Diacetyldihydromorphine (Improved Diamorphine/Heroin analog)

[Hexenstahl]

@Neuroprotection
@AlsoTapered

So what I have gotten out of you two's comments is that the double bonding of the element hydrogen to both the morphine and codeine molecule, causes the duration of action of the parent compound to extend more or less significantly, correct?

I'm not sure if this is overly simplistic, but could it be said that simply attaching two hydrogen atoms to any opioid substance, would prolong the overall duration of action? In other words, if I would turn Levomethadone with which I get substituted, into Dihydrolevomethadone, the half life should become even longer, right?

Btw, the perceived euphoria is always highly individual and I don't believe it can be reduced to a simple binding/affinity mechanism. I myself have tried opioids that according to theory ought to have rather low euphoric potential (Tilidine, Levomethadone) but every time I tried them they have catapulted me to cloud 9. Similarily many opioids that are supposed to be highly euphoric (Heroin, Hydromorphone) have subjectively felt very mediocre to me. So I think the exact cause of what leads to more euphoria is less dependent on the substance itself, but more on its interaction with the individual neurobiology of the person in question.

 

[AlsoTapered]

That double-bond makes the 6-hydroxy allylic (electron-withdrawing) which means the body can more readily gluconate it and remove it.

BUT that double-bond also changes the shape of the C-ring. It's fixed in the 'boat' conformation with both codeine and morphine whereas in the dihydro derivatives, it can interconvene to the 'chair' conformation with the energy for that interconvention being provided by body heat.

That's why minimum energy conformations don't always match active conformation. The body provides a small but often important amount of energy to allow a compound to conform to a near-minimum energy conformations.

 

[Neuroprotection]

@Neuroprotection
@AlsoTapered

So what I have gotten out of you two's comments is that the double bonding of the element hydrogen to both the morphine and codeine molecule, causes the duration of action of the parent compound to extend more or less significantly, correct?

I'm not sure if this is overly simplistic, but could it be said that simply attaching two hydrogen atoms to any opioid substance, would prolong the overall duration of action?

Btw, the perceived euphoria is always highly individual and I don't believe it can be reduced to a simple binding/affinity mechanism. I myself have tried opioids that according to theory ought to have rather low euphoric potential (Tilidine, Levomethadone) but every time I tried them they have catapulted me to cloud 9. Similarily many opioids that are supposed to be highly euphoric (Heroin, Hydromorphone) have subjectively felt very mediocre to me. So I think the exact cause of what leads to more euphoria is less dependent on the substance itself, but more on its interaction with the individual neurobiology of the person in question.

To answer your first question, just want to remind you, I have no real knowledge of chemistry. nevertheless, I would assume that hydrogenation of opioids would only lead to changes in pharmacological effects for certain Chemical categories of opioids and it might only be certain compounds within those categories as well. hydrogenation of many other opioids maybe chemically impossible, or may break apart/change the molecule completely to the point where it becomes inactive or a different drug altogether. i’m sure also tapered would have a lot more knowledge on this.

In regards to your second point, opioid euphoria is a poorly understood Area, which, as you said, is probably highly dependent on the individual’s biochemistry and preferences. in regards to morphine and heroin being the most euphoric, these are just generalisations, probably a mixture of popular opinion and observational studies. maybe some of this comes down to first-time usage of a particular drug and the resulting experience which creates a first impression. in this regard, less potent drugs could be paradoxically more rewarding in some people as there is less chance of negative effects. this is especially true with sedating drugs like alcohol, benzodiazepines and opioids. if more potent versions of these drugs are used or they are taken in higher doses, negative side-effects like blackouts, sedation and severe amnesia are likely to counteract the positive experience and lead to an overall negative first impression. The reverse is often true with lower doses or less potent versions of these drugs. perhaps a better example of what I’m trying to say would be cannabis/cannabinoids. it is more likely that occasional as well as many regular cannabis users enjoy cannabis strains with a low THC level, or higher CBD to THC ratio. this is because mild activation of the CB1 receptor should produce more anxiolytic, rewarding and relaxing affects. meanwhile, stronger activation of the same receptor can lead to confusion, anxiety/panic and paranoia. actually, I’ve heard quite a few reports of people including regular cannabis users preferring The much weaker cannabinoid Delta 8THC over the traditional delta 9THC For the above mentioned reasons. Many actually describe Delta 8 as more euphoric and less intoxicating/impairing than Delta 9THC.
Of course, the picture can change dramatically with the development of high tolerance after long-term use. in that case, more powerful drugs, which would have terrified or knocked out a naive user May simply be quite euphoric in somebody with very high tolerance.
As I said earlier, all this is generalisation and as you rightly pointed out, everyone’s body chemistry is different and will react differently to a particular drug.

