DeathIndustrial88
Bluelighter
Thank you!
When I read sekio say "It was just a simple correction", I wanted to pull my eyes out. No, Sekio, there were no "corrections", because nothing I said was incorrect.
Jesus christ. lol *facepalm*
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N&PD Moderators: Skorpio | someguyontheinternet
What determines how euphoric an opioid is?
- Thread starter TheJuner
- Start date
When I read sekio say "It was just a simple correction", I wanted to pull my eyes out. No, Sekio, there were no "corrections", because nothing I said was incorrect.
Jesus christ. lol *facepalm*
Dead Machination
Bluelighter
- Joined
- Feb 18, 2023
- Messages
- 236
Other than the neuro-chemical processes, it's worth noting that set and setting have a lot to do with the high. I've felt better off a shot of 1 Dilaudid when I was having a stressful shit day than blowing a whole bag of them on a good day.
DeathIndustrial88
Bluelighter
True!
And tolerance.
I find 400mg of tramadol more euphoric than say.... 10mg of hydrocodone.
But I wouldn't find 50mg of tramadol more euphoric than 10mg of hydrocodone.
So there's tons of variables.
AlsoTapered
Bluelighter
That is a very good point. Although hydromorphine tablets are technically prescribed in the UK, I've only known 1 person who was ever given them. Pallidone and Pallidone SR are a second-line treatment usually only given to people in end-stage cancer,
Many people have said that IV hydromorphone has 'an amazing rush but no legs'. I've never used pins (I have a strong aversion after a bad hospital experience) but from what Russian friends (chemists) tell me, desomorphine is 'the same but amplified'. Onset is tremendously fast but duration is only 2-2½ hours. Their are some closely related compounds that are some x6 more potent than desomorphine and have an even more abrupt onset-end curve. I won't name them but you can work them out.
I'm still a bit in the dark as to the claims that Canadian addicts obtain hydromorphone which they sell to obtain 'down fentanyl'. I'm not even sure what 'down fentanyl' is. To begin with, someone for whom 100mg of hydromorphone/day isn't sufficient seems pretty far out and yet (if true) these pills (who SOMEONE is using) are apparently 'mostly' sold to obtain this rather unnervingly named fentanyl derivative.
I keep saying it - fentanyl does bind to an extra site (compared to hydromorphone and methadone) so I do wonder if they do truly substitute. Is it choice or is it because the HM/M don't actually stop withdrawal. As usual, I point out R-4066 (specifically it's acetyl ester derivative that works for 2-3 days) and bezitramide, both of which DO bind to that errant site.
All I know is that while every other nation on earth was introducing methadone maintenance, the Dutch chose Bugodin/Bigodin (bezitramide). The Dutch HAVE now switched to methadone and people who were on bezitramide noted that methadone did NOT fully substitute...
But hey - these are worthless junkies so why BOTHER to even test such a hypothesis? If it's methadone or nothing, 100% of those in treatment ACCEPTED methadone... and then, it was discovered, were using other opioids as well.
sekio
Bluelight Crew
Well, excuse me for maybe helping you (and others) learn something new. I don't think I ever used rough language or insulted you.
I don't follow him around all day like a puppy, we just seem to share interests and post in similar threads. And I was unaware of this until now.
It's more accurately just referred to as "down", for some reason the three main abusable drugs are referred to by directions: "up" is cocaine, "down" was (formerly) heroin and is now any strong opioid, and "side" is meth.
Anyway here in Vancouver it was a slow transition from heroin cut with caffeine, to heroin with small amounts of fentanyl, to fentanyl with small amounts of heroin, and then later mixtures of fentanyl, 4-fluorofentanyl, carfentanil, and caffeine. Now there is also sometimes xylazine. (That's not really relevant to the topic at hand, but, there's your Vancouver drug fact for you).
The ironic thing is, when carfentanil hit the scene, it was actually preferred by a lot of street users, simply because instead of fentanyl's very short half life (the FDA says 219min or ~3.6h) carfentanil has almost twice that with 7hrs. It was a regular complaint that with fentanyl "down" that despite it hitting harder, you could need up to 4-6 doses a day to avoid withdrawals. (which the dealers loved, in addition to making their "points" and "q's" (street units for, presumably, 100mg and 250mg amounts) much, much smaller - a "point" could be as little as 20-30mg of material with fentanyl thanks to it being 30-50% fent sometimes - the end result being more profit on all fronts). Strangely though, a lot of dealers still kept up to 25% actual heroin in their supply, which was a bit confusing, and I always figured was for "flavouring" purposes...
It does substitute when they're in withdrawals, the problem is, if you are habituated to smoking huge amounts of fentanyl/carfent all day your tolerance is going to be so high that you need hundreds of milligrams of IV hydromorph to catch a buzz. I mean, even taking into consideration these people are usually on high doses of methadone, 100-200mg ish, meaning you'd need to IV a LOT of hydromorphone for a comparable effect, compared to much less of the "down".
