Medication Sensitivities

Medication Sensitivity

ME/CFS patients often report abnormal sensitivities to medications and supplements. Medication sensitivity is typically experienced as an outsized response to the dose, substantial side effects, adverse reactions, or a “crash”, an increase in ME/CFS symptoms, following taking the medication. While adverse reactions to medications are not uncommon in healthy individuals, the difference for many ME/CFS patients is the scale of the reaction relative to the size of the dose.

Outsized Responses

To illustrate these outsized reactions to tiny doses, we’ll grab a few posts from the /cfs subreddit of patients' self-reported experiences with Naltrexone, a drug used for substance use disorders. Naltrexone is commonly prescribed to ME/CFS patients at very low doses, referred to as low dose Naltrexone or LDN. Per the Mayo Clinic, Naltrexone is prescribed at 50 mg daily for substance use disorder.

Bad crash from .06 mgRapid worsening at .2 mgSleep disrupted for 6 months after 1 week at .2 mg

Careful with the LDN. They say to start low and go slow…Every crash comes with a risk, I didn’t move for 13 hours, no one could wake me and when I finally did i couldn’t talk or get up for a while. It was a bad crash. I was so hopeful too. I really hope it works for u. Just wanted to give a warning - as always, never “push through” Edited to add: I started at 0.25mg. Gave it a second go 5 days later at 0.06mg… similar reaction. I will not be going for round 3, but my baseline has been down since early November.
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LDN serves as a great example as it demonstrates just how little of a (generally well tolerated) drug can cause extreme reactions. Taking less than 1% of the standard dose disrupts sleep for 6 months. Not being able to talk or move for hours precipitated by an even smaller dose!

Intolerance To…Everything

LDN is not uniquely troublesome for ME/CFS patients. Rather, it’s one of many reaction-causing medications, including multi-vitamins, probiotics, OTC painkillers, CBD, etc. It’s important to understand that there is nothing about the medications or supplements themselves that are causing extreme reactions. It’s simply not physiologically possible. This can be further illustrated by the vast array of benign substances sufferers report reacting to:

SEVERE reactions to everythingValerian root and CBDNot even fishoilCascading sensitivities

I have SEVERE reactions (ER, hospitalizations) from everything (antibiotics, thyroid medicines, painkillers, etc.). I had kids with no painkillers, dental work (drilling, scraping) with no numbing agents (even severe reaction to clove oil for Pete’s sake! My thyroid is trashed but they can’t even remove because of severe reactions to 5 different types of thyroid medications (natural and synthetic).
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The Feedback Loop

With such extensive reactions to subtherapeutic doses and supplements as benign as fish oil, it’s clear these are not classic allergic reactions or run-of-the-mill adverse effects of a supplement simply disagreeing with someone. Further, a patient reacting to one or two or a few substances follows, but reacting to essentially *everything? So what’s happening?

Patients are primed with beliefs, expectations, and fears coming from a few sources:

1. Common wisdom in the ME/CFS space is that patients are ultra-sensitive to medications, and any new substance must be extremely carefully titrated up. They believe their body is vulnerable and weak, able to be thrown off by anything.
2. Patients are often in a state of hypervigilance, monitoring their symptoms, acutely aware of any bodily sensations.
3. Stories are littered throughout the community describing severe reactions to even tiny, imperceptible doses of generally benign drugs.
4. The patient’s own past experiences further reinforce beliefs. A single reaction in the past serves as a felt reminder of the possible negative outcomes.

So before trying the medication/supplement, the groundwork is laid to intensely monitor the body and expect a reaction. After all, the stakes are high! It isn’t “try a medication that probably won’t work, or might make me feel eh, and then I’ll stop”. It’s “be extremely careful with this medication. It could cause a permanent worsening of my condition and there is no way to know.” That’s pretty intense! In this highly sensitized, hyper-vigilant state, it’s easy to see how the mind and body are primed to react.

Once the medication is taken, at the first sign of something wrong, a symptom that could be entirely generated from anxiety and the heightened state of awareness, like heart palpitations, dizziness, flushing, etc, the worst has been confirmed. A bad reaction is happening, as has happened in the past, as has happened to so many others. The mind fixates on the symptoms, perpetuating them, while the fear ratchets up, the possibility that the medication may do extensive damage and cause a crash only intensifying the cycle.

The feedback loop starts, as the patient’s beliefs around their intolerances are strengthened, informed by horrible experiences, a history of adverse reactions, and the collective beliefs and reassurance of the ME/CFS community that this is a “feature” of ME/CFS. As the list of supplements/medications they can’t tolerate lengthens, they become more and more hesitant of taking medications, believing ME/CFS has essentially caused their body to react to *everything.

The Explanation

Fundamentally, this is central sensitization, where the central nervous system becomes sensitized to stimuli. This phenomenon can lead to an exaggerated response to otherwise benign inputs, such medications and supplements, contributing to the perceived intolerance and sensitivity. In many cases, reactions and intolerances described by patients are not physiologically possible.

This also explains why some patients don’t experience sensitivities at all. (Or why they once had severe sensitivities, and no longer have any, despite no change in their ME/CFS.) The sensitivities don’t have any physiological tie-in to ME/CFS, the person’s physiology, or the substance itself - only to their expectations, beliefs, and experiences around the medication(s). It is entirely mediated by the mind. Of course, this excludes true allergies and side effects, which obviously happen to everyone. While the sensitivities reported by ME/CFS patients are very real and significantly impact their quality of life, it is a fundamentally psychosomatic phenomenon.

While this post focuses on sensitivities to medications and supplements specifically, these sensitivities are not at all limited to medications. ME/CFS patients report abnormal sensitivity to essentially every possible stimuli - light, sound, food, chemicals, environmental factors, sunlight, heat, smells, vibrations etc. These sensitivities are all best explained by central sensitization, not an underlying disease process.

What about MCAS?

Idiopathic mast cell activation syndrome (MCAS) is a condition characterized by the inappropriate activation of mast cells, which play a crucial role in the body's allergic responses by releasing chemicals such as histamine. Within the ME/CFS community, MCAS is frequently diagnosed (and self-diagnosed), as a comorbidity, explaining the sensitivities and reactions patients experience.

However, there is minimal evidence supporting the prevalence of MCAS in those who believe they have it. Multiple studies indicate that only about 2-5% of individuals suspected of having MCAS actually meet the diagnostic criteria for the condition. (ref, (opens in a new tab) ref (opens in a new tab)) Through the psychosomatic lens, this suggests that many suspected cases of comorbid MCAS can be better explained by the same psychosomatic underpinnings and central sensitization described above.