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  • N&PD Moderators: Skorpio | someguyontheinternet

Sr 17018 / RC opioid detoxes

Sounds interesting. These types on agent are still quite new though so they could still be doing work with it.

Thomas D. Bannister, Laura M. Bohn, & Cullen L. Schmid, WO2017161017 (to Scripps Research Institute).
Pantouli F, Grim TW, Schmid CL, Acevedo-Canabal A, Kennedy NM, Cameron MD, Bannister TD, Bohn LM. Comparison of morphine, oxycodone and the biased MOR agonist SR-17018 for tolerance and efficacy in mouse models of pain. Neuropharmacology. 2021 Mar 1;185:108439. doi: 10.1016/j.neuropharm.2020.108439. Epub 2020 Dec 17. PMID: 33345829; PMCID: PMC7887086.

The benzimidazole class of piperidine opioid is from the same family as Brorphine though.
 
www.ncbi.nlm.nih.gov

SR-17018 Stimulates Atypical µ-Opioid Receptor Phosphorylation and Dephosphorylation

Opioid-associated overdoses and deaths due to respiratory depression are a major public health problem in the US and other Western countries. In the past decade, much research effort has been directed towards the development of G-protein-biased µ-opioid ...
www.ncbi.nlm.nih.gov www.ncbi.nlm.nih.gov

jpet.aspetjournals.org

Effects of a highly G Protein-Biased Mu Opioid Receptor Agonist, SR-17018, in Non-human Primates

Abstract ID 20391 Poster Board 67 SR-17018 was identified as a G protein-biased mu opioid peptide (MOP) receptor agonist with the highest bias factor and lacked MOP agonist-associated adverse effects in mice. The aim of this study was to determine the functional profile of spinal and...
jpet.aspetjournals.org jpet.aspetjournals.org

DS>NaPD
 
That is impressive. It looks like this compound has revealed a more subtle type of signaling bias for opioid receptors. Rather than being the binary switch between g-protein and beta arrestin 2 downstream signaling, the first paper showed that SR-17018 causes a different pattern of phosphorylation on the receptor, which influences its effects.

As to its tolerance reducing properties, that is also interesting. It seems to produce a withdrawal on its own, and it seems to last for a while, but it seems quite a bit less intense than morphine withdrawal. It also seems to substitute for morphine, I think in the discussion they were considering it a way to lower tolerance for long term treatment. Finally treatment didn’t lower its own binding affinity, or reduce the amount of receptors, so that aspect of tolerance either develops very slowly or is absent. I believe circuit and psychological mechanisms of tolerance and dependence will still apply.These were all done in mice, so things could be different in humans.

I would expect it to be subjectively “weaker” feeling than morphine, and if all of the studies are taken to their most optimistic conclusions, to be a much more effective buprenorphine, with a milder propensity to behave as “liquid handcuffs”.

Smyth2 makes a good point int that it looks like brorphine. Brorphine was thought to have bias and and generally be less addictive and respiratory depression prone, but it hasn’t really differentiated itself from other synthetic opioids to my knowledge.
 
This stuff was available from a certain rc vendor just recently for a short Period. Buyers Comments were rather Bad.
 
My experiences with SR-17018 (combined with ODSMT & for opioid withdrawal)

First, I took <1mg SR as an allergy test, then dosed 10mg orally, followed by 20mg orally 1 1/2 hours later, finally 35mg orally.
I didn't really feel anything from it, to be honest.
I did notice that craving for an ODSMT dose was reduced after I took the 20mg SR. Could be placebo, though.

The interesting thing is that I don't really feel any withdrawal effects from coming down from the ODSMT. My last ODSMT dose was 50h ago. I took kratom two times yesterday, two times today. In a pretty moderate dose. And I feel zero withdrawal effects.
I actually feel very good, which is unexpected. Could be due to taking 40mg ketamine (in 2 lines) in the forest earlier today, though. Ketamine definitely has some antidepressive effects for me following consumption.

Tomorrow, I'll try to skip my morning kratom dose & take maybe 40mg SR instead.
If this works & I'm not craving kratom & not feeling any RLS (which is the first severe withdrawal effect I get), this would be miraculous. I'll report back.

(Edit: I was able to replace my kratom dose with 50mg of SR. Unfortunately I don't have enough to get on SR for a week & try to withdraw from it. I will get more when it's available again.)

So far, SR-17018 isn't "abusable" for me. It's not fun combined with ODSMT.
If it does reduce withdrawal effects & doesn't increase tolerance to other opioids, as others have claimed, it could be an effective treatment for opioid dependancy.

Edit2:
It did have nice opioid effects for me t 100mg oral.
It seems to have similar potency to rectal ODSMT.
It would be no problem at all to replace ODSMT or kratom use with SR use, craving wise.

Btw:
I also tried to mix 10mg of SR with water, which worked at first, until the solution became cloudy & some white solid fell out of solution.
I still applied it rectally & didn't feel more than from oral consumption.

Also, as a side note, my SR doesn't taste bitter & doesn't burn on the tongue at all. I just put it in my mouth & let it dissolve.
 
It appears that Trevena is the first to trial a new class of biased MOR ligands.

I don't think anyone has provided a name to the class of ligand but if one scrupulously follows the chemistry of the class, I suppose that '2-pyridinyl oxaspirodecane' or 2POD might provide a practical shorthand.