(anyway enough about the Vancouver dope scene or DeathIndustrial88 will get all pissy again)
AlsoTapered
Bluelighter
Yeah - Caffeine is traditionally mixed with brown heroin to lower it's MP to make it easier to smoke. Even when people get HAT (heroin assisted treatment), they break open dry-amps of pure diamorphine hydrochloride and add 10% caffeine (I'm told it's 10% by Lifeline Publications and Aspire).
I can understand small amounts of fentanyl to increase the flash and of course because it's cheaper. in an interview George Marquardt mentioned that he chose to make alpha methyl fentanyl because it's duration is almost the same as heroin and so it would be very difficult for a user to detect.
I have to admit being surprised that carfentanil is being made although I have JUST noticed the Ugi reaction:
Which explains a lot. I think the last time I looked at the synthesis of a fentanyl derivative was before 2010 (because, you know, I was doing other stuff) but suddenly it makes sense. It would NOT be difficult to make alpha methyl carfentanil... or indeed swap that second benzene ring for a 2-thiophene, 2-furan or indeed a number of 5 & 6-membered aromatics.
Janssen did prepare a whole load of different fentanyl analogues in which the B ring was a different aromatic. It would appear that some of them were more potent (like the ones I mentioned) but the durations weren't very uniform (the latter). The same arylethyl was also tested on levorphanol derivatives.
www.unodc.org
As you can see, Ro 4-1539 is twice as potent as RO 4-1540 but duration is shorter in animal models. In man those differences seem to be larger and also somewhat more unpredictable. Those MED50 values are also rather low. So I'm going to suggest that the NOP activity sufentanil (TI 15700) compares well with plain fentanyl (TI 470).
I DID post an image & paper on that etonitazene derivative that is x4 more potent than the parent drug. Sadly their was no toxicity data but I'm going to suggest that while x4 more potent, the LD50 won't be HIGHER and so the TI will increase.
It's like the Chinese taking BDPC and making C-8813. As you can see from the paper, they didn't try a whole skew of aromatics, they only produced a single compound BECAUSE they have seen the work on the levorphanol derivatives and Janssen's work on trying EVERY aromatic and concluded that the same issues would turn up.
I can understand small amounts of fentanyl to increase the flash and of course because it's cheaper. in an interview George Marquardt mentioned that he chose to make alpha methyl fentanyl because it's duration is almost the same as heroin and so it would be very difficult for a user to detect.
I have to admit being surprised that carfentanil is being made although I have JUST noticed the Ugi reaction:
Which explains a lot. I think the last time I looked at the synthesis of a fentanyl derivative was before 2010 (because, you know, I was doing other stuff) but suddenly it makes sense. It would NOT be difficult to make alpha methyl carfentanil... or indeed swap that second benzene ring for a 2-thiophene, 2-furan or indeed a number of 5 & 6-membered aromatics.
Janssen did prepare a whole load of different fentanyl analogues in which the B ring was a different aromatic. It would appear that some of them were more potent (like the ones I mentioned) but the durations weren't very uniform (the latter). The same arylethyl was also tested on levorphanol derivatives.
UNODC - Bulletin on Narcotics - 1958 Issue 4 - 006
Braenden, Eddy & Halbach (1955), summarizing the relationship between chemical structure and analgesic action, said "In morphine and its derivatives the methyl substituent on nitrogen seems essential because its substitution by other alkyl groups reduces or abolishes analgesic action." It is...
www.unodc.org
As you can see, Ro 4-1539 is twice as potent as RO 4-1540 but duration is shorter in animal models. In man those differences seem to be larger and also somewhat more unpredictable. Those MED50 values are also rather low. So I'm going to suggest that the NOP activity sufentanil (TI 15700) compares well with plain fentanyl (TI 470).
I DID post an image & paper on that etonitazene derivative that is x4 more potent than the parent drug. Sadly their was no toxicity data but I'm going to suggest that while x4 more potent, the LD50 won't be HIGHER and so the TI will increase.
It's like the Chinese taking BDPC and making C-8813. As you can see from the paper, they didn't try a whole skew of aromatics, they only produced a single compound BECAUSE they have seen the work on the levorphanol derivatives and Janssen's work on trying EVERY aromatic and concluded that the same issues would turn up.
polarthedog
Bluelighter
- Joined
- May 30, 2021
- Messages
- 2,039
There’s also epsilon opiate receptors that were discovered recently
Though I have no idea if they have anything to do with the euphoria
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DeathIndustrial88
Bluelighter
There's also the TOLL-Like receptor. Not technically an opioid receptor but some opioids interact with it.
There's also ORL1 (nociceptin/orphanin receptors)
I mean we can go on and on about receptors.
Some opioids are even NMDA antagonists.
Some opioids are SNRI's.
Some opioids suppress the immune system.
Some opioids enhance the immune system.
And on & on.
