Medical Can an addict ever reach their original high?

[NotASmurf]

Hey all, we know when someone does an action they like the first time (receive a sweet at 4pm or take heroine) then their dopamine rises the first time, but each time it happens afterwards less and less dopamine is released, which is why a drug addict will never feel as great using a drug as the first time, they often increase the dosage, to try chase the original high,
my question,
if you do the action that gives the dopamine reward, then keep repeating the action with same intensity, then each time less is released, but if the person increases intensity of action (ie drug dosage) then will the dopamine net "decrease" less, because it is lowered by an amount, but the increased dose would increase it again (citation needed :P ) the question, is, can they ever reach the intensity of the first high by increasing a dose to a certain amount, A) taking overdose into account B) not taking it into account.

Any help appreciated.

 

[Simon Bridge]

The pleasure of a high (or anything) is multifaceted. Context is important.
All other things remaining equal: most addicts recapture the level of euphoria or even exceed it, by increasing the dose. It is one way accidental overdoses happen.

The overall quality won't be the same because "all other things" do not, and can not, remain equal: your first time, you did not know what was going to happen ... so you had an additional effect from the natural response to the unknown, doing something a bit taboo etc. When you are talking about the intensity of the high, you are usually taking into account many uncontrolled, and uncontrollable, variables. Even the colour of the walls can make a difference.

This also means that you may be able to exceed the euphoria of the first experience on a lower dose: depending on that first experience. Think of the first time you had sex, compared with subsequent times.

(Note: a lot of the research on highs was in the 60's and 70's ... there's probably been some more recently but most focusses on establishing medical doses.)

 

[DiracPool]

the question, is, can they ever reach the intensity of the first high by increasing a dose to a certain amount

I don't know, let's give it a try!

Nope, didn't work.

my question,
if you do the action that gives the dopamine reward, then keep repeating the action with same intensity, then each time less is released, but if the person increases intensity of action (ie drug dosage) then will the dopamine net "decrease" less, because it is lowered by an amount, but the increased dose would increase it again

Well, I'm not too up to date on this, but when I was in school, the mechanism of habituating to the effects of an exogenously introduced drug such as morphine or cocaine was not so much an attenuation of the release of presynaptic vesicles containing dopamine as it was the "downregulation" of postsynaptic dopamine receptors. This means that the more dope you pour into your system the fewer receptors are going to be there to receive and respond to it. This is simply a homeostatic mechanism designed to maintain equilibrium. So, while in the short run you may be able to keep up with the downregulation of your receptors by continually upping the dose, at the end of the day it's a losing battle.

It's not all about downregulation per se, but that;s an accurate model in general to tell you what's going on. There's multiple mechanisms psychoactive drugs use to maintain a high concentration of the chemical in the synaptic cleft, which directly accounts for the "high" a user experiences. For example, some drugs do act to flush the neurotransmitter out of the presynaptic vesicles; I think ecstacy works this way to flush out serotonin. Some drugs block the re-uptake of the chemical into the presynaptic membrane, I think this is how SSRI's work, in general. Some drugs work through second messenger cascades to vary the membrane permeability of neurons. Other drugs like the opiates (heroin) only act secondary on dopamine pathways while other chemicals work more directly, etc.

Again, I'm just reading this off from memory, but at the end of the day it's the effect of the drug on the postsynaptic density of the target receptors that get homeostatically regulated that prevents you from getting that initial high again and why you are forever "chasing it" from thereon.

 

[ebos]

That's why most opiate addicts eventually die of an overdose. Cocaine is even worse. The reason for it is already mentioned above. Less and less receptors are available for the opiates to latch onto. The endorphins no longer have a home to go to. That's why addicts get so sick when they stop. They've just replaced a natural system with an artificial system to the detriment of the natural one. The older the addict, the longer the withdrawals. Young people can grow back the receptors in 3 or 4 days while an old addict (a very rare specimen, I might add) can take 3 or 4 months. I've actually heard that when a person gets too old the receptors never recover so the addict has to use till they die.

 

[Global Cooling]

Would L-dopa increase a users high?

 

[Pythagorean]

The alternative to a higher dosage is moderation, which would allow some homeostasis to be restored before subsequent drug delivery. Though, I suppose at that point it is no longer an addict we are talking about.

 

[NotASmurf]

Thanks all,