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.