Misc pharmacology question

[polarthedog]

Okay, so I know that if you take suboxone or methadone for a long period of time and get addicted, the withdrawals last longer than say heroin withdrawals.

My question is why? just because a drug lasts longer, why would that make the withdrawals last longer than if your constantly on a short acting drug, i mean the receptors are constantly activated, so what's the difference?

Also what is the point of your brain having withdrawal in the first place, why can't you consciously tell your brain "hey, I need this drug, I'm not trying to kill myself, so just don't build a tolerance"

I mean it is your brain, why do you guys think it self sabotages? and why can't the brain just be like "hey I'm bored, lets release a whole lot of dopamine so that i feel better"

I understand that it won't but I don't understand why.

It seems that your own neurochemical balances should be able to be influenced by your will.

 

[Xorkoth]

I'm not quite sure the reason why longer duration substances produce longer withdrawals. As for the rest... well that would certainly be the shit if we could talk to our brains and tell them not to downregulate our receptors when we take drugs. Dare ti dream...

 

[Joey]

The half life being longer is the physical reason to the extent of my knowledge. I’m sure someone can answer this better than I can.

 

[polarthedog]

but why would a longer half life = longer withdrawals? it seems like just the length and intensity of receptor stimulation should influence the length and intensity of withdrawals.

 

[Joey]

but why would a longer half life = longer withdrawals? it seems like just the length and intensity of receptor stimulation should influence the length and intensity of withdrawals.

That is your half life. Those receptors are activated longer. Your experiential tolerance or subjective feel rather isn’t the same as your physical body responding to longer lasting drugs for longer periods of time.

 

[polarthedog]

I don't think your understanding what I'm saying, lets say you take heroin every day, all day, and another guy takes methadone all day every day, your doses are equipotent, you are high the same duration, but then the guy addicted to methadone goes through withdrawal for weeks, and the guy whos addicted to heroin is mostly back to normal in a week. Why wouldn't they go through the same length of withdrawal
this is a hypothetical situation in which their neurochemistry is identical.

 

[DeathIndustrial88]

Im just throwing some guesses out there but..

Maybe the more potent (think subs, fent) the more receptor downregulation, which has to repair.

Also, like the other guy said, the physical part is because of the half-life. So while a person using heroin may feel physically better in less time, they're probably going to have PAWS, as will any opioid addict after they've been going at it long enough.

So somebody who has to wait 2 weeks for the bupe to leave their body + PAWS means a longer perceived withdrawal, than say somebody who's physical withdrawals are over in 5 days.

Once I was on opioids for long enough, I never went back to normal, even after a week of physical withdrawals from a short acting opioid. In fact, I stayed "abnormal" until I finally scored again, even if it wasn't until weeks later. This is why I just ended up getting on maintenance because it got to a point where no length of clean time made me feel normal.

 

[polarthedog]

Also, like the other guy said, the physical part is because of the half-life. So while a person using heroin may feel physically better in less time, they're probably going to have PAWS, as will any opioid addict after they've been going at it long enough.

So somebody who has to wait 2 weeks for the bupe to leave their body + PAWS means a longer perceived withdrawal, than say somebody who's physical withdrawals are over in 5 days.

i guess that might be it, your still not completely down until a week later with sub

 

[DeathIndustrial88]

i guess that might be it, your still not completely down until a week later with sub

yeah, that would be my biggest guess. I've wondered myself the same question and this was the only conclusion I could come up with. lol
Delayed response from longer half lives + PAWS.

Some one who isn't an addict could probably use heroin or bupe and be fine in a weeks worth of clean time, but for people who have been addicted for years, I think, at least mentally, you will always be in withdrawal til your brain either completely reverts back to normal or you get that next hit.

 

[Shady's Fox]

its because the DNA say the opposite, if you was high all the time you will have manic bipolar episode , even productivity, if you was working 18hour/day you will die, so based on that, DNA set limits and always stay on it.

that's why the human body is the greatest mechanism. Period is disgusting but the process isn't because is essentially the human body having a shower, same when you have an infection somewhere your body sends a scout team to investigate

 

[negrogesic]

Duration of receptor occupancy/pharmacokinetics of the drug (ie you can't fully withdraw until the drug is out of your system), fat solubility (ie, does it store in the body), type of receptor activation (ie, efficacy: partial, full, etc) are some variables that effect the duration of withdrawal.

