the nasal passage, according to Marton. He expects the FDA’s decision to be announced sometime around March 2019.

If the product is approved, he said, VA clinics in rural communities like the one in Eureka would likely be able to start offering ketamine treatments as well.

For now, only the location in San Francisco is able to offer the treatment, but Marton said anyone within their service realm, which includes Humboldt County, is invited to consult with the VA about seeking treatment.

“We want to be as thoughtful as we can,” he said. “As we understand more about it … (we) might be able to start helping people who we haven’t been able to help despite throwing everything we have at them.”



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What are the uses of ketamine?

Ketamine is a medication that is used to induce loss of consciousness, or anesthesia. It can produce relaxation and relieve pain in humans and animals.

It is a class III scheduled drug and is approved for use in hospitals and other medical settings as an anesthetic.

However, it is also a commonly abused “recreational” drug, due to its hallucinogenic, tranquilizing and dissociative effects.

Controversy has arisen about using ketamine “off-label” to treat depression. Off-label uses of drugs are uses that are not approved by the the United States, (U.S.) Food and Drug Administration (FDA).

Ketamine is safe to use in controled, medical practice, but it has abuse potential. Used outside the approved limits, its adverse mental and physical health effects can be hazardous. Prolonged use can lead to tolerance and psychological addiction.

Fast facts on ketamine:Here are some key points about ketamine. More detail is in the main article.

  • Ketamine is similar in structure to phencyclidine (PCP), and it causes a trance-like state and a sense of disconnection from the environment.
  • It is the most widely used anesthetic in veterinary medicine and is used for some surgical procedures in humans.
  • It is considered a “club drug,” like ecstasy, and it has been abused as a date-rape drug.
  • Ketamine should only be used as prescribed by a doctor.

 

What is ketamine?

ketamine and dissociation
703-844-0184 | Ketamine Treatment Center | Fairfax, Va 22304

Ketamine can produce feelings of dissociation when used as a drug of abuse.

Ketamine belongs to a class of drugs known as dissociative anesthetics. It is also known as Ketalar, Ketanest, and Ketaset.

Other drugs in this category include the hallucinogen, phencyclidine (PCP), dextromethorphan (DXM), and nitrous oxide, or laughing gas.

These types of drugs can make a person feel detached from sensations and surroundings, as if they are floating outside their body.

 

Therapeutic uses

Ketamine is most often used in veterinary medicine. In humans, it can induce and maintain general anesthesia before, during, and after surgery.

For medical purposes, ketamine is either injected into a muscle or given through an intravenous (IV) line.

It is considered safe as an anesthetic, because it does not reduce blood pressure or lower the breathing rate.

The fact that it does not need an electricity supply, oxygen, or highly trained staff makes it a suitable option in less wealthy countries and in disaster zones.

In human medical practice, it is used in procedures such as:

  • cardiac catheterization
  • skin grafts
  • orthopedic procedures
  • diagnostic procedures on the eye, ear, nose, and throat
  • minor surgical interventions, such as dental extractions

It has been used in a hospital setting to control seizures in patients with status epilepticus (SE), a type of epilepsy that can lead to brain damage and death. However, researchers point out that ketamine is normally used for this purpose after 5 to 6 other options have proven ineffective. Ketamine for the treatment of refractory status epilepticus

It is also an analgesic, and, in lower doses, it can relieve pain.

In 2014, researchers found that a ketamine infusion significantly reduced symptoms of post-traumatic stress disorder (PTSD) in 41 patients who had undergone a range of traumas.

Efficacy of intravenous ketamine for treatment of chronic posttraumatic stress disorder

Researchers are looking into other possible medical uses of ketamine, particularly in the areas of treatment-resistant depression, suicide prevention, and substance use disorders. However, this use is controversial.

 

Treating depression

Researchers for the American Psychological Association (APA) noted in April 2017 that a number of doctors prescribe ketamine “off-label,” for people with treatment-resistant depression.

However, they caution:

While ketamine may be beneficial to some patients with mood disorders, it is important to consider the limitations of the available data and the potential risk associated with the drug when considering the treatment option.”

The FDA has not yet approved it for treating depression.

In a study published in BMC Medical Ethics, researchers urge doctors to “minimize the risk to patients” by considering carefully the evidence before prescribing ketamine off-label for patients to treat depression and prevent suicide.

Citing “questionable practice” regarding the prescription of ketamine, they point out that there is not enough evidence to prove that ketamine is safe, and that some studies supporting its use have not been sufficiently rigorous in terms of research ethics.

They call for open debate, more research, and for doctors to try all other options first, before prescribing ketamine.

The National Institutes of Health (NIH) are currently supporting research into whether ketamine may help people with treatment-resistant depression.

 

Effects

Ketamine use can have a wide variety of adverse effects, including:

  • drowsiness
  • changes in perceptions of color or sound
  • hallucinations, confusion, and delirium
  • dissociation from body or identity
  • agitation
  • difficulty thinking or learning
  • nausea
  • dilated pupils and changes in eyesight
  • inability to control eye movements
  • involuntary muscle movements and muscle stiffness
  • slurred speech
  • numbness
  • amnesia
  • slow heart beat
  • behavioral changes
  • increased pressure in the eyes and brain

It can also lead to a loss of appetite, upset stomach, and vomiting.

When used as an anesthetic in humans, doctors combine it with another drug to prevent hallucinations.

Risks

Ketamine is considered relatively safe in medical settings, because it does not affect the protective airway reflexes, and it does not depress the circulatory system, as other anesthetic medications do.

However, some patients have reported disturbing sensations when awakening from ketamine anesthesia.

Ketamine can cause an increase in blood pressure and intracranial pressure, or pressure in the brain.

People with the following conditions cannot receive ketamine for medical purposes:

  • brain swelling
  • glaucoma
  • brain lesion or tumor

It is used with caution in those with:

  • coronary artery disease
  • increased blood pressure
  • thyroid disease
  • chronic alcohol addiction
  • acute alcohol intoxication
  • aneurysm
  • chest pain
  • mental illness

These effects may be stronger in people aged over 65 years.

Some people may have an allergy to the ingredients. Patients with any type of allergy should tell their doctor before using any medication.

Anyone who is using this drug for therapeutic purposes on a regular basis should have regular blood pressure checks.

As a drug of abuse

Ketamine is most often used in the dance club setting as a party drug. It produces an abrupt high that lasts for about an hour. Users report euphoria, along with feelings of floating and other “out of body” sensations. Hallucinations, similar to those experienced with LSD, are common.

In 2014, 1.4 percent of 12th graders reported using ketamine for recreational purposes. This was down from 2002, when 2.6 percent reported using it.

Street names include:

  • Cat Valium
  • KitKat
  • Special K
  • Vitamin K
  • The horse tranquilizer
  • Ket
  • Purple
  • Super K
  • Jet

It is taken orally as a pill, snorted, smoked with tobacco or marijuana, or mixed into drinks. Most often, it is cooked into a white powder for snorting. Taken orally, it can cause severe nausea and vomiting.

Regardless of how it is ingested, its effects begin within a few minutes and last for less than an hour.

Higher doses can produce more intense effects known as being in the “K-hole,” where users become unable to move or communicate and feel very far away from their body.

Some users seek out this type of transcendental experience, while others find it terrifying and consider it an adverse effect.

Adverse effects

Unwanted effects include:

  • addiction
  • psychosis
  • amnesia
  • impaired motor function
  • high blood pressure
  • respiratory problems
  • seizures

As the user can become oblivious to their environment, ketamine abuse puts the person at risk of accidental injury to themselves and vulnerable to assault by others.

Problems with co-ordination, judgment, and the physical senses can continue for up to 24 hours. If an individual is using ketamine in a recreational setting, a sober friend should remain with them to ensure their safety.

Long-term effects include bladder and kidney problems, stomach pain, and memory loss.

If addiction and dependence develop, there is also a risk of depression.

Frequent, illegal use of ketamine can lead to serious mental disorders and major physical harm to the bladder, known as ketamine-induced ulcerative cystitis.

Ketamine and alcohol

Ketamine toxicity alone is unlikely to lead to death, according to the WHO. However, combining it with other substances, such as alcohol, can increase the sedative effects, possibly leading to a fatal overdose.

In the U.S., 1,550 emergency department (ED) visits were due to illegal ketamine use, and 71.5 percent of these also involved alcohol.

Overdose

The risk of overdose is high, because, for a recreational user, there is only a slight difference in dosage between obtaining the drug’s desired effects and an overdose.

Addiction

Ketamine is a Class III controlled substance. Prolonged use can cause dependence, tolerance, and withdrawal symptoms. Quitting can lead to depression, anxiety, insomnia, and flashbacks.

Chronic users have been known to “binge” their ketamine use in an attempt to experience again the dissociative, euphoric effects of their early first use.

The complications of long-term use can be fatal.

A final word

Ketamine is an anesthetic drug, used in human and veterinary medicine. It is important to distinguish the valid medical uses from the non-medical, recreational use of the drug.

