Miscellaneous Calculating cross tolerance for redosing.

[Phobos33]

Sup guys, haven't been active on here for a hot minute and i figure that Bluelight might be the best place to ask cause i can't stand Reddit and even less any psychedelic related subs so here i am expecting to possibly get some valuable informations from knowledgeable individuals and i know for a fact that there are plenty of you here who knows their shit inside out and also alot of educated minds on here.

So as the title suggests, i have a particular question i need answers to so here's a little background info.

I have something like 222 tabs of really fucking good and properly dosed acid and 219 gels of the same xtal. I recently had my first ever 2C-B experience last Friday and i made sure to have no tolerance when i tested the caps. I loved it so fucking much that i ended up remembering another really reputable vendor that sells both 2C-B HBR and Mescaline HCL and bought a gram of mescaline and 2 grams of 2C-B. In the near future i will be purchasing a disposable DMT vape pen from a really reputable vendor so basically i'm gonna have plenty of fun substances to start experimenting with combos and what not.

So here's where i need a bit of your expertise. I know there exists a LSD/shroom tolerance calculator(i've been using it for a long time and has served me well for when i wanna trip several times a week or less) tho i've never seen a tolerance calculator that actually takes into account the tolerance of multiple substances and can give you the accurate dosage required for one substance taking into consideration the tolerance of other compounds. I dunno if that makes any sense?

Like say i did 2x 100ug tabs of acid 4 days ago and i want to experiment comboing both 2C-B and LSD for the first time. If i wanted to get the equivalent of 200ug i'd have to drop 316.1ug. What about if i wanted to combine it with 20mg of 2C-B? I know 20mg would definitely feel like waaaaaay less if not barely anything due to cross tolerance.

I know if you just dose 2C-B by itself, tolerance barely sets in which makes it easy to go back to doing the same amount you last did in no amount of time. The same can't be said about LSD and it usually takes 13 days for your system to be at baseline tolerance wise.

Hopefully i made enough sense and any of you can enlighten me about this particular subject because with the amount of tabs i have, i can afford tripping pretty regularly and with my access to cheap, top quality and pure 2C-B, i wanted to experiment with combining both and possibly experiment with DMT too in the near future.

I don't wanna hear about you guys telling me to slow down and not do psyches this often because blah blah blah, i don't give a shit. I've been doing this for a long time pretty regularly and i have yet to transform into a drooling vegetable.

Thanks in advance for anyone who can educate me on this topic and i wish you all to have a good one, peace!

 

[iom]

I don't wanna hear about you guys telling me to slow down and not do psyches this often because blah blah blah, i don't give a shit. I've been doing this for a long time pretty regularly and i have yet to transform into a drooling vegetable.

Well I have no idea how frequently you are thinking of using these things, but I can give you several reasons why you should give a shit about psychedelic use frequency:

1. You will need much more material to get the same "level" of effects, which will burn through your stash much more quickly.
2. When choosing doses, whether or not you have a "calculator" to help you, you will struggle to correctly estimate your tolerance and will be more prone to under or overshooting the dose. Your trips won't be as fun when your dose is less suited to the set and setting.
3. Tolerance is likely not the same for all effects, and "trippy" tolerance is likely to be higher than tolerance for many unwanted side-effects. Even if the intensity is matched, the quality of the trip will likely be poorer.
4. Over use of some or all of these drugs may have long-term effects that don't appear until much later in your life.

Now in general, cross-tolerance assessment is a rather rough business. Each pairing of substance (taken in either order) can have a different tolerance curve, and that curve won't necessarily be the same between individuals or even different conditions involving the same individual. Furthermore, cross tolerance data is usually based on two administrations in sequence and does not consider multiple uses involving more than two psychedelics. (Three-way crosses!)

I suggest keeping things simple and spacing things out enough so that tolerance doesn't need to be compensated for. On those occasions in which it is especially desired to trip more frequently than usual, consider keeping the same dosages and accepting weaker experiences as a necessary consequence. This is almost always better than trying to repeatedly up the dosage because psychedelic tolerance rises so fast.

