Microdosing does little more than a placebo
Microdosing psychedelic substances like LSD and psilocybin has been heavily promoted in recent years by providers who claim it can have significant benefits. However, most scientific studies show that the doses described as microdosing are not significantly more effective than a placebo. Also watch the video below, which discusses the limited effect of microdosing.
Microdosing as a placebo explained
Everyone has MAO (monoamine oxidase) in their bodies. MAO is an enzyme found primarily in the mitochondria of cells, particularly in the liver, kidneys, gastrointestinal tract, and central nervous system, such as the brain. There are two types of MAO enzymes, called MAO-A and MAO-B, and they are involved in the breakdown of various neurotransmitters such as serotonin, dopamine, and norepinephrine. The first step in the breakdown process is inactivating these neurotransmitters, including psychedelics, by making them react with oxygen more rapidly than normal.
After taking, for example, 1mg of psilocybin, which is considered a microdose, your MAO enzymes may be able to absorb this 1mg within a few minutes and react with oxygen, rendering it ineffective. This microdose may not release any psychoactive substances into the brain. If your brain does receive psilocybin with the first 1mg microdose, your body may produce more MAO, rendering the subsequent microdoses ineffective.
So the enzyme MAO throws a spanner in the works when it comes to effective microdosing.
So why does macrodosing work better?
If you view the MAO enzymes as the first reservoir or bucket of 1-2mg and you only add 1mg of psilocybin, it won't overflow. Only if you exceed the capacity of your MAO enzymes in one go will the reservoir overflow and reach the brain. The minimum amount you need to experience the effects of psychedelic substances is called the threshold level. If you macrodose, you'll always exceed this threshold level and will start to take advantage of the effects of psilocybin, for example. With a high dose of psilocybin, you'll need more time between sessions.
A high micro dose or a low macro dose?
If you increase your intake to microdose, you'll be moving towards a low macrodose. This can help you still feel some effects of the psychedelic substance. After a few of these higher microdoses, you'll notice that this effect disappears. The body starts producing more MAO, which increases your threshold level. One thing you can do is take a one- to two-week break from psychedelic use. After this period, your MAO levels will return to normal.
Does old-fashioned microdosing work after all?
We know that tryptophan, the building block of serotonin, is difficult to absorb and barely reaches the brain. Psilocin, however, enters the brain very easily if you take the threshold level into account. Now, tryptophan and psilocin are closely related, as tryptophan is a precursor to psilocin. It's possible that even oxidized psilocin is converted into a building block for serotonin in the brain, which could then have a positive effect on mood in the long run. This could explain the long-lasting positive effects without microdosing having much of an impact in the short term.
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