Does this make sense for improving an opioid high?

[Alien47]

First Idk if potentiating is the right word but Would this improve the high in anyway of oxy and other opiates and opioids. There?s dopamine supplements (I think they are mainly called mood enhancer or something but you get it) such as Mucuna dopa That contain L-dopa which from what I understand is a precursor for dopamine which everyone knows is the main neurotransmitter responsible for giving us our feel good feelings. So if by taking these supplements that increase ur potential dopamine reserves would it not make it so that there is more dopamine available for being released when u take something that stimulates the release of dopamine such as opioids? Maybe I?m understanding something wrong about either how exactly opiates make u high or how L-dopa works but from what I understand (or think I understand lol) about the two things it makes complete sense that taking the L-dopa before taking your opiates would increase the amount of dopamine that can be released therefore making the high more intense. Let me know if What im saying makes sense in theory or in actuality if someone has already thought of it, If I?m not pls let me know why pls because I mean I like learning more about the way our bodies function anyways so yeah, Thanks.

(Sry if posted in wrong section of the forums)

 

[Tzcatlipoca]

First Idk if potentiating is the right word but Would this improve the high in anyway of oxy and other opiates and opioids. There?s dopamine supplements (I think they are mainly called mood enhancer or something but you get it) such as Mucuna dopa That contain L-dopa which from what I understand is a precursor for dopamine which everyone knows is the main neurotransmitter responsible for giving us our feel good feelings. So if by taking these supplements that increase ur potential dopamine reserves would it not make it so that there is more dopamine available for being released when u take something that stimulates the release of dopamine such as opioids? Maybe I?m understanding something wrong about either how exactly opiates make u high or how L-dopa works but from what I understand (or think I understand lol) about the two things it makes complete sense that taking the L-dopa before taking your opiates would increase the amount of dopamine that can be released therefore making the high more intense. Let me know if What im saying makes sense in theory or in actuality if someone has already thought of it, If I?m not pls let me know why pls because I mean I like learning more about the way our bodies function anyways so yeah, Thanks.

(Sry if posted in wrong section of the forums)

The assumption that dopamine is the main neurotransmitter responsible for feeling good is false if anything. The claim that opiates stimulate the release of dopamine is thoroughly false as well. If you wish to potentiate opiates with OTC pharmaceuticals look no further than grapefruit or dxm.
Best,
Tez

 

[Keif' Richards]

Tez. I'm sorry, but this is absolutely the last time I'm going to let you post misinformation as fact without consequence. To be fair to other members looking on whom I have been significantly more harsh with previously, English is not Tez's first language. There's only so much I can allow Tez. Please refrain from posting at all, anywhere unless you are absolutely positive that what you're presenting is actually factual.

Some of this is still fairly hypothetical, but Dopamine is believed to be the neurotransmitter responsible for the underlying addictive properties of virtually all psychoactive drugs known to man. Here is a reference for said statement:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050051/

You didn't just challenge this guy, you called him "thoroughly false". Dopamine and Opioids are in fact, inexorably linked. You need to be more careful. The next time, you're getting an infraction. If any of this is unclear, now would be a good time to broach that subject with me.

OP, unfortunately, we really discourage threads that merely focus upon achieving a more "recreational/fun" experience. We're not idiots, we know that that's why a lot of us are here, but we sometimes like to pretend like our motivations are scientific or academic. If it's not concerned directly with your safety and is purely about getting high, it's not appropriate material.

 

[Tzcatlipoca]

Tez. I'm sorry, but this is absolutely the last time I'm going to let you post misinformation as fact without consequence. To be fair to other members looking on whom I have been significantly more harsh with previously, English is not Tez's first language. There's only so much I can allow Tez. Please refrain from posting at all, anywhere unless you are absolutely positive that what you're presenting is actually factual.

Some of this is still fairly hypothetical, but Dopamine is believed to be the neurotransmitter responsible for the underlying addictive properties of virtually all psychoactive drugs known to man. Here is a reference for said statement:

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3050051/

You didn't just challenge this guy, you called him "thoroughly false". Dopamine and Opioids are in fact, inexorably linked. You need to be more careful. The next time, you're getting an infraction. If any of this is unclear, now would be a good time to broach that subject with me.

