Does the flap of a butterfly’s wings in Brazil set off atornado in Texas?
Edward Lorenz
Unpredictability is a defining hallmark of complexsystems.
Neil Theise, Notes on Complexity
This post was prompted by an email I received from amigraine sufferer in Sweden.
“Dear Dr. Mauskop,
I wanted to share an unusual personal observation about microdoses of alcoholthat might interest you.
Some background: I am a 64-year-old woman with chronic daily migraine for over40 years. In recent years, I have developed cutaneous allodynia — tenderness ofthe scalp that builds up after several days of ongoing migraine, sometimes as adistinct band of tenderness stretching from the forehead back toward the neck.
One relevant piece of context: I have been essentially teetotal my entire adultlife, and I am also unusually sensitive to alcohol as a migraine trigger — evena small amount hidden in food or ”low alcohol drinks” given to me as ”nonalcoholic drinks” can reliably provoke an attack within minutes.
Given that sensitivity, what happened recently surprised me. Recalling a singleepisode about 40 years ago where a beer unexpectedly resolved the remainingheadache after days of migraine, I decided, out of desperation during a periodof persistent scalp tenderness, to try an extremely small “microdose” of rum —2 drops (roughly 0.06–0.1 ml of liquid, so a fraction of a milliliter of actualethanol), taken orally, mixed into a non-alcoholic drink.
Within 10 minutes, the scalp tenderness largely resolved. I have now repeatedthis observation multiple times over about two weeks, including on differentdays with different baseline migraine activity, and the effect has beenconsistent. On days with more persistent tenderness, I have repeated the 2-dropdose a few times, totaling perhaps 6–8 drops spread across a day — still apharmacologically negligible amount of alcohol overall. I have not noticed anyof my usual alcohol-triggered migraine response at these doses, nor any otherside effects. I have also noticed improved sleep on nights following thetenderness relief, and wonder whether the tenderness itself may be triggeringsome of my nocturnal migraine attacks.
I recognize this is a single case and an unconventional one, but I am a carefuland experienced self-observer. I wanted to tell you this in case you havepatients with similar symptoms and triggers like me, maybe someone else couldbenefit from this microdosing alcohol method?”
This woman has written to me several times before. She is anastute observer, and I don’t think her experience is due to the placebo effect.
I recently had a patient, a man in his late 30s, marriedwith two children and a high-pressure corporate job, who was having a persistentdisabling migraine for two years. He was admitted to an inpatient headacheprogram and had tried a large number of medications and treatments withoutrelief. He would get temporary relief from prednisone, and to keep his job, he continuedtaking it despite developing many side effects. As a last resort, I started himon methadone, and his migraine stopped; he was able to stop prednisone, lostthe weight he gained due to prednisone, became as productive as he was beforehis migraine started, and was able to enjoy his family, and they could enjoy beingwith him. The dose that dramatically relieved his suffering was 2.5 mg twice aday. A typical starting dose for methadone when treating pain is 5 to 10 mgevery 8 hours. Some patients end up on 60 mg a day or more. The usual dose totreat addiction is 60 to 120 mg a day.
I should add that the vast majority of migraine sufferers donot respond to opioid drugs and many feel worse from them, mostly due tonausea, sedation, and other side effects. Also, prescribing opioids longer-termrequires written consent and vigilance about the potential for addiction,serious side effects, and tolerance (needing ever higher doses).
Another example of a small dose of medicine causing profoundrelief of symptoms is low-dose naltrexone. Naltrexone is an opioid antidotethat is used to treat drug overdoses and alcohol addiction. The usual dose is50 mg a day. Low-dose naltrexone is started at 1.5 mg nightly, and typically itis increased to 4.5 mg nightly. The theory about its potential mechanism ofaction in fibromyalgia and other painful conditions is that this small dosesuppresses our endogenous opioid system. By the morning, this effect wears off,and the system rebounds and produces more endorphins, which relieve pain. Anotherpossible explanation is its effect on the brain’s glial cells (blocking Toll-likereceptors) with anti-inflammatory/immunomodulatory effects.
Lithium is prescribed for mania in bipolar disorder or for severedepression. We also use it for cluster headaches. The typical dose is 900 mg aday. This dose can cause serious side effects, and patients are closely monitored.Ina blog post last year, I mentioned research indicating that people living inareas with higher lithium levels in drinking water have lower rates ofdepression. Lithium deficiency in the brain is thought to accompany Alzheimer’sdisease. Lithium in a small dose of 5 to 10 mg a day is available withoutprescription as a dietary supplement.
Melatonin is often taken to help with sleep. Supplementmakers typically promote a dose of 3 mg, and some people take up to 10 mg.However, you may get better results with 0.3 mg (300 mcg). If you wake up inthe middle of the night, you may want to take 300 mcg in an extended-releaseformulation.
Doxepin is an old antidepressant that is dosed at 75 to 150mg a day. However, for insomnia, as little as 3 mg is sufficient.
Many people have heard about microdosing psychedelicmushrooms. A renowned author, Ayelet Waldman, describes her recovery fromprofound depression in a memoir, A Really Good Day: How Microdosing Made a MegaDifference in My Mood, My Marriage, and My Life.
And, of course, there is microdosing GLP-1s, which somepeople find very helpful not just for weight loss but for other symptoms as well.This may be due to an anti-inflammatory effect or some other unknown effect ofthese drugs.
I have also seen patients who responded to very smallamounts of various other prescription drugs. Many of these people report beinghypersensitive to drugs. A small dose works well for them without the side effectscaused by typical dosing.
I should mention homeopathy, since it also uses highlydiluted extracts of plants, minerals, or animal substances. Homeopathy positsthat the more diluted the substance is, the better it works. The dilutionprocess involves vigorous shaking that supposedly changes the structure of thewater the product is dissolved in. However, after all the dilutions, the activeingredient usually is not detectable. This is very different from usingminuscule but detectable amounts of drugs and herbal products, and in myopinion, is a good placebo. Placebo has its role. It is considered unethical toprescribe a placebo without informing the patient that they are not getting anactive substance. Interestingly, in one study at Harvard, patients withirritable bowel syndrome who were told they were getting a placebo still feltbetter from it. I think homeopathic remedies are ethical placebos. The rarecases where I recommend it is for people who are very anxious about a headachegetting out of control if they don’t take some medicine. They end up taking over-the-counteror prescription drugs every few hours, risking serious side effects. Thesedays, every pharmacy has a rack of homeopathic remedies for every possible symptom,including headaches and migraines. Mentioning your specific symptom on the labelcan certainly enhance the placebo effect.
