Phenethylamines 2C-B, worth trying on its own?

[Allylbenzene]

The N,N dimethyl homolog of mescaline seems to be inactive at comparable doses. Do you have any examples of tertiary amine phenethylamines maintaining 5HT2a agonism/psychedelic effects?

There are no examples as far as i'm aware. It's why I wrote the proposed pathway. It would be nice to properly characterise the metabolites that are formed under different enzyme environments (eg full ALDH inhibiton).

The potential for ALDH inhibition to potentiate/promote activity of different substances was being discussed prior to someone applying it to mescaline. I participated on the forum many years ago so followed the discussion as it evolved. ALDH inhibition was also found to significantly potentiate the effects of plain phenethylamine & tryptamine, likely involving their aldehyde metabolites. This implies some sort of amination occuring but I haven't found any research on this beyond formation of bio-active tetrahydroisoquinolines/beta carbolines via dopamine/phenethylamine/serotonin and acetaldehyde/dopaldehyde. (eg tetrahydropapaveroline, salsolinol, 1MeTIQ, tryptoline)

Acetaldehyde is a highly reactive compound that interacts with several endogenous neurochemicals in the brain to form a number of additional biologically active products (Cohen and Collins, 1970; Davis and Walsh, 1970; Walsh et al., 1970; Cohen, 1976). With regard to neurobiological and behavioral testing of the byproducts of ACD, the majority of attention has focused on two main classes of compounds which are formed through condensation of ACD with the catecholamines. The first class of compounds, the tetrahydroisoquinoline alkaloids (THIQs), are formed through both the direct and indirect condensation of ACD with the monoamines: dopamine, epinephrine, and norepinephrine (Cohen, 1976). The tetrahydro-beta-carbolines (TBCs) on the other hand, are formed through the reaction of ACD with the indoleamines: tryptophan and tryptamine (Buckholtz, 1980). The THIQs tetrahydropapaveroline (THP) and salsolinol (SAL) have received the most attention as to their role in alcohol use-disorders as both compounds can be detected in the brain following EtOH administration. The TBCs have received considerably less attention and contradictory data exists as to their contribution to the neurobiological effects of EtOH.

www.frontiersin.org/journals/behavioral-neuroscience/articles/10.3389/fnbeh.2013.00104/full

Mescaline metabolites & ALDH inhibition

The major and minor metabolic routes of mescaline are presented in (Fig. 5). In rabbit, mescaline metabolism occurs mainly in the liver by the action of an amine oxidase. While showing a significantly lower expression of amine oxidase, the lung also contributes for the clearance of mescaline, due to a larger blood flow, in comparison with the liver [75]. Mescaline undergoes detoxification mainly by oxidative deamination into an intermediate and unstable aldehyde, 3,4,5-trimethoxyphenylacetaldehyde, that is rapidly oxidized to the inactive TMPA or reduced to the inactive 3,4,5-trimethoxyphenylethanol [68, 71, 76, 77]. The fact that the peak of mescaline effects does not coincide with its peak concentration in brain, provided evidence on the contribution of its metabolites for hallucinogenic effects. In agreement, a study with rats treated with calcium carbimide (i.e., an aldehyde dehydrogenase inhibitor) showed that the metabolism into acid and alcohol follows the oxidation of mescaline to the aldehyde, whose concentration increased by metabolic inhibition, thus implicating this metabolite in the effects of the drug [43, 77]. The enzyme responsible for the deamination of mescaline to the aldehyde derivative is still a controversial issue among the scientific community. This reaction may be carried out by a monoamine oxidase (MAO) or a diamine oxidase (DAO). Studies with mice have shown that this route is inhibited by TPN, nicotinamide, iproniazid, semicarbazid, and other inhibitor compounds of mono or diamine oxidase [43, 78]. However, some authors discredit the role of these enzymes, as there are studies where their inhibition showed little relevance in the alteration of the metabolic profile, suggesting the existence of a mescaline oxidase [76, 79].

