Structure-Activity Relations and Synthesis of over 70 new Diarylethylamines (Diphenidine type Dissociatives)

So many new drugs to explore!

I should note that the publication of this paper for the most part renders my old post on Diarylethylamines and the corresponding flowchart more or less obsolete. The answers I sought out in my hypothesizing in that article have largely been answered by this publication, and I am too lazy to completely revise the whole article and the chart. All the information anyone could gain from that article is more or less contained in this dissertation and even just this summmary.

Hot off the presses is the PhD dissertation of my friend and colleague Michael Dybek (you can find the full document here)- a comprehensive analysis of the 1,2-Diarylethylamines, the class of dissociative drug to which belong drugs like Diphenidine, Ephenidine, and MXP. Other compounds within this fascinating class are known to be opioids (MT-45, AD-1211, Diphenpipenol), antidepressants (Lanicemine), and stimulants (A-D2PV). This class of drugs is actually derived from the Phenethylamine structure- but there is another aromatic ring in the alpha position, and the amine is substituted to be at least a secondary or tertiary ring structure. This paper delves into an vast range of variations on that basic scaffold, analyzing how substitutions on the two rings or variations on the amine affect the activity on the NMDA receptor (In other words, dissociative activity). A total of 80 compounds, 67 of which do not yet exist in literature, are analyzed in this regard. 34 of the compounds are also analyzed for their off-target affinity at other receptors, like K-opioid, M-opioid, Sigma, and Muscarinic, and for monoamine transporters, which can modulate antidepressant or stimulant effects.

Structure of various Diarylethylamines

For the chemistry people (you can skip this bit if you’re not a chemistry person), the synthesis and analysis of every compound is extensively detailed. All of these compounds are synthesized from an incredibly simple and elegant and usually high-yielding one pot reaction- It is ridiculously accessible, save for some of the more exotic substitutions they can all be made in one step from common, inexpensive reagents- this is data that I think could revolutionize development and study of this class of compound! It is a synthesis so simple even I can do it! All are produced through a combined modified Mannich-Barbier reaction, in which the benzyl group comes from the corresponding benzyl bromide which reacts with Zinc dust. Trifluoroacetic acid helps optimize for a higher yield by etching the Zinc. This reaction was performed in THF at room temperature. After allowing the organometallic halide nucleophile to form, the amine and the α-position substitution (as an aldehyde) are added, yielding the final product which can be extracted via an acid-base workup. All of this is performed at room temperature, and most of the compounds easily crystallize (though I have to caution against using alcohols as a recrystallization solvent, as it forms a seemingly unbreakable solvate with EtOH). This simple process can offer a high yield and makes it incredibly easy to make substituted analogues. Some extra work may need to be done for certain analogues to produce certain expensive or unstable intermediates that aren’t commercially viable or to protect/deprotect to form target substitutions.

While this class of compound has a very high affinity for the NMDA receptor, with lead compound Diphenidine having an even greater affinity than even PCP, they are curiously impotent in vivo, with active doses of Diphenidine in the range of 60-140 mg in my experience. So far there hasn’t been a definitive explanation for this disparity. Also stymying their popularity is the fact that they can instill a seeming week long cross tolerance with other dissociatives- perfect for the occasional user but unfortunately not preferable for the heavy users who drive the markets. The only compounds that had a higher affinity than Diphenidine were the 2-Chloro and 2-Methyl analogue (with the 3-MeO and the 2F analogue coming pretty close too!), so it is to be expected that every other compound in this study would dose in the range of >100 mg. They are also primarily active orally, and are incredibly painful to dose intranasally. Most disso fanatics I know love snorting things, so this also takes out some of the thrill. Some experimented with vaporizing diphenidine, which apparently induced extreme compulsive redosing, with some users describing it as “dissociative crack”- though there are unconfirmed claims of toxic byproducts being produced by pyrolysis of these compounds, so I would caution against that ROA until that is studied further. Despite all these detractive qualities, I find these to be fascinating and worthwhile compounds that I encourage people to explore and hypothesize and generally be curious about! There are probably incredible, beautiful discoveries out there that have been clearly mapped out for us, just waiting to be documented!

