Recreational opiates - tweaking opiates for pleasure

[tantric]

A complete loon mentioned this idea to me, designing new opiates purely as recreational drugs, maximizing the different effects. He also though he'd remove the addictive potential, but we know better. Has this been hashed out anywhere?

You know the scene in 'Naked Lunch' where Will's wife says, 'It's a literary drug'? The same effect that led to Kubla Khan? I want that effect - that which allows me to write beautiful prose effortlessly. I've done it, mostly morphine, but it didn't end well. Does anyone have a clue if that's a specific signal?

 

[dopamimetic]

The first thing I would remove is the depressive effect on respiration ... I don't know for sure, but I've read that tianeptine counter-acts morphine induced respiratory depression, and since it's an opioid by itself this structure might be worth exploring further, maybe creating a longer acting and/or more potent derivate.

But do opioids really increase creativity that much? Never looked really for that, could be but I'd say only when used sparingly and then much of the effect is of dopaminergic nature imo - probably there would be better suited drug classes for procreativity, like nootropics ...

Besides of that, the arylcyclohexylamine based opioids fascinate me. I've tried 3-HO-PCE a few times, the amount I had was too small to reach pronounced effects but what I got out of it was remarkably different from any other drug. More stoning and with few physical effects at all. Also ACHs could be made combined opioids, NMDA antagonists and DRIs which is very promising but also very addictive...

 

[tantric]

if you're curious, here's a link to an introduction and sample chapter from the psychedelic fantasy/new weird book i was writing: Meeting of the Bored

 

[neurotic]

you'd want to get rid of respiratory depression i guess, that's the only deterrent.

both painkilling, euphoria and respiratory depression are mediated by mu, but there are different subtypes, so you probably can have one without the other, just need a selective enough drug.

a combination of an agonist with a no-BBB-crossing antagonist would be nice too. constipation sucks

 

[dopamimetic]

Thanks for the link will look into it for sure, albeit my English language skills are somewhat limited..

neurotic, in Germany they sell the medium-strength opioid tilidine combined with naloxone to avoid misuse, and the leaflet suggests the naloxone would help against the constipation. Naloxone has an oral bioavailability of <1% afaik, but to antagonize these receptors in the intestine it doesn't need to be bioavailable, right? Edit: Oral naloxone does help.

I thought that antinociception and respiratory depression were caused by the same mechanisms, that by raising the pain threshold the reaction to CO2 levels are slowed too…? But of course a subtype-selective euphoria-only opioid would be nice. Do you think one could also separate the sedation from the other effects, so that selectively activating the "euphoria" receptor would actually become stimulating?

 

[aced126]

Surely a laxative with no CNS effects exist?

Also does anyone know biochemically why naloxone has a low BA whereas similar structures like most other opioids have much higher BAs comparatively?

 

[serotonin2A]

Surely a laxative with no CNS effects exist?

Also does anyone know biochemically why naloxone has a low BA whereas similar structures like most other opioids have much higher BAs comparatively?

Naloxone undergoes first-pass metabolism.

 

[aced126]

Oh yeah that. Says on wiki that liver enzymes convert it to naloxone-3-gluconoride. Why does oxymorphone have a BA 3 times higher tho? Seems like it should have the same if it undergoes similar metabolism.

 

[adder]

Oxymorphone having 3 times higher oral bioavailability is an overstatement, I guess. The oral BA for both oxymorphone and naloxone is around 10%, basically different studies will produce a bit different results, but it's generally ~10% from what I've seen. The only structural difference between naloxone and oxymorphone is the moiety on the nitrogen atom and I doubt that the N-allyl moiety in naloxone is metabolised much. Pentazocine on the other side has a N-dimethylallyl moiety which has two allylic carbon atoms with no electron-donating group on them (like amine for instance), so they are quite susceptible for metabolic attack. However, the structure certainly must have an impact on the rate of first-pass metabolism. Levorphanol for instance has a free phenolic 3-OH group just like morphine does and it's oral bioavailability is ~50%. It's a very basic morphinan derivative if you look at its structure with only 3-hydroxy and N-methyl substituents added to the morphinan skeleton. Perhaps it's less susceptible for first-pass metabolism because it has fewer polar regions, so it can't be taken up by UGT enzymes as effectively as much more polar morphinan-6-one derivatives?

Edit: Perhaps you're right, the oral BA for naloxone seems to be appreciably lower than for oxymorphone, but I can't quickly find a study that would compare the oral BA of both naloxone and oxymorphone. If naloxone is indeed more prone to first-pass metabolism, then the allyl moiety must be the reason why. It could be that a more lipophilic substituent on the amine increases affinity to enzymes mediating glucuronidation.

