Most pleasurable opioid based on pharmacology?

[Feretile]

I've begun to wake up to tapentadol being a basically GOOD opioid scaffold.... spoilt. I'm sure tahexadol (full agonist) would be a very good option. Cheap as well.

 

[JTemperance]

I experienced bupre & tramadol synergy during
w/drawal also

Likewise. I was still pretty sick on 6-8mg of buprenorphine after a few days, but 150mg of staggered tramadol made me feel like a million bucks – didn't need, or even really want, any pregabalin/gabapentin or clonidine/tizanidine, just a normal 2-4mg dose of loperamide.

 

[Xorkoth]

Oh - and O-desmethyltramadol was a popular RC. It was banned after some scummy vendor cut it into kratom and killed some kids.

Oh yeah, I know that. I haven't ever tried it, but have heard good things from basically anyone who has. I didn't know that was why it was banned. Actually I didn't even know it was banned.

 

[Nas47]

Tramadol went from inactive to very active for me. Tried it during my oxy and heroin use with no effect hardly. Then one day in the midst of buprenorphine withdrawal when kratom and loperamide weren’t doing shit for me, I tried it again. Within an hour I was flying so high from 100mg. My theory is that either Bupe and tramadol share some receptor profile or my enzymes changed.

We know heroin oral bioavailability is much higher for dependent users than naive, so enzymes do change over time with these drugs I’m sure.

-GC

Its very interesting.I have heard it too.That tram sucesfully slowing down symptoms of bupe withrawl.Its a weird drug indeed.Both of them.Can hit you high unpredictably or give you nothing like high.Both of them have AD properties on its own

 

[Feretile]

These is a myth that buprenorphine blockades other opiates - it competes. I've felt CODEINE on top of 8mg of buprenorphine. I have often wondered if bup desensitises the mu receptors. That would actually make it less attractive as a treatment. Maybe thienorphine will not have the same issue since it's durations is so long.

OT - 7-PET & thienorphine both suggest that replacing the pentyl moiety of Bentley compounds with an arylethyl increases duration.

 

[Nas47]

These is a myth that buprenorphine blockades other opiates - it competes. I've felt CODEINE on top of 8mg of buprenorphine. I have often wondered if bup desensitises the mu receptors. That would actually make it less attractive as a treatment. Maybe thienorphine will not have the same issue since it's durations is so long.

OT - 7-PET & thienorphine both suggest that replacing the pentyl moiety of Bentley compounds with an arylethyl increases duration.

Bupr de facto makes your mu receptor more dense.Upregulating them..and it has a high affinity for kappa receptors,where acts like antagonist(full maybe).I am not a chemist,but there enough a look over his molecule to know that it could be......strange.a complex component..in one case could be partial on other(opiate naive) full mu agonist with high or low intrinsic activity.A huge dose could act like antagonist of mu receptor may be...Its from this bentley compounds yes?

 

[emkee_reinvented]

I've seen many posts on this message board where users descibed heroin/morphine as the best opioid.

I found this excerpt in the wikipedia article on morphine. The parcipitants in the study (→below) clearly prefered morphine and it's ester diamorphine over any other opioid. Is there a pharmacological reason for the more pleasurable effects of the two drugs, despite similar mechanism of action to other opioids? Or was the only reason for this outcome that the participants were former heroin users?

"Morphine is a highly addictive substance. In controlled studies comparing the physiological and subjective effects of heroin and morphine in individuals formerly addicted to opiates, subjects showed no preference for one drug over the other. Equipotent, injected doses had comparable action courses, with no difference in subjects' self-rated feelings of euphoria, ambition, nervousness, relaxation, drowsiness, or sleepiness. [...] When compared to the opioids hydromorphone, fentanyl, oxycodone, and pethidine/meperidine, former addicts showed a strong preference for heroin and morphine, suggesting that heroin and morphine are particularly susceptible to abuse and addiction. Morphine and heroin were also much more likely to produce euphoria and other positive subjective effects when compared to these other opioids."
-Source: https://en.wikipedia.org/wiki/Morphine#Reinforcement_disorders (The links to the mentioned studies are given there.)

Oral DextroMoramide seem's despite its irradical absorption a good candidate.

 

[polyboss]

M

These is a myth that buprenorphine blockades other opiates - it competes. I've felt CODEINE on top of 8mg of buprenorphine. I have often wondered if bup desensitises the mu receptors. That would actually make it less attractive as a treatment. Maybe thienorphine will not have the same issue since it's durations is so long.

OT - 7-PET & thienorphine both suggest that replacing the pentyl moiety of Bentley compounds with an arylethyl increases duration.