Now I'll give some of my rules of thumb. If I want to trip twice in a row and don't want the second trip to feel substantially diminished, I wait at least 3 days. For me, a trip taken 2 days after can be reasonably effective but definitely diminished. A trip taken one day after is usually a disappointment and waste. For more than two consecutive trips, I think it's best to put more time between one or both, like 5 days. For semi-regular tripping over a long period of time, I think once every 3 weeks on average is a reasonable limit. I do think it depends on the substance. Weekly ayahuasca and peyote drinkers seem to be fine. I suspect the latter experience some modest tolerance with this periodicity, but this should be easy to compensate for because it is modest. This is key. If the increase in tolerance is small, it's much easier to adjust to compensate for it, with or without a "calculator".

I also will caution that psychedelics have significant action at 5-HT2B receptors. Chronic activation of these receptors is associated with valvular heart disease. It is unknown what risks psychedelics pose in this regard, but I believe 2C-B has particularly strong activity at 5-HT2B (where it also likely amplifies serotonin release, similar to MDMA). As such I would caution against using 2C-B more than occasionally. Also, using 2C-B and many other psychedelics frequently may cause serotonin dysregulation in ways similar to frequent use of MDMA. I don't think either LSD or DMT are nearly as likely to do these things, but it's not clear.

Good luck whatever you do. If you decide to trip a lot, I'm sure you'll figure out pretty quickly what works and what doesn't. Just don't forget to take a break from time to time to assess things. A lot of times people will trip overly frequently and try to match the rising tolerance, and they almost alway regret it for the reasons I gave above.

 

[Phobos33]

Not exactly the answer i was expecting or wanted but thanks nonetheless for the effort put into it.
Funny you mention that chronic activation at 5-HT2B receptors can lead to valvular heart disease cause yesterday i stumbled upon an article that i haven't read yet claiming that using LSD alot can lead to valvular heart disease over time tho both LSD and 2C-B don't act on the same receptors.

 

[iom]

You're welcome. I was hoping others might chime in with their own suggestions, but not so far I guess.

LSD and 2C-B definitely act on the same receptors for the most part. This includes 5-HT2A, 5-HT2B, 5-HT2C, 5-HT1A, and also probably alpha and/or beta adrenergic receptors. Of course, their activity at each of these receptors is different in both quantity and quality, and specifics remain unclear. The available data give only a very blurry picture of things.

To my best knowledge, the risk of valvular heart disease from psychedelics as well as MDMA arises through interactions with the 5-HT2B. As far as I know, no evidence exists (one way or the other) as to the actual risks with any of these drugs. The exception is MDMA, but I've only seen a handful of studies of this risk, and they were problematic in various ways like having small sample sizes and potential population sampling problems. This is a subject that needs a lot more research, and it looks like now psilocybin is getting some attention in this regard because it actually has a rather high affinity for 5-HT2B, even as far as psychedelics go.

Anyway, the data I've seen suggests LSD is quite low affinity at 5-HT2B compared to other psychedelics, and so it might be safer to use more frequently than most other psychedelics. Admittedly though, affinity data is far from infallible, and of course there may be other long term risks that have not been discovered yet. For comparison in the data I've seen, 2C-B is high affinity, and DMT is in between.

FWIW, I believe @Xorkoth ended up taking DOC approximately once per week for a long time, maybe years? Anyway, DOC is like 12-24 hours long, and I believe it probably induces a lot of tolerance as far as psychs go. As far as I know though, he didn't encounter much tolerance with that tripping interval. Too bad he doesn't post much here anymore, but maybe he'll drop in here and comment on this subject.

 

[Phobos33]

Cool, thanks again for the info.

 

[Shinji Ikari]

In my experience the tolerance created hy LSD is stronger than the tolerance created by most phenethylamines and tryptamines.

