• N&PD Moderators: Skorpio | thegreenhand

What opiates have been proven in studies to be more desirable than morphine?

Dipipanone (& cyclizine) is quite spectacular in the euphoria it produces (and all without a queasy tummy!), although the cyclizine does rather limit the upper dose if you have tolerance because of the anticholinergic effects of the cyclizine.

Ketobemidone is supposed to be the opioid for euphoria, but as pointed out, hardly anybody has tried it (it also has NMDA antagonist activity, so who knows what it's like). I always thought 3-phenyl-3-propionyloxytropane would make for a euphoric opiate. As well as being a sort of prodine derivatibe, it's a 3-phenyltropane and might have some dopamine reuptake inhibitor activity. Now that would make for a combination speedball in one molecule!
 
From my Trip Reports thread:

I liked morphine/codeine better than oxycodone and actually associated this partly with a "morbid" feeling they have but which oxycodone lacks. I found oxycodone sort of bland or utopian in comparison. This may be because morphine has slight kappa agonist activity and oxycodone does not. A way to test this hypothesis would be to try buprenorphine (which is a kappa antagonist) and on another occasion, morphine along with a kappa antagonist, and see how these compare. I thought that maybe others had a morbid component to their opioid euphoria at times but from the responses to a thread I created this does not appear to be the case.
 
negrogesic said:
Supposedly opioids of the benzimidazole (etonitazene being the most famous) class are quite euphoric, ive never met anyone who has used or knew anyone who used opioids of this class....

Ambien, midazolam, triazolam and alprazolam all have an imidazo or triazolo ring and are considered some of the best benzos/z-drugs. Maybe there is a connection between euphoria and pentagonal nitrogen-containing rings even with different types of compounds and different classes of drugs.

In general (out of 8 tried), if a benzo/z-drug has such a ring, it agrees with me, otherwise it does not. Therefore I was sort of disappointed that zopiclone meets my criterion as it falls somewhere in between the 2 classes in terms of its effects. I can get around this by strengthening the requirement so that the pentagonal ring must have double bonds as well.

If possible a benzo/z-drug should be developed that has both an imidazo and a triazolo ring, or maybe even several types of rings that meet the above criterion. This should create more euphoria considering that triazolam has both a triazolo ring and the extra chlorine of Ativan.
 
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I just posted this in another thread but it seems applicable here:

Well as this excerpt from the kappa receptor wikipedia page points out, dysphoria may mistakenly associated with the kappa receptor:

It has long been believed that kappa-opioid receptor agonists are dysphoric. This misconception traces back to early articles in the 1980s about human tests with κ-opioid receptor agonists. It was stated that:

"Both doses of ketocyclazocine substantially elevated scores on the LSD subscale of the ARCI as did the high dose of cyclazocine (fig. 2C). Morphine failed to increase scores significantly on this scale which measures dysphoria."[1]

It is now widely accepted that κ-opioid receptor (partial) agonists have hallucinogenic ("psychotomimetic") effects, as exemplified by salvinorin A. These effects are generally undesirable in medicinal drugs and could have had frightening or disturbing effects in the tested humans, but they are not per se dysphoric

Yes kappa agonists can counteract (somewhat) the mu receptor, and this may prove unenjoyable to most (highly selective κ-agonist like salvinorin). However the kappa agonist properties (and particularly 6-MAM) may certainly contribute to phenanthrenes dissociative dream-like state. Its also my conjecture that it may add to the "rush", this is highly speculative though (obviously, fentanyl has a rush as well, but significantly different and qualitatively less fuzzy)...

DAM (morphine too obviously) and 6-MAM also have affinity to the sigma receptor, and while many people also associate this receptor with pronounced dysphoria, some people may enjoy sigma agonists (though i dont even know of any pure sigma agonists, generally its combined with a whole range of other actions)....

Though these receptors may not be euphoric in the form of pure agonists, they may certainly add something that is hard to define in regards to phenanthrenes...
 
Also, kappa effects were first observed with nalorphine so the effects of kappa agonism were probably conflated with and/or compounded by opioid withdrawal or at least mu-antagonist dysphoria and abrupt cessation of an opioid high.
 
bupropion said:
Ambien, midazolam, triazolam and alprazolam all have an imidazo or triazolo ring and are considered some of the best benzos/z-drugs. Maybe there is a connection between euphoria and pentagonal nitrogen-containing rings even with different types of compounds and different classes of drugs.

In general (out of 8 tried), if a benzo/z-drug has such a ring, it agrees with me, otherwise it does not. Therefore I was sort of disappointed that zopiclone meets my criterion as it falls somewhere in between the 2 classes in terms of its effects. I can get around this by strengthening the requirement so that the pentagonal ring must have double bonds as well.

If possible a benzo/z-drug should be developed that has both an imidazo and a triazolo ring, or maybe even several types of rings that meet the above criterion. This should create more euphoria considering that triazolam has both a triazolo ring and the extra chlorine of Ativan.

Depressants have much more important characteristics than the ring type- and minor structural similarites between depressants and opioids are rendered irrelevant simply by the fact that their binding is so absolutely different.
 
^ Beaten to the bit about that's not the sort of thing you can do from one group to another. The SAR of one group (say opiates/oids) is different to that of the benzodiazepines as they're not trying to fit into identical receptors.

SAR stuff requires a bit more lateral thinking...
 
Can you guys tell me something about the mechanism of buprenorphine. I found it to be a fantastic opioid IV, but not for its rush or lack thereof, instead an onset of 1-2 minutes but a very prolonged high. Taking it any other way, it really takes its time. Why is that the case with buprenorphine and other long acting opioids like methadone? And does the intensity of a rush of an opioid correspond to its overall duration?