 

[Hexenstahl]

I have no real knowledge of chemistry

Don't worry, I have just begun studying chemistry in my free time as a hobby (but I treat it the same way a serious student does who embarks on a career as a chemist) so I'm "naive" in that regard as well. AlsoTapered and I actually talk a lot about chemistry in our PMs and I greatly enjoy these discussions because he has a lot of knowledge and most importantly experience that one can learn from. I consider him an invaluable member of the BL community and I hope he remains here for as long as he feels comfortable.

What you said about cannabis is very interesting because I have noticed that I really dislike all these modern, overbred strains with an astronomically high THC content. These strains feel more like stressful psychedelics to me rather than an herb that is supposed to relax me. I always enter this really weird mental state where I feel like I'm trapped in some fever dream with recurring, very negative, self-loathing thought loops, my senses become overintensified to the point where food starts tasting bad, music starts sounding strange (because I hear all these nuances in such an isolated manner. I dunno how to explain it. It's one of those "had to be there to know it" kind of experiences.) and I get these semi-hallucinations that are really uncomfortable. Paranoia, panic attacks and the whole shebang...it's really not a comfortable drug for me.
That's why I'm always baffled when I read people on sites like leafly saying things like "oh yeah this strain just makes me so mellow and relaxed and motivates me to go to work..." WAIT WHAT?? Go to WORK?! To me cannabis is one of the most unfunctional drugs. I could never imagine being functional on this shit. I can't even talk straight when high on weed. I feel like I'm just spouting a word salad and I double and triple guess my words to make sure I'm REALLY saying the right things and even then I wonder if I haven't just embarassed myself. It's like weed gives me social anxiety which I normally don't have at all.

I suppose my brain chemistry is just primed to be anti-weed lol. I actually used to do a whole bunch of drugs in the past but I have settled for opioids only because they give me all I was looking for in cannabis but was never able to find: a powerful sense of well-being. Yep, that's what opioids do for me. Maybe opioids are for me what cannabis is for all those potheads on leafly who write about these beautifully sounding experiences they had with strain xyz.
I wish there was a strain that would just relax me. None of this mental shit going on. Just pure relaxation. I have tried so many but I think I just don't react well to the cannabinoid substance class, just like some people don't react well to cocaine, no matter how pure it is or how often they try it...

 

[AlsoTapered]

With cannabis, selective breeding has been concentrated on increasing Δ9-THC content BUT recent studies seem to suggest that MOST people found THC alone to be dysphoric and also seems to affect long-teem mental health. But Δ9-THC and CBD combined seemed to produce a much more euphoric response AND CBD is known to be a neuroleptic.

I conclude that people like different strains based on the ratio of Δ9-THC to CBD.

I've posted elsewhere that cannabis consumption and incidence of schizophreniform disorders are more closely correlated than ANY other drug be it LSD, crack cocaine or (meth)amphetamine. While all those latter compounds can induce acute mental illness, cannabis seems unique in it's ability to alter brain chemistry.

https://michaellinnell.org.uk/michael_linnell_archive/mental_illness/pdf/MH2_David.pdf

Someone actually posted footage of someone given first Δ9-THC & CBD one one day, then given Δ9-THC alone the next. The response was UTTERLY different.

If I had to guess, I would suggest that CBD acts at a silent agonist at the CB1`receptor so that Δ9-THC and CBD are COMPETING for receptor occupation producing different acute and chronic changes.

 

[someguyontheinternet]

To answer your first question, just want to remind you, I have no real knowledge of chemistry. nevertheless, I would assume that hydrogenation of opioids would only lead to changes in pharmacological effects for certain Chemical categories of opioids and it might only be certain compounds within those categories as well. hydrogenation of many other opioids maybe chemically impossible, or may break apart/change the molecule completely to the point where it becomes inactive or a different drug altogether. i’m sure also tapered would have a lot more knowledge on this.