When properly administered by a trained medical professional, ketamine is a safe and valuable medication.

Used in recreational settings, however, ketamine abuse can produce unpredictable physical and mental health results. In the long term, it can lead to psychological damage and, in some cases, death.

Any drug use should be prescribed by a doctor who knows the patient’s full medical history.

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What is ketamine?

Ketamine Nasal SprayKetamine is a drug currently approved by the FDA for use as a general anesthetic during minor surgical procedures such as biopsies. It is widely known as a recreational drug because of its ability to induce cognitive-dissociative, hallucinogenic, and euphoric states in humans. Recently, it has been implicated in research as a potential therapeutic agent in depression especially in patients who have failed previous standard therapies.

Why ketamine?

Standard pharmacologic therapies for depression take several weeks of treatment before patients experience relief. Ketamine is different in that it has been shown to reduce depression symptoms and suicidal ideation in as little as forty minutes. This is considered a potentially lifesaving breakthrough in the treatment of depression because ketamine can rapidly reduce symptoms especially in emergency situations.

How does it work?

The most common medications used in depression affect serotonin in the brain. Ketamine works by a different mechanism. It has been shown to block the glutamate receptors in the brain resulting in its famous hallucinogenic effects. Ketamine has been shown to act on several other receptors, but it is theorized that at low doses, blocking glutamate receptors in the brain may be the reason for its anti-depressive effects.

Who should (and shouldn’t) take ketamine?

Ketamine has not been approved by the FDA for treatment of depression. Although, because of new studies, psychiatrists have been prescribing ketamine “off-label” for patients who did not respond to selective serotonin reuptake inhibitors (SSRIs) such has Celexa (citalopram), Zoloft (sertraline), or Prozac (fluoxetine) for immediate treatment of symptoms.

Ketamine has been shown to transiently yet significantly increase blood pressure following administration. Patients with high blood pressure should use caution when using ketamine. Ketamine has also been shown to be associated with increases in psychosis or dissociative properties.

Ketamine nasal sprays offer a quick and convenient way to administer ketamine for patients who need immediate relief, although they are currently not available commercially, so you will not find them at your local community pharmacy. Compounding pharmacies have the proper experience, equipment, and personnel to safely compound and customize this medication for you.

References

  1. Ketalar [package insert]. Chestnut Ridge, NY 10977: Par pharmaceutical; 2017 https://www.accessdata.fda.gov/drugsatfda_docs/label/2017/016812s043lbl.pdf
  2. Browne CA, Lucki I. Antidepresssant effects of ketamine: mechanisms underlying fast-acting novel antidepressants. Front Pharmacol December 2013.
  3. Lapidus K, Levitch CF, Perez AM, et al. A randomized controlled trial of intranasal ketamine in major depressive disorder. Biol Psychology 2014;76:970–976
  4. 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(4):399-405.

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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

 

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Ketamine for Refractory Neuropathic Pain

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Although the mechanisms underlying the development and maintenance of neuropathic pain are still poorly understood, both µ-opioid and NMDA receptors have been implicated.Although the mechanisms underlying the development and maintenance of neuropathic pain are still poorly understood, both µ-opioid and NMDA receptors have been implicated.

A randomized controlled trial investigating treatments for chronic neuropathic pain revealed that a ketamine regimen is superior to methadone, or ketamine combined with methadone, in alleviating neuropathic pain and associated sensory changes.1

Neuropathic pain is known to arise from a number of conditions and treatments, including chemotherapy, metabolic diseases, and trauma, and is often associated with allodynia and burning or shooting pain. Although the mechanisms underlying the development and maintenance of neuropathic pain are still poorly understood, both µ-opioid and N-methyl-D-aspartate (NMDA) receptors have been implicated.2

The µ-opioid receptor agonist methadone and the NMDA receptor antagonist ketamine thus may represent therapeutic targets to treat neuropathic. The adverse effects associated with these drugs (eg, hallucination, delirium for ketamine, somnolence, vomiting for methadone), however, preclude their use as first-line treatment.3,4

 

As a way to minimize drug-related adverse events, multimodal analgesia can be used. In a previous study, the authors of the current analysis showed that a combination of oral methadone and ketamine was effective in alleviating refractory neuropathic pain with minimal adverse effects.5The previous study was conducted in 18 patients; the current researchers conducted a double-blind randomized clinical trial in which 42 patients aged 22 to 77 years who had refractory neuropathic pain for >6 months, as indicated by poor response to common treatments (ie, opioids, antidepressants, anticonvulsants), were enrolled.

diagnostic algorithm was used, in which the following criteria had to be met for a positive diagnostic: independent assessment of somatosensory dysfunction by an experienced pain clinician, affected proprioception, unaffected motor or autonomic functions, and confirmation of diagnosis for patients meeting the aforementioned conditions.

The patients were randomly assigned to 3 treatment groups with 14 patients in each, all administered orally 3 times per day: methadone (3 mg), ketamine (30 mg), or a methadone (3 mg)/ketamine (30 mg) combination. Supplemental analgesics were allowed during treatment.

Baseline characteristics, including patient demographics, diagnosis, pain score, and use of analgesics were similar across the 3 treatment groups, which were found to be equally effective in reducing pain (the trial’s primary outcome), as indicated by visual analog scale scores, at 7 (40% reduction), 15 (60% reduction), and 30 days (70% reduction). In addition, the 3 treatments showed similar efficacy in reducing the occurrence of burning and shooting pain (methadone, P =.01 for both; ketamine, P =.03 and P =.01, respectively; methadone/ketamine, P =.02 and P =.04, respectively). However, the ketamine-only treatment was the only effective one in reducing the incidence of allodynia (P =.02).

Adverse effects (ie, nausea, vomiting, dizziness, hallucinations, constipation, and migraine) had similar incidence across treatments, with the exception of somnolence, which occurred more often in the methadone cohort (92%) than in the ketamine (19%) or methadone/ketamine (46%) treatment groups (P =.001).

The researchers concluded that “Collectively, these findings showed that methadone/ketamine was not better than methadone or ketamine for improving refractory neuropathic pain. However, ketamine was more effective in reducing allodynia compared with methadone or methadone/ketamine.” In addition, they noted that further studies should be conducted to investigate the mechanisms underlying the absence of synergy between ketamine and methadone.

 

References

  1. Rigo FK, Trevisan G, Godoy MC, et al. Management of neuropathic chronic pain with methadone combined with ketamine: a randomized, double blind, active-controlled clinical trialPain Physician. 2017;20(3):207-215.
  2. Ingram SL. Association of mu-opioid and NMDA receptors in the periaqueductal gray: what does it mean for pain control? Neuropsychopharmacology. 2012;37(2):315-316. doi: 10.1038/npp.2011.241
  3. Noppers I, Niesters M, Aarts L, Smith T, Sarton E, Dahan A. Ketamine for the treatment of chronic non-cancer painExpert Opin Pharmacother. 2010;11(14):2417-2429. doi: 10.1517/14656566.2010.515978
  4. Gagnon B, Almahrezi A, Schreier G. Methadone in the treatment of neuropathic painPain Res Manag. 2003;8(3):149-154.
  5. De godoy MC, Dalmolin GD, Rigo FK, et al. Management of chronic neuropathic pain of different causes with the combination of oral methadone along with ketamine: A report of 18 casesEur J Anaesthesiol. 2013;30(10):638-640. doi: 10.1097/EJA.0b013e32835f9a3b

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Approximately one-third to one-half of patients with generalized Social Anxiety Disorder (SAD) do not experience adequate clinical benefit from current evidence-based treatment for SAD. This includes treatment with conventional approaches such as selective serotonin reuptake inhibitors (SSRIs) or venlafaxine and cognitive behavioral therapy (CBT). Failure of anxiety relief in patients with SAD is a source of substantial morbidity, distress, and decreases in quality of life.
Symptoms
Feelings of shyness or discomfort in certain situations aren’t necessarily signs of social anxiety disorder, particularly in children. Comfort levels in social situations vary, depending on the individual’s personality traits and life experiences. Some people are naturally reserved and others are more outgoing.
In contrast to everyday nervousness, social anxiety disorder includes fear, anxiety and avoidance that interferes with your daily routine, work, school or other activities.

