Opioids Vote for your favorite Opiate (in terms of warmth, Euphoria, bliss, etc.)

[Northwesternparacelsus]

Oxymorphone slams
Panda is very real my DOC

Very interesting will watch thread. We were overdue for a vote here!

Heroin 3) close

 

[4DQSAR]

@Northwesternparacelsus - WSB infamously wrote "Letter from a master addict to dangerous drugs" to the British Journal of addiction in 1956 and I may be wrong but I don't think oxymorphone had been used medically at that point BUT he suggested it would be the most euphoric opioid.

In fact his understanding of QSAR was probably better than most doctors and while now we know some of the ideas were wrong, with the information to hand, he had good reason to list things like diacetyloxymorphone and diacetyldihydromorphine.

Even now we only have a small number of animal models which purely measure analgesic activity to guesstimate if he was right or wrong since as far as I know none of the other things he suggested had ever undergone human trials.

 

[RUC4]

i've never heard of or tried tilidine. it has piqued my curiosity.

 

[DeathIndustrial88]

i've never heard of or tried tilidine. it has piqued my curiosity.

I think it's more commonly used in Europe.

I believe @Hexenstahl wrote a whole post about this opioid & it being their favorite. At least I think it was tilidine. It has some unique properties, I believe dopamine reuptake inhibitor properties, which occurs because of it's metabolite nortilidine.

I'd love to try it myself too, personally. It's basically an opioid & a stimulant in one.

 

[DeathIndustrial88]

There's so many opioids out there, rare or just not used much that I will probably never get to try & it just makes me sad. lol

People think an opioid is an opioid is an opioid.... but every opioid has it's own unique feel & energy to it. And everyone's bodily chemistry is different, so what might be boring for one person is gonna be fun for another. There's so many variables & experiences to be had.

I'd love to try tilidine, dilaudid, opana, levomethadone, O-desmethyltramadol (in it's pure form). There's just so much.

 

[4DQSAR]

I believe dopamine reuptake inhibitor properties, which occurs because of it's metabolite nortilidine.

Dinortilidine overlays cypenamine.

Now I don't know if nortilidine is in effect 'methylcypenamine/methcypenamine' although it IS flagged as a drug of abuse in some databases.

 

[DeathIndustrial88]

Dinortilidine overlays cypenamine.

Now I don't know if nortilidine is in effect 'methylcypenamine/methcypenamine' although it IS flagged as a drug of abuse in some databases.

Not sure myself. Never heard of cypenamine til now. Sounds like an experimental psychostimulant drug.

But Googles AI overview definitely says it has dopamine reuptake inhibitor properties. Along with NMDA antagonists properties.

Yes, Tilidine possesses dopamine reuptake inhibitor (DRI) properties, but this activity is exclusively attributed to its primary active metabolite, nortilidine. [1, 2]
While the parent drug tilidine itself is a weak prodrug with minimal pharmacological activity, it undergoes rapid first-pass metabolism in the liver to form nortilidine. Nortilidine functions as a dual-action compound: [1, 2]

• • Mu-Opioid Receptor Agonist: It binds strongly to μ-opioid receptors to provide morphine-equivalent pain relief.
  • Dopamine Reuptake Inhibitor: It blocks the dopamine transporter (DAT), preventing the reabsorption of dopamine and increasing extracellular concentrations of the neurotransmitter in the brain. [1, 2, 3]

Additionally, specific isolated isomers of nortilidine exhibit NMDA antagonist properties. This diverse pharmacological profile contributes to both its effective pain-blocking capabilities and its high potential for misuse, which is why medical preparations of the drug (such as Valoron N) frequently combine tilidine with the opioid antagonist naloxone to deter intravenous abuse.


That last part is confusing, because why would anyone wanna abuse IV Tilidine if it needs to undergo first-pass metabolism in the liver into it's active metabolite?

