Pharmacology Yet another adderral thread - question regarding tolerance, euphoria and retaining efficacy

[Juicewrldfan]

Just had a thought- They say if you don’t experience euphoria anymore that it doesn’t mean the medication isn’t treating the symptoms.

What is the biological process responsible for this? What I mean is how is it that a drug can still treat symptoms but not retain euphoria? (which I don’t want euphoria btw slippery slope and all that)

I understand how tolerance is about homeostasis but how does one become tolerance to the euphoria but not the targeted symptoms being treated? It’s really just a curiosity.

 

[Rectify]

When I used to take Adderall as prescribed (1 × 30 mg pill per day), it only worked for an hour every day. Why? Your body just gets used to it. BUT if and when I had 90 or 120 mg and had not used for 3 or 4 days, the euphoria and stimulation and that feeling of being ALIVE would hit me like a ton of bricks.

 

[Juicewrldfan]

When I used to take Adderall as prescribed (1 × 30 mg pill per day), it only worked for an hour every day. Why? Your body just gets used to it. BUT if and when I had 90 or 120 mg and had not used for 3 or 4 days, the euphoria and stimulation and that feeling of being ALIVE would hit me like a ton of bricks.

Yeah I’m trying to avoid euphorias pull…

I have severe adhd complicated I strongly feel by low T. I got back my results today and I have 225 and it should be 300 and that was fasting and I’m the morning when I think T is highest in men hence morning wood.

I just found it interesting that you can treat something and it not become tolerant to the targetted symptoms being treated but the euphoria is gone…

I’m extrapolating what you said. You are saying that it’s just we become used to the feeling?

 

[Rectify]

Amphetamine is a releaser of dopamine, norepinephrine, and adrenaline. But if you take it every day at subtherapeutic dosages, your neurons become depleted of those neurotransmitters. However, if you give them 3 days to recuperate, you are all Gucci again.

 

[GetMeOutOfThisCRAP]

I know it is a different substance, but for example opioids like morphine tablets still continue to be effective for pain relief even long after the user "can't" or "doesn't get high anymore." Substances aren't purely about blasting dopamine or endorphins out of your system for euphoria.

Even after the initial adderall effects perhaps 45 minutes to an hour after blasting the brain's dopamine out of the receptors, there's always a little bit more dopamine left (unless you're using meth or something for example which heavily depletes the dopamine receptors way more effectively than adderall). The adderall continually releases that dopamine supply still retained in the receptors hours after the euphoria has fully receded. Tolerance isn't an exact science. My best answer would be that euphoria is an indication of a good amount of dopamine being released from the receptors. Even if your tolerance to adderall sky-rockets from heavy abuse, the drug would still continue to work focus wise because the brain never really loses all of its dopamine within the receptors--just huge supplies of dopamine that produce "euphoria."

 

[Juicewrldfan]

I know it is a different substance, but for example opioids like morphine tablets still continue to be effective for pain relief even long after the user "can't" or "doesn't get high anymore." Substances aren't purely about blasting dopamine or endorphins out of your system for euphoria.

Even after the initial adderall effects perhaps 45 minutes to an hour after blasting the brain's dopamine out of the receptors, there's always a little bit more dopamine left (unless you're using meth or something for example which heavily depletes the dopamine receptors way more effectively than adderall). The adderall continually releases that dopamine supply still retained in the receptors hours after the euphoria has fully receded. Tolerance isn't an exact science. My best answer would be that euphoria is an indication of a good amount of dopamine being released from the receptors. Even if your tolerance to adderall sky-rockets from heavy abuse, the drug would still continue to work focus wise because the brain never really loses all of its dopamine within the receptors--just huge supplies of dopamine that produce "euphoria."

Medically, I don't know for sure but pretty sure serotonin syndrome is a very dangerous condition that occurs when the brain is fully absent of dopamine and endorphins. I'd imagine one would succumb to serotonin syndrome if they blasted 100% of the dopamine out of their system. I have no idea if this is correct lol.

Oh so dopamine kinda modulates serotonin…

Now that I think of it I think my Dr once told me they all modulate each other. When one increases another does or goes down I forget probably depends on medication

 

[GetMeOutOfThisCRAP]

Oh so dopamine kinda modulates serotonin…

Now that I think of it I think my Dr once told me they all modulate each other. When one increases another does or goes down I forget probably depends on medication

I have no medical science background lol but I'll look into it. They are definitely all related, though. Seritonin, endorphins, and dopamine.

I wonder if stimulants release endorphins as well similar to opiates. That would explain some of the euphoria some people experience from stimulants. Regardless, when it comes to euphoria you're specifically locating the "high" and pleasurable aspect of any drug. Whether the drug functions for its intended purpose or not is an entirely different story. The feelings of euphoria do not last forever. Eventually your brain releases less dopamine from the receptors when your stimulant tolerance is so high. Adderall still releases at least some dopamine no matter what tolerance you're at (which is why the drug continues to work even if one experiences zero euphoria). Some actually do not receive any euphoria from stimulants whatsoever though even on zero tolerance.

 

[Juicewrldfan]

So- adderral was a bad idea…told my doctor I do t want it anymore because of risk of abuse but still have about 30 IR but don’t have the heart to flush them but I was thinking about just putting them up for a rainy day. I don’t need to tho…idk..