In regards to your second point, opioid euphoria is a poorly understood Area, which, as you said, is probably highly dependent on the individual’s biochemistry and preferences. in regards to morphine and heroin being the most euphoric, these are just generalisations, probably a mixture of popular opinion and observational studies. maybe some of this comes down to first-time usage of a particular drug and the resulting experience which creates a first impression. in this regard, less potent drugs could be paradoxically more rewarding in some people as there is less chance of negative effects. this is especially true with sedating drugs like alcohol, benzodiazepines and opioids. if more potent versions of these drugs are used or they are taken in higher doses, negative side-effects like blackouts, sedation and severe amnesia are likely to counteract the positive experience and lead to an overall negative first impression. The reverse is often true with lower doses or less potent versions of these drugs. perhaps a better example of what I’m trying to say would be cannabis/cannabinoids. it is more likely that occasional as well as many regular cannabis users enjoy cannabis strains with a low THC level, or higher CBD to THC ratio. this is because mild activation of the CB1 receptor should produce more anxiolytic, rewarding and relaxing affects. meanwhile, stronger activation of the same receptor can lead to confusion, anxiety/panic and paranoia. actually, I’ve heard quite a few reports of people including regular cannabis users preferring The much weaker cannabinoid Delta 8THC over the traditional delta 9THC For the above mentioned reasons. Many actually describe Delta 8 as more euphoric and less intoxicating/impairing than Delta 9THC.
Of course, the picture can change dramatically with the development of high tolerance after long-term use. in that case, more powerful drugs, which would have terrified or knocked out a naive user May simply be quite euphoric in somebody with very high tolerance.
As I said earlier, all this is generalisation and as you rightly pointed out, everyone’s body chemistry is different and will react differently to a particular drug.

Why do you say that opioid euphoria is poorly understood? Isn't it the modulation of the VTA->NAc->VP pathway that causes euphoria and addiction? The reinforcement I thought was due to this pathway

 

[someguyontheinternet]

With cannabis, selective breeding has been concentrated on increasing Δ9-THC content BUT recent studies seem to suggest that MOST people found THC alone to be dysphoric and also seems to affect long-teem mental health. But Δ9-THC and CBD combined seemed to produce a much more euphoric response AND CBD is known to be a neuroleptic.

I conclude that people like different strains based on the ratio of Δ9-THC to CBD.

I've posted elsewhere that cannabis consumption and incidence of schizophreniform disorders are more closely correlated than ANY other drug be it LSD, crack cocaine or (meth)amphetamine. While all those latter compounds can induce acute mental illness, cannabis seems unique in it's ability to alter brain chemistry.

https://michaellinnell.org.uk/michael_linnell_archive/mental_illness/pdf/MH2_David.pdf

Someone actually posted footage of someone given first Δ9-THC & CBD one one day, then given Δ9-THC alone the next. The response was UTTERLY different.

If I had to guess, I would suggest that CBD acts at a silent agonist at the CB1`receptor so that Δ9-THC and CBD are COMPETING for receptor occupation producing different acute and chronic changes.

Isn't CBD an inverse agonist at CB1?

Also there's some recent research on THC and modification of a dopaminergic pathway

Daily Δ9-Tetrahydrocannabinol and Withdrawal Increase Dopamine D1-D2 Receptor Heteromer to Mediate Anhedonia- and Anxiogenic-like Behavior Through a Dynorphin and Kappa Opioid Receptor Mechanism - PubMed

Chronic THC increases nucleus accumbens dopamine D₁-D₂ receptor heteromer expression and function, which results in increased dynorphin expression and kappa opioid receptor activation. These changes plausibly reduce dopamine release to trigger anxiogenic- and anhedonic-like...

pubmed.ncbi.nlm.nih.gov

 

[Neuroprotection]

Why do you say that opioid euphoria is poorly understood? Isn't it the modulation of the VTA->NAc->VP pathway that causes euphoria and addiction? The reinforcement I thought was due to this pathway

Yes, you’re right. I meant to refer to the lack of knowledge that exists about why individual opioids may differ in their euphoric potential despite having exactly the same Receptor target or similar receptor binding affinity. also, dopamine is believed to be The main player in opioid euphoria as you said, however, opioids are believed to be able to generate a dopamine independent reward. this probably occurs when opioids inhibit medium spiny neurons in the nucleus accumbens, The same thing that dopamine is able to do via dopamine receptors and this is the action that generates a reward signal.