Emotional and behavioral symptoms
Signs and symptoms of social anxiety disorder can include persistent:
• Fear of situations in which you may be judged
• Worrying about embarrassing or humiliating yourself
• Concern that you’ll offend someone
• Intense fear of interacting or talking with strangers
• Fear that others will notice that you look anxious
• Fear of physical symptoms that may cause you embarrassment, such as blushing, sweating, trembling or having a shaky voice
• Avoiding doing things or speaking to people out of fear of embarrassment
• Avoiding situations where you might be the center of attention
• Having anxiety in anticipation of a feared activity or event
• Spending time after a social situation analyzing your performance and identifying flaws in your interactions
• Expecting the worst possible consequences from a negative experience during a social situation
For children, anxiety about interacting with adults or peers may be shown by crying, having temper tantrums, clinging to parents or refusing to speak in social situations.
Performance type of social anxiety disorder is when you experience intense fear and anxiety only during speaking or performing in public, but not in other types of social situations.
Physical symptoms
Physical signs and symptoms can sometimes accompany social anxiety disorder and may include:
• Fast heartbeat
• Upset stomach or nausea
• Trouble catching your breath
• Dizziness or lightheadedness
• Confusion or feeling “out of body”
• Diarrhea
• Muscle tension
Avoiding normal social situations
Common, everyday experiences that may be hard to endure when you have social anxiety disorder include, for example:
• Using a public restroom
• Interacting with strangers
• Eating in front of others
• Making eye contact
• Initiating conversations
• Dating
• Attending parties or social gatherings
• Going to work or school
• Entering a room in which people are already seated
• Returning items to a store
Social anxiety disorder symptoms can change over time. They may flare up if you’re facing a lot of stress or demands. Although avoiding anxiety-producing situations may make you feel better in the short term, your anxiety is likely to persist over the long term if you don’t get treatment.
Ketamine
Converging lines of evidence from neuroimaging and pharmacological studies support the importance of glutamate abnormalities in the pathogenesis of SAD. In a previously conducted clinical study, an elevated glutamate to creatinine ratio was found in the anterior cingulate cortex of SAD patients when compared to healthy controls. Elevated brain glutamine levels have also been demonstrated in patients with SAD. Moreover, nonclinical rodent studies have established a strong link between glutamate regulation and anxiety.
Ketamine is a potent antagonist of the N-methyl-D-aspartate (NMDA) receptor, a major type of glutamate receptor in the brain. Ketamine is routinely used for anesthetic induction because of its dissociative properties. However in research studies and in some physician accounts of off-label clinical use, ketamine is an effective treatment for reducing symptoms of depressive and anxiety disorders. In multiple controlled clinical studies, ketamine has produced a rapid antidepressant effect in unipolar and bipolar depression. Ketamine’s anti-depressant effects peak 1-3 days following infusion and is observed long after ketamine has been metabolized and excreted by the body and after ketamine’s sedative and dissociative effects have dissipated.
The results of several clinical studies suggest that ketamine may also have significant anxiolytic effects. Patients with major depressive disorder given a single ketamine infusion have shown strong and significant reductions in comorbid anxiety symptoms. A trial including 11 depressed patients demonstrated a significant reduction in anxiety symptoms (Hamilton Anxiety Rating Scale (HAM-A)) following ketamine infusion. This improvement is supported by one of the earlier placebo-controlled trials of ketamine which demonstrated that the psychic anxiety item was one of 4 (out of 21) items on the Hamilton Depression Rating Scale (HAM-D) demonstrating significant improvement after ketamine infusion.

 

The National Institute of Mental Health Highlights Ketamine for Depression

 August 25, 2018

The National Institute of Mental Health (NIMH) issued a highlight on ketamine for treating depression.

The most commonly used antidepressants are largely variations on a theme; they increase the supply within synapses of a class of neurotransmitters believed to play a role in depression. While these drugs relieve depression for some, there is a weeks-long delay before they take effect, and some people with “treatment-resistant” depression do not respond at all.

The delay in effectiveness has suggested to scientists that the medication-induced changes in neurotransmitters are several steps away from processes more central to the root cause of depression. One possibility for a more proximal mechanism is glutamate, the primary excitatory, or activating, neurotransmitter in the brain. Preliminary studies suggested that inhibitors of glutamate could have antidepressant-like effects, and in a seminal clinical trial, the drug ketamine—which dampens glutamate signaling—lifted depression in as little as 2 hours in people with treatment-resistant depression.34

The discovery of rapidly acting antidepressants has transformed our expectations—we now look for treatments that will work in 6 hours rather than 6 weeks. But ketamine has some disadvantages; it has to be administered intravenously, the effects are transient, and it has side effects that require careful monitoring. However, results from clinical studies have confirmed the potential of the glutamate pathway as a target for the development of new antidepressants. Continuing research with ketamine has provided information on biomarkers that could be used to predict who will respond to treatment.35Clinical studies are also testing analogs of ketamine in an effort to develop glutamate inhibitors without ketamine’s side effects that can then be used in the clinic.36 Ketamine may also have potential for treating other mental illnesses; for example, a preliminary clinical trial reported that ketamine reduced the severity of symptoms in patients with PTSD. 37 Investigation of the role of glutamate signaling in other illnesses may provide the impetus to develop novel therapies based on this pathway.

Left: Change in the 21-item Hamilton Depression Rating Scale (HDRS) following ketamine or placebo treatment.
Right: Proportion of responders showing a 50 percent improvement on the HDRS following ketamine or placebo treatment.34

Source: Carlos Zarate, M.D., Experimental Therapeutics and Pathophysiology Branch, NIMH

One of the imperatives of clinical research going forward will be to demonstrate whether the ability of a compound to interact with a specific brain target is related to some measurable change in brain or behavioral activity that, in turn, can be associated with relief of symptoms. In a study of ketamine’s effects in patients in the depressive phase of bipolar disorder, ketamine restored pleasure-seeking behavior independent from and ahead of its other antidepressant effects. Within 40 minutes after a single infusion of ketamine, treatment-resistant depressed bipolar disorder patients experienced a reversal of a key symptom—loss of interest in pleasurable activities—which lasted up to 14 days.38 Brain scans traced the agent’s action to boosted activity in areas at the front and deep in the right hemisphere of the brain. This approach is consistent with the NIMH’s RDoC project, which calls for the study of functions—such as the ability to seek out and experience rewards—and their related brain systems that may identify subgroups of patients with common underlying dysfunctions that cut across traditional diagnostic categories.

The ketamine story shows that in some instances, a strong and repeatable clinical outcome stemming from a hypothesis about a specific molecular target (e.g., a glutamate receptor) can open up new arenas for basic research to explain the mechanisms of treatment response; basic studies can, in turn, provide data leading to improved treatments directed at that mechanism. A continuing focus on specific mechanisms will not only provide information on the potential of test compounds as depression medications, but will also help us understand which targets in the brain are worth aiming at in the quest for new therapies.