It is a monumental work that clearly maps out development of this class of drug within the scope of dissociative activity and I encourage curious researchers to delve deep into it! It is also 604 pages long, so for people who want to know the juicy Structure Activity Relations, here is the meat of it:

First, a little nomenclature- numbered substitutions are for the α-position aromatic ring, double prime” numbers are substitutions on the benzyl ring, the amine is designated as a 6-member Piperidine (as in Diphenidine) by P, a 5 member pyrrolidine by Py, and any secondary alkyl amines by the basic alkane abbreviations (methyl, ethyl etc.). α-position denotes anything attached to the carbon that is connected to the nitrogen, the β-position denotes the next carbon over, between the α-carbon and the benzyl ring.

Generalized structure of a Diarylethylamine, showing positional nomenclature

As Diphenidine is considered the base structure and lead compound of this class, it will serve as a standard and point of reference for the other Diarylethylamines. A good number to remember is 18.2 ± 2.2 nM, this is the Ki value for Diphenidine, the number that represents its affinity for the NMDA receptor. A lower number means a higher affinity, which usually (but not always) corresponds to a higher potency.

So lets get cracking- what variations exist that are worth exploring?

First, here's the master list, with affinity for the NMDA receptor noted:

First we look at substitutions on the α-position phenyl ring. Affinity is highest at the 2 position and lowest at the 4 position. In some cases, such as a Methyl or Fluorine substitution, the loss of affinity was fairly linear, in others, such as the Chlorine or Trifluromethyl, there was a very steep loss at the 4-position to render the compound inactive.

Thus, for α-phenyl substitutions, it is clear that affinity is in rank order of 2>3>4.

There is a notable exception however- with a methoxy group, the rank order is 3>2>4, reminiscent of arylcyclohexylamines. No idea why this is the one exception. Would be curious to see if thiomethyl or ethoxy have the same trend.

Then we look at the different substitutions-

For halogens affinity rank order at the 2 position was Cl>F>Br>I. This pattern probably holds for the other positions. A CF3 substitution had an even lower affinity than Iodine.

Looking at the benzyl ring, substitutions in general had a lower affinity than substitutions at the α-phenyl ring. The rank order for substitutions at that position appears to be 3”>2”>>4”, (which also follows the SAR pattern for arylcyclohexylamines) with substitutions on the 4”-position being completely inactive. The only substitution that really appeared to yield anything in an active range on this ring was a fluorine and 3”-Me.

We can then look at the Amine- Diphenidine, with the piperidine, had the highest affinity. Pyrrolidine, and a variety of secondary alkyl substitutions were also assayed, giving us the rank order of:

P (18.2 ± 2.2) >E( Ephenidine)(66.4 ± 3.7)>iP (Isopropylphenidine)( 98.1 ± 6.3)>Pr(124.5 ± 8.9)>Allyl(161.5 ± 14.4 )>Py(280.0 ± 18.0)>cP(333.0 ± 19.8)>tB(254.2 ± 2.8)>>DPMe( 813.0 ± 7.2 ). Interestingly, the 2-Cl substitution for all of these yielded a higher affinity except for the Pr and tB amine.

Replacing the phenyl ring with a Thiophene also yielded appreciable affinity- with the 3-Thiophene being higher (48.8 ± 4.3), but with both having an affinity between Diphenidine and Ephenidine (2 thiophene was 65.1 ± 12.2). The 2-Furan saw an affinity just a bit lower than Isopropylphenidine (119.4 ± 2.1). Heterocycles, namely 2-Benzothiophene, 2,3-MD, and 3,4-MD were also assayed, with the benzothiophene being inactive, and the 2,3-MD (51.7 ± 8.4) having a higher affinity than 3,4-MD (131.2 ± 12.0, both within an appreciable range! And while these substituents had lower NMDA affinity, they displayed higher affinity for different monoamine transporters (more on that later), meaning they could see higher stimulant or even entactogenic effects relative to Diphenidine.