Pharmacokinetic and Pharmacodynamic Aspects of Peyote and Mescaline: Clinical and Forensic Repercussions - PMC

Mescaline (3,4,5-trimethoxyphenethylamine), mainly found in the Peyote cactus (Lophophora williamsii), is one of the oldest known hallucinogenic agents that influence human and animal behavior, but its psychoactive mechanisms remain poorly ...

pmc.ncbi.nlm.nih.gov

Another interesting study on mescaline activity & drugs in general

Novel, unifying mechanism for mescaline in the central nervous system: Electrochemistry, catechol redox metabolite, receptor, cell signaling and structure activity relationships - PMC

A unifying mechanism for abused drugs has been proposed previously from the standpoint of electron transfer. Mescaline can be accommodated within the theoretical framework based on redox cycling by the catechol metabolite with its quinone ...

pmc.ncbi.nlm.nih.gov

 

[Skorpio]

Mescaline metabolites & ALDH inhibition

Pharmacokinetic and Pharmacodynamic Aspects of Peyote and Mescaline: Clinical and Forensic Repercussions - PMC

Mescaline (3,4,5-trimethoxyphenethylamine), mainly found in the Peyote cactus (Lophophora williamsii), is one of the oldest known hallucinogenic agents that influence human and animal behavior, but its psychoactive mechanisms remain poorly ...

pmc.ncbi.nlm.nih.gov

That paper also mentions high levels of protein binding causing delays in pharmacokinetics. The fact that mescaline’s potency correlates in vivo and in vitro argue against its main effects being caused by some cryptic metabolite.

I always feel that a single paper with good primary data is worth a million reviews.

Another interesting study on mescaline activity & drugs in general

Novel, unifying mechanism for mescaline in the central nervous system: Electrochemistry, catechol redox metabolite, receptor, cell signaling and structure activity relationships - PMC

A unifying mechanism for abused drugs has been proposed previously from the standpoint of electron transfer. Mescaline can be accommodated within the theoretical framework based on redox cycling by the catechol metabolite with its quinone ...

pmc.ncbi.nlm.nih.gov

This paper feels even more loose. I really don’t know what to say, but it feels like they are coming up with novel metabolic routes that can’t be detected due to forming protein adducts (which totally can be screened for by mass spec). Idk it kind of feels like they are trying to reinvent the wheel with a square wheel. They say that both 2C-X compounds and mescaline both form quinones through demethylation and oxidation, which cause their effects catalytically, but don’t explain the vast differences of pharmacokinetics.


Weird and far out theories can be fun, but the problem with them is that they require quite a bit of data to compete with mainstream approaches (especially when they contradict them).

 

[chris_p]

Huge line of 2cb down the hatch. Didn't measure it. Wish me luck.

Last time I did a line this size I had visuals on par to a complete 100% DMT breakthrough. The things I saw were out of this dimension yet I was still mentally there somehow and able to appreciate everything I was witnessing. I'm starting to seriously get hooked on this stuff

 

[kiely]

yes

 

[4DQSAR]

They sold it as 2.5-DiMethoxy 6 5 mg pill s, that was to vague, for me,
took 10 mg felt nada.
Binned the rest, 2C-T2 was the last sold open under its real name, downhill after.

Nexus was 2C-B they sold in sex-shops, smart-shops sold it as 2C-B.

I think these were 10mg tablets and our 'tasters' took two each.

 

[Bitchniggaz]

I think these were 10mg tablets and our 'tasters' took two each.

Every 2cb pill ive tried has been very weak.

 

[4DQSAR]

Every 2cb pill ive tried has been very weak.

It was 2-CT-7 and evidently 20mg is pretty darn active.

 

[Shinji Ikari]

m starting to seriously get hooked on this stuff

I had a feeling you would. The novelty does wear off, somewhat, and tolerance does become a factor eventually, somewhat.

Really don't know how you're bringing yourself to rail lines of the stuff though my goodness. Just little bumps make the insides of my ears itch.

 

[4DQSAR]

I've never sampled 2CB. Is it significantly different to 2CI?

 

[Shinji Ikari]

I've heard I is a bit more visual and less forgiving at higher doses but I've never had the opportunity to try it. 2cb is really easy to find in my part of the world, the rest of the series not so much.

 

[iom]

I've never sampled 2CB. Is it significantly different to 2CI?