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23014 Beaumont Goochland
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23015 Beaverdam Hanover
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23018 Bena Gloucester
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23021 Bohannon Mathews
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23022 Bremo Bluff Fluvanna
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23023 Bruington King And Queen
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23024 Bumpass Louisa
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23025 Cardinal Mathews
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23027 Cartersville Cumberland
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23030 Charles City Charles City
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23031 Christchurch Middlesex
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23032 Church View Middlesex
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23035 Cobbs Creek Mathews
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23038 Columbia Goochland
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23039 Crozier Goochland
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23040 Cumberland Cumberland
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23043 Deltaville Middlesex
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23045 Diggs Mathews
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23047 Doswell Hanover
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23050 Dutton Gloucester
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23055 Fork Union Fluvanna
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23056 Foster Mathews
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23058 Glen Allen Henrico
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23059 Glen Allen Henrico
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23060 Glen Allen Henrico
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23061 Gloucester Gloucester
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23062 Gloucester Point Gloucester
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23063 Goochland Goochland
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23064 Grimstead Mathews
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23065 Gum Spring Goochland
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23066 Gwynn Mathews
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23067 Hadensville Goochland
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23068 Hallieford Mathews
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23069 Hanover Hanover
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23070 Hardyville Middlesex
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23071 Hartfield Middlesex
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23072 Hayes Gloucester
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23075 Highland Springs Henrico
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23076 Hudgins Mathews
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23079 Jamaica Middlesex
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23081 Jamestown James City
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23083 Jetersville Amelia
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23084 Kents Store Fluvanna
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23085 King And Queen Court House King And Queen
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23086 King William King William
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23089 Lanexa New Kent
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23090 Lightfoot York
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23091 Little Plymouth King And Queen
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23092 Locust Hill Middlesex
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23093 Louisa Louisa
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23101 Macon Powhatan
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23102 Maidens Goochland
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23103 Manakin Sabot Goochland
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23105 Mannboro Amelia
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23106 Manquin King William
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23107 Maryus Gloucester
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23108 Mascot King And Queen
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23109 Mathews Mathews
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23110 Mattaponi King And Queen
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23111 Mechanicsville Hanover
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23112 Midlothian Chesterfield
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23113 Midlothian Chesterfield
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23114 Midlothian Chesterfield
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23115 Millers Tavern Essex
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23116 Mechanicsville Hanover
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23117 Mineral Louisa
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23119 Moon Mathews
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23120 Moseley Chesterfield
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23123 New Canton Buckingham
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23124 New Kent New Kent
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23125 New Point Mathews
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23126 Newtown King And Queen
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23127 Norge James City
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23128 North Mathews
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23129 Oilville Goochland
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23130 Onemo Mathews
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23131 Ordinary Gloucester
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23138 Port Haywood Mathews
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23139 Powhatan Powhatan
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23140 Providence Forge New Kent
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23141 Quinton New Kent
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23146 Rockville Hanover
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23147 Ruthville Charles City
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23148 Saint Stephens Church King And Queen
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23149 Saluda Middlesex
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23150 Sandston Henrico
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23153 Sandy Hook Goochland
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23154 Schley Gloucester
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23155 Severn Gloucester
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23156 Shacklefords King And Queen
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23160 State Farm Goochland
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23161 Stevensville King And Queen
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23162 Studley Hanover
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23163 Susan Mathews
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23168 Toano James City
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23169 Topping Middlesex
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23170 Trevilians Louisa
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23173 University Of Richmond Richmond City
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23175 Urbanna Middlesex
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23176 Wake Middlesex
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23177 Walkerton King And Queen
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23178 Ware Neck Gloucester
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23180 Water View Middlesex
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23181 West Point King William
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23183 White Marsh Gloucester
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23184 Wicomico Gloucester
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23185 Williamsburg James City
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23186 Williamsburg Williamsburg City
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23187 Williamsburg Williamsburg City
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23188 Williamsburg James City
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23190 Woods Cross Roads Gloucester
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23192 Montpelier Hanover
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23218 Richmond Richmond City
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23219 Richmond Richmond City
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23220 Richmond Richmond City
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23221 Richmond Richmond City
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23222 Richmond Richmond City
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23223 Richmond Richmond City
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23224 Richmond Richmond City
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23225 Richmond Richmond City
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23226 Richmond Henrico
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23227 Richmond Henrico
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23228 Richmond Henrico
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23229 Richmond Henrico
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23230 Richmond Henrico
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23231 Richmond Henrico
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23232 Richmond Richmond City
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23233 Richmond Henrico
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23234 Richmond Chesterfield
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23235 Richmond Chesterfield
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23236 Richmond Chesterfield
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23237 Richmond Chesterfield
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23238 Richmond Henrico
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23240 Richmond Richmond City
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23241 Richmond Richmond City
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23242 Richmond Henrico
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23249 Richmond Richmond City
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23250 Richmond Henrico
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23255 Richmond Henrico
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23260 Richmond Richmond City
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23261 Richmond Richmond City
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23269 Richmond Richmond City
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23273 Richmond Richmond City
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23274 Richmond Richmond City
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23276 Richmond Richmond City
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23278 Richmond Richmond City
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23279 Richmond Richmond City
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23282 Richmond Richmond City
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23284 Richmond Richmond City
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23285 Richmond Richmond City
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23286 Richmond Richmond City
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23288 Richmond Henrico
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23289 Richmond Richmond City
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23290 Richmond Richmond City
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23291 Richmond Richmond City
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23292 Richmond Richmond City
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23293 Richmond Richmond City
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23294 Richmond Henrico
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23295 Richmond Richmond City
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23297 Richmond Chesterfield
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23298 Richmond Richmond City
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23301 Accomac Accomack
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23302 Assawoman Accomack
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23303 Atlantic Accomack
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23304 Battery Park Isle Of Wight
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23306 Belle Haven Accomack
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23307 Birdsnest Northampton
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23308 Bloxom Accomack
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23310 Cape Charles Northampton
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23313 Capeville Northampton
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23314 Carrollton Isle Of Wight
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23315 Carrsville Isle Of Wight
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23316 Cheriton Northampton
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23320 Chesapeake Chesapeake City
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23321 Chesapeake Chesapeake City
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23322 Chesapeake Chesapeake City
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23323 Chesapeake Chesapeake City
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23324 Chesapeake Chesapeake City
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23325 Chesapeake Chesapeake City
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23326 Chesapeake Chesapeake City
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23327 Chesapeake Chesapeake City
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23328 Chesapeake Chesapeake City
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23336 Chincoteague Island Accomack
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23337 Wallops Island Accomack
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23341 Craddockville Accomack
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23345 Davis Wharf Accomack
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23347 Eastville Northampton
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23350 Exmore Northampton
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23354 Franktown Northampton
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23356 Greenbackville Accomack
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23357 Greenbush Accomack
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23358 Hacksneck Accomack
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23359 Hallwood Accomack
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23389 Harborton Accomack
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23395 Horntown Accomack
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23396 Oak Hall Accomack
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23397 Isle Of Wight Isle Of Wight
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23398 Jamesville Northampton
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23399 Jenkins Bridge Accomack
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23401 Keller Accomack
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23404 Locustville Accomack
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23405 Machipongo Northampton
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23407 Mappsville Accomack
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23408 Marionville Northampton
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23409 Mears Accomack
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23410 Melfa Accomack
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23412 Modest Town Accomack
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23413 Nassawadox Northampton
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23414 Nelsonia Accomack
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23415 New Church Accomack
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23416 Oak Hall Accomack
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23417 Onancock Accomack
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23418 Onley Accomack
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23419 Oyster Northampton
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23420 Painter Accomack
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23421 Parksley Accomack
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23422 Pungoteague Accomack
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23423 Quinby Accomack
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23424 Rescue Isle Of Wight
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23426 Sanford Accomack
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23427 Saxis Accomack
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23429 Seaview Northampton
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23430 Smithfield Isle Of Wight
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23431 Smithfield Isle Of Wight
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23432 Suffolk Suffolk City
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23433 Suffolk Suffolk City
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23434 Suffolk Suffolk City
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23435 Suffolk Suffolk City
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23436 Suffolk Suffolk City
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23437 Suffolk Suffolk City
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23438 Suffolk Suffolk City
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23439 Suffolk Suffolk City
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23440 Tangier Accomack
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23441 Tasley Accomack
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23442 Temperanceville Accomack
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23443 Townsend Northampton
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23450 Virginia Beach Virginia Beach City
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23451 Virginia Beach Virginia Beach City
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23452 Virginia Beach Virginia Beach City
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23453 Virginia Beach Virginia Beach City
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23454 Virginia Beach Virginia Beach City
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23455 Virginia Beach Virginia Beach City
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23456 Virginia Beach Virginia Beach City
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23457 Virginia Beach Virginia Beach City
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23458 Virginia Beach Virginia Beach City
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23459 Virginia Beach Virginia Beach City
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23460 Virginia Beach Virginia Beach City
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23461 Virginia Beach Virginia Beach City
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23462 Virginia Beach Virginia Beach City
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23463 Virginia Beach Virginia Beach City
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23464 Virginia Beach Virginia Beach City
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23465 Virginia Beach Virginia Beach City
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23466 Virginia Beach Virginia Beach City
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23467 Virginia Beach Virginia Beach City
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23471 Virginia Beach Virginia Beach City
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23479 Virginia Beach Virginia Beach City