 

[4DQSAR]

I wrote and deleted the apart about NMDA activity because it's another example of papers woozing from a study in which EVERY class of receptor tilidine had even slight affinity for and it's only their we see it mentioned. I am guessing somewhere along the line it was seen as useful to someone to suggest tilidine MAY be able to treat pain that a pure opioid could not. I believe levodromoran and ketobemidone are examples of where those specific medications have significant NMDA activity therefore are better able to treat certain types of pain.

As for addition of naloxone, I strongly suspect political reasons. Same as saying something is a 'mixed agonist' or 'partial agonist'. Both terms are so opaque as to be meaningless.

 

[Hexenstahl]

As DI88 said, Tilidine is indeed my favourite, and I had the privilege of trying a lot of opioids thanks to the Darknet, the RC market (research chemicals) and my sister who works as a nurse in a palliative care hospital. What I can say with absolute certainty after all these years of trying all sorts of agonists, is that the potency of an opioid has zero relation to its euphoric potential INCLUDING its nociceptive potential. I had cases where a bunch of codeine was more effective at killing my past shoulder pain than superduper "strong" oxycodone. This is true for the entire non-side effect spectrum of opioid medication. That's the reason why analgetic potency is a total misnomer in my opinion, because the only thing an opioid's potency tells you is its dosage in relation to the opioid of reference, which is why we should be referring to it as dose/dosage sensitivity because this is what it actually is.
Drop the whole potency nonsense because it creates wrong expectations, both in the field of science and pain management, as well as in the recreational field (perhaps especially there). This is why doctors have to experiment so much when it comes to the right opioid agonist for their patient. It's because opioids are a wild mix. Sure, they are the most reliable drug class, but they are a wild mix (or maybe our brain chemistry is?).

Let me give you an example: most people say Heroin is one of the most euphoric opioids they have taken. Well, it turned out I didn't actually like it that much when I took it. I remember when I made the switch from Tilidine to Heroin I was somewhat disappointed. Both because its stronger sedation covered a great portion of the euphoria like a leaden blanket, as well as the fact that its duration felt less stable than Tilidine. Or how about an opposite example: Morphine. Tons of people say morph is not euphoric. I hadn't tried this agonist for a very long time because I was operating under that very same assumption. I thought that if 99% of all the people I have heard from keep saying that morph isn't worth it, then it must be true. Then one day my plug's dealer ran out of his usual palette of opioids and instead gave him a whole bunch of MS Contin 30 mg blisters, which I took ofc because that beats having no opioid high at all lol. When I dropped that pill I was amazed at how good I felt. I was weirdly sedated and motivated at the same time. It was a bit like heroin without the lead blanket feeling I described earlier.

So long story short: every opioid is unique, there is no true consensus on which one is the most euphoric. If you want proof of this, check out this thread in a swiss-german drug forum where people have made lists about their favourite opioids, ranked from most to least euphoric. Aside from Heroin, there is a great amount of interindividual variance when it comes to the perception of which opioids are the best. https://forum.eve-rave.ch/viewtopic.php?t=37344

I think we should make a list here too, wouldn't that be fun? Lemme be the one who throws the first stone

#1 Tilidine
#2 Oxymorphone (only had one genuine pill from the USA that was not pressed fent bs)
#3 Levomethadone
#4 Oxycodone
#5 Morphine
#6 Pantopon
#7 Shire Opium
#8 Codeine
#9 O-Desmethyltramadol
#10 Tramadol
#11 Heroin (golden triangle)
#12 Heroin (afghan brown)
#13 Heroin (mexican black tar)
#14 Hydrocodone
#15 Hydromorphone (waaaay too short, otherwise it would replace Morphine)
#16 Kratom (it is beyond me how people can actually gulp down massive amounts of this awful tasting powder. Euphoria isn't always there, but if it is, it's meh)
#17 Methadone (it's just a sleeping pill)
#18 DHC (feels like the down-syndrome version of codeine to me)
#19 Buprenorphine (tried this crap for the first and last time a couple months ago)
#20 Ro4-1539 (holy mother of god, never again)

Wishlist: 1-Iodomorphine, Oxymorphazone, 14-Cinnamoyloxycodeinone, Dihydroheroin and that Tilidine derivative @Opiophiliclab mentioned on his blog.

