Microdosing doesn’t do much more than a placebo

Microdosing of psychedelic substances such as LSD and psilocybin has been widely promoted in recent years by providers who claim it can do a lot. However, most scientific studies show that the said doses that fall under microdosing do not work significantly better than a placebo. Also watch the video below that talks about the minor effect of microdosing.

Microdosing as placebo explained

Everyone has MAO (monoamine oxidase) in the body. MAO is an enzyme found mainly in the mitochondria of cells, particularly in the liver, kidneys, gastrointestinal tract and the 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 of the breakdown is to inactivate these neurotransmitters, as well as psychedelics, by making them react with oxygen faster than normal.

After ingesting, say, 1mg of psilocybin, which is considered microdose, it may be that the capacity of your MAO enzymes is large enough to trap this 1mg within a few minutes and react with oxygen rendering it ineffective. From that microdose, perhaps nothing psychoactive at all can enter the brain. Should your brain at the first microdose of 1mg do receive psilocin then it may be that your body is producing more MAO and the following microdose will no longer work.

So the enzyme MAO throws a spanner in the works when it comes to microdosing effectively.

So why does macrodosing work better?

If you think of the MAO enzymes as the first catch basin or bucket of 1-2mg and you throw in only 1mg of psilocybin, this basin does not overflow. Only if you exceed the capacity of your MAO enzymes in one go does that container overflow and can head for the brain. The minimum amount you need to experience effects of psychedelic substances is called the threshold level. If you start macrodosing then you always exceed that treshold level and you do start using the effects of psilocybin, for example. With a high dose of psilocybin you do need more time between sessions.

A high microdose or low macrodose?

If you start taking more to microdose then you are moving toward a low macro dose. This can help you still notice something of the psychedelic substance. After a number of higher microdoses you will notice that the effect will disappear. The body will produce more MAO, which will increase your threshold level. One of the things you can do is to set a period of one to two weeks without using psychedelics. After this period the MAO level will be back to normal.

So does old-fashioned microdosing work after all?

We know that absorption of tryptophan, the building block of serotonin, is difficult and barely enters the brain. Psilocin, however, enters the brain very easily if you take into account the treshold level. Now tryptophan and psilocin are closely related since tryptophan is the precursor to psilocin. It could be that you even convert oxidized psilocin in the brain to a building block for serotonin, which in turn could be positive for mood in the long run. This could then explain the long-term positive effects without microdosing having much short-term impact.

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