But I still stand by the fact that most euphoric opioids bind to the sub-receptor mu2. Which is what makes drugs like heroin more euphoric than say buprenorphine or fentanyl, even though both buprenorphine & fentanyl are highly more potent than heroin.
"Opioids are a group of analgesic agents commonly used in clinical practice. There are three classical opioid receptors (DOP, KOP and MOP), while the novel NOP receptor is considered to be a non-opioid branch of the opioid receptor family." - -https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4590096/
Oh no, looks like @sekio & @AlsoTapered need to "correct" the National Library of Medicine & the NIH.
DeathIndustrial88
Bluelighter
You didn't help me "learn something new".
You're delusional, as nothing I said was incorrect nor did you add any information that I didn't already know.
You STILL can't respond without trying to act as though you "taught" me something or I "needed to be corrected".
Instead of saying "yeah my bad, you're right".
Get over yourself.
I've been studying pharmacology for over 10 years, you didn't teach me anything new on this thread. Nor did I need correcting (for the 900 millionth time).
It's insulting to try & tell some one that you "taught" or "corrected" them when they didn't need either of those things in the first place And you continue to still act confused like "I didn't insult you". lol Yeah okay.
Keep acting like you're the smartest person in the room bro.
"Har Har, Deathindustrial will get pissy again har har".
Aren't you a mod? Shouldn't you be correcting people who actually need correcting instead of rambling with AlsoTapered about how "smart" you guys both are?
I find it hilarious that neither one of you had any genuine rebuttal to my last comment, you guys just continue on talking about shit that isn't even relevant to OP's question anymore trying to make yourselves look & feel just "oh so smart", when in reality you aren't any smart or better than any one else here.
Anyone claiming benzos cause liver damage has a lot of nerve trying to "correct" some one else. And sekio, you've lost your credibility to me by seeing you spend more time defending AlsoTapered rather than admitting that nothing I said was incorrect. Don't wanna hurt your own ego eh? Would rather sit here bullshitting with some one who tried to get a person to stop taking their clonazepam (very dangerous & could kill somebody with a seizure if not done correctly) instead.
And guess what...
THERE ARE STILL 3 MAIN OPIOID RECEPTORS.... MU, KAPPA & DELTA.
Please tell me the NIH/Pubmed needs "correcting" as well. You won't, because you both know you're full of shit.
"There are three classical opioid receptors (DOP, KOP and MOP), while the novel NOP receptor is considered to be a non-opioid branch of the opioid receptor family."
Basic opioid pharmacology: an update
Opioids are a group of analgesic agents commonly used in clinical practice. There are three classical opioid receptors (DOP, KOP and MOP), while the novel NOP receptor is considered to be a non-opioid branch of the opioid receptor family. Opioids can ...
www.ncbi.nlm.nih.gov
Yeah, let me go around & comment & "correct" everything you say (when it isn't incorrect to begin with) and see how you like it.
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DeathIndustrial88
Bluelighter
Pentazocine is also an opioid that is postulated to have weak sigma 1 agonism btw.
And from what I've read, the sigma receptor was still considered an opioid receptor all the way up until 1996.
I'm not completely sure about that, but if true, that would mean AlsoTapered was incorrect about that as well.
It was identified as an "opioid receptor in 1976"... but that doesn't mean that they "haven't been classified as opioid receptors since the 70s"...
Sounds like they were classified as such well into the 90's when the sigma1 & sigma 2 were first cloned.
But you know, just a simple CORRECTION.
And from what I've read, the sigma receptor was still considered an opioid receptor all the way up until 1996.
I'm not completely sure about that, but if true, that would mean AlsoTapered was incorrect about that as well.
It was identified as an "opioid receptor in 1976"... but that doesn't mean that they "haven't been classified as opioid receptors since the 70s"...
Sounds like they were classified as such well into the 90's when the sigma1 & sigma 2 were first cloned.
But you know, just a simple CORRECTION.
AlsoTapered
Bluelighter
I've seen a zeta, epsilon, lambda & iota receptor mentioned but the papers I saw always used the term them 'putative' types. I think it's because if you can only find one or two ligands that interact with them, it's hard to prove that they aren't like the sigma i.e. you have to exclude them from the rest of the CNS.
But of course, if you have reference proving their being opioid receptors then I'm keen to read about them. NOP took a long time to be accepted even though we were USING an opioid that appears to produce the majority of it's analgesic action via NOP (sufentanil) and even now, I'm only aware of 2 other ligands (possibly 3 but it's unproven) that have significant affinity.
polymath
Bluelight Crew
This C-8813 is an interesting compound if its delta receptor affinity causes it to have a higher therapeutic index because of less respiratory depression. But too much delta receptor activity can cause epileptic seizures, so if someone addicted to another opioid takes a dose of C-8813 adjusted to their tolerance level, it can cause problems. I think the convulsion risk from tramadol is also partly caused by this. The idea of creating a molecule that is simultaneously mu agonist and dissociative also has this problem, but there the problem is that a tolerance adjusted dose can make you unconscious or way too much intoxicated in some situation where it's dangerous. This was a bit off topic, but had to mention this.
