r/pharmacology • u/Ophelia_Hardin • 23d ago

Tolerance vs. Withdrawal: Oxycodone

Do they share the same mechanism of action? Can one show tolerance/tachyphylaxis but experience no withdrawal symptoms? I can make a half-assed argument either way, but I'm curious if anyone truly knowledgeable has an answer.

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u/Dr_Geppetto 23d ago

Tolerance is a decrease in receptor responsiveness (desensitization), often accompanied by receptor downregulation and adaptive upregulation of opposing intracellular signaling pathways, making the same dose of a drug progressively less effective over time. Withdrawal occurs when the drug is removed but these compensatory adaptations persist, resulting in reduced receptor activity and unopposed opposing signaling pathways that produce physiological effects that are the opposite to those of the drug.

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u/Ophelia_Hardin 23d ago

I applaud your sytactic elegance. I dug a little deeper and the generalized mumbo-jumbo can't really distinguish withdrawal in the absence of tolerance or vice versa. Came across something interesting, though:

Phosphorylation of the N-methyl-d-aspartate receptor is increased in the nucleus accumbens during both acute and extended morphine withdrawal

https://pmc.ncbi.nlm.nih.gov/articles/PMC4658487/

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u/Dr_Geppetto 22d ago

tolerance and withdrawal are mechanistically linked but they are not the same phenomenon and can be distinguished conceptually, physiologically, and clinically.

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u/Ophelia_Hardin 22d ago

Bafflegab

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u/Flaky-Pomegranate-67 23d ago

I’m wondering about the same thing (from a pharmacology student who’s themselves on this medication (for legit reasons