I originally posted this in R/askdrugnerds but got zero response so I thought I'd try here...

I know there are a myriad of factors that will affect down regulation, but for arguments sake let's consider this a Fermi Estimate. I also know there are a lot of other factors such as long term cognitive problems and decreased risk aversion to name just two so please don't go into any of those other problems. I want to focus just on down regulation of receptors involved in the positive feelings side of the recreational chemical usage.

Let's assume you are rotating through many the basic chemical groups (psychedelics, MDMA every 8 weeks, cocaine, adderral, ketamine, weed, kratom, GHB, etc.) taking only one of these non-alcohol chemicals a night, but doing something both Friday and Saturday, also drinking about 4-6 shots of hard liquor as shots or in mixers on Friday and Saturday, and drinking a couple beers or glasses of wine 3-4 times a week (not on the weekend).

We are talking fairly normal amounts of each chemical. For example, 4 25-35 mg lines of cocaine or 150 mg of MDMA or 100 mg of ketamine insufflated. Also, assuming chemicals have been tested and are actually what they are with normal to minimal cuts.

What range do you think would cause noticeable (to your general feeling of well being) down regulation of the receptors to where you haven't recovered enough and you don't feel as good as you could because you are not starting from ground zero, or whatever you want to call it even though by taking drugs at all you technically don't have a perfect ground zero anymore due to permanent long term chemical changes in your brain?

Obviously doing most of these chemicals one time every decade will not cause any significant negativity for you. Obviously doing them every day, all week long would cause some permanent irreversible damage. So, for the average person, doing a decent rotation through the various chemicals noted above, how often would you feel comfortable doing them?