I believe there exist some types of functional receptor selectivity that aren't even completely understood yet. For instance, for some reason n,n-di-isopropyltryptamine causes mostly only auditory hallucinations even though it should be just one 5-HT2A agonist among the others. So it's possible that the differing amount of euphoria from different opioids is also caused by something that can't be explained just by looking at their affinities at the other receptors, or mu1/mu2 selectivity or how much they affect the known types of secondary messengers.
AlsoTapered
Bluelighter
I don't have any reference to the delta affinity of BDPC - at the time I don't think science had firmly grasped that mu/delta ligands combine to produced unexpectedly strong analgesic activity. So I don't know if C-8813 differs in it's mu/delta ratio when compared to BDPC. I think the LD50s were quite similar suggesting BDPC also derives it's analgesic action through the same mu/delta thing.
I posted a link to a huge series of levorphanol derivatives. The N-phenylethyl was x10 as active as it's parent, the N-2-(thiophen-2-yl)-ethyl was x30 and the N-2-(furan-2-yl)-ethyl was x60 as active as it's parent. But when you looked ad the MED50, all three were more or less the same AS the parent.
I posted a link to a huge series of levorphanol derivatives. The N-phenylethyl was x10 as active as it's parent, the N-2-(thiophen-2-yl)-ethyl was x30 and the N-2-(furan-2-yl)-ethyl was x60 as active as it's parent. But when you looked ad the MED50, all three were more or less the same AS the parent.
Your observations about opioids are comprehensive and reflective of the intricate nature of opioid pharmacology and their subjective effects. The factors that determine the euphoria of opioids are indeed multifaceted and don't depend on a single factor. Here are some key points to consider:
- Molecular Mechanism: While the primary euphoric action of opioids is believed to result from their agonism of the μ-opioid receptor (MOR), it's not as straightforward as "higher affinity = greater euphoria." The intrinsic activity (whether a drug is a full agonist, partial agonist, or antagonist), receptor binding kinetics, and downstream signaling can also influence the effects of the drug. For instance, partial agonists like buprenorphine might bind with very high affinity to MOR but not activate it to the same degree as full agonists, resulting in less euphoria.
- Additional Receptors and Mechanisms: As you pointed out, some opioids also interact with other receptors and pathways, like NMDA receptors, KOR, and SNRI activity. The influence of these other actions on euphoria is not entirely understood but can alter the overall subjective experience.
- Pharmacokinetics: This involves how the drug is absorbed, distributed, metabolized, and excreted. For example, how quickly a drug reaches the brain (onset of action) can influence the intensity of the "rush" or euphoria. A faster onset often correlates with a more intense euphoric experience.
- Lipophilicity: More lipophilic drugs can cross the blood-brain barrier more rapidly, leading to a faster onset of action. For example, heroin, which is more lipophilic than morphine, quickly crosses the blood-brain barrier and is then metabolized to morphine in the brain, leading to a rapid and intense onset of effects.
- Individual Variability: Different individuals can have different reactions to the same drug due to genetic factors, previous drug exposure (tolerance or sensitization), and individual brain chemistry.
- Route of Administration: As you've observed with the combination drug, the route of administration can significantly impact the onset, intensity, and duration of the euphoric experience.
- Historical and Social Context: The perceived quality of the euphoria can be influenced by societal beliefs, expectations, and previous experiences. If a user expects a drug to be more euphoric, the placebo effect can enhance the experience.
- Potency: While potency is often associated with the potential for overdose, it doesn't directly correlate with euphoria. As you've mentioned, some less potent opioids can be subjectively more euphoric than more potent counterparts.
- Combination with Other Drugs: As seen in the dipipanone/cyclizine combo, combining opioids with other drugs can produce unique and intensified effects.
Dextro .45
Bluelighter
Oxycodone is the most euphoric Opioid on earth. Synthesized from theBaine alkaloid in Germany in like 1924 or something….it’s not sedating like Morphine like opioids, Hydromorphone (Dilaudid) Diacetylmorphine (Heroin) all synthesized in za fazza land using doutchmarks lmao
NAZI scientists conducted studies on Eukadol (Oxycodone) against all other opioids and was found to possess subjective reinforcing effects very similar to Cocaine. Significantly analgesic properties combined with profound narcotic stimulant like euphoria.