I definitely think so, and I don't regard them as especially interchangeable either. I would say B compared to I is less visual, less stimulating, a little less lucid, more entactogenic, more warm/positive mood push, and a bit easier going overall. I do like them both a lot.

 

[4DQSAR]

Well thanks for those responses, @Shinji Ikari and @iom - when I resided in The Netherlands, 2CB and 2CC were both brought under legal control but not 2CI. We rightly or wrongly suspected the reason was that para iodination of 2CH with 124I would make it useful as a tracer (PET scanner). To be fair, I don't think 2CI had been encountered, even in 'smart shops'.

With both your comments, it does sound as if the dose-response curve isn't reliable so it wouldn't lend itself to being pilled up (as 2CB was).

 

[emkee_reinvented]

Every 2cb pill ive tried has been very weak.

10 mg is the border,15 mg and you are in a cartoonist trip.

 

[emkee_reinvented]

I think these were 10mg tablets and our 'tasters' took two each.

Not in R_dam, A*dam was i assume way more involved we had 1 smart-shop.

At the start. Never had 2C-I, do have DOI and that is a bad MF,

 

[4DQSAR]

...DOI and that is a bad MF,

Yeah, long, long ago independent researchers were producing small samples and the trip-reports were not good. Like 2CI, was DOI omitted from de opiumwet because it had potential research uses?

The ONLY 2,5-dimethoxy-4-<something> compounds that interest me are 2CN and DON. Report on 2CN were that it was sort of OK with 'psychedelic tofu' was the term used. But DON is chiral and I really wonder if one enantiomer is a potent 5HT2a agonist (trippy) while the other is purely a monoamine modulator (so possibly more like MDA).

There ARE chiral reductions of the nitroolefin. You don't get 100% of one isomer, but you can shift it so that something like 75% is one isomer, 25% the other one. I mention this because someone has patented the concept of specific ratios of MD(M)A and related drugs to optimize the expereinces they produce. So one assumes the same methodology could be applied.

 

[xdrc]

Well thanks for those responses, @Shinji Ikari and @iom - when I resided in The Netherlands, 2CB and 2CC were both brought under legal control but not 2CI.

I think 2C-C was available as a clearnet chemical from NL up until the recent NPS law, while 2C-I was unobtainium? I just checked the Opiumwet and it mentions 2C-B and 2C-I, not 2C-C. So your memory here is faulty. It is true however that DOI was not included (presumably due to its status as widely accepted standard as scientific 5-HT2A agonist), whereas DOC and DOB were. Now of course there is the analogue law based on structural elements.

 

[iom]

With both your comments, it does sound as if the dose-response curve isn't reliable so it wouldn't lend itself to being pilled up (as 2CB was).

I'm not sure what you mean here, but 2C-I was more popular back when most RCs were sold as (mostly) pure powders. The NL where I think smart shops 2C-T-2 and 2C-T-7 tablets. I don't recall one way or the other about 2C-I being sold in such a way.

My problems with tablets are two-fold in that they are difficult to divide precisely and are all too often poorly manufactured and have inconsistent dosage. I want precise control over my dosage. More than +/- 10% error means that I have trouble getting the level of experience I want, which is often setting-dependent.

 

[Bitchniggaz]

10 mg is the border,15 mg and you are in a cartoonist trip.

My reference is 2cb powder that i had many years ago.
That stuff hit hard with insane visuals at +20mg.
When ive tried the pills i always took at least 2 with very weak results.
Only times ive gotten anything out of them was when combined with LSD.
Could be that they are so hard pressed that the absorption was to slow idk.

 

[Generation *DMT*]

This substance is very dose sensitive. Make sure you have a milligram scale.

 

[notsmokeymcpot42088]

2c-b is a good one -- I had a friend that fuckin IV'd it which I can't imagine (If I recall that one burns like holy hell if you snort it) but he said it was alot like MDMA mixed with LSD.. Orally it has some empactogen qualities as well.

First RC they made illegal I think? (I'm sure that isn't correct but first I can recall)

The body load is rough with any 2c-x product I have tried. I prefer the nbome but that is an unusual experience.