Do all psychoactive substances induce tolerance eventually?

For that matter, do all receptor-binding substances induce tolerance eventually?

It seems certain that different substances take different amounts of time to produce tolerance. Is there a pattern here? Do all receptor antagonists take similar amounts of time, or does it vary by receptor type?

(How do we know medications are not a zero-sum game?)

  • $\begingroup$ It also depends on concentration. If you're not over-stimulating the cell, tolerance won't be induced. Many patients do quite well on the same dosage of psychoactive drugs for years. Remember, the goal with drug therapy is to make up for the brain's imbalance in neurotransmitters, not to flood the system with them. That's what addicts do. $\endgroup$ – MattDMo Apr 15 '16 at 2:02

In general receptor-binding substances cause an "overflow" of your own already produced neurotransmitter. Your brain reacts by reducing the receptors. Also your own neurotransmitter production may be down-regulated by negative feedback. When you take away the "medication" afterwards, there are less receptors together with less neurotransmitter, causing withdrawal symptoms.

When you put in more substance in a control loop, there will always be some sort of "adaption" in order to reinstate a new balance (1). If you take in just enough drugs to balance the neurotransmitter-receptor system in a way, that the signal transduction in terms of nerve pulses remain the same, you have reached a tolerance stage, but not an effect stage. Still, medication is not "useless", since not all receptors will be dissipated. It is a matter of dose rate to increase the nerve pulses; once there is relatively more neurotransmitter (2) available than before medication, one should obtain a constant effect or an effectively altered control loop balance.

(1) https://books.google.at/books?id=z9TUch7m144C&pg=PA34&lpg=PA34&dq=receptor+regulation+up+down+neurotransmitter+drugs&source=bl&ots=2-4GRChqBi&sig=6e0YM-UrfgnMlw6e-rXR2Or7Qxc&hl=de&sa=X&ved=0ahUKEwixr_D25ZDMAhWB7RQKHcF9DqYQ6AEIHzAA#v=onepage&q=receptor%20regulation%20up%20down%20neurotransmitter%20drugs&f=false

(2) http://www.merckmanuals.com/professional/clinical-pharmacology/pharmacodynamics/drug-receptor-interactions

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  • $\begingroup$ Please add some references to support your claims. Unsourced answers may be challenged and removed. $\endgroup$ – MattDMo Apr 15 '16 at 13:47
  • $\begingroup$ So, in other words: "No, medications are not a zero-sum game, as long as the dosage is such than an effect stage is reached, rather than a tolerance stage." $\endgroup$ – DJG May 23 '16 at 5:01

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