Read upon it….the original patent for Eukadol (Oxycodone)
Those c@ck scker Sackler family knew it when Purdue Pharma has their jacked up aggressive sales reps on Dexedrine & OxyContin hitting their bonuses, huge kickbacks to doctor’s and physicians to vacation trips to the tropics, etc
U.S. Govt charged them 2.5 Billion I believe for causing a cluster f@ck of an opioid epidemic
Doctors scared to prescribe opioids to legitimate pain patients in fear of the DEA knocking on their door
No other opioid EVER gave me the incredible euphoric warmth & Dopaminergic narcotic pleasure than oral Oxycodone. I.V. Dilaudid & Heroin sleepy nod after the initial rush of pleasure. REAL pharmaceutical Diamorphine (Heroin) could go head to head with Oxycodone
Oxycodone & Methylphenidate (Ritalin) only 2 drugs to give me TRUE powerful euphoria. The dopaminergic stimulant and the Mu-Opioid agonist …..both finger f@cking the pleasure centres in the reward pathway. Totally unreal
An oral Brompton Cocktail and a pharmaceutical I.V. Speedball with pure Cocaine & Diamorphine
Would be my last meal followed by a strong Jin cocktail and a fresh Belmont cigarette
I’d be good to go….
NAZI scientists conducted studies on Eukadol (Oxycodone) against all other opioids and was found to possess subjective reinforcing effects very similar to Cocaine. Significantly analgesic properties combined with profound narcotic stimulant like euphoria.
Read upon it….the original patent for Eukadol (Oxycodone)
Those c@ck scker Sackler family knew it when Purdue Pharma has their jacked up aggressive sales reps on Dexedrine & OxyContin hitting their bonuses, huge kickbacks to doctor’s and physicians to vacation trips to the tropics, etc
U.S. Govt charged them 2.5 Billion I believe for causing a cluster f@ck of an opioid epidemic
Doctors scared to prescribe opioids to legitimate pain patients in fear of the DEA knocking on their door
No other opioid EVER gave me the incredible euphoric warmth & Dopaminergic narcotic pleasure than oral Oxycodone. I.V. Dilaudid & Heroin sleepy nod after the initial rush of pleasure. REAL pharmaceutical Diamorphine (Heroin) could go head to head with Oxycodone
Oxycodone & Methylphenidate (Ritalin) only 2 drugs to give me TRUE powerful euphoria. The dopaminergic stimulant and the Mu-Opioid agonist …..both finger f@cking the pleasure centres in the reward pathway. Totally unreal
An oral Brompton Cocktail and a pharmaceutical I.V. Speedball with pure Cocaine & Diamorphine
Would be my last meal followed by a strong Jin cocktail and a fresh Belmont cigarette
I’d be good to go….
Your statement contains a mixture of facts and colloquialisms. Here's a breakdown:
- Euphoria: The euphoric effects of opioids can vary greatly between individuals. While some may find oxycodone particularly euphoric, others might have different experiences. It's subjective and can be influenced by various factors, including dosage, tolerance, personal chemistry, and the context in which the drug is used.
- Synthesis: Oxycodone was indeed synthesized from thebaine, which is one of the natural alkaloids found in the opium poppy. The drug was first synthesized in 1916 (not 1924) by German scientists at the pharmaceutical company Merck.
- Comparison with Other Opioids: Each opioid has a unique profile of effects. For instance, while morphine might be more sedating for some, oxycodone could be less so. However, it's a bit of an oversimplification to say that oxycodone is not sedating at all; it can still cause drowsiness, especially in high doses or in opioid-naive individuals.
- Colloquial Language: Phrases like "za fazza land" and "doutchmarks" are playful colloquialisms and not formal or scientific language. Germany, historically associated with the Deutsche Mark before the adoption of the Euro, was indeed the birthplace of several opioids, but the casual tone may not be appropriate for all discussions, especially ones that involve serious topics like drug use and addiction.
Dextro .45
Bluelighter
Yes Sir
AlsoTapered
Bluelighter
Oxycodone was first synthesized in 1916 and was on the market by 1921. The Nazi party was formed in 1920 and was just one of a large number of ultra-nationalist parties for years, so I very mcuh doubt they had anything to do with the development of the drug, a myth that many people appear to harbour.
Otto Eisleb developed MPPP then prodine in the mid 1930s while working for a one of the companies that were part of the I. G. Farbenindustrie group. He later went on to develop ketobemidone.
Methadone was developed by Gustav Ehrhart and Max Bockmühl between 1937 and 1939 (they made a large series of compounds including phenadoxone, dipipanone as well as many other homologues. This is regarded as the first example of 'rational design' i.e. they recognized the key moieties and tried every combination possible so they could predict activity and then back it up with experimentation.
Methadone was first trialled in 1942 but wasn't widely adopted as it was considered 'too toxic'. Interestingly the Germans only adopted parenteral administration of methadone because oral administration results in wide variations in bioavailability, peak plasma level and T½ (49-78%, 2.5-5.5 hours, 19-25 hours). The majority of methadone undergoes sequential N-demethylation followed by cyclization (amine + ketone <---> imine) and being a reversible reaction means that the levels of dinormethadone (which is cardiotoxic) can vary based on genetic factors. This is why even today, monitoring of the QT time of all patients receiving methadone for pain is still undertaken (at least one BLer suffered a heart attack due to methadone's cardiotoxicity).
