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Do you have to build up tolerance to euphoria?

Dreynar

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Do you have to develope tolerance to antidepressant effects of DRIs?

I asked something similar in a similar thread, but I didn't got satisfactory answer so I want to take it from another angle.

I'm curious about Dopamine Reuptake Inhibitors and why more drugs of that class are not developed for depression and other purposes. The answer that I've got is that in the early time of psychiatry people thought that amphetamin is an anti-depressant and because of consant tolerance growth and need of dosage increase they resign from it. But DRIs are not like amphetamine bacause you don't really build up tolerance to them, usually. For example Ritalin is a drug that can be used for years without (almost) any tolerance. The only problem is that this drug is too egdy and couse anxiety. It's nothing like meth or cocke.

But I know there are other selective DRIs that are euphoric like Desoxypipradril and others.

So my my question is: Do you build up tolerance to the drug or to the Euphoria coused by a DRI when using it everyday?

Does anyone used such drugs like Desoxypipradril or others euphoriant DRIs everyday? If you don't develope tolerance to the drug but to euphoria do you develope than complete tolerance to euphoria? Is it possible to take something like Desoxypipradril and have anti-depressant effects from it for years?
Or if you develope partial tolerance to euphoria can such kind of drug be a benefit for depression even if partial tolerance has developed?
 
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Some reports state that at low doses, some of the "magic" is kept, but that's a low amount of it.

What stimulants do consistently is make it easier to keep one engaged with something, and keep one awake. This is whether it's ritalin or meth. Raise the dose, and you raise the incident of side-effects, but you just get to keep (oftentimes not all) the euphoria. I'd imagine what they do with chronic dosing is increase the catalytic reaction to norepinephrine and epinephrine.

If you think about it, this is an adaptation.

Tryptamines work is odd manners. For instance, both a 5-Ht2a agonist and antagonist dowregulates 5-HT2a receptor expression. And 5-ht3 is an ionotropic receptor, the only one of the serotonin sub-regions.
 
yeah you can build tolerance to euphoria. i can never get the same euphoria from heroin or cocaine as before since ive abused them both but i guess thats ok, natural normal response avoiding them i guess
 
I think homeostatic changes will occur while one's brain is in a state the produces euphoria, this will make it harder to achieve the euphoria next time.

As an example, lets say that euphoria requires (vast oversimplification)

1. Increased glutamate release in areas 1/2/3
2. Increased dopamine release in areas 4/5/6
3. Increased serotonin release in areas 7/8/9

4. Decreased glutamate release in areas 10/11/12
5. Decreased dopamine release in areas 13/14/15
6. Decreased serotonin release in areas 16/17/18

If such a pattern of neurotransmitter release (or you could map it onto ions instead of transmitters if you like) results in receptor activation/deactivation that leads to the integrated network activity of the brain that correlates to euphoria, then tolerance will be gained no matter the drug or source of the euphoria because e.g. the receptors in areas 1-9 will downregulate and the receptors in areas 10-18 will upregulate, therefore making it harder for the respective effects at those receptors to produce that integrated network state of brain activity.

It just might be that some mechanisms that lead to such integrated network activity (releasing agents/amphetamines) have biochemical effects that are more likely to induce tolerance, compared to say natural rewards
 
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But, is it possible to keep some of the anti-depressant effects (magic) for a longer period of time? Because when I took Ritalin everyday/couple times a day I always felt better in the begining. Later it less than in the begining but even after months of taking this drug, the feeling in the begining was always there. The only problem is that I hate this drug because after this feeling good (which lasted 40-60 min.) I got anxiety and paranoia.
 
Typically euphoria is always felt to some degree when drugs are administered very quickly (e.g. insufflation or I.V), the brain just may not be able to compensate quick enough to numb the euphoria.
 
Typically euphoria is always felt to some degree when drugs are administered very quickly (e.g. insufflation or I.V), the brain just may not be able to compensate quick enough to numb the euphoria.

There are consequences to increased dopamine that may start to take over around that 60 minute mark, and maybe are competitively inhibiting the desirable effects.
 
But is there any drug, that would give this awesome anti-depressant effects for a longer period of time?

Never took it but from what I read the most intresting effects are from Desoxypipradril. It's an ultimate anti-anhedonia drug, but it also works for ADHD, although it's not very stimulative.

So is it possible to create a drug of that effects, but something that would be safer to use?
 
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