Obscure and Unknown: Halogenated Mescaline Analogues

*WARNING* The substances mentioned in this series have little to no record of human use, and thus the effects they have on humans are either poorly understood or entirely unknown. Much of what this information is simply hypotheses based on animal trials or very small human sample sizes. Very little information exists about their acute or long-term toxicity. Under no circumstances should any of these substances be ingested by a human outside of a clinical setting where psychological and physiological effects can be closely monitored and extremely precise doses can be prepared and TITRATED. DO NOT seek any of these out if you do not have access to those resources.

the Mescaline molecule with the ring positions labeled

For this installment of obscure and unknown, I will be looking at halogenated mescaline compounds. Mescaline a as a base molecule is a phenethylamine with methoxy groups at the 3,4, and 5 positions on the phenyl ring. Substitutions can arise from several places on the molecule. The ones listed here show substitutions either on the end of the 4-methoxy group or at the 2 and 6 positions on the phenyl ring. In my opinion, these compounds show the potential to be much much more interesting than the mescaline analogues we see on the market right now (Escaline, Proscaline, Allylescaline, Methallylescaline etc.) Why those ones, with frankly unremarkable psychedelia and a heavy body load have been mass produced and marketed as opposed to these ones is beyond me- They don't seem like the most difficult syntheses but perhaps someone who knows their organic chemistry better can correct me there. 

Today I will be looking at Trifluoromescaline, 2-chloromescaline, 2,6,-Dichloromescaline, and 2,6-Dibromomescaline.

Trifluoromescaline

Trifluoromescaline is an intimidating looking molecule- Fluorine is a notoriously testy atom, with its extreme reactivity-it is notable in a number of extremely deadly toxins like Sarin or Hydrofluoric acid, though basic knowledge of organic chemistry denotes that it can be stabilized within certain compounds and doesn't need to be marred by these scary associations.

This molecule gives us not just one but three Fluorines to work with. What do they do when included in a structure like this? Fluorine increases the bioavailability of these compounds and also results in higher retention, meaning an increase in potency and duration can be expected. The only other known trifluoromethyl psychedelic is 2C-TFM, which indeed doses in the >10 mg range. 

Indeed Trifluoromescaline stands out a great deal in both of those regards. In his seminal literature review, "Fluorine in psychedelic phenethylamines", Daniel Trachsel cites Trifluromescaline of having a dosage range of 10-40 mg and a marathon duration of 14-24 hours1! That is a potent damn psychedelic. (I tried to track down his source for that to elaborate on the specific effects and how exactly this was tested on human beings to get that result. I couldn't find one and am presuming that the brave Mr. Trachsel pulled a Shulgin and tested it on himself). As Mescaline can dose in the 300+ mg range, a compound active at 10-40 mg is a massive increase in potency. This sounds like a really interesting compound to study for those who seek longer trips.

It should be noted that increase hydrophobicity and retention courtesy of the highly electronegative fluorines can sometimes be indicative of higher toxicity. Tread carefully.

2-Chloromescaline

2-Chloromescaline is an odd little compound that is only mentioned in the paper "Cactus Alkaloids XXXVI. Mescaline and related compounds from Trichocerus peruvianus" by Pardanani et al. You may look at that title and think- wait a minute? This is a naturally occurring cactus alkaloid? Why is there no information on this? Well this odd compound appearing in extractions remarkable to the researchers performing the study too, who later found out that it was actually a byproduct of their extraction process. Though this compound has 0 history of human use, the paper acknowledges that it has a similar log-P value to DOM, indicating that it is active insofar as being accepted by receptors. This is still just conjecture based on physical properties and the true effects it will have on a human nervous system cannot be known until it is tried. It is expected that this would have a higher potency and longer duration than mescaline.



2,6-Dichloromescaline

Information on this compound comes exclusively courtesy of two intrepid explorers, "The Inner Frontiersman" and "Toad", published in the 1997 Spring Entheogen review (Oh to have been a part of the 90's psychonaut community). They produced the compound themselves, based on a theoretical synthesis in 3. Inner frontiersman was the guinea pig, while Toad provides commentary on the synthesis.