 

[Hexenstahl]

Why do you say that opioid euphoria is poorly understood? Isn't it the modulation of the VTA->NAc->VP pathway that causes euphoria and addiction?

If it was that easy then you could simply develop a drug which blocks that pathway, add it to opioid medications and thus prevent any euphoria from being felt and solve the problem of addiction. How exactly euphoria is caused, by what mechanism in specific and how strongly is indeed very poorly understood. There is also no motivation to research in this direction because our current puritanical society demonizes and vilifies this aspect of opioids even though it is the most important effect in terms of antidepressant action. But since we don't use opioids as antidepressants anymore (even though they are most effective at this compared to all that tricyclical bs that we have been fed for decades upon decades) no scientist will research in this direction as nobody is going to finance such research unfortunately.

If we understood what exactly causes euphoria we could synthesize an opioid specifically for use in psychiatric medication against depression. An opioid could be manufactured that puts less emphasis on antinociceptive action and instead puts maximum effort on firing up those neurons which lead to euphoria in the most intense manner. Kind of like fentanyl, only that instead of potentiating the analgesic potential 100x, we could potentiate the euphoric potential 100x. We would basically end up with a sort of fentanyl for psychiatric patients suffering from major depressive disorder. These patients would end up terribly addicted but honestly, an addiction to a non-toxic substance is a million times better than suffering from a disorder that prevents you from living life.

Since I myself suffer from major depressive disorder and wouldn't even be able to get out of bed (literally) without opioids, I gladly prefer being dependent on such an opioid rather than feeling dead inside. My depression became so bad by the end (before I discovered opioids) that I developed mutism (inability to speak, which is a kind of stupor). I literally lacked the motivation and drive to speak to people. This is just how bad my depression had gotten. I am 100% sure I would have long committed suicide if not for opioids. Our ancestors realized that depression is a kind of emotional pain and they treated that pain successfully with Opium. But today we think for some irrational reason that only physical pain somehow legitimizes the use of opioid medication. This has spawned an entirely new class of ineffictive and dangerous antidepressants which has only made everything worse...

 

[someguyontheinternet]

If it was that easy then you could simply develop a drug which blocks that pathway, add it to opioid medications and thus prevent any euphoria from being felt and solve the problem of addiction. How exactly euphoria is caused, by what mechanism in specific and how strongly is indeed very poorly understood. There is also no motivation to research in this direction because our current puritanical society demonizes and vilifies this aspect of opioids even though it is the most important effect in terms of antidepressant action. But since we don't use opioids as antidepressants anymore (even though they are most effective at this compared to all that tricyclical bs that we have been fed for decades upon decades) no scientist will research in this direction as nobody is going to finance such research unfortunately.

If we understood what exactly causes euphoria we could synthesize an opioid specifically for use in psychiatric medication against depression. An opioid could be manufactured that puts less emphasis on antinociceptive action and instead puts maximum effort on firing up those neurons which lead to euphoria in the most intense manner. Kind of like fentanyl, only that instead of potentiating the analgesic potential 100x, we could potentiate the euphoric potential 100x. We would basically end up with a sort of fentanyl for psychiatric patients suffering from major depressive disorder. These patients would end up terribly addicted but honestly, an addiction to a non-toxic substance is a million times better than suffering from a disorder that prevents you from living life.

Since I myself suffer from major depressive disorder and wouldn't even be able to get out of bed (literally) without opioids, I gladly prefer being dependent on such an opioid rather than feeling dead inside. My depression became so bad by the end (before I discovered opioids) that I developed mutism (inability to speak, which is a kind of stupor). I literally lacked the motivation and drive to speak to people. This is just how bad my depression had gotten. I am 100% sure I would have long committed suicide if not for opioids. Our ancestors realized that depression is a kind of emotional pain and they treated that pain successfully with Opium. But today we think for some irrational reason that only physical pain somehow legitimizes the use of opioid medication. This has spawned an entirely new class of ineffictive and dangerous antidepressants which has only made everything worse...

