2cb and 5-meo-mipt tolerance?

[Sarapteropus]

Hey all, haven't found my answer in the psych forums and I'm not sure where to find RC discussion...

Planning on taking 2cb on Saturday night, and then keen to do moxy the next afternoon. Is there any info on potential tolerance following 2cb (I'm assuming it's a different level of tolerance to other psychs, given I know it's possible to take this days in a row and redosing is fairly easy)? In particular, any cross tolerance with moxy?

Cheers!

 

[T. Calderone]

(Homeless -------- > Psychedelic Drugs)

 

[Solipsis]

Actually cross tolerance should be fairly limited as 2C-B acts mostly via 5HT2C agonism and if anything hardly or non-agonistic activity at 5HT2A while moxy acts rather on 5HT1A as agonist and also some 5HT2A agonism which is fairly different.
I guess it's a bit of a mystery how 2C-B can be such a potentially colorful and pleasant psychedelic from 2C while attempts of using other 2C agonists this way have been unsuccessful, like lorcanserin. (Although of course a good number of other phens also act on 2C - possibly something more is necessary, or a different signalling pathway.)

2C-B and moxy are both sort of aphrodisiac-like or potentially tactile in ways so it's interesting to note that they are yet so different.

 

[Sarapteropus]

That helps heaps, thanks man! Ended up not doing it but handy to know for next time!

 

[Kaleida]

I guess it's a bit of a mystery how 2C-B can be such a potentially colorful and pleasant psychedelic from 2C ....

Hey Solipsis, do you mind if I ask what makes you so sure this is the case? I've seen studies suggesting that 2C-B has low efficacy partial agonist properties at 5-HT2A receptors by at least one pathway too, but I don't recall those proving that those receptors still couldn't be entirely responsible for the psychedelic effect, and I have seen another very recent study as well where it along with most other 2Cs was shown to have an efficacy of around 40%, similar to DMT and actually higher than both LSD (28%) and psilocin (16%). So it would seem to me that the picture might be more complex than it first appears. Another question I think worth asking is does serotonin have any actual "psychedelic" effect, and if it would actually be possible to have too little efficacy at the psychedelic pathway to not create a net positive effect?

Of course, if you do have some more conclusive data on 2C-B and 5-HT2C I'd love to see that too.

 

[Solipsis]

I guess your study was more recent than this one then?

http://onlinelibrary.wiley.com/doi/10.1038/sj.bjp.0705722/abstract

What's conclusive in science when there's conflicting studies? Best thing to do is see where the methods of each may be flawed..?

In this one the efficacy seems pretty damn low too: http://jpet.aspetjournals.org/content/321/3/1054

As mentioned above, 2C-N elicited only PLA2-AA release, and 2C-B induced little activation of the 5-HT2A receptor, eliciting weak responses (5–10%) in both AA release and IP accumulation. These results also agree with our previous reports in different models (Sáez et al., 1994; Acuña-Castillo et al., 2002), suggesting that phenethylamines can be hallucinogenic even if they have low efficacy at 5-HT2A receptors, at least in the two pathways studied here. However, it will be necessary to evaluate the effects of these compounds on other signaling pathways (e.g., phospholipase D) coupled to 5-HT2A receptors. As noted by Nichols (2004), it is possible that the effects in the phospholipase D pathway might be relevant to the mechanism of hallucinogenesis by these compounds.

Hence the hardly or non agonistic nature I mentioned

 

[Kaleida]

Yeah, definitely more recent than those, it's from 2015. Here's the PDF link: click.

I can't claim to know too much about these things, but they apparently use some newer fluorescent labeling design that they believe will give more accurate efficacy results. Notably, in addition to finding the higher values for 2C-B and other 2Cs, they also found that NBOMes by this test actually had lower efficacy than their normal phenethylamine counterparts. This is discussed a bit in the paper.

And yeah, I don't doubt that 2C-B is a weak partial agonist by some measures based on the research, but I suppose that just doesn't necessarily change the fact that 5-HT2A could still be responsible for the psychedelic effects in my mind. My primary issue comes again as I've said with the question of whether or not serotonin itself has any "psychedelic" activity. After all, partial agonists only behave as antagonists by displacing more efficacious agonists, so if serotonin has no psychedelic effect then it wouldn't really even apply here would it? Even 5% efficacy would be more than nothing.

 

[Kaleida]

Just to add a thought to that.... It's not really that efficient to think of the efficacy in those tests as doing what serotonin couldn't do I know, because they're gotten by measuring against serotonin. But, here's an example of something that LSD and DOI, but notably not TCB-2, do that serotonin does not: link. Basically, LSD and DOI increase D2 receptor activity through a 5-HT2A receptor dependent mechanism while TCB-2 and serotonin don't. So, in this case for instance, how do we know that 2C-B might not do something like that even despite acting as a very low efficacy agonist?