Additionally, you need more 2cb to push past that tolerance than you would were you taking acid again or a tryptamine like psilocybin. So if we say that 300ug would feel more like 200ug with your tolerance, then 30mg of 2cb might feel more like 10 or 15mg. I'm guessing this is because 2cb has a lower affinity for fewer receptors.

Fyi the numbers I used are just arbitrary examples. The point is that it will likely take a higher dose of 2cb relative to other psychedelics to push past that tolerance.

Good thing about 2cb is you can redose and tolerance won't become an issue until you've been redosing for multiple consecutive days. Bad thing about 2cb is that oral doses take ages to kick in and the body load gets increasingly sucky the higher you go. Your best bet would be to dose nasaly or rectally, maybe 10 mg every 15 minutes until you're where you want to be.

You could also try pre-loading on 2cb a couple of hours before dropping acid. Makes the comeup and transition from threshold to comeup to peak feel much more smooth and grounded. One of the best trips of my life started with 30mg of 2cb followed by 200ug of acid a couple of hours later.

Edit* I know the vendor you mean. I thought they'd gone off grid when the garden went kaput and was delighted to accidentally stumble upon them while browsing the markets just last week. I've got a gram of their mescaline on order myself, the 2cb will have to wait until payday

 

[Phobos33]

In my experience the tolerance created hy LSD is stronger than the tolerance created by most phenethylamines and tryptamines.

Additionally, you need more 2cb to push past that tolerance than you would were you taking acid again or a tryptamine like psilocybin. So if we say that 300ug would feel more like 200ug with your tolerance, then 30mg of 2cb might feel more like 10 or 15mg. I'm guessing this is because 2cb has a lower affinity for fewer receptors.

Fyi the numbers I used are just arbitrary examples. The point is that it will likely take a higher dose of 2cb relative to other psychedelics to push past that tolerance.

Good thing about 2cb is you can redose and tolerance won't become an issue until you've been redosing for multiple consecutive days. Bad thing about 2cb is that oral doses take ages to kick in and the body load gets increasingly sucky the higher you go. Your best bet would be to dose nasaly or rectally, maybe 10 mg every 15 minutes until you're where you want to be.

You could also try pre-loading on 2cb a couple of hours before dropping acid. Makes the comeup and transition from threshold to comeup to peak feel much more smooth and grounded. One of the best trips of my life started with 30mg of 2cb followed by 200ug of acid a couple of hours later.

Edit* I know the vendor you mean. I thought they'd gone off grid when the garden went kaput and was delighted to accidentally stumble upon them while browsing the markets just last week. I've got a gram of their mescaline on order myself, the 2cb will have to wait until payday

Thanks for the reply and the good intentions behind it but you didn't teach me anything i already knew.

i was simply trying to see whether or not someone knew of some kind of mathematical formula(like the one they use for that one LSD tolerance calculator you can easily find on google) that takes into consideration 2 or more compounds when you already have some pre established tolerance to one compound(like LSD for example). I know it was a dumb question to ask right from the start but i tried anyways because i've seen alot of people on here going into deep details about chemistry, neuro-chemistry and what not so i figure "surely somebody already has this shit down or something close to it".

Also yeah, dude came back 2 months ago. I tried someone else's 2C-B HCL because they were offering a sample of 4 caps in exchange of a review so all i had to pay was the shipping and something a little over 1$ for the caps and i ended up getting a 5th one as a freebie.

Kinda feel bad cause the vendor who sold it to me seems like such a fucking nice dude with a nice energy but his stuff was pretty pricey and someone reminded me about the other vendor and it made me remember the thread he made 2 months ago about his comeback so i went and compared both of their prices and ended up going with the legend. The only difference between both aside from prices is that his salt is the HBR one rather than HCL. Which tbh i don't mind that much, just that i read that you basically need about 15% more than a HCL dose if you wanna get an equivalent dosage. Thing is i've read countless times about people swearing that even with the same dosage equivalency, the HCL salt has a bit more punch to it.