 

[4meSM]

I don't think your understanding what I'm saying, lets say you take heroin every day, all day, and another guy takes methadone all day every day, your doses are equipotent, you are high the same duration, but then the guy addicted to methadone goes through withdrawal for weeks, and the guy whos addicted to heroin is mostly back to normal in a week. Why wouldn't they go through the same length of withdrawal
this is a hypothetical situation in which their neurochemistry is identical.

For the sake of simplicity, let's assume that in this scenario both morphine and methadone have reached a "steady state" concentration.

Now, both guys will sudently stop taking their respetive drugs and the opioid concentration will start to drop.
The drug will now begin to unbind from the receptors and the unbound fraction will undergo metabolism/elimination. This is a dynamic process dictated by equilibrium constants, most drugs are constantly going in and out of the receptors but, in the case of high-affinity drugs, the equilibrium is of course shifted towards the bound form. However, once the drug gets metabolized into an inactive form, it won't be able to go back and bind to its receptor of choice again (e.g. the mu opiod receptor), this is what the term "half-life" usually alludes to (also called beta or elimination half-life).
Moreover, the drug will also get redistributed into different tissues/organs/fat, the lenght of this process is represented by the alpha half-life (also called distribution half-life) which will also be different for each substance.

So the body will inevitably end up getting rid of the drug, but the time it takes for the receptors to finally be "free from the drug" will vary. In this example, methadone will stay bound to the receptors for a significantly longer period of time than morphine, which is why methadone WD takes longer to start.
In other words, methadone will be cleared out of the receptors (slowly), and once the concentration goes bellow a certain amount then the sickness will come... At this point there's still quite a bit of methadone in your brain/blood though, yet not enough compared to what you're used to.
Let's say that the body can't quite reach homeostasis and adjust to an opioid "free" environment when there's still a bunch of potent exogenous opioids floating around. And then there's the PAWS thing...

 

[DeathIndustrial88]

I have a pharmacology question...

I've read that opiates/oids decrease dopamine in the brain (antipsychotic properties) and I've also read that they release it (hence the euphoria, motivation, etc...)
Are both true? And how/why?

 

[deficiT]

The body simply processes and eliminates shorter acting drugs quicker, hence a shorter withdrawal.

 

[DeathIndustrial88]

as for euphoria opiates inhibit GABA (inhibitory neurotransmitter) in NAc (reward system) so dopamine can easily do its work there, as for pain , opiates do opposite by increasing GABA in some places in the brain that control substance P (pain signal neurotransmitter), as for antipsychotic properties if it was true i don't know how

Thanks for the response.

It's difficult now a days to find much info on the antipsychotic properties of opioids, but they use to be used to treat neurosis and psychosis back in the day.
There use to be lots of articles and research on opioids for mental health, but I think with the demonization of opioids going on, it's even harder to find this information.

A quick google search popped up with this... not exactly informative but it shows that at least there is some word about opioids possessing antipsychotic properties out there.

Psychiatry Online

ajp.psychiatryonline.org

Also this.....

https://www.researchgate.net/publication/237716123_Methadone_reduces_the_need_for_antipsychotic_and_antimanic_agents_in_heroin_addicts_hospitalized_for_manic_andor_acute_psychotic_episodes

Opioids use to be the go to meds for depression, anxiety, psychosis, etc.... but because they're addictive and actually feel good, they were replaced with SSRIs and antipsychotic meds, which also cause hellish dependence except you don't feel good. lol

 

[polarthedog]

I have a pharmacology question...

I've read that opiates/oids decrease dopamine in the brain (antipsychotic properties) and I've also read that they release it (hence the euphoria, motivation, etc...)
Are both true? And how/why?

maybe they release dopamine in one part of the brain, but lower in another

 

[DeathIndustrial88]

maybe they release dopamine in one part of the brain, but lower in another

This is what I'm guessing.

Generally psychosis happens when there is too much dopamine in one part of the brain. So maybe they raise it in one part but lower it in another (maybe through some indirect action they have). Great point.