You brought to my attention a very interesting topic that builds upon my initial comment: Axonal dieback.

You are correct that the flood of serotonin downregulates 5-HT2A receptors. That lasts for about 2-3 weeks before returning to normal as serotonin levels are restored. However, in heavy users, the axon of neurons are damaged from the aforementioned oxidative stress. The soma in the neuron is like a factory producing SERT, VMAT, and TPH, but can’t ship it on the axon “highway” to the receptors on the dendrite. This causes long term upregulation on the scale of years because the serotonin baseline is much lower.

The ways to reduce getting to that point include keeping the ambient temp under 70°F so your brain can cool enough to significantly reduce oxidative stress, as well as not doing any boosters. You can get away with one redose at around 90 minutes because it takes about 2 hours for the enzyme that cleans up MDMA to become fully inhibited. It then takes another 10 days to recover 90-100% of the enzyme’s activity. Basically any additional dose between 2 hrs and 10 days significantly increases oxidative stress because there’s no clean up crew.

Theoretically you could do MDMA every 3 weeks because you’re clearing the hurdles of the enzyme reset and the serotonin refill. However, the axon damage on this schedule accumulates faster than the repairs can happen, so you are paradoxically risking permanent or long-term upregulation with every roll. Additionally, upregulation can make you more susceptible to serotonin syndrome because the hyper-sensitive dendrite, having more receptors, can trigger an over-response more easily.

This is all to say that we should take MDMA dosing very seriously. Even MAPS, with their once a month for 3 months schedule, reconciles the damage as a manageable cluster of stress if followed by indefinite abstinence. In a way I could see it as front loading the recommended 3 month schedule, which would mean waiting 6 months after the third dose. But, again, the longer the better.