R. Grewe developed levorphanol in 1942 in response to Germany losing access to Turkish opium. Again, rational design allowed him to recognize the necessary elements of the structure and the original synthesis involved some quite inspired and novel organic chemistry techniques.
While thebaine is found in trace amounts in the opium poppy, it was quickly recognized that several related poppy species that had NOT preciously been used medically and indeed were considered toxic were found to contain considerably more thebaine as well as oripavine, a precursor to both oxycodone and oxymorphone These poppies also produced alkaloids when grown at higher latitudes which meant they could be grown within Germany itself.
Obviously euphoria is subjective, whatever the source. Personally oxycodone simply causes me anxiety but it is known to directly affect serotonin reuptake and recently cases of serotonin syndrome have been reported in patients prescribed oxycodone and citalopram (a commonly prescribed antidepressant). It has long been known that oxycodone directly increases dopamine levels and reduces norepinephrine levels. None of these effects are mediated by the drugs opioid activity.
So it's not unexpected that many some find oxycodone uniquely euphoric.
As I have previously noted, the weak opioid tramadol is considered to be uniquely euphoric in nations in which it is a prescribed analgesic. In this case it's well worth the effort of comparing it's structure with that of cypenamine (a psychostimulant about ¼ the potency of amphetamine) and dinortilidine (the ultimate metabolite of tilidine). Tilidine increases levels of dopamine as well.
So it's not unexpected that many people find tiidine uniquely euphoric. Reports from the German-language forum, Land der Träume repeatedly remark upon the stimulant rather than the opioid activity of the drug. Nortilidine was briefly sold as an RC within Germany and Land der Träume users reported that the drug was evidently a much stronger opioid (it is, x10 more potent in animal models) but also that the opioid activity was brief but the stimulant activity was relatively longer than tilidine.
Pethidine (Demerol) is only in the dihydrocodeine range as an analgesic and the majority of users reported in semi-structured interviews that it was NOT the opioid activity that was sought but the potent dopamine reuptake inhibition produced by the major metabolite, norpethidine. Due to the T½ of norpethidine being substantially longer than that of pethidine, medical professionals are warned of the accumulation of norpethidine, a compound that fully substituted for cocaine in rats trained to discriminate between cocaine, saline and amphetamine. It's worth noting that pethidine is substantially cheaper than cocaine, the preferred drug amongst those interviewed
So it's not unexpected that some people find pethidine to be uniquely euphoric.
Physeptone (methadone) tablets prescribed for pain. Although these tablets are intended for oral administration, the previously mentioned issues make them unattractive to anybody who isn't prepared to ready to prepare them for injection but since they are small and contain no excipients to prevent modification, their is a clique of people who ARE prescribed this formulation and while somewhat unpleasant to snort, it was discovered that they can readily be dissolved in hot water, allowed to cool and plugged. This overcomes the physiological uncertainties and reliably provide pain relief within moments. So this is slightly different but people suffering from chronic, severe, visceral pain can expect relief within 2-3 minutes, faster, in fact, than many injected opioid analgesics.
So it's not unexpected that people suffering severe pain find Physeptone uniquely effective.
In The Netherlands, a synthetic opioid called Dipidolar (piritimide) has a small but loyal following. As well as possessing a rapid onset (thus providing a powerful 'flash'), it also possesses potent sedative effects. This combination of effects is sought within a certain demographic of opioid users and in semi-structured interviews, clients reported that when 'Dip' (rhymes with pipe) was unavailable they would inject other opioids and oxazepam (the only widely used benzodiazepine in The Netherlands( with the inherent increased difficulty, reduced safety and increased cost. It should be noted that the duration of action of piritimide is longer than that of morphine and heroin - virtually the only street-opioids found in The Netherlands,
So it's not unexpected that some people find piritimide uniquely euphoric.
In the UK a combination opioid/antiemetic called Diconal was the preferred drug among some users. Although only available as tablets, users would crush the pills in a spoon, add water and apply a flame to the bottom of the spoon. The resulting slurry was then filtered (usually through a cigarette filter) and injected. While diconal is closely related to methadone, the intravenous administration of cyclizine produced stimulation, euphoria and hallucinations. When Diconal was unavailable, users would purchase cyclizine (a [P] antiemetic) and crush the pills along with Physeptone (UK brand of methadone tablets). When methadone tablets were unavailable they would consume methadone linctus orally and continue to crush, filter and inject cyclizine tablets.
So their is strong evidence that some people found this compound opioid analgesic uniquely euphoric. In addition, they were prepared to substitute the opioid and the method of ingestion as it was/is the combination of these drugs that produce a unique ASC.
I could continue with a list of combinations consumed by US users such as 'T and blues' in which the opioid mixed agonist/antagonist (pentazocine) was mixed with the antihistamine tripelennamine. The common feature in each case (with the exception of oxycodone) is that every one of these opioids is considered to be substantially LESS potent than morphine. In fact, in some cases the opioid activity was not sought but rather the unique ASCs that mixing them with other classes of medication.