Disubstitutions had a lower affinity than most other substitutions.

Graphical representation of structure activity relations for NMDA affinity for ring substitutions

34 compounds were also analyzed for peripheral receptor effects. While the main focus of this post is NMDA antagonism, one of the peripheral effects I’d like to look into is at the monoamine transporters. These control the flow of the neurotransmitters Dopamine, Serotonin, and Norepinephrine. Affinity for these transporters leads to reuptake inhibition, which increases the concentration of the corresponding neurotransmitter, as seen in many pharmaceuticals like SSRI’s, NDRI’s, SDRI’s etc. Cocaine is a reuptake inhibitor for all 3 transporters! (Other stimulant drugs can modulate rote monoamine neurotransmitter flow; they are called releasers. Examples of this are NDRA’s, like amphetamine, or releasers for all 3, like MDMA. We are looking at reuptake inhibition though)

All of this is to say, the monoamine transporters are like 3 levers that can be adjusting synergistically to achieve a variety of effects.

Some patterns emerge, like DAT affinity being modulated by a rank order of 3>2”>3”>4>4”>2. So interestingly, while the 2 position strongly increased NMDA affinity, it pretty much eliminated affinity for the dopamine transporter (oddly enough with the exception of 2-Cl-DPP. Most of the compounds were not active at SERT, and those that were only had moderate affinity, with the highest being 4”-F-DPPy. All of this translates into some yet unknown complicated interworking of synergistic effects that would produce a unique subjective experience for each compound!

Graphical representation of structure activity relations for monoamine transporter affinity for ring substitutions

I know this has been a very long and dense summary (to be fair it is a vast amount of data), but I hope it can be of use to those interested enough to delve into this massive contribution to our understanding of dissociatives and dissociative structure-activity relations.

Happy explorations, fellow researchers!

2022 In Review

2022 was the single most eventful, trajectory-shifting year of my life. A lot happened. I got married to the love of my life and we live happily together. My nephew was born, the first of his generation of our family. I have had calm, reasonable discussions with my parents about drug use and our relationship is better than it has ever been. I was in the bridal party for the wedding one of my closest friends. Another one of my closest and oldest friends and recurring character in many of my reports moved several states away. I got super into Warhammer 40k, it eats up a lot of my time and energy now :p I had a sanctuary room built into my house as a wedding present and it is my paradise. I have actually finally met more of my online drug friends and fans in person which is super cool.

I lost one of my dearest friends to a drug overdose. I still have trouble grappling with their absence and will love them forever.