OP, unfortunately, we really discourage threads that merely focus upon achieving a more "recreational/fun" experience. We're not idiots, we know that that's why a lot of us are here, but we sometimes like to pretend like our motivations are scientific or academic. If it's not concerned directly with your safety and is purely about getting high, it's not appropriate material.

Excuse me? I'll only tolerate so much nonsense before I speak up. The study you linked DOES NOT link opiates to any dopamine receptor activity, the following is an except from the study;

These studies use positron emission tomography (PET) to measure, in one instance (1), changes in DA induced by acute alcohol administration in healthy subjects (with [11C] raclopride, a radioligand that binds to D2 and D3 receptors (D2R and D3R) and that is sensitive to competition with endogenous DA) and, in the other (2), μ opioid receptor (mOR) availability in cocaine abusers (with [11C] carfentanil, an mOR specific radioligand.

Unless you can link a study describing a mu/delta/kappa ligand to possess Dopamine receptor affinity, OPIOID ACTIVITY is not DIRECTLY RELATED to DOPAMINE RELEASE. In fact, one study has found a decline in dopaminergic and serotonergic activity in brains of patients treated daily with morphine for a month. If you had actually read the ncbi article you linked you'd see it deals with administration of alcohol and not opioid ligands. Instead of google and copypasta-ing random threads from ncbi to detract from my posts next time try contributing helpful information or at least relate similar experiences.
You of all people should know better than going into unwarranted power trips and threatening those who try to help with "infractions"

All due respect,
Tez

 

[Scrofula]

No, opioids don't directly affect dopamine. Just indirectly. Same with alcohol and cigarettes.

I think people get confused because they mix up the roles that dopamine play with meth and stim use, ADD drugs, and addiction. The release of dopamine in response to smoking meth is a whole different animal than any dopamine that might be released when you smoke a cigarette or shoot heroin.

Dopamine is just a signalling molecule used by the reinforcement circuitry in our brains. The brain cells that handle stuff like, "having sex was great, I should do that more often and continue the species," just happen to use dopamine to communicate. Your brain does not gush with dopamine to reward you for doing something, key cells might squirt a little out as a normal process of being a brain cell just doing its signalling thing.

That gets hijacked with stimulants, which force some brain cells to dump their reserves. The meth users then obsess over things like phenylalanine supplements to re-build their dopamine reserves. This is a different form of dopamine release than the kind involved with opioids--addiction is just a regular brain-cell phone call, not burning up any reserves, while meth is an all-frequency max volume blast that blows out everyone's eardrums. Two very different processes.

There's no question that dopamine is required for the usual opioid addiction. Opiates don't directly touch it, just like they don't touch glutamate receptors. But you need glutamate in your retina to see your dope, to cause dopamine signalling that makes you crave it. Which probably requires serotonin signalling to give you mixed feelings about it and acetylcholine to finally reach for it.

And to get to OP, even if taking those supplements worked to rebuild dopamine reserves (L-Dopa does, but that's Rx), there's nothing about the use of opioids to suggest your dopamine reserves have been depleted or damaged. That's not how opioids work, and would cause pretty terrible symptoms, like paralysis and death.

And because outside your opioid circuitry your brain is just signaling like normal, there's no reason that building up more dopamine would mean a louder signal. Actually, that might make you extra-addicted, not more high.

 

[Keif' Richards]

Excuse me? I'll only tolerate so much nonsense before I speak up. The study you linked DOES NOT link opiates to any dopamine receptor activity, the following is an except from the study;

These studies use positron emission tomography (PET) to measure, in one instance (1), changes in DA induced by acute alcohol administration in healthy subjects (with [11C] raclopride, a radioligand that binds to D2 and D3 receptors (D2R and D3R) and that is sensitive to competition with endogenous DA) and, in the other (2), μ opioid receptor (mOR) availability in cocaine abusers (with [11C] carfentanil, an mOR specific radioligand.