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23480 Wachapreague Accomack
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23482 Wardtown Northampton
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23483 Wattsville Accomack
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23486 Willis Wharf Northampton
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23487 Windsor Isle Of Wight
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23488 Withams Accomack
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23501 Norfolk Norfolk City
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23502 Norfolk Norfolk City
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23503 Norfolk Norfolk City
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23504 Norfolk Norfolk City
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23505 Norfolk Norfolk City
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23506 Norfolk Norfolk City
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23507 Norfolk Norfolk City
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23508 Norfolk Norfolk City
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23509 Norfolk Norfolk City
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23510 Norfolk Norfolk City
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23511 Norfolk Norfolk City
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23512 Norfolk Norfolk City
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23513 Norfolk Norfolk City
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23514 Norfolk Norfolk City
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23515 Norfolk Norfolk City
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23517 Norfolk Norfolk City
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23518 Norfolk Norfolk City
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23519 Norfolk Norfolk City
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23520 Norfolk Norfolk City
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23521 Norfolk Norfolk City
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23523 Norfolk Norfolk City
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23529 Norfolk Norfolk City
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23541 Norfolk Norfolk City
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23551 Norfolk Norfolk City
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23601 Newport News Newport News City
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23602 Newport News Newport News City
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23603 Newport News Newport News City
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23604 Fort Eustis Newport News City
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23605 Newport News Newport News City
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23606 Newport News Newport News City
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23607 Newport News Newport News City
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23608 Newport News Newport News City
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23609 Newport News Newport News City
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23612 Newport News Newport News City
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23628 Newport News Newport News City
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23630 Hampton Hampton City
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23651 Fort Monroe Hampton City
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23661 Hampton Hampton City
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23662 Poquoson Poquoson City
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23663 Hampton Hampton City
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23664 Hampton Hampton City
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23665 Hampton York
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23666 Hampton Hampton City
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23667 Hampton Hampton City
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23668 Hampton Hampton City
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23669 Hampton Hampton City
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23670 Hampton Hampton City
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23681 Hampton Hampton City
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23690 Yorktown York
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23691 Yorktown York
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23692 Yorktown York
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23693 Yorktown York
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23694 Lackey York
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23696 Seaford York
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23701 Portsmouth Portsmouth City
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23702 Portsmouth Portsmouth City
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23703 Portsmouth Portsmouth City
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23704 Portsmouth Portsmouth City
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23705 Portsmouth Portsmouth City
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23707 Portsmouth Portsmouth City
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23708 Portsmouth Portsmouth City
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23709 Portsmouth Portsmouth City
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23801 Fort Lee Prince George
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23803 Petersburg Petersburg City
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23804 Petersburg Petersburg City
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23805 Petersburg Petersburg City
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23806 Petersburg Petersburg City
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23821 Alberta Brunswick
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23822 Ammon Dinwiddie
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23824 Blackstone Nottoway
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23825 Blackstone Nottoway
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23827 Boykins Southampton
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23828 Branchville Southampton
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23829 Capron Southampton
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23830 Carson Dinwiddie
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23831 Chester Chesterfield
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23832 Chesterfield Chesterfield
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23833 Church Road Dinwiddie
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23834 Colonial Heights Colonial Heights City
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23836 Chester Chesterfield
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23837 Courtland Southampton
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23838 Chesterfield Chesterfield
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23839 Dendron Surry
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23840 Dewitt Dinwiddie
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23841 Dinwiddie Dinwiddie
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23842 Disputanta Prince George
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23843 Dolphin Brunswick
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23844 Drewryville Southampton
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23845 Ebony Brunswick
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23846 Elberon Surry
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23847 Emporia Greensville
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23850 Ford Dinwiddie
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23851 Franklin Franklin City
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23856 Freeman Brunswick
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23857 Gasburg Brunswick
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23860 Hopewell Hopewell City
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23866 Ivor Southampton
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23867 Jarratt Greensville
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23868 Lawrenceville Brunswick
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23870 Jarratt Greensville
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23872 Mc Kenney Dinwiddie
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23873 Meredithville Brunswick
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23874 Newsoms Southampton
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23875 Prince George Prince George
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23876 Rawlings Brunswick
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23878 Sedley Southampton
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23879 Skippers Greensville
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23881 Spring Grove Surry
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23882 Stony Creek Sussex
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23883 Surry Surry
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23884 Sussex Sussex
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23885 Sutherland Dinwiddie
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23887 Valentines Brunswick
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23888 Wakefield Sussex
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23889 Warfield Brunswick
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23890 Waverly Sussex
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23891 Waverly Sussex
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23893 White Plains Brunswick
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23894 Wilsons Dinwiddie
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23897 Yale Sussex
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23898 Zuni Isle Of Wight
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23899 Claremont Surry
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23901 Farmville Prince Edward
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23909 Farmville Prince Edward
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23915 Baskerville Mecklenburg
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23917 Boydton Mecklenburg
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23919 Bracey Mecklenburg
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23920 Brodnax Brunswick
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23921 Buckingham Buckingham
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23922 Burkeville Nottoway
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23923 Charlotte Court House Charlotte
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23924 Chase City Mecklenburg
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23927 Clarksville Mecklenburg
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23930 Crewe Nottoway
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23934 Cullen Charlotte
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23936 Dillwyn Buckingham
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23937 Drakes Branch Charlotte
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23938 Dundas Lunenburg
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23939 Evergreen Appomattox
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23941 Fort Mitchell Lunenburg
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23942 Green Bay Prince Edward
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23943 Hampden Sydney Prince Edward
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23944 Kenbridge Lunenburg
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23947 Keysville Charlotte
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23950 La Crosse Mecklenburg
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23952 Lunenburg Lunenburg
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23954 Meherrin Prince Edward
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23955 Nottoway Nottoway
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23958 Pamplin Appomattox
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23959 Phenix Charlotte
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23960 Prospect Prince Edward
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23962 Randolph Charlotte
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23963 Red House Charlotte
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23964 Red Oak Charlotte
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23966 Rice Prince Edward
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23967 Saxe Charlotte
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23968 Skipwith Mecklenburg
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23970 South Hill Mecklenburg
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23974 Victoria Lunenburg
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23976 Wylliesburg Charlotte
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24001 Roanoke Roanoke City
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24002 Roanoke Roanoke City
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24003 Roanoke Roanoke City
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24004 Roanoke Roanoke City
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24005 Roanoke Roanoke City
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24006 Roanoke Roanoke City
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24007 Roanoke Roanoke City
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24008 Roanoke Roanoke City
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24009 Roanoke Roanoke City
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24010 Roanoke Roanoke City
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24011 Roanoke Roanoke City
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24012 Roanoke Roanoke City
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24013 Roanoke Roanoke City
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24014 Roanoke Roanoke City
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24015 Roanoke Roanoke City
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24016 Roanoke Roanoke City
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24017 Roanoke Roanoke City
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24018 Roanoke Roanoke
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24019 Roanoke Roanoke
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24020 Roanoke Roanoke
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24022 Roanoke Roanoke City
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24023 Roanoke Roanoke City
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24024 Roanoke Roanoke City
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24025 Roanoke Roanoke City
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24026 Roanoke Roanoke City
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24027 Roanoke Roanoke City
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24028 Roanoke Roanoke City
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24029 Roanoke Roanoke City
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24030 Roanoke Roanoke City
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24031 Roanoke Roanoke City
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24032 Roanoke Roanoke City
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24033 Roanoke Roanoke City
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24034 Roanoke Roanoke City
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24035 Roanoke Roanoke City
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24036 Roanoke Roanoke City
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24037 Roanoke Roanoke City
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24038 Roanoke Roanoke City
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24040 Roanoke Roanoke City
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24042 Roanoke Roanoke City
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24043 Roanoke Roanoke City
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24044 Roanoke Roanoke City
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24045 Roanoke Roanoke City
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24048 Roanoke Roanoke City
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24050 Roanoke Botetourt
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24053 Ararat Patrick
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24054 Axton Henry
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24055 Bassett Henry
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24058 Belspring Pulaski
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24059 Bent Mountain Roanoke
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24060 Blacksburg Montgomery
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24061 Blacksburg Montgomery
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24062 Blacksburg Montgomery
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24063 Blacksburg Montgomery
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24064 Blue Ridge Botetourt
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24065 Boones Mill Franklin
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24066 Buchanan Botetourt
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24067 Callaway Franklin
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24068 Christiansburg Montgomery
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24069 Cascade Pittsylvania
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24070 Catawba Roanoke
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24072 Check Floyd
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24073 Christiansburg Montgomery
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24076 Claudville Patrick
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24077 Cloverdale Botetourt
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24078 Collinsville Henry
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24079 Copper Hill Floyd
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24082 Critz Patrick
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24083 Daleville Botetourt
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24084 Dublin Pulaski
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24085 Eagle Rock Botetourt
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24086 Eggleston Giles
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24087 Elliston Montgomery
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24088 Ferrum Franklin
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24089 Fieldale Henry
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24090 Fincastle Botetourt
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24091 Floyd Floyd
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24092 Glade Hill Franklin
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24093 Glen Lyn Giles
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24095 Goodview Bedford
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24101 Hardy Franklin
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24102 Henry Franklin
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24104 Huddleston Bedford
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24105 Indian Valley Floyd
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24111 Mc Coy Montgomery
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24112 Martinsville Martinsville City
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24113 Martinsville Martinsville City
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24114 Martinsville Martinsville City
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24115 Martinsville Martinsville City
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24120 Meadows Of Dan Patrick
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24121 Moneta Bedford
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24122 Montvale Bedford
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24124 Narrows Giles
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24126 Newbern Pulaski