 

[Ozymandeus]

Best overall: good ol diacytelmorphine

Best pharma: oxymorphone (that drug had legs for dayyyyyyys . The high lasts so long it has different phases to it. First several hours feels like a more energetic version of oxy, then it turns into nod city for another 6 hours. Crazy shit.)

 

[Ozymandeus]

#3 Levomethadone

Never heard of this. Is this an RC or was I unaware methadone was chiral and you somehow obtained that pure isomer?

 

[4DQSAR]

Ro4-1539 is non-selective. It's a potent analgesic in animal models, yes, but that's because it mediates analgesia via KOR and DOR agonism.

Interesting that one popped up as oddly, Ro 4-0335 was misprinted in the original UNODC document and in fact is an order of magnitude more potent than the paperwork suggests. The screwup was the researchers producing the chiral N-substituent but the document referring to the (far) less potent stereoisomer.

It always shocks me to hear when vendors don't even bother to obtain the original papers and rely on an animal model of analgesia as a metric for potency or safety much less subjective activity in man.

The fact that the achiral phenacyl derivative in the same list is stated as being more active when we have a VAST amount of data from the pethidines, prodines and many other classes that the phenactyl was synthesized first then reduced and the two stereoisomers were shown to display a huge disparity in their activity and how in every single case the (S) enantiomer is around an order of magnitude more potent than the (R) enantiomer.

 

[Hexenstahl]

Never heard of this. Is this an RC or was I unaware methadone was chiral and you somehow obtained that pure isomer?

Levomethadone is available as a prescription drug here in Germany under the brand name "Polamidon". It is twice as potent as Methadone and lasts twice as long. If you are completely opioid naive and drop some Pola you'll be legit high for 48h plus another day of afterglow. You'll need one hell of a long break after that though if you don't want to develop a tolerance, which is why I don't recommend it to newbies. It is prescribed only to two sorts of patients: those who react badly to literally all other opioids and those in maintenance therapy.

EDIT:
don't understand why good ol' Göring packed his suitcases with short acting DHC instead of Polamidon when fleeing Berlin. Maybe broken supply lines...

 

[MedicinalUser247]

Oxymorphone is a real winner in my book.

 

[4DQSAR]

EDIT:
don't understand why good ol' Göring packed his suitcases with short acting DHC instead of Polamidon when fleeing Berlin. Maybe broken supply lines...

Because methadone was judged 'too toxic' in the human trials (which also noted the dependence liability was far higher than morphine).

As for his favourite, plain old morphine, well, when Turkish opium was no longer available, morphine became unavailable.

The reason why his personal doctor had a Gladstone (doctors) bag totally full of DHC was because using Göring's authority, he went to the factory where codeine was reduced to dihydrocodeine and seized every single pill in the place. Before trial he had to be detoxified as by all accounts the guy was necking dozens each day (DHC only having a soft ceiling).

Long ago my next door neighbour retold how he was a guard at the trials and how like many senior Nazi leaders, Göring had a false tooth containing cyanide. After Himmler used his, all suspects had their dental work checked but classy as always Göring shoved his false tooth up his arse to avoid detection.

Now you know the above - reconstruct Göring's last minutes. Glorious or not

 

[Psychonauticunt]

Levomethadone is also available here as an alternative to racemic methadone. It is primarily prescribed with the rationale that since practically all the desirable pharmaceutical effects - as far as we know - come from the levorotatory isomer, the dextro counterpart could potentially be responsible for some side of the side effects.

It is 2x the potency, but it definitely does not have twice the duration.

 

[4DQSAR]

@Psychonauticunt - thank you for filling in that detail. The two isomers of methadone are subject to different enzymatic metabolic pathways With CYP2C19 being specific to levomethadone (dextromethadone is metabolized faster since CYP2B6 performs the same sequatial N-demethylation).