Unless you can link a study describing a mu/delta/kappa ligand to possess Dopamine receptor affinity, OPIOID ACTIVITY is not DIRECTLY RELATED to DOPAMINE RELEASE. In fact, one study has found a decline in dopaminergic and serotonergic activity in brains of patients treated daily with morphine for a month. If you had actually read the ncbi article you linked you'd see it deals with administration of alcohol and not opioid ligands. Instead of google and copypasta-ing random threads from ncbi to detract from my posts next time try contributing helpful information or at least relate similar experiences.
You of all people should know better than going into unwarranted power trips and threatening those who try to help with "infractions"

All due respect,
Tez

Sadly though Tez, I never said what you're implying. I merely said that Dopamine is believed to be the neurotransmitter ultimately responsible for the addictive and reinforcing characteristics of almost all substances known to be addictive. This is true. I know it is. The only difference is that you just skipped right ahead to being an asshole instead of trying to discuss it. I wouldn't have taken that tone if every other post you created weren't blatant misinformation.

To be clear, you are making statements over and above what I actually said, in a way more specific manner and then pointing out the incorrect nature of your own statements. The shitty thing is that you didn't just stick up for yourself, you talked shit in the process and accused me of being on a power trip. You're still wrong and now you're wrong and look like a fool.

I never said that Opioid ligans stimulate Dopamine production. I said that Dopamine and Opioids are inexorably linked. Why did we just exchange all of those PM's of mutual understanding only to have this shit come up? I thought we made it clear that it wasn't personal, but if you keep posting misinformation, I will be forced to give you an infraction. You said you understood. Now I'm greeted with a meltdown complete with name-calling.

 

[Tzcatlipoca]

No, opioids don't directly affect dopamine. Just indirectly. Same with alcohol and cigarettes.

I think people get confused because they mix up the roles that dopamine play with meth and stim use, ADD drugs, and addiction. The release of dopamine in response to smoking meth is a whole different animal than any dopamine that might be released when you smoke a cigarette or shoot heroin.

Dopamine is just a signalling molecule used by the reinforcement circuitry in our brains. The brain cells that handle stuff like, "having sex was great, I should do that more often and continue the species," just happen to use dopamine to communicate. Your brain does not gush with dopamine to reward you for doing something, key cells might squirt a little out as a normal process of being a brain cell just doing its signalling thing.

That gets hijacked with stimulants, which force some brain cells to dump their reserves. The meth users then obsess over things like phenylalanine supplements to re-build their dopamine reserves. This is a different form of dopamine release than the kind involved with opioids--addiction is just a regular brain-cell phone call, not burning up any reserves, while meth is an all-frequency max volume blast that blows out everyone's eardrums. Two very different processes.

There's no question that dopamine is required for the usual opioid addiction. Opiates don't directly touch it, just like they don't touch glutamate receptors. But you need glutamate in your retina to see your dope, to cause dopamine signalling that makes you crave it. Which probably requires serotonin signalling to give you mixed feelings about it and acetylcholine to finally reach for it.

And to get to OP, even if taking those supplements worked to rebuild dopamine reserves (L-Dopa does, but that's Rx), there's nothing about the use of opioids to suggest your dopamine reserves have been depleted or damaged. That's not how opioids work, and would cause pretty terrible symptoms, like paralysis and death.

And because outside your opioid circuitry your brain is just signaling like normal, there's no reason that building up more dopamine would mean a louder signal. Actually, that might make you extra-addicted, not more high.

THANK YOU SCROFULA! That's all I wanted to say and much more.
Keif'Richards you claimed I was giving misinformation for saying dopamine does not have a direct relationship with opioids, this same claim you drove in head over hammer up to this point in the thread, you are calling me an asshole for citing the truth, was your own tone open to discussion? NO. Enough hypocrisy. You left me no room to explain myself instead directly skipped to "you are incorrect, do not misinform" instead of trying to understand my argument.
None of my posts here is "blatant misinformation" and I INVITE YOU to prove this wrong. I fail to see how you still claim that "I proved myself wrong". I am not wrong, I do not look like a fool for stating what I find to be correct. When we exchanged those PMs I had not seen this post of yours accusing me of such nonsense that I have never committed. What you are greeted with is not a meltdown nor ANY name calling, I presented a watertight case complete with a lovely explanation of why and how my information was indeed correct. You on the other hand resorted back to your "OH I AM YOUR SUPERIOR, FOOL" tone and you have used such language and I quote "asshole", "shitty, shit", "fool"
I dare you find one offensive word in my post. Infract me if you like for saying "No dopamine and opioids do not interact that way, mate", then the public will be able to see how you treat those you call friend.