You say that like circuit specific drugs are easy to develop. How would that work in practice?

 

[Hexenstahl]

You say that like circuit specific drugs are easy to develop. How would that work in practice?

I'm not sure I understand exactly what you mean. Could you please elaborate a bit more? I want to avoid misunderstanding you before replying.

 

[someguyontheinternet]

You said that if the circuit I mentioned were responsible, they could create something to block that circuit and add it to opioids. How would this be accomplished in practice? What protein/receptor is the target? Does that receptor exist in other neuronal circuits?

 

[Hexenstahl]

You said that if the circuit I mentioned were responsible, they could create something to block that circuit and add it to opioids. How would this be accomplished in practice? What protein/receptor is the target? Does that receptor exist in other neuronal circuits?

This is precisely why I agreed with Neuroprotection on how we don't really understand euphoria. You then disagreed with im and implied that we do understand it and how it is the modulation of a specific pathway that causes euphoria. Well, if that was the case then we could, just like in other cases where blockage of a certain pathway is desired and has been accomplished with medication, develop a new substance which does exactly that, but we can't and this further confirms that we have an incomplete understanding of this process.

How would this be accomplished in practice? What protein/receptor is the target?

Lol if I knew this I'd be in the lab synthesizing that chemical, then patent it and make hundreds of millions if not billions of dollars off of it.
That was the whole point of my comment: to explain how we don't know what to target and how to accomplish that in practice. To this date we only have differing hypotheses that compete with one another, but nobody has come up with precisely proving what exactly causes opioid euphoria.

 

[Neuroprotection]

This is precisely why I agreed with Neuroprotection on how we don't really understand euphoria. You then disagreed with im and implied that we do understand it and how it is the modulation of a specific pathway that causes euphoria. Well, if that was the case then we could, just like in other cases where blockage of a certain pathway is desired and has been accomplished with medication, develop a new substance which does exactly that, but we can't and this further confirms that we have an incomplete understanding of this process.


Lol if I knew this I'd be in the lab synthesizing that chemical, then patent it and make hundreds of millions if not billions of dollars off of it.
That was the whole point of my comment: to explain how we don't know what to target and how to accomplish that in practice. To this date we only have differing hypotheses that compete with one another, but nobody has come up with precisely proving what exactly causes opioid euphoria.

Thank you so much. if I remember correctly, you mentioned that euphoria is now demonised as an evil effect. to be honest, that’s partly linked to The role of euphoria in taking people down the path of addiction. however, I personally believe there is something much deeper, something subconscious, which causes many people to feel that euphoria is somehow undeserved, and the same goes for any good feeling if it comes without hard work or a lot of suffering/sacrifice. if challenged, most people won’t probably admit to having these feelings, but then they would say something like “is it really good/right to feel that way all the time“ or“This opens the door to a lot of ethical problems“.. I fully understand drug prohibition if one agrees with it on the basis of severe societal harms, but I do feel that many people have a dislike or aversion to even the idea of harmless drugs based on a bizarre moral principle that doesn’t even exist in the worlds major religions.

 

[someguyontheinternet]

This is precisely why I agreed with Neuroprotection on how we don't really understand euphoria. You then disagreed with im and implied that we do understand it and how it is the modulation of a specific pathway that causes euphoria. Well, if that was the case then we could, just like in other cases where blockage of a certain pathway is desired and has been accomplished with medication, develop a new substance which does exactly that, but we can't and this further confirms that we have an incomplete understanding of this process.


Lol if I knew this I'd be in the lab synthesizing that chemical, then patent it and make hundreds of millions if not billions of dollars off of it.
That was the whole point of my comment: to explain how we don't know what to target and how to accomplish that in practice. To this date we only have differing hypotheses that compete with one another, but nobody has come up with precisely proving what exactly causes opioid euphoria.