My addiction doctor says I need high dose of Hydromorphone for my surgery because my bupe shot, no other opioid will work. Medically backed up stuff. See my recent thread post.

 

[Feretile]

M

My addiction doctor says I need high dose of Hydromorphone for my surgery because my bupe shot, no other opioid will work. Medically backed up stuff. See my recent thread post.

Hydromorphone will compete more efficiently, but buprenorphine has a Ki 0.5, hydromorphone Ki 0.6.

Oxymorphone, fentanyl & levorphanol all have higher affinity that buprenorphine so would work better. I suspect your doctor is very carefully calculating the dose so you don't wind up with a larger habit.

But whatever an opioids mu affinity, other opioids (not just bup) will compete for the available receptors.

 

[DeathIndustrial88]

Bupe & tram have amazing synergy. It should be common practice to prescribe both for maintenance. lol I'd be happy with that.

First time I tried bupe (was ignorant at the time about it but was told to take just a tiny sliver of it), was after taking my usual 400mg of tramadol.
I went to work that day and could NOT stop nodding while standing up.
It was so bad that other employees kept coming up to me asking me if I got enough sleep. lol

Bupe gives that heavy opioid sedation, but trams give you the euphoria & stimulation. Trams also use to give me this lovey-dovey feeling (so did heroin), like I just want to tell everyone around me how great they are & I feel more romantic & confident. lol Bupes never given me that, unfortunately.

 

[Feretile]

I would be fascinated to know if this is a common response or just one person having an unusual metabolism/receptor group.

The UK has seen a LOT of tramadol deaths and I am wondering if someone has figured out the synergy.

Of course, tramadol does work on monoamine transports, so is it the opiate activity. Since I have had a similar experience with bup & codeine.... could it be that bup is a CYP2D6 inducer? OR, and this really is out there - will tramadol/codeine N-methylate norbuprenorphine? THAT could lead to fatal overdoses.

 

[DeathIndustrial88]

I would be fascinated to know if this is a common response or just one person having an unusual metabolism/receptor group.

The UK has seen a LOT of tramadol deaths and I am wondering if someone has figured out the synergy.

Of course, tramadol does work on monoamine transports, so is it the opiate activity. Since I have had a similar experience with bup & codeine.... could it be that bup is a CYP2D6 inducer? OR, and this really is out there - will tramadol/codeine N-methylate norbuprenorphine? THAT could lead to fatal overdoses.

Interesting to ponder.

Although I haven't seen any conclusive evidence that norbuprenorphine can get or stay passed the blood brain barrier, so it's effects must be simply peripheral.

Most people who die from tramadol are people who end up with seizures, IMO, rather than the classic respiratory depression of other opioids.
Metabolism could effect how strong of an experience one has tho, which could possibly lead to classic opioid OD.
But in my 10+ years of using, I've never ODed on any opioid for some reason. (prolly cause I was smart & didn't like other drugs like alcohol mucking up my opiate buzzes).
Closest I came to an OD was when I was given crappy fentanyl. Which I had a suspicion that it was fent (no vinegar smell, was a white powder & not brown/tan rocks) so I only tried a little bump.
That little bump had me nodding like I was gonna fall asleep forever & die. Had I dug into it like I would a bag of heroin, I'd probably would have died.

 

[polyboss]

Bupe & tram have amazing synergy. It should be common practice to prescribe both for maintenance. lol I'd be happy with that.

First time I tried bupe (was ignorant at the time about it but was told to take just a tiny sliver of it), was after taking my usual 400mg of tramadol.
I went to work that day and could NOT stop nodding while standing up.
It was so bad that other employees kept coming up to me asking me if I got enough sleep. lol

Bupe gives that heavy opioid sedation, but trams give you the euphoria & stimulation. Trams also use to give me this lovey-dovey feeling (so did heroin), like I just want to tell everyone around me how great they are & I feel more romantic & confident. lol Bupes never given me that, unfortunately.

I have a similar experience to tram alone but have never experienced sedation on buprenorphine since one should be opioid tolerant before it's use. If you aren't currently dependent on opioids, a high enough dose of buprenorphine is enough to cause irreversible overdose. Be careful!!
Tram is lovely on it's on imo. Almost stimulating even, like an oxy but not quite. I haven't taken doses greater than 400 mg for seizure reasons, so it's best to use an nmda antagonist and stagger gabapentin half an hour before starting the tram stagger (100 mg first dose empty stomach, 50 mg every 40 minutes after that).

Interesting to ponder.

Although I haven't seen any conclusive evidence that norbuprenorphine can get or stay passed the blood brain barrier, so it's effects must be simply peripheral.