Been up all night. That shit didn’t turn out as I hoped. I knew it was gonna turn into an issue. I mean I’m not like addicted to where I can’t stop just addicted to the point I may burn thru 60 pills I two days…dunno how unless I hid more I. Some other places. I hid them all around the house

But man this sucks for so many reasons. O e I relapsed. Two I feel so guilty about it…cant believe I put myself in a position like that again like stupid…and my therapist wanted me to and my wife and I should have know better. Amphetamines suck really. They are too much umph…take the drivers seat like and yeah no sleep need to get some sleep bad but all I got is weed really meh a lil amanita and kratom and suboxone. I’ll sleep when I finish coming down I guess. God I hate amphetamines come downs hate the sadness at times and then the paranoia at times

 

[Juicewrldfan]

So- adderral was a bad idea…told my doctor I do t want it anymore because of risk of abuse but still have about 30 IR but don’t have the heart to flush them but I was thinking about just putting them up for a rainy day. I don’t need to tho…idk..

Been up all night. That shit didn’t turn out as I hoped. I knew it was gonna turn into an issue. I mean I’m not like addicted to where I can’t stop just addicted to the point I may burn thru 60 pills I two days…dunno how unless I hid more I. Some other places. I hid them all around the house

But man this sucks for so many reasons. O e I relapsed. Two I feel so guilty about it…cant believe I put myself in a position like that again like stupid…and my therapist wanted me to and my wife and I should have know better. Amphetamines suck really. They are too much umph…take the drivers seat like and yeah no sleep need to get some sleep bad but all I got is weed really meh a lil amanita and kratom and suboxone. I’ll sleep when I finish coming down I guess. God I hate amphetamines come downs hate the sadness at times and then the paranoia at times

Hot damn aside from nutrition (got that covered, hydration and not taking anymore how can I help this come down. More intense than other times. Not sure if maybe weed. People on Reddit were swearing my trazadone but I thought that wasn’t used alot cause the metabolite but someone else said that the metabolite is not able to bind so idk what to being e lol.

I do have trazadone

 

[Skorpio]

Euphoria is complicated and a much "higher level" sensation than something like "reward". Euphoria requires both hitting receptors that can produce it, but also has circuit level requirements (one that is important is novelty. The more one takes a drug, the more they become used to it and euphoria will likely diminish).

This is a big factor in why people can like drugs less, even after long tolerance breaks. Receptor downregulation occurs quickly, and reverses relatively quickly (at least for GPCRs). What limits euphoria, is the brain getting used to the drug and engaging different circuits than it did during the honeymoon period.

Formation of brain circuits is a form of learning (and high dopamine levels increase the rate of learning, ie the rate of formation of new circuits, and their strength). Once these are formed, it takes orders of magnitude more time for them to disappear than it would from receptor downregulation. Even then, having a circuit previously formed will make relearning a much quicker process (like when you learn something and forget it, it is easier to learn the second time, and you will remember it for longer).

This phenomenon is quite under-appreciated by many drug users, and I believe it to be the source of questions of why drugs today lack the magic of when people started (though some drugs through supply issues are worse so it is risky to overgeneralize).

 

[snmfmy]

Just had a thought- They say if you don’t experience euphoria anymore that it doesn’t mean the medication isn’t treating the symptoms.

What is the biological process responsible for this? What I mean is how is it that a drug can still treat symptoms but not retain euphoria? (which I don’t want euphoria btw slippery slope and all that)

I understand how tolerance is about homeostasis but how does one become tolerance to the euphoria but not the targeted symptoms being treated? It’s really just a curiosity.

Usually it has to do with receptor density changes, surface expression of receptor genes/rna, sometimes changes to binding affinity with the agonist/substrate -- or a combination of the above.

How the receptors, ligands, etc modulate the currents associated with subunits, and subunit combinations.

Some effects are abolished (anorexic and euphoric effect of some amphetamines/phenylethylamines) yet anti-hyperactive &increased focus effects remain.

OTOH, several substituted cathinones have no loss of euphoria and other effects, even after an entire weekend of compulsive re-dosing, after years of use. However certain (negative) sympathomimetic effects are magnified by dose magnitude.

The same is true for some benzos, sedation and anxiolytic action fades, yet muscle relaxation effects continue. The morphological changes to GABA receptors are different for different benzos.

That's my understanding.

 

[garygroundwork]

Hot damn aside from nutrition (got that covered, hydration and not taking anymore how can I help this come down. More intense than other times. Not sure if maybe weed. People on Reddit were swearing my trazadone but I thought that wasn’t used alot cause the metabolite but someone else said that the metabolite is not able to bind so idk what to being e lol.

I do have trazadone

Xanax is your friend here.

 

[Juicewrldfan]

True - just zero street connections anymore since I started getting clean years ago I stopped talking to anyone from there and lost everyone’s numbers so for better or worse.

that said, I quit amphetamines and amphetamine like drugs. Just wreak havoc on me because I can’t seem to use them responsibly. And in that case I don’t need them or shouldn’t be getting them so I called my doctor and told him not to prescribe anymore. I can’t trust myself with them.

 

[garygroundwork]

that said, I quit amphetamines and amphetamine like drugs. Just wreak havoc on me because I can’t seem to use them responsibly. And in that case I don’t need them or shouldn’t be getting them so I called my doctor and told him not to prescribe anymore. I can’t trust myself with them.

yeah same .

im trying to take a break now.

 

[Juicewrldfan]

yeah same .

im trying to take a break now.

Yeah it was a real struggle for me. I had to cut off my script and trust me I tried every way I could think of to not have to do that. I went to extreme lengths to try to use it responsibly.

But as long as it’s not in my face I can stay away from it right now and honestly it will be indefinitely because I get really umm suicidal after binge because I lose everything when I binge, jobs, relationships, self respect..that’s what dies the most damage. Losing self respect and worse replaced with self loathing but that’s how it does me.