Obscure and Unknown: PEA-NDEPA's

*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.

Today we'll be looking at a series of Psychedelics that are highly modified variations of the Phenethylamine base structure. These are the PEA-NDEPA's (Phenyethylamino-N,N-diethylpropanamides), which have a structure reminiscent of Lysergamides with almost all of their rings broken. All of the information on this series of compounds comes from a single researcher on Bluelight posting under the username Hans Meyer, who had to translate most of his posts from German. Hans Meyer claims to have personally manufactured and self-experimented with all of the compounds mentioned here1. The veracity of this information is dubious, as he mentioned he had no reliable way to characterize the substances he produced, and they are a sample size of one. Nonetheless, it is still interesting information to examine and perhaps a route of further exploration for other enterprising researchers, who could hopefully produce more data on the characterization of these chemicals.

Generalized structure of a PEA-NDEPA

The Phenethylamine structure is understood as a phenyl ring, to which an ethylamine group is attached. This can clearly be seen in the PEA-NDEPA structure. However, a lot more is attached too. Most of the basic phenethylamines are simple stimulants, such as amphetamine and methamphetamine (which see only an extra methyl group attached to the ethylamine chain, and an addition one attached to the nitrogen in methamphetamine). Other substitutions however, lead to phenethylamines having powerful psychedelic properties. Hans has logically followed the path of the substitutions that are seen in psychedelic phenethylamines of any sort, which is primarily substituting methoxy groups onto various positions on the ring (2,3,4 and 5), or sometimes placing other substitutions in the 4 position. This resembles the structures of the 2C-x series of psychedelics (methoxy groups on 2 and 5 and a variable substitution on 4) and the mescaline analogues (methoxy groups on the 3,4, and 5 positions). He also sometimes slides a carbon onto the alpha position, yielding a psychedelic amphetamine reminiscent of the DOx series. He builds off of these familiar structures however, with a long and complex substitution attached to the Nitrogen.

The structure of LSD with the structure of the PEA-NDEPA within it highlighted (minus any phenyl ring substitutions and some hydrogens)

Complex substitutions on the nitrogen in 2,5 dimethoxy phenethylamines can be seen in the NBx series (25I-NBOMe, 25C-NBOMe, 25I-NBOH, 25E-NBOH, etc.), which have an additional substituted phenyl ring branching off the nitrogen. This yields a family of powerful full 5HT2A agonists, with intense psychedelic effects, sometimes harmful physical effects, and an extremely high potency rivaled only by the lysergamides. So it should follow that attaching a chain reminiscent of the structure of a lysergamide onto that nitrogen should also yield a highly potent psychedelic.


If we look at the structure of LSD, we can clearly see the PEA-NDEPA structure hiding out in there. It looks as if every ring except for the base phenyl ring in LSD has been broken open, leaving a long continuous chain tracing their former outlines. One thing to note is that this removes a lot of the constrained stereochemistry created by the rings, allowing most of the atoms in the chain to freely rotate. In my piece on Tricyclic Tryptamines, I mention that it is still fully unknown what structural properties exactly make a molecule psychedelic. Little modifications can have all sorts of effects- for example, it is determined that keeping the constrained ring structure of LSD but breaking the top ring by removing the 9-10 double bond removes the psychedelic properties2. So it is interesting that breaking almost every ring, including that one brings back psychedelic properties. The 9-10 double bond with intact rings is not psychedelic, but without them it is. Odd. 

In his thread Hans also experimented with other complex substitutions on the ethylamine chain, like phenyl rings (giving us a few obscure variations on the NBx structures) along with other random chain structures. I will only be looking at the PEA-NDEPA series in this post however. Hans cited his old age and concern for negative health effects in not pushing his doses too far beyond the threshold level. 

Anyways, lets look at the specific compounds that our friend Hans produced. 

TMA-2-NDEPA

TMA-2-NDEPA

TMA-2-NDEPA was the first PEA-NDEPA mentioned by Hans. The structure is based on the psychedelic TMA-2 (Trimethoxyamphetamine 2), which got glowing reviews from Shulgin in PiHKAL. The basic TMA (Trimethoxyamphetamine) is simply the amphetamine analogue of mescaline, with methoxy groups on the 3,4, and 5 positions. TMA-2 is a slight variation on that with the methoxy groups on the 2, 4, and 5 positions, as seen here.