Most people who die from tramadol are people who end up with seizures, IMO, rather than the classic respiratory depression of other opioids.
Metabolism could effect how strong of an experience one has tho, which could possibly lead to classic opioid OD.
But in my 10+ years of using, I've never ODed on any opioid for some reason. (prolly cause I was smart & didn't like other drugs like alcohol mucking up my opiate buzzes).
Closest I came to an OD was when I was given crappy fentanyl. Which I had a suspicion that it was fent (no vinegar smell, was a white powder & not brown/tan rocks) so I only tried a little bump.
That little bump had me nodding like I was gonna fall asleep forever & die. Had I dug into it like I would a bag of heroin, I'd probably would have died.

I too got lucky. even when I was purposely taking fentanyl I never od'd. I was taking benzos on top of it too, I was dumb and that is why I'm on sublocade. Not sure what stopped me.

Hydromorphone will compete more efficiently, but buprenorphine has a Ki 0.5, hydromorphone Ki 0.6.

Oxymorphone, fentanyl & levorphanol all have higher affinity that buprenorphine so would work better. I suspect your doctor is very carefully calculating the dose so you don't wind up with a larger habit.

But whatever an opioids mu affinity, other opioids (not just bup) will compete for the available receptors.

Thank you for your response, yes that binding affinity is what I'm seeing around. I think it's BS he's even trying with hydromorphone since it would take 16mg just to break through bupe. Don't think I can ask for stuff like that, lost that privilege. Not a cancer patient, so they won't send me home with fentanyl or levorphanol. Didn't even know oxymorphone was still around, however I do read that it isn't technically as strong as hydromorphone.

 

[DeathIndustrial88]

I have a similar experience to tram alone but have never experienced sedation on buprenorphine since one should be opioid tolerant before it's use. If you aren't currently dependent on opioids, a high enough dose of buprenorphine is enough to cause irreversible overdose. Be careful!!
Tram is lovely on it's on imo. Almost stimulating even, like an oxy but not quite. I haven't taken doses greater than 400 mg for seizure reasons, so it's best to use an nmda antagonist and stagger gabapentin half an hour before starting the tram stagger (100 mg first dose empty stomach, 50 mg every 40 minutes after that).

I too got lucky. even when I was purposely taking fentanyl I never od'd. I was taking benzos on top of it too, I was dumb and that is why I'm on sublocade. Not sure what stopped me.

Thank you for your response, yes that binding affinity is what I'm seeing around. I think it's BS he's even trying with hydromorphone since it would take 16mg just to break through bupe. Don't think I can ask for stuff like that, lost that privilege. Not a cancer patient, so they won't send me home with fentanyl or levorphanol. Didn't even know oxymorphone was still around, however I do read that it isn't technically as strong as hydromorphone.

I hear you friend!

I actually started off with using bupe off the streets many years ago. And then eventually just ended up on it as maintenance since even after withdrawing from heroin or trams, I still never felt "normal" again & would always cave. Even after 5 years of daily bupe use, I still get pretty tired from it some days. But it never feels pleasurable like a full agonist would.

I agree it's best to stagger your tram doses too for more of an opioid effect.

 

[Feretile]

You cannot simply equate mg for mg. The MW of hydromorphone is somewhat lower, it's LogP differs and it doesn't target the different opiate receptors to the same extent. There are still questions regarding norbuprenorphines ability to pass the BBB although since it's affinity for the receptors is much lower in any case, it doesn't matter one way or the other.


When on bup, I suffered anxiety and a pharmacist actually ADVISED me to take some codeine at bed-time. It worked. I have a feeling that the pharmacists know more about the interaction of opiate prodrugs with buprenorphine. If someone has ever taken oxycodone after bup, i would love to know if that follows the same pattern.

If it does, I'm going to suggest that norbuprenorphine O-demethylates and maybe N-methylates.

Don't forget, it took drug agencies a decade to discover 'cyclone' which is oral methadone + IV cyclizine. Apparently people would shoot up 1 or 2 pills (terrible idea) every 30 minutes to produce a 'heroin-like' rush. Well, at 25p a pill, even junkies could afford it. But the point is - it wasn't noted for a DECADE!

 

[cdin]

oxymorphone, hands down

 

[Nas47]

H

 

[Feretile]

OK - more recent experience - nortilidine 50mh insuffused. Starting with what you know, it's like snorting 50MG M but it's also like snorting z 2 x dextramphetamine so very 'ups. Then, after about 5 minutes it gets 'silly. and I do mean that one laughts out loud. Emotionally the effects are like a low dose of MDMA and it has a slightly trippy feeling like a low dose of K..