That these concoctions were not more common might partly be explained by some users being hesitant to inject the contents of pills, partly because the subjective effects are considered to be so intense, partly because unintoxicated users watching those under the influence of these combinations ware concerned and partly because the death-toll surrounding these groups is widely known to be so high,
But the fact that clusters of users sprung up demonstrates that the ASCs must be highly euphoric given that the risks in all cases have been highlighted thus few first-time users could be ignorant of the risks.
They all appear to produce compulsive behavior:
I would just add that the oral forms of cyclazine contain the hydrochloride salt which is far less water-soluble than the lactate intended for injection so it was not uncommon for Lifeline clients asking for 5mL syringes and green-top or blue-top needles which are both long and of a larger diameter than the usual orange-top syringes generally used by regular heroin users, Generally they indicate that people are using deeper veins such as the femoral or are injecting into arteries.
Whatever the specifics, the ONLY opioid I ever had a preference for was 'peach' (10mg) Palfium (dextromoramide), a potent (x3 M) but short-acting opioid that has the unique feature of producing an IV-like rush even when taken orally. The problem with Palfium was that one day you could take 5 and feel fine, the next day you might only consume 3 but overdose.
I freely admit that I do not understand the specifics of ANY of the above except for Physeptone BUT the compulsion is well recorded if not well understood because few people survive for a sufficient length of time for medical experts to intervene.
Otto Eisleb developed MPPP then prodine in the mid 1930s while working for a one of the companies that were part of the I. G. Farbenindustrie group. He later went on to develop ketobemidone.
Methadone was developed by Gustav Ehrhart and Max Bockmühl between 1937 and 1939 (they made a large series of compounds including phenadoxone, dipipanone as well as many other homologues. This is regarded as the first example of 'rational design' i.e. they recognized the key moieties and tried every combination possible so they could predict activity and then back it up with experimentation.
Methadone was first trialled in 1942 but wasn't widely adopted as it was considered 'too toxic'. Interestingly the Germans only adopted parenteral administration of methadone because oral administration results in wide variations in bioavailability, peak plasma level and T½ (49-78%, 2.5-5.5 hours, 19-25 hours). The majority of methadone undergoes sequential N-demethylation followed by cyclization (amine + ketone <---> imine) and being a reversible reaction means that the levels of dinormethadone (which is cardiotoxic) can vary based on genetic factors. This is why even today, monitoring of the QT time of all patients receiving methadone for pain is still undertaken (at least one BLer suffered a heart attack due to methadone's cardiotoxicity).
R. Grewe developed levorphanol in 1942 in response to Germany losing access to Turkish opium. Again, rational design allowed him to recognize the necessary elements of the structure and the original synthesis involved some quite inspired and novel organic chemistry techniques.
While thebaine is found in trace amounts in the opium poppy, it was quickly recognized that several related poppy species that had NOT preciously been used medically and indeed were considered toxic were found to contain considerably more thebaine as well as oripavine, a precursor to both oxycodone and oxymorphone These poppies also produced alkaloids when grown at higher latitudes which meant they could be grown within Germany itself.
Obviously euphoria is subjective, whatever the source. Personally oxycodone simply causes me anxiety but it is known to directly affect serotonin reuptake and recently cases of serotonin syndrome have been reported in patients prescribed oxycodone and citalopram (a commonly prescribed antidepressant). It has long been known that oxycodone directly increases dopamine levels and reduces norepinephrine levels. None of these effects are mediated by the drugs opioid activity.
So it's not unexpected that many some find oxycodone uniquely euphoric.
As I have previously noted, the weak opioid tramadol is considered to be uniquely euphoric in nations in which it is a prescribed analgesic. In this case it's well worth the effort of comparing it's structure with that of cypenamine (a psychostimulant about ¼ the potency of amphetamine) and dinortilidine (the ultimate metabolite of tilidine). Tilidine increases levels of dopamine as well.
So it's not unexpected that many people find tiidine uniquely euphoric. Reports from the German-language forum, Land der Träume repeatedly remark upon the stimulant rather than the opioid activity of the drug. Nortilidine was briefly sold as an RC within Germany and Land der Träume users reported that the drug was evidently a much stronger opioid (it is, x10 more potent in animal models) but also that the opioid activity was brief but the stimulant activity was relatively longer than tilidine.
Pethidine (Demerol) is only in the dihydrocodeine range as an analgesic and the majority of users reported in semi-structured interviews that it was NOT the opioid activity that was sought but the potent dopamine reuptake inhibition produced by the major metabolite, norpethidine. Due to the T½ of norpethidine being substantially longer than that of pethidine, medical professionals are warned of the accumulation of norpethidine, a compound that fully substituted for cocaine in rats trained to discriminate between cocaine, saline and amphetamine. It's worth noting that pethidine is substantially cheaper than cocaine, the preferred drug amongst those interviewed
So it's not unexpected that some people find pethidine to be uniquely euphoric.