Regards,
Tzcatlipoca

 

[Scrofula]

Mr. Tzcatlipoca, I'm glad we agree on mechanisms. But like my restraining order, this is about the meaning of "release" and shouldn't make the neighbors upset, dammit. I don't know why you couldn't have taken a subtly gloating, "we're both right" approach? Or just clarified what you meant and why it wouldn't work for OP (after rewording your first post to be a little softer)?

 

[Tzcatlipoca]

Mr. Tzcatlipoca, I'm glad we agree on mechanisms. But like my restraining order, this is about the meaning of "release" and shouldn't make the neighbors upset, dammit. I don't know why you couldn't have taken a subtly gloating, "we're both right" approach? Or just clarified what you meant and why it wouldn't work for OP (after rewording your first post to be a little softer)?

Yes Sir Mr. Scrofula
You are indeed correct and I recognize my mistake I should have initiated conversation with a "Yes sir both statements are correct" instead of a "No that's not how it works". However I plead innocent to the horrendous accusations made by Keif'Richards. My reaction afterwards was geared towards a clarification and I would request you to consider my answers were peaceful after Keif spoke to humiliate me in public(and called me names no less)
Thank you for keeping peace,
Yours Humbly,
Tzcatlipoca

 

[zephyr]

Chillax guys. These things happen.

 

[Cotcha Yankinov]

The claim that opiates stimulate the release of dopamine is thoroughly false as well.

I hope we're not getting lost in the weeds due to a lexical ambiguity here, but one mechanism by which Mu Opioid Receptor activation leads to dopamine release is by MOR mediated inhibition of inhibitory interneurons.

As an example, Mu Opioid Receptors are expressed pre-synaptically on GABAergic interneurons, where agonist binding to MORs leads to a decrease in GABA release. Its often the case that the pre-synaptic GABAergic interneuron's post-synaptic counterpart is a dopamine neuron in some brain regions - as the extracellular GABA decreases, the excitability of the dopamine neuron rises and it releases more dopamine.

If you wish to potentiate opiates with OTC pharmaceuticals look no further than grapefruit or dxm.

One of the reasons why NMDA antagonists help with tolerance and potentiate opioid's effects is that excitatory NMDA receptors are highly expressed on inhibitory interneurons such as GABA interneurons. By blocking the NMDA receptors, you essentially shunt cell firing of the inhibitory interneurons which are normally releasing e.g. GABA to inhibit downstream neurons, especially dopamine neurons. This therefore acts synergystically with MOR agonist mediated inhibition of inhibitory interneurons.


With regards to dopamine's relation to addiction, its important to understand that all cell types communicate with each other by expressing each other's respective receptors. As an example, most serotonin receptors are expressed on non-serotonergic cells. If serotonin receptors were only expressed on serotonin releasing cells, those serotonin cells would only be able to communicate with each other, and not other cell types. Dopamine receptors are everywhere, and so are opioid receptors.

CY

 

[Cotcha Yankinov]

taking these supplements that increase ur potential dopamine reserves would it not make it so that there is more dopamine available for being released when u take something that stimulates the release of dopamine such as opioids?

While the reserves of neurotransmitters can run dry in some situations, this doesn't seem to be a problem in opioid use.

A situation where replenishing reserves can be desirable is with regards to 5-HTP/L-tryptophan and serotonin releasing agents like MDMA. MDMA can deplete serotonin reserves, but this is because MDMA has a very different mechanism of action than an opioid, and the serotonergic system is also fundamentally more vulnerable to "run out of fuel" compared to the catecholamine systems like dopamine.

 

[Alien47]

Thank u guys very much for the information, there was actually a lot that i didn?t know about till now on the way certain drugs actually affect the brain. Thanks for the insight on the topic guys.

Also sry if my post started anything. I asked a question I clearly knew less about then I had thought. A good amount of what u guys said did go right over my head lol. But I still picked up a lot of info so thanks again.

 

[Scrofula]

I asked a question I clearly knew less about then I had thought.

How would you know if you hadn't asked? And know you more then you started with.

(Some of us here live for nerd fights over technical things that come up.)