It does appear to have been introduced into more general medical usage in a couple of nations.

Be very careful of animal models used to study the abuse and dependence liability of psychoactive compounds. Long ago I decided to read more about the 'antagonist' isomer of viminol. It turns out that it isn't in fact an antagonist. So, given how PMZ-21 was discovered not to be a biased agonist, I would approach this class carefully.

Don't get me wrong. IF these new medicines offer the potential to release people from the bondage of opioid dependence, I'm all for it.
 
SR-17018 trial #2:

First took 30mg. I still have some amphetamine in my brain & maybe a small amount of alcohol from a party I attended last night. My last line of speed was around 10h ago. My last kratom dose was 8h ago.
Didn't feel much from it.

Then I took 100mg. 1 1/2h later another 100mg. 1 1/2h later another 80mg. I feel a bit sedated. Don't have opioid craving right now. The rest Amph stimulation probably reduces the effects. I feel like I can finally sleep soon.

All doses were taken orally.


SR-17018 trial #3

Started the day with ~70mg orally. Took another 80mg in the late afternoon. Slight craving thoughts appeared, nothing major, easy to ignore. An hour after the second dose the craving went away & came again 6h later.

Now, in the night, I just dosed 50mg rectally. More like 45mg actually. I used 3ml of water. It goes to solution difficultly & crashes out as a white solid very quickly. I just applied it anyway, hoping the cloudy liquid will still work.

T+ 5min: I kinda feel a nice tingling sensation in my lower body, which I often got from boofing O-DSMT. It's probably a learned reaction to the anticipation of getting my μ-opioid receptors agonised.
Whether that's purely placebo or actually due to the SR molecules reaching my brain - I don't know.

I should note that I had pretty substantial kratom (or better yet O-DSMT, which I don't have) craving half an hour ago.
I was tempted to just drink a cup of kratom juice and call it a day. But the thought of keeping this experiment going & seeing whether my tolerance will be lowered & just boofing some SR deterred me from going the tested and true kratom route.

It's now about 39h since my last kratom dose. I haven't consumed any psychotropic substance today - apart from caffeine in the afternoon & the two SR doses. If 200mg of SR could sustain me and stop the cravings, this would be a very feasible solution to my opioid use disorder.
It would cost **** a day. Way more than kratom, way less than the .5-.8g O-DSMT I used daily at times.

T +40min: I don't feel much of an opioid effect but the craving is gone. I'm motivated to keep on continuing this experiment & just take SR for at least 7 days. Then I'll go to a vacation to a different country & don't wanna take it over the border with me - so I'll switch to kratom again. If my tolerance is way lower by then, this stuff would be amazing.

Mind you - I'm making myself a lab rat here.
Worst case is, it could lead to my untimely death.
Don't experiment with it if you don't wanna take that risk.
 
I took the SR for about 7 days & switched back to Kratom.
I also consumed ODSMT (a worse, less potent batch) during my vacation on 3 seperate days.

My tolerance wasn't lowered significantly after 7 days of SR use.
I took Kratom or ODSMT for the last 7 years though, so I propably just need more than one week of SR maintenance to substantially reduce my tolerance.

I didn't feel any side effects from the SR.
Craving was controlled most of the time.

In high doses (100mg oral/sublingual) there was a sedative effect. No euphoria. Not really recreational.

I did have the feeling, rectal application (which I tried 4 or 5 times in doses of 40-60mg) does work.
It is kinda weird & I felt a bit bloated after that.
Not worth it, since it's not water soluble imo.

I didn't feel any withdrawal effects apart from moderate craving.


I will order more soon.
I think I'm not ready to get off opioids completely right now.
So my plan is to reduce tolerance first.

I'd like to get on SR for 2 weeks & then see how well kratom works after that.

Another interesting use would be to alternate Kratom / ODSMT use with SR (f.e. 1 day on kratom / ODSMT, then 1-3 days of SR, then 1 day of kratom/ODSMT) to potentially sustain tolerance on a steady level & reduce withdrawal.
 
I think it important to note that SR-17018 is a partial agonist so the typical description appears similar to buprenorphine, for example. A double-blind trial would really be of use here.

I didn't read the details at the time but apparently one (of the many) papers was retracted because the researchers had assigned a potency for some examples by testing the affinity and making a guess. I think it was also responsible for the researchers not declaring the stuff a partial agonist.

But if it's safe (compared to street opioids), is of appropriate quality then if it helps just one person, it's made a bug difference.
 
Can say that my partner and I have both successfully used SR to cold turkey off Oxycodone. Definitely not enough time to reduce tolerance. But so nice to relax and be normal without getting high for a week. I hope more of this gets produced and spread. A true miracle
 
Smyth2 said:
Oxycodone is addictive.
Click to expand...

Almost all opioids agonist are addictive. Some may have greater or lesser tolerance issues.

As I see it, one should carefully assess the analgesic activity of an opioid compared to it's dependence liability. Oxycodone is odd in that it's more active if consumed orally (first-pass metabolism) than via any other ROA. I think that was the logic that made people think it wouldn't be abused. But some people appear happier to get a short intense effect that is subjectively different. After all, if consumed orally, around hald the activity is due to the oxymorphone that is an active metabolite of the stufff.
 
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