Opioids How do Opioids Actually Work ?

[evo4ever]

Hey all.

I've been thinking about this for a while now. I've always known that Opioids cause euphoria and pleasure by making the brain release more Dopamine than normal but how does this actually work? Stimulants like Cocaine and Methamphetamine block the reuptake of Dopamine from the pre-synaptic neuron causing a huge amount of Dopamine to be "trapped" in the synapic cleft which gives you that euphoric feeling. Now Opioids don't work like that, does anyone know how Opioids cause a higher than normal build up of Dopamine in the brain? I know Opioids bind to Opioid receptors but where does the higher than normal Dopamine build up occur? Cheers guiys.

 

[Vastness]

Interesting question, I admit I didn't know specifically, but in a nutshell it seems to be that...

By attaching to their mu receptors, exogenous opioids reduce the amount of GABA released (see animation). Normally, GABA reduces the amount of dopamine released in the nucleus accumbens. By inhibiting this inhibitor, the opiates ultimately increase the amount of dopamine produced and the amount of pleasure felt.

The "see animation" bit refers to this page - https://thebrain.mcgill.ca/flash/i/i_03/i_03_m/i_03_m_par/i_03_m_par_heroine.html - which goes into a little more detail about the effects of opiates and opioids on different neurotransmitter systems.

 

[evo4ever]

So it appears Opioids act as an indirect dopamine releasing agent causing too much dopamine to be released into the synaptic cleft by the pre-synaptic neuron which causes repeated action potentials by the post-synaptic neuron hence the euphoria!

 

[Hylight]

this is amazing ! !

will be doing current research asap!!

i have been intrigued with this awhile now

 

[evo4ever]

That website also has animations for how other drugs work!

 

[Vastness]

So it appears Opioids act as an indirect dopamine releasing agent causing too much dopamine to be released into the synaptic cleft by the pre-synaptic neuron which causes repeated action potentials by the post-synaptic neuron.

Evidently, yes, although that latter part of the explanation is essentially how all neurotransmitters work. Also, "too much", is somewhat relative, I mean, too much for what? To my knowledge it's not possible for the downstream dopamine increase that opiates induce to increase dopamine levels to such an extent that it's actually dangerous, so as to induce dopamine psychosis or even fatal arrhythmia, such as in stimulant overdose - where for sure one can be said to have "too much" dopamine, and probably too much norepinephrine and maybe other stuff too. Too much for the behaviour not to be somewhat addictive, probably, although opiate receptor downregulation itself is arguably more of a contributing factor to addiction, at least over the long term. Personally I'd just say it induces the release of "more" dopamine, rather than too much, but maybe that's semantics...

 

[evo4ever]

Evidently, yes, although that latter part of the explanation is essentially how all neurotransmitters work. Also, "too much", is somewhat relative, I mean, too much for what? To my knowledge it's not possible for the downstream dopamine increase that opiates induce to increase dopamine levels to such an extent that it's actually dangerous, so as to induce dopamine psychosis or even fatal arrhythmia, such as in stimulant overdose - where for sure one can be said to have "too much" dopamine, and probably too much norepinephrine and maybe other stuff too. Too much for the behaviour not to be somewhat addictive, probably, although opiate receptor downregulation itself is arguably more of a contributing factor to addiction, at least over the long term. Personally I'd just say it induces the release of "more" dopamine, rather than too much, but maybe that's semantics...

Higher than normal would be more appropriate than too much. In the downstream Dopamine neuron it releases higher than normal amounts of Dopamine which causes more Dopamine to bind to its receptor on the post-synaptic Dopamine neuron which causes a cascade effect.

Plus its unlikely that u would suffer from Dopamine toxicity due to Monoamine Oxidase enzymes in the synaptic cleft. If you were to knock out these enzymes with MAOI's then it could lead to toxicity, however I'm not sure if monoamine oxidase enzymes target Dopamine but they certainly do target Serotonin.

 

[sekio]

monoamine oxidase enzymes target all monoamines, Wiki: Monoamine oxidase A (MAOA) generally metabolizes tyramine, norepinephrine (NE), serotonin (5-HT), and dopamine (DA) [...]. In contrast, Monoamine oxidase B (MAOB) mainly metabolizes dopamine (DA) [..].

It also matters where the dopamine is released. Generally pleasurable/reinforcing effects happen when dopamine release occurs in the nucleus accumbens (NAcc), whereas dopamine release in the substantia nigra is more involved in motor control than anything else. In the chemoreceptor trigger zone dopamine release can cause nausea!

My understanding was that opioid drugs produce their effects by supressing the release of GABA and promoting dopamine release.

 

[OpiateKiller]

Interesting question, I admit I didn't know specifically, but in a nutshell it seems to be that...


The "see animation" bit refers to this page - https://thebrain.mcgill.ca/flash/i/i_03/i_03_m/i_03_m_par/i_03_m_par_heroine.html - which goes into a little more detail about the effects of opiates and opioids on different neurotransmitter systems.

This is fascinating that by GABA restriction, opiates could boost dopamine ultimately. Now how does benzos tie into the cycle, because Benzos increase GABA right? So if you're addicted to benzos and opiates you got so much going on brain wise you're in deep trouble

 

[sekio]

benzos do not increase GABA levels, they simply make the existing GABA act more effectively.

Vigabatrin and tiagabine are drugs that do increase GABA levels and neither are super recreational as I understand it. Muscimol acts as a direct GABA-A agonist and as I understand it is actually more of a dreamlike hallucinogen than a benzo type sedative.

 

[Hylight]

. . and so the opioids do cross the blood brain barrier and are significantly exceptionally potent.
i did notice in looking over information, a partcular paragraph that stood out. However is a bit off topic but never the less still pertains to the opioid.

there is an extremely huge consumption of the opioid along with large consumption of just about everything else in modernization.

this led to a paragraph that caught my eye : Global shortages, lol. yes, and i did lol. tried not to.

so what this is basically saying is that it is
that supply is being regulated to maintain the balance of distribution socio-geographically and i would suppose for socio-economic purposes also.

Global shortages
Morphine and other poppy-based medicines have been identified by the World Health Organization as essential in the treatment of severe pain. As of 2002, seven countries (USA, UK, Italy, Australia, France, Spain and Japan) use 77% of the world's morphine supplies, leaving many emerging countries lacking in pain relief medication.[244] The current system of supply of raw poppy materials to make poppy-based medicines is regulated by the International Narcotics Control Board under the provision of the 1961 Single Convention on Narcotic Drugs. The amount of raw poppy materials that each country can demand annually based on these provisions must correspond to an estimate of the country's needs taken from the national consumption within the preceding two years. In many countries, underprescription of morphine is rampant because of the high prices and the lack of training in the prescription of poppy-based drugs. The World Health Organization is now working with administrations from various countries to train healthworkers and to develop national regulations regarding drug prescription to facilitate a greater prescription of poppy-based medicines.[245]

Another idea to increase morphine availability is proposed by the Senlis Council, who suggest, through their proposal for Afghan Morphine, that Afghanistan could provide cheap pain relief solutions to emerging countries as part of a second-tier system of supply that would complement the current INCB regulated system by maintaining the balance and closed system that it establishes while providing finished product morphine to those suffering from severe pain and unable to access poppy-based drugs under the current system.

is there nothing left that the species has not over indulged in and over consumed. especially when involving fineness and superiority. in my perspective and opinion !

so sorry for the rant. it just amonts to allot of excess dopamine release, and process of, if the fact is also included together with the pain relief.☹