Also I've heard that there is a ceiling effect with buprenorphine. Can a non-tolerant user overdose? If so, is there any way to revive him or her (naloxone not being an option)?

And welcome back to the boards, negrogesic. You taught me a lot. F&B same goes for you, don't fight over answering, now.
 
Lednicer developed some 1-aryl-4-piperidylcyclohexanols that were highly potent and strongly Mu binding. I imagine these would be better than either fentanyl or morphine. Methadone? You're kidding. The whole point of methadone ws to bind to the receptors with as little effect as possible. Not even a decent enalgesic
 
^ What!? Methadone is an excellent analgesic - it just doesn't have the same abuse potential as most other opioids/opiates
 
Right, as ^^^ says, methadone is a strong pain killer with a high affinity for the mu receptor (~10nM).
The whole point of methadone ws to bind to the receptors with as little effect as possible
This is not true, it was designed by german scientists in WWII as a substitute for morphine, and they obviously wanted it to have strong affinity (i.e the older name, dolophine, "end of pain"). Also keep in mind some of methadone's family members (palfium, dipipanone)...

Also, in regards to buprenorphine, it is a partial mu-agonist and relatively weak kappa antagonist, and this is why it imposes a "ceiling" on itself at higher doses (at high enough doses the k-antagonist properties limit respiratory depression). It is exceedingly rare for someone to overdose on buprenorphine, ive never even heard of it happening once on its own (this doesnt mean it hasnt, though i would be somewhat skeptical). If one were to die from buprenorphine it would possibly be due to the metabolite norbuprenorphine, but this occurs in such low amounts that i have a hard time imagining this occurence (the dose would probably have to be spectacularly large). Also, i think naloxone may only somewhat reverse the respiratory depression (probably only in large doses as well; though im not entirely sure)...
 
Not only is methadone a *strong* painkiller, I'd go out on a limb to say it's the best I've ever had. I was moved around from hydrocodone to methadone to morphine to levorphanol when my back pain was really bad. I'm all better now, but I remember the methadone as having by far the best ability to take away pain, all day long. This effect could be helped along by its NMDA-antagonist properties, but it's still just a very strong, powerful opioid agonist, and it can be a lot of fun if you're not chasing a rush.
 
Id say dipipanone and dextromoramide are the most plesurable of the synthetic opiates also they work well orally unlike morphine. Ive been prescribed a lot of different opiates and id choose these too over everything man made or non man made with maybe two exceptions freeze dried diamorphine ampules and 6 mam if they made it ;)
 
Also i think methadone is a very strong painkiller yes it lacks euphoria compared to say morphine but one thing it does have is strength id say its at least 3x more potent than oral morphine maybe more. The strongest opioid cocktail ive ever had was 300mg of methadone and 50mg of diconal saved specially for amsterdam back in 2002. Fentanyl is strong but seriously lack euphoria like methadone.
 
Also, kappa effects were first observed with nalorphine so the effects of kappa agonism were probably conflated with and/or compounded by opioid withdrawal or at least mu-antagonist dysphoria and abrupt cessation of an opioid high.
Over the past 50 years there have been numerous human trials with kappa-selective agonists (with no affinity for mu) and they all produce sedation, hallucinations, and dysphoria. It has nothing to do with mu-blockade. I think the evidence is pretty convincing that kappa activation produces dysphoria. It is thought that kappa activation via dynorphin release is one of the mechanisms responsible the dysphoric effects of stress. Kappa activation also increases the threshold for intracranial self-stimulation (ICSS), and generates conditioned place aversion by reducing dopamine transmission. All of those effects are consistent with dysphoria. http://www.ncbi.nlm.nih.gov/pubmed/23921954 http://www.ncbi.nlm.nih.gov/pubmed/23542927 http://www.ncbi.nlm.nih.gov/pubmed/20372879 http://www.ncbi.nlm.nih.gov/pubmed/19864633 http://www.ncbi.nlm.nih.gov/pubmed/18184783 (any many many more...)
 
Fentanyl citrate, not like the kind on the the patch, not fentanyl hcl, or any pill or lollipop. It is only made by a chemist whom I found access too. Best ever 5mg equal to shooting an oxy 80.
 
Fentanyl citrate, not like the kind on the the patch, not fentanyl hcl, or any pill or lollipop. It is only made by a chemist whom I found access too. Best ever 5mg equal to shooting an oxy 80.

Fentanyl citrate is the salt that is found in pharmaceutical preparations, including the patch, lollopop...

And it doesn't sound like the fentanyl you are getting is very good. 5 mg fentanyl IV should be equivalent to at least 600 mg oxycodone IV.
 
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Well....I m quitting my addiction now, but I was in a morphine "diet" for over a year, oral and plugged , everyday, from 180 to 450mg range, with little or no euphoria at all. I tried IV morphine once and it was another story...but for me oxycodone is the "king" of opiates , but I didnt tried hidromorphone, oxymorphine and other stronger drugs because they are not available in my country...over here there is morphine, oxy, tramadol, codein and that´s it. in hospitals they have nubain, morphine and demerol in ampoules...
 
if you dont experience euphoria from oral morphine its simply because the dose is too low,u need very high doses of oral morphine even for slightly tolerant users.When i take 700-900 mg morphine oral its much more euphoric and long lasting and with the same side effects as when i take 80-120 mg oxycodone oral.Oxy is more of rushy high but is much shorter and lacks the dreamy,super content smile-nodding type of high morphine gives,also with mega doses like this you in for 10 hours of strong effects,whereas oxy even with equivalence dosing you get max 5-6 hours
 
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