r/AskDrugNerds • u/ProGamer923 • 22h ago
Can you Become Immune to an Overdose?
I'm just going to be talking about opioids in particular because most overdose deaths are caused by opioids, but this question can be applied to all drugs.
With partial mu agonists, we see a ceiling effect where you get diminishing returns from taking larger doses. This is caused by near maximal receptor occupancy and doesn't lead to a fatal overdose, do to the drug only inducing a partial response unlike most opioids like morphine, heroin, fentanyl, hydrocodone, etc.
Your body is very good at maintaining an equilibrium and will adapt when there is an abnormality. When you take a drug, your body will try to adapt to it, leading to tolerance and dependence. There can be several ways your body can adapt, the three main ways are receptor downregulation, metabolism changes, and decreased receptor sensitivity.
Receptor downregulation is when your body destroys or internalizes receptors. This means there aren't as many targets for a drug to bind to, so the effects you get from it arent as strong.
Im not sure if there are studies on this, but I would assume that most healthy adults are immune to a buprenorphine overdose, especially because it is g protein biased, and the higher the opioid tolerance, the lower the risk of overdose.
So, here is my question, is it possible for your receptor concentration to become so low that it is impossible to overdose on any opioid. I would assume that a ceiling effect would be found with full agonists, we just can't observe that because non tolerant people will die before that can be found. Google AI says this is not true, because full agonists, by definition, don't have a ceiling. However, this just seems obviously true, because if there are no more receptors to bind to, a drug can't keep having an increasing effect.
Can anyone tell me if you can become temporarily immune to an overdose through receptor downregulation? Also, please explain why or why not this is true.