We can understand the function of a pathway without knowing how to target it in isolation. In order to target a circuit in isolation there needs to be a unique protein to target like the subtypes of Nav channels in peripheral pain sensation. When you administer a drug it gets distributed everywhere meaning that it will bind with whatever it can irrespective of the circuit. If there is a subtype of a protein in many places it will bind with them

Receptor types and transmitters are reused in numerous circuits all over the brain. If the receptor is used in so many circuits, how do you only target one of those circuits? As far as I know there is a limit to circuit specificity when it comes to subtype

 

[Neuroprotection]

what a wonderful discussion This has been so far. whilst I still believe we don’t fully understand The exact causes of euphoria, One common target is the nucleus accumbens. it’s one of the major reward centres thought to be deeply involved in conditions like depression and addiction. all addictive and euphoric drugs are believed to act in this region, usually releasing dopamine into it either directly or indirectly. dopamine then goes on to inhibit nucleus accumbens neurons, Specifically, GABAergic medium spiny neurons MSNs. somehow, the brain interprets this as a reward signal and leads to the generation of affects like motivation and desire. interestingly, the same process can also lead to a phenomenon called stress resilience, whereby an organism subject to severe long-term stress does not succumb to behaviours like learned helplessness, Anhadonia or social avoidance, all of which are indicative of depression. collectively, these affects push the organism to keep on fighting thus increasing its chance of survival. notice I didn’t mention pleasure yet? well, that’s because actual pleasure/liking is thought to be generated by very small hotspots in the brain and are independent of dopamine, thought to rely, instead on opioid peptides, endogenous cannabinoids and GABA. isn’t it strange then, that humans seem to seek out dopaminergic drugs and no purely pleasurable compound has been developed? One reason might be that the pursuit of pleasure or other goals is actually what makes us happy rather than the attainment of direct pleasure/bliss itself. this is why anticipating something amazing can often feel much better than actually receiving that thing. I would recommend you check out my threads on dopamine and Delta FOSB for more information on this.

 

[Neuroprotection]

We can understand the function of a pathway without knowing how to target it in isolation. In order to target a circuit in isolation there needs to be a unique protein to target like the subtypes of Nav channels in peripheral pain sensation. When you administer a drug it gets distributed everywhere meaning that it will bind with whatever it can irrespective of the circuit. If there is a subtype of a protein in many places it will bind with them

Receptor types and transmitters are reused in numerous circuits all over the brain. If the receptor is used in so many circuits, how do you only target one of those circuits? As far as I know there is a limit to circuit specificity when it comes to subtype

You are definitely right about circuit specific drugs being impractical. this is why I’ve been interested in things like electrical brain stimulation using magnetic fields. i’m wondering if specific stimulation of the nucleus accumbens could cause very large amounts of Delta FOSB to build up, thus reversing Anhadonia and depression in humans as well as giving us all the ability to become super resilient and resistant to stress.

 

[Hexenstahl]

that’s partly linked to The role of euphoria in taking people down the path of addiction.

My answer to this is always the same: so what? Everyone is addicted to something. Some people are useless do-nothings who binge-watch netflix all day long, others are addicted to playing video games, sex, smartphones, gambling, drinking alcohol (oh now THAT is the right type of drug, right?), etc.
So why is it such a huge issue when euphoria causes me to be addicted to a substance that does absolutely no harm to my body or even my mind, much less to other people?

I personally believe there is something much deeper, something subconscious, which causes many people to feel that euphoria is somehow undeserved, and the same goes for any good feeling if it comes without hard work or a lot of suffering/sacrifice.

I don't believe that to be the case honestly. I think this whole aversion towards opioids and really drugs in general is a rather modern phenomenon that was kickstarted by the puritan movement in the early 20th century and finally got hold of society when the Anti-Opium law was passed in 1930, but prior to that Opium was part of so many medicines and has always been used recreationally since thousands of years, even though it never replaced alcohol in the west unfortunately. So I don't see this animosity towards opioids as something that has a deep, underlying root cause, but instead it is entirely driven by propagandistic indoctrination that is barely a century old. The fact that people don't even really know why they are against it, except repeating like programmed bots anti-drug talking points, proves that this has no deeper cause and is a superficial, albeit tenacious aversion.

