Whether you follow Fadiman's protocol, Stamets' protocol, or your own, there is a consensus that taking breaks during your microdosing practice is essential. The length of your microdosing period and the length of breaks from microdosing are still debated. However, one thing is known for sure, and that is that LSD and psilocybin mushrooms build tolerance if you use them successively, for days in a row, hence the break between mircrodosing or “ON” days.
Tolerance: Your body adapts to the continued presence of a substance, hence one will inevitably needs to intake more to generate the same effect in the future. Did you know that we build tolerance because our bodies love to stay balanced, and will adjust to anything we consume.
Did you know? We build tolerance because our bodies love to stay balanced. They will adjust to anything
Cross-tolerance Between Classical Hallucinogens
Psilocybin mushrooms, LSD, and mescaline affect your neuro-receptors in very similar ways in that they all have an affect upon our serotonin 5-HT2A receptors. The relationship of classical psychedelics with the 5-HT2A receptors produce cross-tolerance for any of these substances. In other words, when your body develops a tolerance to psilocybin, the effects of LSD and mescaline will also be weaker. However, psychedelics like DMT in ayahuasca don't work in quite the same way on your brain.
The Reset Time
You can quickly build up a tolerance to classic psychedelics, but the good news is that you also lose it just as quickly. For this reason, breaks are recommended and many people suggest that the longer the OFF period, the more intense the effect on your days ON.
Microdosing for months at the time is not unheard of as you want to do it long enough for your brain to rewire. However, you also should listen to your body and take breaks when it feels right.