Physeptone (methadone) tablets prescribed for pain. Although these tablets are intended for oral administration, the previously mentioned issues make them unattractive to anybody who isn't prepared to ready to prepare them for injection but since they are small and contain no excipients to prevent modification, their is a clique of people who ARE prescribed this formulation and while somewhat unpleasant to snort, it was discovered that they can readily be dissolved in hot water, allowed to cool and plugged. This overcomes the physiological uncertainties and reliably provide pain relief within moments. So this is slightly different but people suffering from chronic, severe, visceral pain can expect relief within 2-3 minutes, faster, in fact, than many injected opioid analgesics.
So it's not unexpected that people suffering severe pain find Physeptone uniquely effective.
In The Netherlands, a synthetic opioid called Dipidolar (piritimide) has a small but loyal following. As well as possessing a rapid onset (thus providing a powerful 'flash'), it also possesses potent sedative effects. This combination of effects is sought within a certain demographic of opioid users and in semi-structured interviews, clients reported that when 'Dip' (rhymes with pipe) was unavailable they would inject other opioids and oxazepam (the only widely used benzodiazepine in The Netherlands( with the inherent increased difficulty, reduced safety and increased cost. It should be noted that the duration of action of piritimide is longer than that of morphine and heroin - virtually the only street-opioids found in The Netherlands,
So it's not unexpected that some people find piritimide uniquely euphoric.
In the UK a combination opioid/antiemetic called Diconal was the preferred drug among some users. Although only available as tablets, users would crush the pills in a spoon, add water and apply a flame to the bottom of the spoon. The resulting slurry was then filtered (usually through a cigarette filter) and injected. While diconal is closely related to methadone, the intravenous administration of cyclizine produced stimulation, euphoria and hallucinations. When Diconal was unavailable, users would purchase cyclizine (a [P] antiemetic) and crush the pills along with Physeptone (UK brand of methadone tablets). When methadone tablets were unavailable they would consume methadone linctus orally and continue to crush, filter and inject cyclizine tablets.
So their is strong evidence that some people found this compound opioid analgesic uniquely euphoric. In addition, they were prepared to substitute the opioid and the method of ingestion as it was/is the combination of these drugs that produce a unique ASC.
I could continue with a list of combinations consumed by US users such as 'T and blues' in which the opioid mixed agonist/antagonist (pentazocine) was mixed with the antihistamine tripelennamine. The common feature in each case (with the exception of oxycodone) is that every one of these opioids is considered to be substantially LESS potent than morphine. In fact, in some cases the opioid activity was not sought but rather the unique ASCs that mixing them with other classes of medication.
That these concoctions were not more common might partly be explained by some users being hesitant to inject the contents of pills, partly because the subjective effects are considered to be so intense, partly because unintoxicated users watching those under the influence of these combinations ware concerned and partly because the death-toll surrounding these groups is widely known to be so high,
But the fact that clusters of users sprung up demonstrates that the ASCs must be highly euphoric given that the risks in all cases have been highlighted thus few first-time users could be ignorant of the risks.
They all appear to produce compulsive behavior:
I would just add that the oral forms of cyclazine contain the hydrochloride salt which is far less water-soluble than the lactate intended for injection so it was not uncommon for Lifeline clients asking for 5mL syringes and green-top or blue-top needles which are both long and of a larger diameter than the usual orange-top syringes generally used by regular heroin users, Generally they indicate that people are using deeper veins such as the femoral or are injecting into arteries.
Whatever the specifics, the ONLY opioid I ever had a preference for was 'peach' (10mg) Palfium (dextromoramide), a potent (x3 M) but short-acting opioid that has the unique feature of producing an IV-like rush even when taken orally. The problem with Palfium was that one day you could take 5 and feel fine, the next day you might only consume 3 but overdose.
I freely admit that I do not understand the specifics of ANY of the above except for Physeptone BUT the compulsion is well recorded if not well understood because few people survive for a sufficient length of time for medical experts to intervene.
TheJuner
Bluelighter
- Joined
- Apr 18, 2023
- Messages
- 76
Interesting. I’m not sure I agree fully but do you perhaps have a link to the study you mentioned about the addiction liability of oxy?
AlsoTapered
Bluelighter
I made a mistake - NOT tramadol, TILIDINE.
www.ncbi.nlm.nih.gov
BTW the above link is the VERY FIRST result Google returns. I can't help thinking that it was MORE effort to ask than to just, you know, actually LOOK.
Likeability and Abuse Liability of Commonly Prescribed Opioids
Nonmedical use of prescription opioid analgesics is associated with epidemic levels of morbidity and mortality. There are several factors that affect the abuse liability of the various opioids, including likability or the pleasurable subjective effects. ...
www.ncbi.nlm.nih.gov
BTW the above link is the VERY FIRST result Google returns. I can't help thinking that it was MORE effort to ask than to just, you know, actually LOOK.
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