Opioids Synthetic nicotine blocking my opioids?

[Synaps3]

I was debating whether to put this here or in the pharmacology sub. I think I might get more answers there given it requires some advanced understanding, but I don't want to over step.

I'm a pretty heavy nicotine user. I use either 36mg or 50mg salt depending on my device (36 with 20W and 50 with 11W device). Yesterday is the first day I used synthetic nicotine salt. I noticed towards the end of the day yesterday that I wasn't feeling right. I would take a hit and still get a good rush, so I thought it was working, but it was ONLY the rush. It's like the effect would disappear immediately after the hit. It was deceiving because the hits were still good initially. I read people not liking the synthetic because lack of throat hit, but I don't really care about that - it's the effects that are thoroughly messed up.

I woke up today with a bad headache and throughout the day started developing really bad anxiety. I use an opiate everyday. One and 1/6th, 8mg dilaudid pill a day - half oral, half intranasal - divided in two sessions. When I took my first dose today, literally nothing happened and my eyes stayed huge the whole day.

A few hours ago, I found an old bottle of natural nicotine salt that I thought was kind of crappy and harsh, but it did work alright back in the day. I just loaded that up in a pod and WOW. I'm coming back to normal. I'm still not feeling the pill much, but it's getting better and my anxiety has gone down a TON! I now just took my second dose and my eyes look "normal", but definitely not small and I barely feel the effects. It is better than earlier though.

It's so weird to me how significantly this nicotine effected my opioid tolerance. So it's either the synthetic nicotine, or it could possibly be the lack of extreme menthol in the new juice. Cause the new juice I got wasn't much menthol and they do say that menthol enhances the nicotine receptors, but I doubt it would have that much effect cause I used to use tobacco or other flavors.

Anybody know why this happened? Is it the synthetic or the lack of menthol?

 

[Snafu in the Void]

Synthetic nicotine has been the majority of all juices since vaping's inception. There should not be any subjective difference.

Vaping has only ever given me a very brief momentary rush and no lasting buzz... with tolerance, only tobacco provides that to a small degree.

"Synthetic" does not cause lack of throat hit, freebase nicotine causes lack of throat hit. Salt nic does not cause this.

Nicotine of any kind should have zero effect on your high from daily intake of dilaudid, and looking at your pupils is a very poor and inaccurate measure of anything in your system.

I honestly don't even understand what you're asking. I think you may be confusing "synthetic" nicotine for oldschool freebase nicotine which is generally considered inferior to salt nic these days.

 

[Synaps3]

Synthetic nicotine has been the majority of all juices since vaping's inception. There should not be any subjective difference.

No. Most of it used to be extracted from tobacco. I don't remember even seeing synthetic nicotine or TFN (tobacco free nicotine) several years ago (like 2017).
TFN has R and S isomer mixed and some people say the R causes adverse effects such as migraine or anxiety (but the mechanism has not been scientifically proven).

Vaping has only ever given me a very brief momentary rush and no lasting buzz

I would say that about the synthetic. Extracted natural freebase is the longest lasting. There's also WTA juice which might be even longer, but I never tried it.

"Synthetic" does not cause lack of throat hit, freebase nicotine causes lack of throat hit. Salt nic does not cause this.

No.

Nicotine of any kind should have zero effect on your high from daily intake of dilaudid, and looking at your pupils is a very poor and inaccurate measure of anything in your system.

Well, it did for me. I have no doubt at this point. I was certainly in withdrawal from that synthetic crap and it was some sort of fusion of nicotine and opiate withdrawal. The way I felt was like I hadn't used any nicotine or opiate. I just want to understand the reasons better cause I'm a nerd and want to avoid in future Maybe R nicotine is an opioid blocker? Maybe natural extract contains some other stuff that blocks metabolism? Maybe the menthol blocks metabolism (I see it inhibits some P450 enzymes)? The R being inactive in juice making it weaker? This one I know is a "No" cause it felt the same strength and I vaped enough.
I've never had my pupils lie to me. If they are small, I'm always good hehe.

Either way. Hopefully tomorrow I will buy some other non-synthetic juice brand just to be sure it's not me becoming habituated to my current brand. (I did try several bottles of synthetic yesterday and they were all bad, it wasn't only one. Kinda mad how much money I spent on this synthetic juice.)

 

[G_Chem]

“There is significant regulatory and economic need to distinguish analytically between tobacco-derived nicotine (TDN) and synthetic nicotine (SyN) in commercial products.”