I loved it.

But as others have said, those effects only last 15-20 minutes but it backs of into a stimulating opioid activity.

I WARN people that it would be so, so easy to keep redosing every 30 minutes. I only HAD 100MG SO 2 lines. The second kicked in much faster and was stronger but I assume that it eas because some of the first dose was still in my system.

Men may like the fact that it does not protract from sexual function or (and I find this the REAL issue) orgasm. My wife also took it and reported similar deelings.

I really doubt nordesomorphine is freely available but what I will say is that if she sees me snorting a line.... she climbs into bed. I am no stud. She IS very imaginative and so we got up to all kinds of things.

I suspect chronic use, like other opioids, blunts sexual response but I'm sure everyone knows that person who says that sex is better on coke, well I do not believe it. nortilidine really does pack a punch.

I am sure that it's because it is not a potent opioid that is important. That and the fact that it seems to act in a manner unlike other opioids.

Sorry not go into detail..... I am 6 feet away from our bed and I am getting dsmnds.

NB YMMV. Just because it works for me is now way to suggest that it is the average or even the usual subjective effects. I also strongly recommend that people do not redose. Nortilifine (and it's bioisosteres) have a steep dose/response curve and it is not a drug for people who are not familiar with opioids. At a guess, I would say it is as strong as M and snorting 50Mg of M is a lot unless you are a regular.

So, a nice trick for those who know but I feel damned sure that some dummy will snort a whole gram, go over and their family and the forces of law and order will blame the people who made the stuff.

OT - 3 ex-GFs likes Foxy Methoxy. I HATE it, but I have to say that it led to amazing sex.

Better if you do not need ANYTHIJNG.

 

[Rectify]

Heroin or morphine if IV. If you're dealing with pills, then Roxicet 30 mg oxycodone are snortable. Oxycontin used to be "good," but now it's abuse resistant. Hydrocodone is even quite nice just by mouth. I used to could get hydrocodone cough syrups (Lean, Sizzurp) which sometimes came flavored with cherry or something real nice. But no more. If you are desperate, you could always try sourcing some poppy pods from a florist and make morphine containing tea, but you'll be drinking a lot of it and will soon have a terrible physical dependency to the dope and probably a nasty psychological addiction as well. Also, your large intestines will mostly shut down, and you will have tons of bricks to sh*t out. Also, because opiates prime the body for death, you will feel miserable and won't be the same in the head again. Your whole life will go into the shitter. You will constantly lie, cheat, scam, and steal to get your fix, until you finally overdose and finally die, which let's face it, is every heroin junkies ultimate wet dream! Fentanyl is not particularly euphoric, is hard to consistently dose correctly when bought on the street, and doesn't last very long either. Codeine is not really worth doing and really is only about as abusable as dextromethorphan, or DXM. You might as well Choose Life, mate. #TEAM_STIMULANTS.

 

[Feretile]

Are you old enough to remember Dextromoramide, Dipipanone and such?

Neither were THAT strong (former x3M, latter x2M) but it was the RUSH, plateau and cruise back to zero that were all amazing. I haven't tried the mixtures you have but I do appreciate that all of the wonderful effects were mediated by just 1 compound.

As I said, I am confident that swapping the cycloppentane moiety of dextromoramide being swapped a pyrrolidine ring will work - it will be more lipophilic and so it's potency should be slightly higher.... but although based on a lot of QSAR study, nobody can confirm that. Diconal (dipipanone + cyclizine was amazing and maybe a large part was because Diconal tablets were 10mg dextromoramide + 30mg cyclizine so IV use gave a rugh generally agreed to be the best of all drugs ever. I mean, it was BANNED because people sought it out for that effect.

In short, what one wants is a potent opioid with fast onset mixed with a first generation antihistamine (all of which increase effects of opioids).. From what I know, the antihistamines make the opioid cross the BBB very fast and so the initial concentration of the drug is within the CNS and it's distribution that moves it equally throughout the body.

ALL of these compounds were either administered IV or snorted. The volume of distribution means that it STAYS in the fatty tissue of the brain. Oh, and dipipanone actively (like all 3,3-diphenylheptanone) opioids act the same way.

I BET that a lot of the 3,3-diphenylheptanone opioids that would do the same. I mean drugs that were not about when cyclizine was developed.

I mean, the N-pyrrolidine homologue of dipipanone is MORE potent (and legal in many places), the pyrrolidine homologue of dextromoramide homologue of dextromoramide is legal and as for methadone, well, from R-4065 downwards - durations of 72 hours are USED. There are analogues with a duration of over 7 days!!!!