Perhaps most relevant and what has actually changed my life directly the most (getting married is a big deal but functionally very little changed in our lives!), I began working at a lab that specializes in the study of novel psychoactive compounds, especially psychedelics and dissociatives. To say I am honored that I get to be a part of this research is an understatement, it is the opportunity of a lifetime and I am blessed beyond measure that I had the fortune to find this position. I work entirely with chemistry, with synthesizing novel dissociatives. Chemistry is not my strong suit and it is not my background but nonetheless I persist. I have learned so much in my year in this position- it is a revolutionary workplace where drug use can be discussed openly and candidly, with dedicated passionate people on all sides who are making incredible discoveries every day. Everyone has been more than accommodating with me, a relative outsider and neophyte in the field. I am extremely excited for when we publish the projects I have been working on and I can discuss them publicly! (For now though, please do not pry me about any of our work- I will share it when I am allowed!) As much as I am passionate about drugs, about studying them and learning about their effects, about structure-activity relations and the vast taxonomy contained within- I think this has asserted that this is not what I want to do for the rest of my life, for my entire career. I am lacking so much foundation in organic chemistry and pharmacology that ultimately just makes me feel like I am treading water over an immense void every day. The work is exceptionally challenging in a way that doesn't feel manageable or sustainable for me. Perhaps this was an experiment to see if an outsider can be taught organic chemistry on the job- and I guess the answer is, I can follow directions, I can complete tasks as instructed, but I don't REALLY know what I'm doing. I don't know what is happening on a fundamental level, I cannot discuss theories or really conceive alternate solutions or explanations for when I observed things not happening as predicted (the vast majority of the time, as chemistry dictates). And it's silly to complain about, after all I have not really put in concerted effort to learn these fundamentals on the side. Perhaps at a different point in my life I would have been more than capable, but the drive and passion and motivation isn't there for me. I am mentally exhausted at the end of every day and usually just want to get home and do drugs. I have realized that ultimately, among all the passion and study, what I like most about drugs is just taking them. I am feeling my age, which is still relatively very young, but I very much do not have the time and mental energy I had when I was younger. Perhaps this is more a function of working full time and just not being able to adapt to that lifestyle- I am a born housewife admittedly. I am not sure if this is a field in which I will continue- my true passion still lies with zoology, particularly entomology or marine invertebrate zoology. I love the creatures of this world and their infinite beauty and diversity more than anything, it is one of the few things that still stirs a deep passion in me, where I feel like I could comfortably do the work indefinitely- and more importantly, it is a field where I feel like a have a definite foundation, where I am confident in my knowledge and understanding and eager to learn more, where I feel competent and well-applied. 

I am probably never going to leave the world of drugs behind, I just like them too much. This project *gestures to entire blog* will continue indefinitely, though I would expect the rate of posting to slow even more. But perhaps I will leave this world behind someday- it quickly feels like it is reaching a point of complete unsustainability. I have crossed that cursed bridge of using dissociatives just about daily, and it is very difficult to go back. Even on days when I don't use them I probably use some other drug, like benzos, misc GABAergics, gabapentinoids or opioids. I am chronically bored and understimulated, yet also chronically tired and burned out, and drugs are the only relief from both. My dissociative tolerance is creeping up. I feel I can no longer accurately report doses of things anymore, and the experiencecs with individual drugs are largely blending together into a general dissociative slush ranging from heavy-stimulating. I worry that I will not be able to report on new compounds with the detail and resolution that I was able to before. I don't like this trajectory, and I don't know any way off of it. I don't remember what it is like to live sober anymore. I get depressed and moody when I can't access my drugs of choice. I am fully, undeniably, addicted now. So long as I have access, I will use them regularly and compulsively. I do not know how I will behave if I do not have access. That situation has not presented itself yet. The only way I can forsee this concluding, unfortunately, is coming to a head and having it cause some sort of catastrophe that forces my hand in one way or another. Until then, I have established a new sickly equilibrium, a baseline comfort that is very very very hard to break. I am making a concerted effort to break out of my dissociative stasis and revisit psychedelics, especially now that I have the space to do so. 

I haven't written much this year, just a handful of reports. Lizard Labs running into legal troubles and now ending most of their dissociative production capability is a big blow to morale. Sourcing things has become increasingly difficult. I guess what I am most proud of writing is this bio-characterizing of the wholly novel dissociatives POxP and PThP.  I would love to see these explored further.

I don't think I will ever do as many new drugs as I did in 2021 and that is okay. That is not even remotely sustainable. 31 is still a lot though, this is my second biggest year in that regard. As I do every year, I am going to rank every new drug I tried in 2022. Have fun!

1.FXE - FXE is fantastic. It's not that deep. It's a lot of fun though. I can't think of a more perfect party drug. It is another attempt to hit that MXE bullseye but it also misses, because nothing will be MXE. But it works well on its own. Its forgiving, stimulating, casual and fun, I could do this forever. It's so great. It can be profound if you really force it to be. It is not as profound as DMXE. But it doesn't need to be that, sometimes you just wanna have fun with your friends.