Hans worked his doses up from .77 mg, administering the doses sublingually. At this dose and at 1.53 mg, no effects were noted. When bumped up to 2.61 mg, he noted (translated from German): 

"tastes terrible; fast coming of a vague effect; weak but positive; other quality than TMA-2; gently/kindly; partly euphoric; sociable; recreated; power more or less than TMA-2."3

By power, Hans clarifies, "the 'intensity' in this case is the sum of all my perceptions, - not objective - effects, of my subjective evaluation." The duration of this experience was about 5-9 hours. At an oral dose of 3.62 mg he noted:

"low effects; distraction; weak-kneed; allover unpleasant, may be because of getting stuck in coming up. Mind-altering yes - but unpleasant like TMA-2 itself (to me!) at higher doses; but nevertheless recreated; more power than TMA2."3

So this indicates that the substance is likely less powerful when dosed orally- perhaps it is a prodrug to something that induces stronger unpleasant physical effects, something that is bypassed when it is dosed sublingually. It seems like an uncomfortable psychedelic stimulant otherwise. Hans notes that it is very difficult to take sublingual doses beyond 3 mg because of the intensely bitter and unpleasant flavor3. As with all of his products, he did not push doses far beyond just being able to discern if the drug was psychedelic or not, so this may dose higher than what is mentioned here.

DMPEA-NDEPA

DMPEA-NDEPA is the NDEPA analogue of 3,4-Dimethoxyphenethylamine, a naturally occurring compound found in cactus species that contain mescaline. It is itself an analogue of the neurotransmitter Dopamine, (which has -OH groups on the 3 and 4 positions). 3,4-DMPEA is not known to be psychoactive in any way. With that in mind, it is curious that this would be one of the few NDEPA structures attempted by Hans. 

With doses from ~10-50 mg orally, he noted tinnitus and irritation. Finally, at a dose of 106 mg, he noted greater tinnitus, "higher morale", "funny talks", and "easily find formulations" (remember this is very roughly translated from German)4. I take this to mean a general euphoria, psychedelic increase of humor, and the sort of synthesis and free flow of thoughts that psychedelics can generate. The duration of this experience was about only 2 hours. These are still just barely threshold effects, if not just a strong placebo, and it likely doses a bit higher than this as Hans took low doses.

The notable steep drop in potency between this and the previous NDEPA (a near 35-fold drop in potency!) raises interesting questions about the base compound here, 3,4-DMPEA. 3,4-DMPEA has for the most part only seen some tests in animals- if you do some simple proportions- whereas TMA-2 doses at about 40 mg and TMA-2-NDEPA doses at around 3 mg, then you can perhaps take 3,4,-DMPEA to have psychoactive effects at doses far beyond which most other phenethylamine psychedelics are taken. Of course this is just conjecture, it may just not have psychedelic properties at all, at any dose. It would follow that DMPEA-NDEPA would dose exceptionally high too, as 100 mg yielded only threshold effects. It could perhaps be pushed further than seen here.

M-NDEPA

M-NDEPA

M-NDEPA is an PEA-NDEPA based on the structure of mescaline, whereas mescaline is a phenethylamine with methoxy groups on the 3, 4, and 5 positions on the phenyl ring. Mescaline is a notoriously high dosing psychedelic, so it follows that even attached to the NDEPA structure, which seems to jack up potency, it would still be relatively higher dosing. 

Hans cautiously worked upwards from 2.5 mg orally, not noting any effects at that dose or at 25 mg. At a dose of 76 mg however, he noted:

"Realy terrible taste like burnt rubber. Morale high; funny talks; easily find formulations; sociable; visual enhanced clarity; recreated; more (or less ?) power compared to Mescaline."5

We see some key phrases repeated here, suggesting another jovial sociable psychedelic with laughs and most notably, clear visuals which so far haven't been mentioned much with the other NDEPA compounds. The duration was about 4 hours. Hans also notes that the pattern seen between the 2C-x compounds and the DOx compounds of the amphetamine version having a massively increased potency still holds true for the NDEPA's. 

DOM-NDEPA

DOM-NDEPA

DOM-NDEPA is, as the name implies, the DOM variation of the NDEPA, with an alpha carbon denoting its status as an amphetamine, 2,5 dimethoxy groups, and a methyl group on the 4 position. DOM is a highly potent psychedelic, so it would follow that DOM-NDEPA would also be exceptionally potent.

