What is Chronic Fatigue Syndrome

Chronic fatigue syndrome (CFS), also known as myalgic encephalomyelitis (ME), post-viral fatigue syndrome (PVFS) and various other names, is a syndrome (or group of syndromes) of u...

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Discussion:
Excitatory Neurotoxicity and CFS
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Dr. Paul Cheney Discusses the Benefits of Klonopin
by Carol Sieverling
October 12, 2001



Editor’s Note: The following is based on a recent interview conducted by Carol Sieverling with Dr. Paul R. Cheney, M.D., Ph.D., and the article "CFIDS Treatment: The Cheney Clinic’s Strategic Approach" (CFIDS Chronicle, Spring 1995). Dr. Cheney gave permission to share this information, but has not reviewed or edited it.

Many CFIDS specialists prescribe the drug Klonopin. In the October 1999 issue of The Fibromyalgia Network, nine CFS/FM specialists summarized their most effective treatments, and six included Klonopin. Interestingly, the three who did not are primarily FM specialists.

Dr. Cheney prescribes Klonopin to address a condition associated with CFIDS called "excitatory neurotoxicity." To explain this condition to patients, he draws a line with "seizure" on the far left and "coma" on the far right. A big dot in the middle represents where healthy people are when awake. A dot somewhat to the right of the middle indicates where healthy people are when asleep – slightly shifted toward coma. He highlights in red the left portion of the line, from seizure to the middle, and labels it "Neurotoxic State" (damaging to the brain). He highlights in blue the right portion of the line, from coma to the middle, and labels it "Healing State."

In CFIDS, an ongoing injury to the brain shifts patients toward seizure. A dot to the left of the middle, marked "injury," represents the position of CFIDS patients. This puts us in the red "Neurotoxic" zone. When we shift toward seizure, we often experience "sensory overload." It’s as if our brain’s "radar" is too sensitive. Our neurons (nerve cells) are sensing stimuli and firing when they should not. This causes amplification of sensory input. Light, noise, motion and pain are all magnified. At the beginning of their illness, many patients report feeling exhausted, yet also strangely "wired." The "wired" feeling is the slight shift towards seizure that occurs as a result of the excitatory neurotoxicity.

Cheney frequently uses the term "threshold potential" when discussing excitatory neurotoxicity. (Think of the threshold - bottom - of a doorway. The lower it is, the more accessible it is. When it is at floor level, everything can enter. When it is raised, access is restricted to taller people. If it is too high, no one can enter.) Threshold potential refers to how much stimulus it takes to make neurons fire. If the threshold potential is too low, even slight stimulation is "allowed to enter" and is detected by the neurons. This causes the neurons to fire, resulting in sensory overload. If the threshold is dropped to nothing, all stimuli get through and the neurons fire continuously, resulting in a seizure. If the threshold is raised, only stronger stimuli can make neurons fire. A healthy person’s threshold potential naturally rises at bedtime, promoting sleep. If the threshold potential is too high, you feel drugged or drowsy. If the threshold potential is raised extremely high, coma results.

Two receptors in the brain, NMDA and GABA, determine the threshold potential. During the waking hours of a healthy person, NMDA and GABA should be equally active. This balances the person in the middle of the seizure/coma continuum. NMDA stimulates, and GABA inhibits. If NMDA increases, one moves toward seizure. If GABA increases, one moves toward coma.

In CFIDS, NMDA is more activated than GABA, lowering the threshold potential. This causes neurons to fire with very little stimulation, resulting in sensory overload. This condition of excitatory neurotoxicity is dangerous. Dr. Cheney emphasizes that in an attempt to protect itself, the body will eventually kill neurons that fire excessively. He states that brain cell loss can result if this condition isn’t addressed.

How can the brain be protected against excitatory neurotoxicity? Klonopin. This long acting benzodiazepine has been Dr. Cheney’s most effective drug for CFIDS over the years. He believes that Klonopin and the supplement magnesium may be two of the most important treatments for CFIDS patients because of their neuroprotective qualities. He recommends two or more 0.5 mg tablets of Klonopin at night. Paradoxically, very small doses (usually a quarter to a half a tablet) in the morning and mid-afternoon improve cognitive function and energy. If the daytime dose is low enough, you’ll experience greater clarity and think better. If the daytime dose is too high, you’ll become drowsy. Adjust your dose for maximum benefit, taking as much as possible without drowsiness. Adjust the morning dose first, then take the same amount mid-afternoon if needed, then take three to four times the morning dose at bedtime. Dr. Cheney recommends doubling the dose during severe relapses.

Dr. Cheney most frequently prescribes the combination of Klonopin and Doxepin, along with the supplement "Magnesium Glycinate Forte." Magnesium Glycinate alone is a good choice for the more budget minded(www.ImmuneSupport.com sells it as "Magnesium Plus".) A common dosage of magnesium is 200 mgs at bedtime. Too much magnesium can cause diarrhea, though glycinate is usually the best tolerated form.

Cheney prescribes Doxepin in the form of a commercial elixir (10mg/ml). At low doses, this tricyclic antidepressant acts as a very potent antihistamine and immune modulator. Doxepin acts synergistically with Klonopin to assist sleep, and may improve pain. Patients tend to be very sensitive to Doxepin, which can cause morning fog and fatigue if the dose is too high (5 to 10 mg or higher). He recommends starting at two drops a night and gradually increasing the dose until "morning fog" becomes a problem. Most patients can’t tolerate more than half a cc.

On a handout entitled "Neuroprotection via Threshold Potentials," Cheney lists six substances that can protect the brain. Under the category "NMDA Blockers" Cheney lists:

1. Parenteral magnesium and taurine (intramuscular injections of magnesium and taurine, usually given with procaine)
2. Histamine blockers (Doxepin Elixir)
Under the category "GABA Agonists" (increases GABA) Cheney lists:
3. Klonopin
4. Neurontin
5. Kava Kava
6. Valerian Root
Posted on 07/05/09, 12:07 am
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Reply #1 - 07/05/09  2:07pm
" I'm a HUGE fan of Kava Kava, but it does interact w/different drugs sooo ... I would recommend that before taking ANY herbal supplement one checks w/their naturalist physician. "
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Reply #2 - 07/07/09  8:57am
" Thanks NetJet for this article.
This is a very informative interview with Dr. Paul Cheney about Benefits of Klonopin. I am going for a test of thyroid soon. Lets see what the doctor will say after the results come. "

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