“TDN is ~99.3% (S)-nicotine, whereas SyN can vary from racemic (50/50 (R)/(S)) to ≥ 99% (S)-nicotine, i.e., chemically identical to the tobacco-derived compound.”

Fascinating.. Yea obviously a racemic mixture will be much different in effects. Stimulants of all sorts generally favor the S isomer for positive effects.

-GC

 

[G_Chem]

From various sources below…

“The pharmacology of (S)-nicotine and (R)-nicotine differs substantially, and studies have suggested that (S)-nicotine is more potent than (R)-nicotine. It’s therefore unclear whether synthetic nicotine will have the same biologic effects as tobacco-derived nicotine.”

“S-nicotine extracted from tobacco was considered safer and more economical. Analyses by Reynolds in 1967 and Ligget and Myers in 1978 came to the same conclusion.”

“Little is known about the pharmacological and metabolic effects of R-nicotine in humans. Metabolic studies comparing the fate of R-nicotine in several animal species revealed stereoselective differences in the formation of oxidative metabolites and stereospecific N-methylation of nicotine enantiomers. The degradation kinetics of the resulting S-cotinine and R-cotinine also differed. In contrast to S-nicotine, R-nicotine did not induce weight loss in rats and did not trigger epinephrine release. R-nicotine is a significantly less potent (~10-fold) agonist of nicotine receptors than S-nicotine, however, both stereoisomers interfere with the production of certain lipid mediators involved in regulation of inflammation.”

“S-(-)-nicotine formed predominantly R,S-cis-nicotine-1′-N-oxide, whereas R-(+)-nicotine gave predominantly S,R-trans-nicotine-1′-N-oxide; stereoselective metabolism to cotinine also occurred. A stereo-selective site for the N-oxidation of nicotine is proposed to explain these results.”

Also I’m reading that often manufacturers of E-juice will double the quantity of racemic nicotine to then claim a certain S-isomer quantity. Meaning you could be getting larger than expected amounts of R-nicotine too.

-GC

 

[Synaps3]

I found something incredibly interesting to me. Apparently nicotine actually interacts with the opioid receptor by proxy; meaning it doesn't appear to activate the receptor directly (or we would have known this earlier), but it does influence the u-opioid receptor.
https://www.jneurosci.org/content/jneuro/22/24/10935.full.pdf

This could explain why nicotine seems to enhance opioids sometimes and also why lack of proper S-nicotine may result in mild opioid withdrawal.
I'm glad I finally found it, cause I had a suspicion something like this was going on.
What can you take from this? If you are a vaper or smoker and opioid user - you probably don't want to quit both at the same time. Also, you may be able to lower your opioid tolerance by simply using less nicotine for a couple days. For me, just 1.5 days of using that crappy synthetic nic was enough to make my dose the following day (resuming real nicotine) about 50% stronger. And I don't vape that much (like 1mL (half a pod) 45mg juice per day).

 

[RedRum OG]

If anything nicotine "potentiates" as others have said.

When I'm dopesick nicotine is twice as valuable

 

[Synaps3]

If anything nicotine "potentiates" as others have said.

When I'm dopesick nicotine is twice as valuable

Yes, I agree. Earlier I was talking about how the synthetic nic doesn't though. The title might be confusing if you didn't read the entire thread.

 

[RedRum OG]

Yes, I agree. Earlier I was talking about how the synthetic nic doesn't though. The title might be confusing if you didn't read the entire thread.

I did read, but was a little confused. The salt brands I used years ago were synthetic, so I assumed all salts were. My mistake there.

Either way what I meant was that no matter the source, they should have similar effects. I think there may be a slightly different balance of enantiomers/isomers, but I think they are qualitatively similar and shouldn't make much of a difference. This is mostly from an anecdotal standpoint- I've never noticed any sort of antagonist or blockade effect, much the opposite if anything- sensitizing. Not a chemist/doctor, though.

 

[Keif' Richards]

I've never heard of such a thing. I have no information leading me to believe that this would be a problem. There could be some kind of interaction, but it's not one that I believe is significant to the user. A liftetime of using Opioids and speaking with others who use Opioids has never led me to a conversation regarding how they believe their nicotine usage is effecting their experience, but that of course does not mean it is not possible.

 

[deadhead4lyfe89]

High amounts of nicotine can give you headaches and sometimes anxiety. Smoking and vaping also increase your heart rate.
I vape 30mg of salt nicotine and I tried 50mg for a bit but it gave me major horrible headaches and increased my anxiety level. But I do have an anxiety disorder from CPTSD. Complex childhood post traumatic stress disorder.