2. 1,4-BDO - GHB, 1,4-BDO, GBL, its all the same. This is a lovely compound for casual use, just quite dangerous in its interactions. I would describe it as Alcohol combined with MDMA without the negative qualities of either (the overstimulation, the nausea and headaches). Aphrodisiac, nostalgic, heavy and comfortable.

3. 1D-LSD - The 1-substituted LSD analogues are interchangeable but this is by far the most potent one that has been made. I love LSD. So I love this. Very simple.

4. Bromazepam - The benzodiazepine that is probably the most reminiscent of etizolam. Euphoric, not too sedating, medium duration, what's not to love.

5. Fluclotizolam - A benzo that is both useful and fun! Great to get to sleep quickly with no hangover. Pleasant and euphoric for just hanging out otherwise. Very agreeable.

6. Isopropylphenidine - Bright, visual, functional diarylethylamine. Notable for how easily I could slip between a heavy dissociative experience and full functionality.

7. Hydromorphone - Short warm simple opioid. Yum. 

8. TMA-2 - Intense and bright and colorful and so so so euphoric but god damn is it all tempered by a vicious body load. 

9. DOC - An incredibly vast and challenging psychedelic. Heavy body load. Intense in a way I haven't experienced in a while. This is beyond the realm of rankings of favorites, just a hefty drug in general, fascinating but so mighty.

10. Deschloroetizolam - Medium length benzodiazepine, but very neutral in terms of euphoria or sedation or anything. Grey, middle of the road, but not bad in any way, still nice.

11. Lemborexant - Makes me sleep. Nothing else. Useful. Can have grogginess the next day though.

12. 4-MetMP - More or less reminded me of 4F-MPH. Same issues with side effects at higher doses. 

13. HHC - Sleepy alt cannabinoid, nothing too exciting

14. Tapentadol- It is an opioid that makes me hear voices. Nice enough I guess. Kinda unnerving.

15. 2B-DCK- What if you just took ketamine and made it less potent  and also shorter lasting. This is one for enthusiasts of snorting enormous quantities of powder. If you're not into that there isn't much value here. Not really any unique qualities. Bulkier halogens are diminishing returns.

16. Propylhexedrine- Bitter benzedrex, I don't like stimulants, I don't like this one. Mostly uncomfortable.

17. Nalbuphine- Definitely an opioid but it just made me feel bad. Straight up dysphoric. Sad as hell.

18. Zopiclone- Feels kinda like zolpidem but not as fun. I got *that* side effect, where everything tastes like bitter metal for the next 24 hrs. Not worth it.

19. PCM- I snorted it and it just hurt and tasted bad and nothing happened. On paper it's psychoactive though. I'll let someone else figure it out.

Needs further exploration:

P2AP - Adamantane analogue of PCP (Adamantane instead of the cyclohexane), I have been titrating this up very slowly and steadily but honestly it scares me. The duration could be immense. It might be a powerful anticholinergic etc. I feel bad, I was not a very good test subject for this, I keep procrastinating on working the dose up.

Desalkylgidazepam - I just wasn't able to find consistent information on this one so I didn't know where to start. I don't have the time or motivation to dose titrate benzos.

Emylcamate - No one likes this one. I am working on finding out why. Not eager to do that though.

2-TFM-Diphenidne - Maybe threshold effects at 120 mg. Maybe not. Need to explore further.

O-PCiPr - It's a dissociative, that is all I can say for now.

Tofisopam - Supposedly the anxiolytic effects of benzos without the sedative or amnesic effects. I haven't given the time to exploring it.

Promethazine - Combined it with codeine pills for uhh I guess you would call it solid lean. Haven't taken it by itself.

3'-MXP - I am not confident this is active. That 3' denotes that the methoxy group is on the benzyl ring, not the alpha phenyl ring like MXP. 

