Endogenous Opioid Release in the Human Brain Reward System Induced by Acute Amphetami

[mllx]

Given that dopamine is no longer regarded by many neuroscientists to be a pleasure neurotransmitter after all.

Please, I need more info about this assertion,where can I find more scientific articles about this subject?

 

[pofacedhoe]

im not familiar with opiates but it seems heroin users dont do much when high and just have their life passing by

this is simply not true. you can go overboard with opiates but if you moderate your use of say poppy tea (morphine drink), it can be one of the most energising relaxing drugs available. you can sleep on it, eat normally, tolerate a much bigger workload and for some reason when i am tired it wakes me up. THE most functional workplace drug i have used, makes you able to tolerate so much and at the same time keep your head together under high stress. plus you don't need to develop a benzo addiction to go with it ala amphetamine.

 

[pofacedhoe]

You have obviously never seen someone who is withdrawing from heavy amphetamine use.

amp withdrawl is a thousand times worse than coming off opiates, its debilitating depressing, leaves you burnt out like a husk and constantly tired. though i will vouch that opiate withdrawl also leaves you very tired but not to anywhere near the same degree.

every year when poppy season comes around i have to endure a poppy withdrawl which is easy if you taper your dose. i would never put myself through amphetamine withdrawl again in a million years as for me its pure pain/boredom/suicidal tendencies

 

[Dysphoric]

All of my whats.


Seems weird to me. Even though I wasn't particularly addicted to amphetamines. I still used them for about a year and a half, 2-3 times a week, and I didn't notice any kind of physical withdrawals other than fatigue for a short amount of time. Moderate depression and boredom hell were about the only pronounced ones. Hell even the cravings were fairly easy to deal with.

I was always under the impression that Amphetamine withdrawals were mental more so than physical.

 

[Hammilton]

I think stimulant abusers have higher rates of relapse, compared to opioid addicts, correct?

I've never used stimulants enough to become addicted to them, I don't really enjoy them all that much, but an occasional night doing lines of amp or methylphenidate has always been enjoyed. When I first tried using these drugs, I was given some Concerta. I dunno if the dose was too high or what, but on the first or second day, as soon as that wore off, the depression and exhaustion I felt were terrible. And that was only the first or second day! Or maybe that was after the first or second time I took the Adderall the doc put me on. I'm not 100% sure, I do remember that my first dose of Adderall XR resulted in me losing my hearing. It was very strange, like wearing ear plugs, though I later learned it's not uncommon with stimulant abusers. There was a study of middle eastern abusers of fenethylline (IIRC, I think the brand name was something like Captogan) that found an important percentage experienced this side effect.

Anyway, whichever drug it was, I did continue on it for a while afterwards, and never experienced anything that strong again, though I did discontinue Concerta and switch to Adderall XR because when Concerta wore off I just wanted to kill everyone. I was so angry and immediately irritable. Yet I can snort methylphenidate at a party or whatever all night and even when it wears off not have that problem. I think it had too long of a duration.

 

[Hammilton]

All of my whats.


Seems weird to me. Even though I wasn't particularly addicted to amphetamines. I still used them for about a year and a half, 2-3 times a week, and I didn't notice any kind of physical withdrawals other than fatigue for a short amount of time. Moderate depression and boredom hell were about the only pronounced ones. Hell even the cravings were fairly easy to deal with.

I was always under the impression that Amphetamine withdrawals were mental more so than physical.

That's certainly true. There are many researchers who do not consider amphetamines to be physically addictive. However, you wouldn't develop a physical dependence on any drug if you were only using it two or three times a week. Certainly not something with a short duration like amphetamines.

 

[Epsilon Alpha]

Exactly where opioid peptides bind plays a massive role in withdrawals. This study doesn't mention actions in the gut, spinal cord, or any other sort of tissues associated with the stereotyped opioid withdrawals. On top of that, many endogenous ligands for opioid receptors don't produce the same kind of downregulation as seen with various pharmaceuticals.

 

[Jabberwocky]

I don't see how activation of opiate receptors play such a huge role in the addictive nature of amphetamines. If you consume a large dose of amphetamines - would opiate receptors also be activated at higher levels? Would this not counteract the side effects of amphs such as dilated pupils, tachcardya and anxiety?

Or are opiate receptors not helpful for the control of this in the body? Correct me if I'm wrong.

 

[som3dankbudz]

Endogenous opiates and amphetamines..

I don't see how activation of opiate receptors play such a huge role in the addictive nature of amphetamines. If you consume a large dose of amphetamines - would opiate receptors also be activated at higher levels? Would this not counteract the side effects of amphs such as dilated pupils, tachcardya and anxiety?

Or are opiate receptors not helpful for the control of this in the body? Correct me if I'm wrong.

I agree with you somewhat Synthetix, I dont think it is a potent enough effect to outweigh or even cross the threshold of feeling any mu-opiate like effect, because if you took more amphetamine, that will most likely out-weigh the any opiate like feeling. Although this doesn't mean it doesn't indeed make amphetamines more addictive it will still aid in rewiring your reward system to the dopamine release even if it isn't "felt", resulting in higher likelihood of addiction. This also explains to me, without a doubt why low-moderate dose amphetamine eliminates my opiate w/d temporarily, and i do this lots when there is lyrica for the comedown. Idk if thats even been mentioned, but backs this up IMO.