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24127 New Castle Craig
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24128 Newport Giles
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24129 New River Pulaski
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24130 Oriskany Botetourt
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24131 Paint Bank Craig
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24132 Parrott Pulaski
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24133 Patrick Springs Patrick
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24134 Pearisburg Giles
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24136 Pembroke Giles
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24137 Penhook Franklin
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24138 Pilot Montgomery
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24139 Pittsville Pittsylvania
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24141 Radford Radford
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24142 Radford Radford
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24143 Radford Radford
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24146 Redwood Franklin
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24147 Rich Creek Giles
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24148 Ridgeway Henry
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24149 Riner Montgomery
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24150 Ripplemead Giles
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24151 Rocky Mount Franklin
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24153 Salem Salem
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24155 Roanoke Salem
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24157 Roanoke Salem
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24161 Sandy Level Pittsylvania
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24162 Shawsville Montgomery
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24165 Spencer Henry
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24167 Staffordsville Giles
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24168 Stanleytown Henry
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24171 Stuart Patrick
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24174 Thaxton Bedford
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24175 Troutville Botetourt
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24176 Union Hall Franklin
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24177 Vesta Patrick
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24178 Villamont Bedford
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24179 Vinton Roanoke
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24184 Wirtz Franklin
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24185 Woolwine Patrick
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24201 Bristol Bristol
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24202 Bristol Washington
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24203 Bristol Bristol
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24209 Bristol Bristol
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24210 Abingdon Washington
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24211 Abingdon Washington
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24212 Abingdon Washington
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24215 Andover Wise
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24216 Appalachia Wise
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24217 Bee Dickenson
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24218 Ben Hur Lee
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24219 Big Stone Gap Wise
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24220 Birchleaf Dickenson
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24221 Blackwater Lee
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24224 Castlewood Russell
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24225 Cleveland Russell
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24226 Clinchco Dickenson
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24228 Clintwood Dickenson
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24230 Coeburn Wise
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24236 Damascus Washington
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24237 Dante Russell
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24239 Davenport Buchanan
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24243 Dryden Lee
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24244 Duffield Scott
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24245 Dungannon Scott
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24246 East Stone Gap Wise
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24248 Ewing Lee
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24250 Fort Blackmore Scott
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24251 Gate City Scott
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24256 Haysi Dickenson
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24258 Hiltons Scott
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24260 Honaker Russell
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24263 Jonesville Lee
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24265 Keokee Lee
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24266 Lebanon Russell
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24269 Mc Clure Dickenson
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24270 Mendota Washington
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24271 Nickelsville Scott
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24272 Nora Dickenson
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24273 Norton Norton City
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24277 Pennington Gap Lee
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24279 Pound Wise
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24280 Rosedale Russell
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24281 Rose Hill Lee
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24282 Saint Charles Lee
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24283 Saint Paul Wise
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24290 Weber City Scott
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24292 Whitetop Grayson
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24293 Wise Wise
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24301 Pulaski Pulaski
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24311 Atkins Smyth
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24312 Austinville Wythe
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24313 Barren Springs Wythe
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24314 Bastian Bland
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24315 Bland Bland
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24316 Broadford Tazewell
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24317 Cana Carroll
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24318 Ceres Bland
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24319 Chilhowie Smyth
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24322 Cripple Creek Wythe
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24323 Crockett Wythe
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24324 Draper Pulaski
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24325 Dugspur Carroll
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24326 Elk Creek Grayson
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24327 Emory Washington
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24328 Fancy Gap Carroll
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24330 Fries Grayson
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24333 Galax Galax City
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24340 Glade Spring Washington
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24343 Hillsville Carroll
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24347 Hiwassee Pulaski
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24348 Independence Grayson
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24350 Ivanhoe Wythe
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24351 Lambsburg Carroll
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24352 Laurel Fork Carroll
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24354 Marion Smyth
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24360 Max Meadows Wythe
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24361 Meadowview Washington
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24363 Mouth Of Wilson Grayson
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24366 Rocky Gap Bland
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24368 Rural Retreat Wythe
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24370 Saltville Smyth
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24374 Speedwell Wythe
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24375 Sugar Grove Smyth
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24377 Tannersville Tazewell
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24378 Troutdale Grayson
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24380 Willis Floyd
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24381 Woodlawn Carroll
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24382 Wytheville Wythe
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24401 Staunton Staunton City
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24402 Staunton Staunton City
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24411 Augusta Springs Augusta
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24412 Bacova Bath
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24413 Blue Grass Highland
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24415 Brownsburg Rockbridge
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24416 Buena Vista Buena Vista City
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24421 Churchville Augusta
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24422 Clifton Forge Alleghany
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24426 Covington Covington City
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24430 Craigsville Augusta
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24431 Crimora Augusta
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24432 Deerfield Augusta
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24433 Doe Hill Highland
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24435 Fairfield Rockbridge
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24437 Fort Defiance Augusta
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24438 Glen Wilton Botetourt
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24439 Goshen Rockbridge
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24440 Greenville Augusta
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24441 Grottoes Rockingham
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24442 Head Waters Highland
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24445 Hot Springs Bath
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24448 Iron Gate Alleghany
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24450 Lexington Lexington City
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24457 Low Moor Alleghany
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24458 Mc Dowell Highland
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24459 Middlebrook Augusta
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24460 Millboro Bath
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24463 Mint Spring Augusta
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24464 Montebello Nelson
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24465 Monterey Highland
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24467 Mount Sidney Augusta
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24468 Mustoe Highland
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24469 New Hope Augusta
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24471 Port Republic Rockingham
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24472 Raphine Rockbridge
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24473 Rockbridge Baths Rockbridge
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24474 Selma Alleghany
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24476 Steeles Tavern Augusta
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24477 Stuarts Draft Augusta
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24479 Swoope Augusta
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24482 Verona Augusta
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24483 Vesuvius Rockbridge
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24484 Warm Springs Bath
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24485 West Augusta Augusta
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24486 Weyers Cave Augusta
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24487 Williamsville Bath
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24501 Lynchburg Lynchburg City
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24502 Lynchburg Lynchburg City
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24503 Lynchburg Lynchburg City
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24504 Lynchburg Lynchburg City
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24505 Lynchburg Lynchburg City
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24506 Lynchburg Lynchburg City
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24512 Lynchburg Lynchburg City
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24513 Lynchburg Lynchburg City
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24514 Lynchburg Lynchburg City
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24515 Lynchburg Lynchburg City
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24517 Altavista Campbell
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24520 Alton Halifax
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24521 Amherst Amherst
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24522 Appomattox Appomattox
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24523 Bedford Bedford
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24526 Big Island Bedford
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24527 Blairs Pittsylvania
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24528 Brookneal Campbell
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24529 Buffalo Junction Mecklenburg
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24530 Callands Pittsylvania
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24531 Chatham Pittsylvania
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24533 Clifford Amherst
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24534 Clover Halifax
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24535 Cluster Springs Halifax
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24536 Coleman Falls Bedford
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24538 Concord Campbell
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24539 Crystal Hill Halifax
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24540 Danville Danville City
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24541 Danville Danville City
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24543 Danville Danville City
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24544 Danville Danville City
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24549 Dry Fork Pittsylvania
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24550 Evington Campbell
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24551 Forest Bedford
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24553 Gladstone Nelson
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24554 Gladys Campbell
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24555 Glasgow Rockbridge
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24556 Goode Bedford
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24557 Gretna Pittsylvania
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24558 Halifax Halifax
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24562 Howardsville Buckingham
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24563 Hurt Pittsylvania
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24565 Java Pittsylvania
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24566 Keeling Pittsylvania
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24569 Long Island Pittsylvania
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24570 Lowry Bedford
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24571 Lynch Station Campbell
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24572 Madison Heights Amherst
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24574 Monroe Amherst
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24576 Naruna Campbell
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24577 Nathalie Halifax
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24578 Natural Bridge Rockbridge
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24579 Natural Bridge Station Rockbridge
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24580 Nelson Mecklenburg
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24581 Norwood Nelson
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24586 Ringgold Pittsylvania
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24588 Rustburg Campbell
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24589 Scottsburg Halifax
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24590 Scottsville Albemarle
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24592 South Boston Halifax
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24593 Spout Spring Appomattox
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24594 Sutherlin Pittsylvania
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24595 Sweet Briar Amherst
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24597 Vernon Hill Halifax
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24598 Virgilina Halifax
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24599 Wingina Buckingham
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24601 Amonate Tazewell
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24602 Bandy Tazewell
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24603 Big Rock Buchanan
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24604 Bishop Tazewell
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24605 Bluefield Tazewell
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24606 Boissevain Tazewell
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24607 Breaks Dickenson
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24608 Burkes Garden Tazewell
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24609 Cedar Bluff Tazewell
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24612 Doran Tazewell
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24613 Falls Mills Tazewell
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24614 Grundy Buchanan
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24619 Horsepen Tazewell
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24620 Hurley Buchanan
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24622 Jewell Ridge Tazewell
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24624 Keen Mountain Buchanan
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24627 Mavisdale Buchanan
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24628 Maxie Buchanan
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24630 North Tazewell Tazewell
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24631 Oakwood Buchanan
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24634 Pilgrims Knob Buchanan
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24635 Pocahontas Tazewell
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24637 Pounding Mill Tazewell
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24639 Raven Buchanan
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24640 Red Ash Tazewell
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24641 Richlands Tazewell
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24646 Rowe Buchanan