PCPy - Was sent a small sample of this. I am not sure why I haven't explored it earnestly, I think I forgot, this is a good reminder! I tried it once, it felt similar to 3-Me-PCP but I didn't catch a lot of the details.

Banisteria caapi  - I smoke it. It has an interesting light stimulating effect and something else that's hard to place. But I haven't dived too deep.

Muscimol - A. muscaria extract that was decarboxylated to yield primarily muscimol. We truly live in the future! I have found it to mostly just be sedating, in the way that benadryl is sedating. Need to explore higher doses.

NEP- Honestly I only took it while I was already on benzodiazepines. I am not sure. I think it was fun though.

1D-LSD

 Age: 27

Weight: 130 lbs

Dosage: 150 µg on tab, sublingual

Setting: Going for a long walk on a rainy but not too cold December day

 

Preface:
So the battle rages on, a 1-substituted LSD analogue is made, it is banned, another is made. The 1-site of the molecule has become contested territory. We have seen the whole host of compounds based on this theme: 1F-LSD, ALD-52, 1P-LSD, 1cP-LSD, 1B-LSD, 1V-LSD, they’ve all been wonderful and successful.

1-Substituted LSD analogues are well understood to be prodrugs of LSD, in other words, the compound that the user would obtain is a legal analogue of LSD, but upon ingestion, their body would convert it to LSD, yielding an LSD experience. While I have tried to nitpick the differences between them, ultimately I wonder if that can just be chalked to set and setting, as the same thing is happening pharmacologically in all cases. Any carbonyl alkane can be strapped into the 1- position. The human body cleaves that group off, leaving behind pure LSD to enter the brain. These carbonyl groups have grown bigger and bigger. The lysergamides are locked in an ever-turning wheel of combat with Germany’s Novel Psychoactive Substances law. It is an arms race where one substitution gets banned, only to be replaced with another larger substitution that circumvents whatever new stipulations the law puts in place. The latest competitor is 1D-LSD, the largest 1-substitution yet.

1D can mean a lot of things, but in this case it means 1-Dimethylcyclobutyl- an obscure moiety that has never been seen in a psychedelic before. It is a hefty cyclobutyl group with methyls on the 1 and 2 positions. It's such an odd structure that it is hard to describe, here is a picture. This probably opens the door to switching those methyls around to wherever one pleases.  Just another entry in the endless game!

­Sadly, the lab producing these brilliant analogues ran into legal difficulties, jeopardizing the further development of this fascinating progression of 1-substituted lysergamides analogues. A safe supply of chemicals was cut off from the world at the behest of the long shadow of the American Drug war. A man sought to make psychedelics more accessible to those who would heal and benefit from them in the face of nonsensical laws, he pushed forward research on the metabolism and effects of different lysergamides, he only sought to expand our knowledge in so many different ways, and now he must suffer under the heel of the ever-stampeding drug war. What cruel times we live in. 1D-LSD may very well be a ghost of now bygone era as we sail warily into the new dark.

Nevertheless- This is an exciting drug. It is perhaps the most potent 1-substituted LSD analogue I have ingested. Assuming the tabs are indeed ~150 µg, this is a hefty experience, probably getting close to the potency of actual LSD. The experience is vast and extensive.

 

T0:00 – Dose taken at home. The tab has an uncharacteristically slight bitter taste. I am with a group of friends- J and C, my longest time partners in crime with whom I have taken many many different research chemicals. Joining us is E and M, who are just taking strong cannabis edibles. J opted for classic mushrooms this time, C wants to revisit his old favorite, 2C-B. Our plan is to just aimlessly walk around the city where we all live. It is a wet day, breezy but not too cold, sometimes the sun tears through the clouds as they rush past high in the sky. Our first stop is to see the campus of the college where we had all graduated and formed so many drug-fueled memories, now that we had been away for years. I am a bit anxious, but in high spirits from the previous night’s dissociative-fueled debauchery. C and M had slept over.

 

T0:20- Getting ready to leave the house- perhaps the first hints of an experience? Or maybe a bit of placebo.