 

[DJHENRU]

It makes sense to me. Opiates don't work on endorphins like the related peptides do right?
Somewhat like the two endogenous ligands for the GABA-a receptor are anxiogenic, & gaba taken IV can cause anxiety.

This was actually a pretty awesome study because maybe this can teach us more about the amino acid phenylalanine's role as a painkiller. I got some heavy duty warmth and euphoria from using it as a potentiator. I think there is established evidence that amphetamine increases opiate analgesia when combined as well.

If AMP gives pleasure through opiate release then why doesn't AMP give an opiate-like withdrawal upon cessation?

Both amphetamine and opiates though can make some pretty big changes to the immune system to an addict.

 

[DJHENRU]

No one here has yet brought up the dietary opiate mimicking peptides in food; whey, gluten, etc roles in being culprits for hindering the capability of learning, and what do pharmacological prophylaxis exactly do to a diet including such things.

 

[Jabberwocky]

som3 - as you've mentioned a low dose of amphetamines can help you through opiate withdrawals, i know this as well as they have helped me immensely during opiate withdrawals at low doses too. however, you don't see the majority of amphetamine addicts using low doses of the stuff, its typically high dose abuse.

DJHenru - your point regarding opiate analgesia being potentiated by low dose stimulants is 100% spot on, along with the euphoric aspects of it too. if i dose oxycodone with 5mg of dexamphetamine, my high is greatly potentiated and it seems as if there is no direct increase in CNS activity while on a low dose. however, at higher doses, the amphetamine will completely wipe out the feelings from opiates. how can this then be explained? i understand that both act in reverse to one another (amphetamine speeds up, opiates slow down) - yet at a low dose its actually the reverse.

pseudoephedrine and caffeine are also normally combined with codeine in order to produce and provide a larger amount of analgesia and i'm assuming it acts in the same method, but not to such a large degree.

 

[JimRaynor]

Are there any studies investigating if and to what degree amphetamine euphoria is mediated through said opioid release i.e. can the euphoria be blocked with opioid antagonists? As you probably know alcohol euphoria can be completely blocked with naltrexone, right? If also AMP euphoria can be blocked it raises the question: Can all drug induced wellbeing be blocked with naltrexone and thus be mediated trough opioid release?

 

[AlphaMethylPhenyl]

To my knowledge there are several drugs whose euphoria is readily blocked by naltrexone

 

[endotropic]

Are there any studies investigating if and to what degree amphetamine euphoria is mediated through said opioid release i.e. can the euphoria be blocked with opioid antagonists? As you probably know alcohol euphoria can be completely blocked with naltrexone, right? If also AMP euphoria can be blocked it raises the question: Can all drug induced wellbeing be blocked with naltrexone and thus be mediated trough opioid release?

Ethanol, nicotine, amphetamines, cannabinoids, opiates (no really), but probably not serotonergics.

Reference for amphetamine:
Effects of naltrexone on the subjective response to amphetamine in healthy volunteers.
http://www.ncbi.nlm.nih.gov/pubmed/15538132

And nicotine:
Naltrexone alteration of the nicotine-induced EEG and mood activation response in tobacco-deprived cigarette smokers.
http://www.ncbi.nlm.nih.gov/pubmed/17696684

I don't know if human studies have been done with serotonergics + naltrexone, but you can find the animal data.

 

[som3dankbudz]

Synthetix- Sorry, I apologize I didn't make myself clear, I meant that I don't believe that endogenous opiate release caused by amphetamines is enough to noticeably alter the subjective effects of amphetamines due to DA/NE release at the vta(sp?) outweighing the opiate effects, especially at high concentrations. Although, I do believe the endogenous opiate release may play some part in the rewiring of the reward system, and contribute to that once loving, or loving amphetamine euphoria. It may be in my head because besides the withdrawal alleviation, there defiantly is a similarity to the euphoria and content aspect in both. When you look past the extreme stimulation with one, and not so much the other(opiates). So it may indeed contribute to he subjective effects somewhat. Something that also sparks my mind is how I've noticed with myself and others, that amphetamines day of,esp. 3 or 4 hours of opiates make my tolerance so much lower and greater euphoria,but higher chance of feeling nauseated at the end of the high.

Ethanol, nicotine, amphetamines, cannabinoids, opiates (no really), but probably not serotonergics.

Reference for amphetamine:
Effects of naltrexone on the subjective response to amphetamine in healthy volunteers.
http://www.ncbi.nlm.nih.gov/pubmed/15538132

And nicotine:
Naltrexone alteration of the nicotine-induced EEG and mood activation response in tobacco-deprived cigarette smokers.
http://www.ncbi.nlm.nih.gov/pubmed/17696684

I don't know if human studies have been done with serotonergics + naltrexone, but you can find the animal data.

Thank you so much for this study, I have searched for it quite a few times before, this reassures me on my hypothesis that mu receptor activity does play some role in subjective effects, it just all connects. Very appreciative endotropic!