This anti-opioid sentiment is more of a western thing anyway. The west is pathologically obsessed with being in control at all times and being productive and disciplined (with the exception of Japan where these qualities are taken to an extreme, which explains why drug use is frowned upon even more in Japan than in the west), which to a certain extent aren't bad qualities, but since an opioid high embodies the exact opposite of these qualities, it is only logical that a culture which is primed to embrace such attitudes comes to hate such a substance class. Society should allow periodical relaxations of such attitudes and learn to be more tolerant.
The middle east for example is very different in this regard. They have a history of Opium use. Just as much as alcohol is (unfortunately) part of western culture, Opium has always been part of middle eastern culture and that is simply because these people have a completely different mentality than we have. Even though Opium is illegal on paper in Iran, nobody really gives a shit when you start smoking Opium in public. It's an unenforceable law to prohibit Opium use.
The west should learn to be more like the east, even if it is only for the sake of our organ health. Seriously, what the fuck is it with the western mind and its degenerate thirst for an utterly toxic substance that harms nerves, cells and even the DNA? Alcohol wasn't even originally made to be drunk, but for conservation, and yet we somehow ended up integrating this crappy substance into our culture.

I fully understand drug prohibition if one agrees with it on the basis of severe societal harms

...and nobody seems to care about the societal harm caused by alcohol. And mind you, we aren't talking about the harm caused by alcohol addicts, but mere "social" drinking.

We can understand the function of a pathway without knowing how to target it in isolation. In order to target a circuit in isolation there needs to be a unique protein to target like the subtypes of Nav channels in peripheral pain sensation. When you administer a drug it gets distributed everywhere meaning that it will bind with whatever it can irrespective of the circuit. If there is a subtype of a protein in many places it will bind with them

Yes, yes and yes. The problem is we don't know how to do that with the proteins/neurons/switches/pathways/receptors that are ultimately responsible for opioid-induced euphoria because we haven't been able to even agree on what the cause of that phenomenon is. If we can figure out the basics, then we can go deeper into the specifics and maybe find out how to develop a drug that prevents euphoria. I do NOT know how to do that. I just said it COULD be possible because we have been able to do similar things with other drug-induced side effects, that's all.

 

[Neuroprotection]

My answer to this is always the same: so what? Everyone is addicted to something. Some people are useless do-nothings who binge-watch netflix all day long, others are addicted to playing video games, sex, smartphones, gambling, drinking alcohol (oh now THAT is the right type of drug, right?), etc.
So why is it such a huge issue when euphoria causes me to be addicted to a substance that does absolutely no harm to my body or even my mind, much less to other people?


I don't believe that to be the case honestly. I think this whole aversion towards opioids and really drugs in general is a rather modern phenomenon that was kickstarted by the puritan movement in the early 20th century and finally got hold of society when the Anti-Opium law was passed in 1930, but prior to that Opium was part of so many medicines and has always been used recreationally since thousands of years, even though it never replaced alcohol in the west unfortunately. So I don't see this animosity towards opioids as something that has a deep, underlying root cause, but instead it is entirely driven by propagandistic indoctrination that is barely a century old. The fact that people don't even really know why they are against it, except repeating like programmed bots anti-drug talking points, proves that this has no deeper cause and is a superficial, albeit tenacious aversion.

This anti-opioid sentiment is more of a western thing anyway. The west is pathologically obsessed with being in control at all times and being productive and disciplined (with the exception of Japan where these qualities are taken to an extreme, which explains why drug use is frowned upon even more in Japan than in the west), which to a certain extent aren't bad qualities, but since an opioid high embodies the exact opposite of these qualities, it is only logical that a culture which is primed to embrace such attitudes comes to hate such a substance class. Society should allow periodical relaxations of such attitudes and learn to be more tolerant.
The middle east for example is very different in this regard. They have a history of Opium use. Just as much as alcohol is (unfortunately) part of western culture, Opium has always been part of middle eastern culture and that is simply because these people have a completely different mentality than we have. Even though Opium is illegal on paper in Iran, nobody really gives a shit when you start smoking Opium in public. It's an unenforceable law to prohibit Opium use.
The west should learn to be more like the east, even if it is only for the sake of our organ health. Seriously, what the fuck is it with the western mind and its degenerate thirst for an utterly toxic substance that harms nerves, cells and even the DNA? Alcohol wasn't even originally made to be drunk, but for conservation, and yet we somehow ended up integrating this crappy substance into our culture.


...and nobody seems to care about the societal harm caused by alcohol. And mind you, we aren't talking about the harm caused by alcohol addicts, but mere "social" drinking.


