Midodrine does have no stimulant effects whatsoever, and still, it can abolish certain instances of “fatigue” and brain fog. Sometimes and for some people, bouts of weakness, lethargy, and brain fog are due to hypotension (low blood pressure) – especially after intense exercise.
Whatever the case, people are tempted to drink coffee or take other stimulants even though in the case of low blood pressure being the issue, it may be more effective to use vasopressors, such as midodrine or etilefrine, instead of central nervous system stimulants.
Personal experience
In my early twenties, I sometimes used to have low blood pressure after heavy cardio workouts. It took a while for me to realize that this kind of exercise-related “fatigue” was not true fatigue but just hypotension.
I experimented with increasing my water & salt intake, fludrocortisone (an analog of aldosterone), and vasopressors. I liked midodrine the most – especially because I could use it very selectively. For example, taking 2.5mg of midodrine before a run would eliminate the light-headedness, “feeling like shit”, or weakness, that sometimes followed for hours after.
At this dosage, side effects were non-existent. As I adapted to a more consistent workout schedule, this bothersome side effect went away, and I stopped using it. However, I found it helpful at the time.
Interestingly, I found that on days I microdosed psychedelics, exercising heavily did not affect my energy levels. LSD or psilocybin are 5HT2A receptor agonists, and it turns out that 5HT2 receptors are widely distributed throughout the cerebral vasculature where they cause vasoconstriction (which is also the mechanism of action of the triptans – drugs that are used in the treatment of migraines).
Another helpful agent in that regard was clenbuterol (a beta2-agonist), however, whenever I used it, it killed my sleep. Some people also (ab)use it as a fat-loss agent, though it is quite harsh on the heart.
How it works
Midodrine activates alpha1-adrenergic receptors that are located on small arterioles throughout the body. Activating these receptors leads to whole-body vasoconstriction, which increases vascular tone, therefore systemic peripheral resistance, and therefore blood pressure.
Midodrine is unable to cross the blood-brain barrier and therefore does not exert (unwanted) central effects such as nightmares, which can be caused by alpha-agonists. Of note, psychiatrists sometimes use alpha-1 receptor antagonists such as doxazosin in the treatment of frequent nightmares.
Etilefrine is a similar drug that is mostly available in Europe. Etilefrine not only works on alpha receptors but also agonizes beta receptors and therefore has slightly more cardiotonic and stimulant effects.
Why does Bryan Johnson have low blood pressure? And why is low blood pressure so common in health-conscious individuals?
Next to low salt intake, there are other reasons that cause low blood pressure in health-conscious individuals: undereating and/or hypoleptinemia.
This is the primary reason behind Bryan Johnson having a blood pressure of 102/61mmHg. While he brags about it and considers it a sign of “perfect” health, this is a sign of terrible vitality due to his adrenergic tone bordering on non-existence (which is also the primary reason behind his “perfect” sleep scores). Most people would feel like absolute shit with a sympathetic nervous system activity that low – and I would bet all of my money that he does too.
The lack of either calories, insulin, or leptin (all partially independently) signals to hypothalamic “energy neurons” (mostly POMC and AgRP neurons but also others) that there is an energy shortage. These neurons in turn control sympathetic nervous system tone via direct connections to various nuclei in the brain stem. Furthermore, these neurons also control all of the major pituitary hormonal axes (HPA, HTA, HPT), and their target hormones (cortisol, testosterone and estradiol, triiodothyronine) have sizeable effects on adrenergic tone.
When “starvation mode” sets in, the combined effect of a direct reduction in SNS activity (more important) and a drop in various hormones (less important), makes many health-conscious individuals feel weak and light-headed. This is also the reason why people start to feel weak when dieting.
Anecdote time. A friend asked what he could do to have more energy. I told him to elevate his caloric intake by 400 calories. A month later he told me that he realized that for the first time in 10 years, he stopped getting lightheaded after standing up. Sometimes it is not a fancy drug that is needed but simply giving the body the energy it needs.
Other experience reports
For a general discussion of stimulants, and links to accounts of stimulants I have experimented with, click here.
For a full list of experience reports, including non-stimulants, click here.
Sources & further information
- Anecdotes: Drugs.com – Midodrine
- Scientific review: Preventing and treating orthostatic hypotension: As easy as A, B, C
- Scientific article: Midodrine for orthostatic hypotension
Disclaimer
The content available on this website is based on the author’s individual research, opinions, and personal experiences. It is intended solely for informational and entertainment purposes and does not constitute medical advice. The author does not endorse the use of supplements, pharmaceutical drugs, or hormones without the direct oversight of a qualified physician. People should never disregard professional medical advice or delay in seeking it because of something they have read on the internet.