 

[THE_REAL_OBLIVION]

I don't about PCE/PCP analogues, but in eastern Canada we've always had "mess" which is heavily cut (with harmless lactose, just so anybody can handle their 12-15 grams made from "pure" which by my calculations is 20% pure, that's enough for people who don't know what they're doing to take way too much PCP at once (or PCE and PCP-y which have both been found often inside law enforcement analysis of "mess". But PCP made me forget all my insecurities and kind of shaking I got when I have to do something in front of other people who are watching. It made me feel super competitive the times I've done with an ex-girlfriend back in 2005 or so (I would also be eating methbombs with her all the time). Anyway, this one time I was kinda mad at her, she pulled a 1/8 bag of mess and we snorted away and went to play billiard with some friends. I emptied tables twice in a row and she was looking at me and said "are you going to let me play?".

Also, all the songs I couldn't get to 5 stars in Guitar Hero 3 on PC, I did so, after almost reaching the p-hole on the way home in the bus. It has this concentrate-on-what-you're-doing-fully and stimulant effects at low doses, so when I got back home and the dissociative effects were more balanced, I went back in the lower-medium dosage effects it can have. It's too bad some people seem to fiend for it like an opiate and do the brain damaging (not Olney's, PCP and relatives (not K) have another form of neurotoxicity I'm sure you are aware of.

So you're saying 3-HO-PCE has mu opiate activity? PCP itself has negligible binding to the 3 opiate receptors. That's pretty interesting. I've had a lot of fun 5-6 years ago shooting up Pentazocine and Demerol. They both seem to have this kind of dissociative effect to them in large doses (250mg of Pentazocine shot at once sure was an interesting experience).

Would be one of my tools to get off Bupe more rapidly. My GP who has all the proofs in the world that I need pain medication and the ORT clinic has given me a referral for when I get off bupe, I'll be getting Oxycodone CR 60mg (generic canadian oxycontin). Anything that can make dose reduction of bupe at the level I'm at would be welcome. I hear getting off the 2mg a day is the hardest...and hell, am I plagued with migraines, chest pains (entirely psychosomatic apparently) or if not, costochondritis, I tend to get that disease and other stuff where I have had to be put on a partial work release and have insurance cover the rest. And that's from going down from 10mg to 8mg. And I'm doing 10mg one day, 8mg 2 days, 10mg again, 8mg twice in a row etc. Yesterday I slipped with my takehomes and had 12mg (what i was on for 3 years) and felt somewhat opiated and not sick in any way.

I'm going to be looking at the most info possible here. It's not that crazy of an idea, back when I was doing DXM heavily from powder where I would make .4g capsules way back in 2001-2002, when I learned it was the isomer of a now unused (at least it was removed in Canada) Levo-Dromoran, which is Levorphanol which is related to levomethorphan which is an opioid also. I made a post way back on usenet speculating on other isomers of opioids and if they could also become dissociatives when only one enantiomer is present.

As far as creativity and opiates. I don't find it to be so, when I was big time into eating Oxy IR 20mg 3 at once every 5-6 hours and when I was unable to do so, shoot up Dilaudid/HM Contin, it made me realllllly happy (obviously) and I would be having a major blast just listening to music and chatting with strangers on IRC.

The best recordings I've made (which since the year 2000 and when I discovered the program named FXBOX which is a guitar amp emulator, just need the right kind of jack to plug your guitar in your sound card). I would come drunk and very high on weed and I'd proceed on just jamming the hell out and came up with amazing riffs, and since I'd tend to forget what I made, I paid for the FXBOX license so I could record myself and I have thousands of files from me getting home from a party or something and getting *it* all out, I think any musician will know what I'm thinking of, especially those who play intense music (hardcore punk/crossover/thrash metal/death metal). I could later go back and crop riffs and paste them back in some order and I would get the idea of a song, guitar-wise. My band really appreciated my "riff bank" laptop, not bragging btw, sober I'm not as good and have problems playing perfectly a song I've learned how to play when I was 15, when I first got an electric guitar. Opiates made me feel like doing nothing was just fine. But I see potential with a hybrid opiate/medium strength dissociative.

 

[adder]

A potential for an extremely pleasurable compounds is IMO in full mu agonists/kappa antagonists, one is 5-ethyl-6-ketolevorphanol, though I'm sure these would be even more addictive than normal opioids. I've been on buprenorphine for almost 4 years and during this time I believe I got specifically dependent on it for its unique effects which are quite stimulating mentally and at the right dose also promoting increased focus to some extent, it's got me really interested how a pure kappa antagonist would feel like. I'm wondering if a pure kappa antagonist could make tapering off buprenorphine easier as its withdrawal definitely have certain unique symptoms and overall it feels quite different from withdrawal from classic opioids at least during the first few days. Dissociatives are not an option for me any more as they make me feel symptoms similar to mild benzodiazepine withdrawal for a few days, that's the price you pay for taking benzos for years, I guess.