T0:40- We are walking to the subway station, the first notes are more definite, warmth and a little bit of a buzz,

T0:50- I can really feel It start to hit me as we wait for the subway. It is raining on and off all day, water leaks down the walls and the tiles are slaked with wet grime. All around is cold metal and dirty air. I feel like a little wide-eyed creature of the tunnels. There is a familiar psychedelic sense of energy pulsing through my limbs, a detached awkwardness with my friends, a bit of nausea stirring in my gut. When I look at the subway tiles ornate paisley floral patterns start to form. I sit quietly, taking in the space of the sooty echoes and sounds of drips around me.

T1:00- I am on the subway now, I am confined and uncomfortable but I am amongst friends. I am definitely experiencing my experience the most intensely out of all of them for now. So much activity stirs around me, it all seems shifted out of order by the grey sky of the surface above. I just curl up in my seat and take in my surroundings.

The chromed metal all over catches the light around it, the drug in my brain catches this light and sets it into motion, a shimmering swirl of glints and shines and quicksilver swirls. Grainy two-dimensional floral patterns slowly crawl across the grimy floor. Everyone around me is pulsing with energy, like migraine auras hovering over their forms. The visuals are still pastel, translucent, only apparent upon focus. It’s hard for me to maintain conversation with my friends. Nausea gently wells through me; a warm tension rolls down my limbs. I can’t wait to be back outside.

T1:05- We get off of the subway, we are back in our old haunt- so many days spent confused, lost, miserable, arrogantly feeling like I had figured the world out already, heartbreak and a deep void of depression, drug fueled hedonism and precious time with friends and lovers- the day is plain and grey now. We break onto the surface and take stock of things- in just a few short years everything looks different, we hardly recognize our environs, no one is here because it is the weekend. The world is spinning and flowing around me like a great breeze swirling leaves around my form. I feel compelled to only walk forward, concentric forms start to crackle from the wet concrete buildings, there are jolts of electricity in my skull.  

T1:15- I sit down and the intensity sets in like a fogbank smothering a skyscraper. We are in the central square of campus, sitting, laughing, joking, reminiscing. The sky is grey above, stratus clouds sit in strips and stripes and blocky spiraling forms churn within these, like an abstracted freeform of the art of Mesoamerican indigenous peoples. They crackle with shy flashes of teal and pink, it all drifts and flows with weight and purpose. I stare at the ground and the concrete forms itself into fronds and spirals and swirls, bold lines and hard angles adorn in their spaces, slowly growing and blossoming. There is not much energy or restlessness or stimulation in the visuals or in my limbs, I am content to sit down, I feel like I am just basking in the experience like a sauna. It is hard to type notes, my fingers feel cold and tight, my skin looks magenta and traced with patterns of bars of color, my phone bends away from me. I would consider this a pretty intense experience. My thoughts are going everywhere, pursuing the depths of anything mentioned in passing. Every word generates a vivid image in my mind, to the detriment of actually understanding conversation. It still feels like it is building, I am still coming up.

 

T1:40- We walk through the neighborhood back to the old house where we all used to live at various points (I was the only constant). More than half of the reports I have written took place in this house. As I walk down the streets the clouds look ever so more energetic, like great creeping caravans of megafauna grazing their way across the sky. The late afternoon light catches the swirls of my visuals in all of its warmth and illuminates them, it is a glorious scene, I am with such nice friends, the day is being swept by gusts of euphoria. The world feels bent around me, like I am surrounded by a great crystalline wind that filters my perceptions into one of colors and motion. There is a spring in my step, a sense that the sky is a great glass dome above, we talk and joke, huddled up and impervious to the strangers walking around us.

