Benzos like Xanax and Klonopin are some of the most powerful therapies I’ve come across for treating my Chronic Fatigue Syndrome.
They boost my energy – paradoxically – for one to three days after taking a dose, and this is typical among people with CFS.
Let’s dig into the science of how benzos address some major mechanisms at play in chronic fatigue.
Introduction to benzodiazepines
Benzodiazepenes are a class of drugs with over 30 varieties.
They work as sedatives (R) in treating anxiety, panic, insomnia, and muscle spasms by depressing activity in the brain (R).
The most common benzos include diazepam (Valium), clonazepam (Klonopin), and alprazolam (Xanax).
Longer-acting benzos like diazepam and clonazepam have different uses (ie, insomnia) than the shorter acting benzos like alprazolam, which is useful for panic disorder.
Use of benzos in chronic fatigue syndrome
Benzos are prescribed by a number of CFS specialists, including Drs. Paul Cheney and Charles Lapp.
Clonazepam is the most commonly prescribed benzo for CFS.
Dr. Lapp believes the best cocktail for sleep in CFS is a combo of clonazepam and the antidepressant trazodone, while Dr. Cheney uses small daytime doses to increase energy.
Patients with fibromyalgia (a related disorder) ranked clonazepam one of the most effective medications, while other sources suggest CFSers on clonazepam improve their cognition, muscle aches, headaches, restless legs, skin tenderness and dysautonomia. (R)
Benzos are useful in treating the nervous system imbalance common in CFS by tamping down the “fight or flight” side of the nervous system.
CFSers report that generic clonazepam is less effective than branded Klonopin.
Diazepam is mostly sometimes used to treat insomnia in CFS, while alprazolam is best used in panic disorder and not on a daily basis. (R)
I’ve noticed that my energy increases the day after I take a dose of Klonopin, and, according to my naturopathic doctor, that may be because it increases deep slow-wave sleep. CFSers experience less of this important stage of sleep than healthy people. (R)
How benzos reduce inflammation
Clonazepam weakly inhibits the cytokines (inflammatory proteins) IL-6 (R) and IL-8. Diazepam is a strong inhibitor of IL-8. (R)
Benzos inhibit IL-8 by preventing adenosine from binding to mast cells, the cells responsible for allergy (a major form of inflammation). (R1, R2)
Benzos broadly inhibit mast cell degranulation, an inflammatory allergic process, and improve symptoms in those with mast cell activation disease. (R1, R2, R3)
How benzos protect the brain
Preventing adenosine from binding to its receptors on cells also helps protect the brain from excitotoxicty, an overstimulated state which kills cells. (R)
Clonazepam binds to GABAa receptors in the brain (R). These are the primary receptors for preventing excitoxicity. (R)
GABAa receptors work by affecting the polarity of the cell strongly enough that it becomes resistant to harm from excitatory neurotransmitters. (R1, R2)
Dr. Cheney believes benzos increase energy because they prevent production of nitric oxide (NO) by the brain’s NMDA receptors, which in turn prevents a chain of oxidative stress. (R)
In the diagram above (from Dr. Martin Pall), both superoxide and peroxynitrite (ONOO) are massive sources of oxidative stress.
Nitric oxide also stimulates release of excitatory glutamate, so benzos prevent excitoxicity via that route also. (R)
Why CFSers benefit from benzos
Why do CFSers struggle with oxidative stress to begin with? The answer may come from a newly discovered phenomenon, Cell Danger Response.
When cells are under attack from a pathogen or toxin, they generate oxidants, AKA reactive oxygen species (ROS), to harden the cells. (Superoxide and peroxynitrite are both types of ROS)
This limits the reach and damage that pathogens and toxins can have on cells.
Why this mechanism doesn’t shut itself off after the threat is taken care of is still unclear. (R)
Dr. Martin Pall believes electromagnetic fields are the driver of this cycle.
ROS, calcium (Ca2, see diagram above) and the cellular energy currency ATP feed each other via complex mechanisms. (R) Perhaps this interplay is why this cycle can go on indefinitely in CFS.
Cautions
Though I’ve been on benzos for seven years now mostly without problems, there was one period of Klonopin use that made me severely depressed.
Other side effects include thirst, GI distress, oversedation, (R) impulsiveness and decreased libido. (R)
Long-term use may see the benefits vanish, dependence develop and side effects like depression grow more intense. (R)
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