Dude, i've never tried mescaline so can you imagine how stoked i am to finally get to try it? The only thing that bums me out is the fact that 1g cost something like 107$(with shipping) if i remember correctly and one standard dosage is 200mg which is like 5 equal doses and i would've loved to be able to experiment with different dosage without going thru it so fast.

 

[Shinji Ikari]

i was simply trying to see whether or not someone knew of some kind of mathematical formula(like the one they use for that one LSD tolerance calculator you can easily find on google) that takes into consideration 2 or more compounds when you already have some pre established tolerance to one compound

Then you should have just said that instead of writing nine paragraphs for my stoned ass to decipher

Anyway I don't think such a thing is really possible. Even those LSD tolerance calculators are someone's best guess, they can't account for things like differences in people's physiology or the accumulated tolerance you'd have from a year of frequent tripping. Add in the largely undocumented differences in tolerances between the hundreds of known psychedelic compounds floating around and there are just too many variables to consider. Even if someone had made one I don't see how it could be accurate.

Kinda feel bad cause the vendor who sold it to me seems like such a fucking nice dude with a nice energy but his stuff was pretty pricey

I dunno where you are but it's handy having a reliable domestic vendor. You might need some in a hurry and not want to wait 2-3 weeks for delivery even if it does cost twice as much. I think most dosing guidelines are based on HCl as well so it can be nice to have a bit on hand if you're sharing friends and don't want the hassle of working out the difference. But yeah like you say it isn't complicated and HBr dissolves a lot easier so it's better for making tinctures and the like. Also, I don't know if our mutual friend is the chemist or just knows the chemist, but his 2cb and mescaline are pure, like best in Europe pure.

Dude, i've never tried mescaline so can you imagine how stoked i am to finally get to try it? The only thing that bums me out is the fact that 1g cost something like 107$(with shipping) if i remember correctly and one standard dosage is 200mg which is like 5 equal doses and i would've loved to be able to experiment with different dosage without going thru it so fast

Mescaline is expensive but the synthesis route is almost identical to 2cb which means it really is a labour of love for the chemist and the vendor, there's no money in it for them.

200mg is just threshold really. Given your experience 400mg is probably a good place to start. Splitting the dose in half and giving it 30 minutes between the two should help avoid nausea and smooth the comeup. Excited for you buddy. Mescaline and LSD is also my favourite drug combo in the world.

 

[brokedownpalace10]

This is a subject that needs a lot more research, and it looks like now psilocybin is getting some attention in this regard because it actually has a rather high affinity for 5-HT2B, even as far as psychedelics go.

Anyway, the data I've seen suggests LSD is quite low affinity at 5-HT2B compared to other psychedelics, and so it might be safer to use more frequently than most other psychedelics. Admittedly though, affinity data is far from infallible, and of course there may be other long term risks that have not been discovered yet. For comparison in the data I've seen, 2C-B is high affinity, and DMT is in between.

Fantastic data here. I would love a chart or list of affinity at 5-HT2B. Where's Mescaline on such a list?

Am I mistaken in my belief that there have been no actual studies of psychedelics and heart issues? That the assumption is completely based on there being issues with similarly acting (on the receptor) drugs such as Phen Fen and Sansert? I do realize that this data, although preliminary, is very indicative, I'm just very curious about this.

It takes three days to lose most tolerance to LSD, as you have said. From one of your posts.

"If I want to trip twice in a row and don't want the second trip to feel substantially diminished, I wait at least 3 days. For me, a trip taken 2 days after can be reasonably effective but definitely diminished. A trip taken one day after is usually a disappointment and waste. For more than two consecutive trips, I think it's best to put more time between one or both, like 5 days."

I could not have put it better.

 

[iom]

Fantastic data here. I would love a chart or list of affinity at 5-HT2B. Where's Mescaline on such a list?

It is my educated guess that mescaline has less relative 5-HT2B affinity than 2C-X and probably mushrooms too, but probably has more than LSD and possibly DMT too. My information is synthesized from multiple sources. It was a very messy process with many caveats, and I didn't really do any kind of write up on it. My view is that even with my effort, I'm only able to make educated guesses really.