BUT it does mean that a person cannot simply be swapped from one to the other assuming that the titration will carry over.

Also while vastly less active (and having cardiotoxic metabolites), dextromethadone is still active and I assume genetic variability will mean just how active varies between those prescribed it.

It's also possible that both isomers of dinormethadone can reveribly form the imine that is actually excreted but nothing says only internal imine formation is possible so the presence of dextromethadone could delay excretion by producing an imine using two molecules - I've never heard of that imine being excreted.

 

[Ozymandeus]

Levomethadone is available as a prescription drug here in Germany under the brand name "Polamidon". It is twice as potent as Methadone and lasts twice as long. If you are completely opioid naive and drop some Pola you'll be legit high for 48h plus another day of afterglow. You'll need one hell of a long break after that though if you don't want to develop a tolerance, which is why I don't recommend it to newbies. It is prescribed only to two sorts of patients: those who react badly to literally all other opioids and those in maintenance therapy.

EDIT:
don't understand why good ol' Göring packed his suitcases with short acting DHC instead of Polamidon when fleeing Berlin. Maybe broken supply lines...

Interesting. Thanks.

I have tried a few of the RC methadone analogs or derivatives available such as methiodone and they are all much less potent than regular methadone and nothing to write home about

 

[Hexenstahl]

It is 2x the potency, but it definitely does not have twice the duration.

Uhm yes it actually DOES have twice the duration. Why else does literally every levometh patient in my clinic, including me, start to feel wd only 40h - 48h after our last dose? With methadone you last only a day on average. It ain't like I pulled this out of my arse. It's based on our experiential evidence. Not trying to sound passive-aggressive or anything. Just saying the way it is, that's all...

EDIT:
I remember both a personal acquaintance as well as a forum member over at eve & rave who in their opioid naive stage reported on literally being high for two entire days off of Pola, so there is also that. Not sure which thread it was, but it is definitely there. Maybe I'll go and search after it when I have the time and the will.

EDIT #2:
also, you can pretty much inductively reason that it very likely lasts that long when you consider how long the duration of the so called "short" acting opioids is for completely opioid naive people and extrapolate that to an opioid with an hl that ranges anywhere between 33h to 55h. Take my fav opioid Tilidine for example: that molecule has an hl between 3h - 5h and as I said in my initial post here, I used to be high for 12h straight after taking this stuff. I'm pretty darn sure that if I had had access to Pola back in those days and taken some, I would have been drooling for two days.

 

[Psychonauticunt]

Uhm yes it actually DOES have twice the duration. Why else does literally every levometh patient in my clinic, including me, start to feel wd only 40h - 48h after our last dose? With methadone you last only a day on average. It ain't like I pulled this out of my arse. It's based on our experiential evidence. Not trying to sound passive-aggressive or anything. Just saying the way it is, that's all...

Then why does nobody I know - and I know a bunch of people on both - report it having twice the duration? Also, why would it have twice the duration, unless dextromethadone somehow makes it metabolize that much faster? Literally half of the methadone is levomethadone, so out of 100mg methadone, that contains 50mg levomethadone. Why would that have half the duration of 50mg of levomethadone in isolation, unless dextromethadone literally halved its duration?

It's not an analogue of methadone, it is the active isomer.

I am also not pulling this out of my arse. Apart from having a lot of experiential evidence, I have read studies on the subject, and also the most recent prescribing guidelines for opioid maintenance therapy for my country. There is nowhere any mention of levomethadone having any meaningful differences in dosage or dosage interval, other than that it is twice as potent. The standard dosing is also still once per day.

I'm not saying the racemic mixture could not have different pharmacokinetics, not at all. But there is no indication that dextromethadone affects metabolism to such an extent that it would halve the duration of levomethadone when taken with it. Nowhere near. They are treated in clinical practice and studies as having equivalent duration, half-life and accumulation, with potency the only meaningful difference.