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24647 Shortt Gap Buchanan
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24649 Swords Creek Russell
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24651 Tazewell Tazewell
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24656 Vansant Buchanan
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24657 Whitewood Buchanan
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24658 Wolford Buchanan
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24701 Bluefield Mercer
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24712 Athens Mercer
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24714 Beeson Mercer
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24715 Bramwell Mercer
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24716 Bud Wyoming
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24719 Covel Wyoming
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24724 Freeman Mercer
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24726 Herndon Wyoming
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24729 Hiawatha Mercer
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24731 Kegley Mercer
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24732 Kellysville Mercer
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24733 Lashmeet Mercer
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24736 Matoaka Mercer
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24737 Montcalm Mercer
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24738 Nemours Mercer
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24739 Oakvale Mercer
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24740 Princeton Mercer
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24747 Rock Mercer
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24751 Wolfe Mercer
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24801 Welch Mcdowell
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24808 Anawalt Mcdowell
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24811 Avondale Mcdowell
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24813 Bartley Mcdowell
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24815 Berwind Mcdowell
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24816 Big Sandy Mcdowell
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24817 Bradshaw Mcdowell
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24818 Brenton Wyoming
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24822 Clear Fork Wyoming
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24823 Coal Mountain Wyoming
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24824 Coalwood Mcdowell
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24826 Cucumber Mcdowell
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24827 Cyclone Wyoming
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24828 Davy Mcdowell
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24829 Eckman Mcdowell
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24830 Elbert Mcdowell
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24831 Elkhorn Mcdowell
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24834 Fanrock Wyoming
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24836 Gary Mcdowell
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24839 Hanover Wyoming
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24842 Hemphill Mcdowell
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24843 Hensley Mcdowell
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24844 Iaeger Mcdowell
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24845 Ikes Fork Wyoming
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24846 Isaban Mcdowell
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24847 Itmann Wyoming
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24848 Jenkinjones Mcdowell
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24849 Jesse Wyoming
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24850 Jolo Mcdowell
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24851 Justice Mingo
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24853 Kimball Mcdowell
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24854 Kopperston Wyoming
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24855 Kyle Mcdowell
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24857 Lynco Wyoming
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24859 Marianna Wyoming
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24860 Matheny Wyoming
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24861 Maybeury Mcdowell
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24862 Mohawk Mcdowell
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24866 Newhall Mcdowell
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24867 New Richmond Wyoming
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24868 Northfork Mcdowell
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24869 North Spring Wyoming
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24870 Oceana Wyoming
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24871 Pageton Mcdowell
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24872 Panther Mcdowell
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24873 Paynesville Mcdowell
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24874 Pineville Wyoming
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24878 Premier Mcdowell
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24879 Raysal Mcdowell
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24880 Rock View Wyoming
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24881 Roderfield Mcdowell
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24882 Simon Wyoming
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24884 Squire Mcdowell
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24887 Switchback Mcdowell
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24888 Thorpe Mcdowell
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24892 War Mcdowell
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24894 Warriormine Mcdowell
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24895 Wilcoe Mcdowell
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24898 Wyoming Wyoming
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24901 Lewisburg Greenbrier
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24902 Fairlea Greenbrier
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24910 Alderson Greenbrier
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24915 Arbovale Pocahontas
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24916 Asbury Greenbrier
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24918 Ballard Monroe
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24920 Bartow Pocahontas
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24924 Buckeye Pocahontas
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24925 Caldwell Greenbrier
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24927 Cass Pocahontas
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24931 Crawley Greenbrier
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24934 Dunmore Pocahontas
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24935 Forest Hill Summers
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24938 Frankford Greenbrier
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24941 Gap Mills Monroe
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24943 Grassy Meadows Greenbrier
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24944 Green Bank Pocahontas
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24945 Greenville Monroe
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24946 Hillsboro Pocahontas
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24951 Lindside Monroe
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24954 Marlinton Pocahontas
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24957 Maxwelton Greenbrier
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24961 Neola Greenbrier
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24962 Pence Springs Summers
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24963 Peterstown Monroe
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24966 Renick Greenbrier
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24970 Ronceverte Greenbrier
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24974 Secondcreek Monroe
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24976 Sinks Grove Monroe
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24977 Smoot Greenbrier
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24981 Talcott Summers
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24983 Union Monroe
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24984 Waiteville Monroe
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24985 Wayside Monroe
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24986 White Sulphur Springs Greenbrier
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24991 Williamsburg Greenbrier
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24993 Wolfcreek Monroe
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25002 Alloy Fayette
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25003 Alum Creek Kanawha
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25005 Amma Roane
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25007 Arnett Raleigh
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25008 Artie Raleigh
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25009 Ashford Boone
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25011 Bancroft Putnam
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25015 Belle Kanawha
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25019 Bickmore Clay
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25021 Bim Boone
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25022 Blair Logan
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25024 Bloomingrose Boone
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25025 Blount Kanawha
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25026 Blue Creek Kanawha
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25028 Bob White Boone
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25030 Bomont Clay
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25031 Boomer Fayette
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25033 Buffalo Putnam
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25035 Cabin Creek Kanawha
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25036 Cannelton Fayette
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25039 Cedar Grove Kanawha
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25040 Charlton Heights Fayette
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25043 Clay Clay
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25044 Clear Creek Raleigh
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25045 Clendenin Kanawha
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25047 Clothier Logan
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25048 Colcord Raleigh
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25049 Comfort Boone
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25051 Costa Boone
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25053 Danville Boone
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25054 Dawes Kanawha
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25057 Deep Water Fayette
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25059 Dixie Nicholas
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25060 Dorothy Raleigh
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25061 Drybranch Kanawha
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25062 Dry Creek Raleigh
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25063 Duck Clay
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25064 Dunbar Kanawha
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25067 East Bank Kanawha
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25070 Eleanor Putnam
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25071 Elkview Kanawha
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25075 Eskdale Kanawha
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25076 Ethel Logan
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25079 Falling Rock Kanawha
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25081 Foster Boone
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25082 Fraziers Bottom Putnam
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25083 Gallagher Kanawha
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25085 Gauley Bridge Fayette
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25086 Glasgow Kanawha
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25088 Glen Clay
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25090 Glen Ferris Fayette
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25093 Gordon Boone
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25102 Handley Kanawha
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25103 Hansford Kanawha
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25106 Henderson Mason
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25107 Hernshaw Kanawha
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25108 Hewett Boone
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25109 Hometown Putnam
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25110 Hugheston Kanawha
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25111 Indore Clay
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25112 Institute Kanawha
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25113 Ivydale Clay
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25114 Jeffrey Boone
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25115 Kanawha Falls Fayette
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25118 Kimberly Fayette
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25119 Kincaid Fayette
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25121 Lake Logan
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25123 Leon Mason
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25124 Liberty Putnam
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25125 Lizemores Clay
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25126 London Kanawha
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25130 Madison Boone
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25132 Mammoth Kanawha
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25133 Maysel Clay
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25134 Miami Kanawha
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25136 Montgomery Fayette
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25139 Mount Carbon Fayette
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25140 Naoma Raleigh
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25141 Nebo Clay
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25142 Nellis Boone
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25143 Nitro Kanawha
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25148 Orgas Boone
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25149 Ottawa Boone
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25152 Page Fayette
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25154 Peytona Boone
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25156 Pinch Kanawha
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25159 Poca Putnam
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25160 Pond Gap Kanawha
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25161 Powellton Fayette
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25162 Pratt Kanawha
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25164 Procious Clay
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25165 Racine Boone
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25168 Red House Putnam
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25169 Ridgeview Boone
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25173 Robson Fayette
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25174 Rock Creek Raleigh
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25177 Saint Albans Kanawha
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25180 Saxon Boone
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25181 Seth Boone
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25183 Sharples Logan
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25185 Mount Olive Fayette
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25186 Smithers Fayette
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25187 Southside Mason
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25193 Sylvester Boone
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25201 Tad Kanawha
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25202 Tornado Kanawha
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25203 Turtle Creek Boone
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25204 Twilight Boone
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25205 Uneeda Boone
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25206 Van Boone
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25208 Wharton Boone
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25209 Whitesville Boone
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25211 Widen Clay
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25213 Winfield Putnam
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25214 Winifrede Kanawha
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25231 Advent Jackson
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25234 Arnoldsburg Calhoun
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25235 Chloe Calhoun
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25239 Cottageville Jackson
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25241 Evans Jackson
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25243 Gandeeville Roane
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25244 Gay Jackson
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25245 Given Jackson
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25247 Hartford Mason
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25248 Kenna Jackson
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25251 Left Hand Roane
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25252 Le Roy Jackson
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25253 Letart Mason
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25259 Looneyville Roane
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25260 Mason Mason
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25261 Millstone Calhoun
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25262 Millwood Jackson
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25264 Mount Alto Mason
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25265 New Haven Mason
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25266 Newton Roane
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25267 Normantown Gilmer
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25268 Orma Calhoun
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25270 Reedy Roane
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25271 Ripley Jackson
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25275 Sandyville Jackson
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25276 Spencer Roane
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25285 Wallback Clay
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25286 Walton Roane
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25287 West Columbia Mason
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25301 Charleston Kanawha
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25302 Charleston Kanawha
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25303 Charleston Kanawha
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25304 Charleston Kanawha
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25305 Charleston Kanawha
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25306 Charleston Kanawha
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25309 Charleston Kanawha
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25311 Charleston Kanawha
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25312 Charleston Kanawha