Let me first warn about the many caveats with this kind of data. First of all, many different assays and methodologies are possible, and they all tend to give widely varying results. In my opinion, the only comparisons that should typically be made is among data from the same study. Furthermore, even within the same study, assessment of different receptor subtypes requires different assays, so comparing affinities of each drug between different receptor subtypes is problematic. However, it is likely useful to compare ratios of the different subtypes for different drugs. Hopefully that makes sense, but it definitely requires a bit of quantitative intuition. I also try to cross-reference with other studies just in case something looks out of line. I know of one very large data set in which all the 5-HT2A data appears way off the mark, which is kind of tragic given how useful it otherwise would be. My last tip would be to pay attention to the test animal and strongly prefer human tissue tests. The 5-HT2A receptor and maybe others differ substantially in properties between different animals, but mice are generally considered to be closer to humans than other animals.

Anyway, a good starting point for data is the PDSP database at https://pdsp.unc.edu. Beware that it will happily display data from many different studies all in the same column, tempting comparisons. Don't give in to the temptation. Instead, follow the citations to the original papers. The original papers usually have much more useful tables for the purpose of doing these comparisons. Another reason to go to the originals is that I have in fact found discrepencies between numbers in PDSP and the actual figures in the cited material.

I'll also post a link to a particular paper I found useful for looking at phenethylamines: https://edoc.unibas.ch/id/document/35331. Mescaline, LSD, and 2C-B are all in there.

Edit: I forgot to respond to this.

Am I mistaken in my belief that there have been no actual studies of psychedelics and heart issues? That the assumption is completely based on there being issues with similarly acting (on the receptor) drugs such as Phen Fen and Sansert? I do realize that this data, although preliminary, is very indicative, I'm just very curious about this.

To my best knowledge, this is correct. I believe I found one study comparing heart function in past MDMA users to those who did not use MDMA. The results appeared concerning, but I would not regard it to be definitive. The sample was small, and I don't think it controlled for various other important factors. I believe some work is on-going now to try to assess valvuopathy risk with psilocybin in advance of its potentialy approval bt the FDA and introduction into clinical practice. I have no idea how these studies are being done and how much solid insight they will contribute, regardless of the headline results. There are obviously ethical problems administering a drug which hypothetically cause damage leading to major surgery in a high percentage of test subjects. OTOH, I've never heard of an epidemic of heart problems in regular users of any psychedelic be it psilocybin or even MDMA. We'll just have to wait and see, I guess.

 

[iom]

Sorry to post again, but I looked at the data in the second link and realized that it does not show mescaline having lower relative 5-HT2B vs. 5-HT2A affinity, and in fact it does not include affinity data for 5-HT2B but rather activation potency. The result is not determined either way because the assay wasn't sensitive enough to detect mescaline action at 5-HT2B. This doesn't mean there was no action at doses required to trip. It's entirely possible that mescaline has more relative affinity (relative to 5-HT2A) than 2C-X and other things, but we can't see that from this data.

I apologize for the confusion, and I must concede that I don't know how mescaline compares to the others with regard to 5-HT2B activity. I wish I had some idea because it is otherwise a very good medicine for me.

 

[brokedownpalace10]

Sorry to post again, but I looked at the data in the second link and realized that it does not show mescaline having lower relative 5-HT2B vs. 5-HT2A affinity, and in fact it does not include affinity data for 5-HT2B but rather activation potency. The result is not determined either way because the assay wasn't sensitive enough to detect mescaline action at 5-HT2B. This doesn't mean there was no action at doses required to trip. It's entirely possible that mescaline has more relative affinity (relative to 5-HT2A) than 2C-X and other things, but we can't see that from this data.

I apologize for the confusion, and I must concede that I don't know how mescaline compares to the others with regard to 5-HT2B activity. I wish I had some idea because it is otherwise a very good medicine for me.

Don't apologize. Some great answers.