Hans was of course completely aware of this pattern and cautiously waded in with an initial dose of 500 μg dosed sublingually. What follows is a somewhat more detailed report with more detailed information on duration, paraphrased here6:

[T0:00]-Dose taken
[T1:30]-Onset (" something is going on.")
[T6:50]-"emotional labile, mind-altering. 1h walking: nature intensively enjoyed. Very good atmosphere, calm, tender, charged with emotions."
[T9:20]-"nearly finished"
[T14:20]-"still quite lively and animated."
[T15:50]-went to sleep

He noted a long afterglow which lasted well into the next day. He considered this to be stronger than an equivalent dose of DOM.
This seems to show the most promise of all the NDEPA's- a pleasant and euphoric trip with noted emotional depth and indisputable stimulating psychedelia. It has a similar long drawn out duration to the DOx compounds. Perhaps retaining the near-DOx structure of the amphetamine carbon and 2,5-dimethoxy groups while switching out the 4 substitution would show the most promise with exploring further NDEPA's. Also noteworthy is the very high potency of this compound, with a worthwhile experience at just 500 μg (though desired effects in other users may be higher, possibly up to 1 mg). I would assume also, that this follows the pattern of potency seen in 2C-x and DOx analogues, where the methyl variant is the least potent, and halogenated variants are much more potent. This makes it much more potent than DOM, and possibly even more potent than the NBOMe compounds, with only the lysergamides being certainly more potent than DOM-NDEPA. Thus the entire DOx-NDEPA series can be predicted to have a similar potency, and could likely be dosed onto tabs without issue. As this dose was sublingual, it is still unknown if this compound would lose some of its effects if only dosed orally, as is seen in the NBOMes which are orally metabolized into being inactive.





In his concluding notes on this series, Hans noted that most of the compounds came in the form of a hygroscopic resin, and he rarely got clean crystals, save for DMPEA-NDEPA. He suggested that sublingual was the easiest and most reliable means for dosing these compounds.
The series within the PEA-NDEPA family that shows the most promise is most likely the ones constructed from reliably understood interesting base phenethylamine compounds, or in other words, the NDEPA analogues of familiar psychedelic phenethylaines such as Mescaline, the DOx family and the 2C-x family. While he didn't attempt to produce any 2C-x-NDEPAs (simply phenethylamines with the 2,5 dimethoxy groups and a variable 4 substitution), it is likely that they would be interesting and worthwhile compounds with a higher potency than 2C-x compounds. Hans however, cites a study from Schulze‐Alexandru et al (1999) that suggests that the 2C-x-NDEPA's may not be active7.
The DOx analogues beyond a 4-methyl group also warrant further exploration- and indeed Hans stated he was interested in testing and producing halogenated DOx compounds, yielding drugs like DOC-NDEPA, but there has been no update in this since 2015. He has mostly been working within the NBx compounds and various other substitutions.
As the substances weren't fully characterized, the veracity of this information is still not confirmed, but it is an extremely interesting look into a series of potential super potent psychedelics that absolutely warrants further study. Hans set out with the noble goal of decontsructing the drug war by inventing novel compounds to circumvent drug laws. He was extremely dedicated and ambitious in this quest, producing the compounds himself and testing them all on himself. Details on the syntheses can be found in the further reading. If you're still out there Hans, I am extremely grateful for your contributions and hope you are recognized further for them. Thank you for your work!

Sources and Further Reading:
1-https://www.bluelight.org/xf/threads/self-experiments-with-new-series-of-nxxx-phenylethylamines.724338/
2-Nichols DE (2012) Structure–activity relationships of serotonin 5‐HT2A agonists. WIREs Membr Transp Signal 1: 559-579.
3-https://www.hyperlab.info/inv/index.php?act=ST&f=17&t=31266
4-https://www.hyperlab.info/inv/index.php?s=&act=ST&f=17&t=30996
5-https://www.hyperlab.info/inv/index.php?act=ST&f=17&t=31331
6-https://www.hyperlab.info/inv/index.php?act=ST&f=17&t=31118
7-Schulze‐Alexandru M, Kovar K-A, Vedani A (1999) Quasi‐atomistic Receptor Surrogates for the 5‐HT2A Receptor: A 3D‐QSAR Study on Hallucinogenic Substances. Molecular Informatics 18(6):548-560