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25313 Charleston Kanawha
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25314 Charleston Kanawha
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25315 Charleston Kanawha
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25317 Charleston Kanawha
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25320 Charleston Kanawha
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25321 Charleston Kanawha
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25322 Charleston Kanawha
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25323 Charleston Kanawha
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25324 Charleston Kanawha
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25325 Charleston Kanawha
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25326 Charleston Kanawha
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25327 Charleston Kanawha
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25328 Charleston Kanawha
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25329 Charleston Kanawha
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25330 Charleston Kanawha
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25331 Charleston Kanawha
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25332 Charleston Kanawha
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25333 Charleston Kanawha
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25334 Charleston Kanawha
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25335 Charleston Kanawha
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25336 Charleston Kanawha
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25337 Charleston Kanawha
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25338 Charleston Kanawha
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25339 Charleston Kanawha
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25350 Charleston Kanawha
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25356 Charleston Kanawha
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25357 Charleston Kanawha
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25358 Charleston Kanawha
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25360 Charleston Kanawha
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25361 Charleston Kanawha
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25362 Charleston Kanawha
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25364 Charleston Kanawha
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25365 Charleston Kanawha
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25375 Charleston Kanawha
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25387 Charleston Kanawha
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25389 Charleston Kanawha
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25392 Charleston Kanawha
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25396 Charleston Kanawha
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25401 Martinsburg Berkeley
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25402 Martinsburg Berkeley
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25403 Martinsburg Berkeley
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25404 Martinsburg Berkeley
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25405 Martinsburg Berkeley
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25410 Bakerton Jefferson
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25411 Berkeley Springs Morgan
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25413 Bunker Hill Berkeley
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25414 Charles Town Jefferson
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25419 Falling Waters Berkeley
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25420 Gerrardstown Berkeley
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25421 Glengary Berkeley
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25422 Great Cacapon Morgan
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25423 Halltown Jefferson
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25425 Harpers Ferry Jefferson
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25427 Hedgesville Berkeley
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25428 Inwood Berkeley
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25429 Martinsburg Berkeley
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25430 Kearneysville Jefferson
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25431 Levels Hampshire
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25432 Millville Jefferson
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25434 Paw Paw Morgan
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25437 Points Hampshire
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25438 Ranson Jefferson
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25440 Ridgeway Berkeley
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25441 Rippon Jefferson
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25442 Shenandoah Junction Jefferson
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25443 Shepherdstown Jefferson
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25444 Slanesville Hampshire
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25446 Summit Point Jefferson
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25501 Alkol Lincoln
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25502 Apple Grove Mason
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25503 Ashton Mason
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25504 Barboursville Cabell
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25505 Big Creek Logan
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25506 Branchland Lincoln
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25507 Ceredo Wayne
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25508 Chapmanville Logan
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25510 Culloden Cabell
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25511 Dunlow Wayne
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25512 East Lynn Wayne
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25514 Fort Gay Wayne
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25515 Gallipolis Ferry Mason
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25517 Genoa Wayne
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25520 Glenwood Mason
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25521 Griffithsville Lincoln
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25523 Hamlin Lincoln
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25524 Harts Lincoln
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25526 Hurricane Putnam
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25529 Julian Boone
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25530 Kenova Wayne
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25534 Kiahsville Wayne
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25535 Lavalette Wayne
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25537 Lesage Cabell
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25540 Midkiff Lincoln
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25541 Milton Cabell
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25544 Myra Lincoln
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25545 Ona Cabell
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25547 Pecks Mill Logan
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25550 Point Pleasant Mason
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25555 Prichard Wayne
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25557 Ranger Lincoln
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25559 Salt Rock Cabell
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25560 Scott Depot Putnam
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25562 Shoals Wayne
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25564 Sod Lincoln
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25565 Spurlockville Lincoln
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25567 Sumerco Lincoln
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25569 Teays Putnam
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25570 Wayne Wayne
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25571 West Hamlin Lincoln
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25572 Woodville Boone
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25573 Yawkey Lincoln
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25601 Logan Logan
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25606 Accoville Logan
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25607 Amherstdale Logan
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25608 Baisden Mingo
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25611 Bruno Logan
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25612 Chauncey Logan
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25614 Cora Logan
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25617 Davin Logan
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25621 Gilbert Mingo
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25624 Henlawson Logan
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25625 Holden Logan
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25628 Kistler Logan
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25630 Lorado Logan
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25632 Lyburn Logan
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25634 Mallory Logan
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25635 Man Logan
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25637 Mount Gay Logan
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25638 Omar Logan
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25639 Peach Creek Logan
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25644 Sarah Ann Logan
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25646 Stollings Logan
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25647 Switzer Logan
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25649 Verdunville Logan
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25650 Verner Mingo
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25651 Wharncliffe Mingo
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25652 Whitman Logan
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25653 Wilkinson Logan
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25654 Yolyn Logan
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25661 Williamson Mingo
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25665 Borderland Mingo
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25666 Breeden Mingo
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25667 Chattaroy Mingo
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25669 Crum Wayne
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25670 Delbarton Mingo
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25671 Dingess Mingo
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25672 Edgarton Mingo
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25674 Kermit Mingo
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25676 Lenore Mingo
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25678 Matewan Mingo
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25685 Naugatuck Mingo
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25686 Newtown Mingo
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25688 North Matewan Mingo
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25690 Ragland Mingo
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25691 Rawl Mingo
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25692 Red Jacket Mingo
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25696 Varney Mingo
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25697 Vulcan Mingo
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25699 Wilsondale Wayne
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25701 Huntington Cabell
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25702 Huntington Cabell
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25703 Huntington Cabell
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25704 Huntington Wayne
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25705 Huntington Cabell
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25706 Huntington Cabell
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25707 Huntington Cabell
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25708 Huntington Cabell
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25709 Huntington Cabell
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25710 Huntington Cabell
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25711 Huntington Cabell
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25712 Huntington Cabell
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25713 Huntington Cabell
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25714 Huntington Cabell
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25715 Huntington Cabell
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25716 Huntington Cabell
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25717 Huntington Cabell
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25718 Huntington Cabell
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25719 Huntington Cabell
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25720 Huntington Cabell
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25721 Huntington Cabell
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25722 Huntington Cabell
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25723 Huntington Cabell
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25724 Huntington Cabell
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25725 Huntington Cabell
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25726 Huntington Cabell
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25727 Huntington Cabell
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25728 Huntington Cabell
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25729 Huntington Cabell
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25755 Huntington Cabell
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25770 Huntington Cabell
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25771 Huntington Cabell
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25772 Huntington Cabell
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25773 Huntington Cabell
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25774 Huntington Cabell
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25775 Huntington Cabell
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25776 Huntington Cabell
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25777 Huntington Cabell
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25778 Huntington Cabell
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25779 Huntington Cabell
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25801 Beckley Raleigh
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25802 Beckley Raleigh
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25810 Allen Junction Wyoming
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25811 Amigo Wyoming
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25812 Ansted Fayette
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25813 Beaver Raleigh
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25816 Blue Jay Raleigh
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25817 Bolt Raleigh
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25818 Bradley Raleigh
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25820 Camp Creek Mercer
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25823 Coal City Raleigh
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25825 Cool Ridge Raleigh
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25826 Corinne Wyoming
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25827 Crab Orchard Raleigh
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25831 Danese Fayette
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25832 Daniels Raleigh
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25833 Dothan Fayette
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25836 Eccles Raleigh
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25837 Edmond Fayette
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25839 Fairdale Raleigh
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25840 Fayetteville Fayette
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25841 Flat Top Mercer
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25843 Ghent Raleigh
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25844 Glen Daniel Raleigh
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25845 Glen Fork Wyoming
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25846 Glen Jean Fayette
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25848 Glen Rogers Wyoming
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25849 Glen White Raleigh
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25851 Harper Raleigh
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25853 Helen Raleigh
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25854 Hico Fayette
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25855 Hilltop Fayette
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25857 Josephine Raleigh
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25860 Lanark Raleigh
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25862 Lansing Fayette
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25864 Layland Fayette
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25865 Lester Raleigh
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25866 Lochgelly Fayette
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25868 Lookout Fayette
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25870 Maben Wyoming
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25871 Mabscott Raleigh
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25873 Mac Arthur Raleigh
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25875 Mc Graws Wyoming
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25876 Saulsville Wyoming
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25878 Midway Raleigh
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25879 Minden Fayette
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25880 Mount Hope Fayette
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25882 Mullens Wyoming
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25901 Oak Hill Fayette
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25902 Odd Raleigh
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25904 Pax Fayette
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25906 Piney View Raleigh
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25907 Prince Fayette
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25908 Princewick Raleigh
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25909 Prosperity Raleigh
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25911 Raleigh Raleigh
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25913 Ravencliff Wyoming
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25914 Redstar Fayette
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25915 Rhodell Raleigh
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25916 Sabine Wyoming
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25917 Scarbro Fayette
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25918 Shady Spring Raleigh
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25919 Skelton Raleigh
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25920 Slab Fork Raleigh
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25921 Sophia Raleigh
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25922 Spanishburg Mercer
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25926 Sprague Raleigh
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25927 Stanaford Raleigh
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25928 Stephenson Wyoming
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25932 Surveyor Raleigh
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25936 Thurmond Fayette
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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.

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