Inner Frontiersman trial began with a dose of 10 mg (though due to scale error he later states it could've been anywhere from 6-21 mg). Several small redoses were administered about 2 hours in. What follows is a long and intense experience, lasting about 22 hours total. It featured intense electric stimulation, uncontrollable laughing, ego dissolution, a "mental sex change", and vivid visuals along with moments of sheer anxiety and terror. The peak was a grueling 9 hours. He recommends perhaps starting with a lower dose, around 3-5 mg. 

The full report is linked in the "Sources and Further Reading" section.


2,6-Dibromomescaline

This is another densely packed phenethylamine, similar to 2,6-Dichloromescaline every single spot on the phenyl ring is occupied. The information on this compound comes from a single erowid trip report, submitted by an author named "tngrn" in 2016. I could find nothing else on this compound beyond a simple mention of its synthesis in 18987, 2 years after the initial discovery of mescaline. Why the hell anyone was playing with substituted psychedelic alkaloids (likely without even understanding they were psychedelic-this predates the term 'Psychedelic') in 1898 is beyond me. If I recall any organic chemistry correctly, it may be because bromination of a phenyl ring isn't the MOST difficult process (though honestly I got a C- in that class. Please issue a correction if necessary). But then it begs the question as to why no one attempted this synthesis for over a century? Nonetheless, the given context for this experiment was that the author attended a psychedelic meetup where this substance was presented by a mysterious figure. If it truly is an easy synthesis, then it can be presumed that this was just a singular batch cooked up in some kitchen chemistry. All participants in this experiment were informed of the dosage and likely duration, indicating that enough testing of this substance had occurred to establish those properties. How this information came about however, is entirely lost to time.

The dose of 50 mg was administered in solution. The onset was about 45 minutes after dosing. It should be noted that dosing in solution usually yields a faster onset than dosing in gel caps. The effects described are unique and fascinating- This appears to be a primarily visual substance, with the author noting little change in his physical, mental, or emotional state. Pure psychedelic eye candy- though it was not the intricate kaleidoscopic visuals of other psychedelics. Colors were desaturated, textures were glossed over, nothing was particularly bright or vivid. His reaction to these visuals was entirely neutral. No closed eyed visuals were noted. In total darkness however, the author noted vivid visuals of stripes and bands. The effects seem to have maintained their intensity for about 6 hours, with the author going to sleep at T6:30.

This demonstrates an interesting and unique compound, though this is also a sample size of 1. Given these unique properties it is a surprise to me that this compound has never been produced for the market, given the presence of all variety of other mescaline analogues (most of which are in my experience, inferior to what is described in this report). I hope we explorers will be able to taste this someday, it seems that its unique properties would have use somewhere in the realm of utilitarian use of psychedelics, or at least as an interesting novelty!


Sources and further reading:
1- Trachsel D (2012) Fluorine in psychedelic phenethylamines. Drug Test Anal, 4(7-8):577-90
2- Trachsel, D (2003), Synthese von neuen (Phenylalkyl)aminen zur Untersuchung von Struktur–Aktivitätsbeziehungen. Mitteilung 2. HCA, 86: 2610-2619. (In German)
3- Pardanani JH, McLaughlin JL, Kondrat RW, Cooks RG (1977), Cactus Alkaloids XXXVI. Mescaline and related compounds from Trichocerus peruvianus. Lloydia, 40(6):585-90.
4-The Inner Frontiersman, Toad (1997) Dichloromescaline https://www.designer-drug.com/pte/12.162.180.114/dcd/chemistry/dichloromescaline.html
5- tngrn. "Almost Exclusively Visual: A Night of Zebras: An Experience with 2,6-Dibromomescaline (exp109137)". Erowid.org. Dec 3, 2017. erowid.org/exp/109137
7- https://chemistry.mdma.ch/hiveboard/newbee/000469542.html a hive thread that cites some further reading (towards the bottom)