Yes, yes and yes. The problem is we don't know how to do that with the proteins/neurons/switches/pathways/receptors that are ultimately responsible for opioid-induced euphoria because we haven't been able to even agree on what the cause of that phenomenon is. If we can figure out the basics, then we can go deeper into the specifics and maybe find out how to develop a drug that prevents euphoria. I do NOT know how to do that. I just said it COULD be possible because we have been able to do similar things with other drug-induced side effects, that's all.

Some amazing points you made here.
I’m fascinated by your description of opium/opioids as being highly addictive, but relatively harmless to the body/mind. this has been something I’ve been wondering for a long time, I’ve never heard of heroin induced psychosis or violent behaviour, perhaps the only drawback might be criminal activity linked to addiction which could be overcome by legalisation.

I am a Muslim ethnically from the Middle East although I was born and raised in The UK. interestingly, it seems to be that Islamic scholars there and even those in western countries have taken on a very fearsome reactionary stance on all drugs even if they don’t alter judgement. Some Muslims have gone as far as to consider tobacco/nicotine an intoxicant. not all Islamic scholars are like this, but those with the most popularity are.

In regards to anti -opioid sentiment being a relatively new puritanical phenomena, you are correct. however, there seems to have always existed a stream of thought among some people that anything causing a pleasant mood or which is very enjoyable/addictive is inherently evil and should be prohibited, even if it doesn’t cause any major negative effects. many Christians, and even some Islamic scholars wanted coffee to be banned because they despised its stimulant effect. I really do hope safe recreational and functional drugs can be developed which don’t cause loss of control/judgement, brain damage, or any other nasty side-effects like alcohol and many other drugs.

Your point about addiction not being A bad thing is really interesting to me. I actually created a thread about this. here’s the link to it, please check it out, I hope you find it interesting and relevant.

Could addiction be therapeutic?

okay, this probably sounds like a really stupid question and maybe it is. however, certain experiences I’ve had in my life have brought me to the conclusion that addiction to certain substances have a therapeutic effect and could help me push through the day. of course, I’m talking about...

bluelight.org

 

[Hexenstahl]

perhaps the only drawback might be criminal activity linked to addiction which could be overcome by legalisation.

Exactly! That is what I always tell prohibitionists. The societal cost of prohibition is a lot higher than simply legalizing all drugs and regulating its production where they can then be sold in pharmacies like in the 19th century. You could simply walk into a pharmacy and buy a gram of cocaine or Laudanum and it didn't cause an "epidemic".

interestingly, it seems to be that Islamic scholars there and even those in western countries have taken on a very fearsome reactionary stance on all drugs even if they don’t alter judgement.

I think it is because this attitude has become globalized just like many other things today. I could be wrong though. It's just that when I dabbled in middle eastern history for a while, I couldn't help but notice how most of the time the cultures over there had a much more relaxed attitude towards opium. We have a couple of people here in our maintenance clinic who have a muslim background (very kind and hospitable people btw) and I always tell them how I wish the west had the same anti-alcohol mindset as their cultures do. Ofc it shouldn't result in prohibition and such things as death penalty, but I think society would benefit a whole lot if we could create an associative chain between alcohol and feelings of disgust in children, which would ensure that they are much less likely to touch alcohol when they grow up and have similarily healthy organs as many muslims do. There is a reason why illegal organ harvesting is often conducted in the middle east. It's because these people have tremendously healthy organs due to the absence of ethanol in their bodies. If I had children I would much prefer it if they simply smoked a joint instead of going to the Oktoberfest or Volksfest and drink away their brain cells.

there seems to have always existed a stream of thought among some people that anything causing a pleasant mood or which is very enjoyable/addictive is inherently evil and should be prohibited

Yeah these extremists always existed I suppose. However, the thing is that these extremists have taken over society to the point where this attitude is no longer considered to be extreme and this has resulted in the war on addicts.

I really do hope safe recreational and functional drugs can be developed which don’t cause loss of control/judgement, brain damage, or any other nasty side-effects like alcohol and many other drugs.

I fully agree with you there! This might become possible one day as science advances.

Your point about addiction not being A bad thing is really interesting to me. I actually created a thread about this. here’s the link to it, please check it out, I hope you find it interesting and relevant.

Thank you for the link. I will definitely read it now that I have nothing to do anymore.