The neighborhood looks completely different in the face of monolithic gentrification. I guess you can’t really go back. We post up outside our old house, we wonder who lives there now, I wonder what energies we had laid into the house. I try and project myself through time, imagine myself there so many times, on so many drugs, in so many emotional states, but I can’t, it doesn’t resonate, that part of my life is so far gone. It makes me sad to not be able to go back, even in this form, with my mind so raw and vulnerable, it makes me sad I cannot feel this space, that this is all it was, a physical structure of brick and wood and concrete, just like any other. I guess we didn’t leave any energy behind, just a mess of scavenged junk and animal bones and improvised weapons that were too difficult to move out. We sigh and decide to take a long walk back to my house. My emotions are raw and I feel sensitive, not in an anxious vulnerable way but in a way of comfort and acceptance in being among deeply familiar company. The intensity at last feels like it has reached its peak. I am immersed into this experience as fully as I can be. I can still walk, I feel functional, I feel nauseous and uncomfortable, and I realize I will be in motion for what is to be the most intense part of an already intense experience.

T2:00- Walking through the neighborhood, I have a destination in mind and I am navigating everybody there. I am still competent enough to do that least. I am flustered though, there is a great whirlwind around me in a million colors, my brain is cast about its currents and the world is buffered from me by a psychedelic haze. Little spots of visuals try and eke out an existence everywhere I look, eyespots with angular tendrils surrounding them, blossoming spiraling forms, adding chromatic traceries to the otherwise dulled greys of the day. I feel like I am 18 again. I try to take notes while walking, I’m walking very fast, it is very hard to type. My hands don’t’ look the shape they should, they don’t feel or move the way they should, it all feels like extra steps have been added to otherwise simple processes. I am content to let it overtake me and crawl about me, I am happy to submit myself to the drug in public, so long as I can still walk and appear normal. I take in so much of what is around me, my thoughts circle back on themselves, analyze themselves, leaving me in a half-attentive daze as I move. And yet so many beautiful things from the world stick out to me, one particular graffiti tag, the color of a car briefly contrasted with the bridge it drives under, a brief flare of music from another passing car, it is a world of ornate details and I am blessed to just walk by gathering theses sensations in my wake. Auditory effects are mostly nondescript- I feel often when I take psychedelics in public the ambient city noises around me will doppler and reverberate and echo, but I am not noticing much of that this time around.

Nausea wells up in my as I walk, I fight with all my might to hold it down. I am walking fast, not stopping, I feel like I am trying to outrun the full weight of this experience. I am talking with J a bit but I am mostly just in my public solitude, marveling at the swirling world before me, marveling at the patches of peach sunlight, the golden beams they cast down on the shimmering buildings below. The sky is still great glassy dome reflecting and refracting light in a perpetual dance down upon us. Everything is in its place, everything is as it should be and is altered as it needs to be, everything is beautiful. I am physically uncomfortable but enraptured in comfort. My friend remarks that the sky looks so weird today, in a poetic sense.

 

T2:30- We reach our next destination, a stretch of abandoned elevated rail line that is densely rusted and graffitied and overgrown, easily accessible through a hole in a fence near my old house. We slip in one by one and climb a steep hill of wet railroad ballast. Climbing through fences and up steep wet hills is betraying our age. We walk right through the living room of a homeless encampment but no one is home. Everything is damp and the sky is a great golden pink above, the filtered misty light carrying a gentle luminosity down to every slick wet surface. We laugh and joke as we walk the tracks, everyone is in high spirits, no one is really feeling their drugs other than the people who took edibles. I am having the most intense experience by far.
I sit down and the full weight of my rolling peak crashes down on me, greater than before. The distant sky is spirals tumbling into each other. The buildings around me shimmer into polychromatic ghost images. The plants shift and embrace and entwine around me, the ballast below my feet smears and shifts and bulges with tints of red and blue and green. I am dizzy and it feels like a great rainbow void in the sky above is swirling a funnel cloud vortex into my skull, in the most benign way that can happen. A shiver runs down my back, I am sweaty, my hands are clammy and angular polygons form and unform and drift faintly on my skin. The world is huge, the wind is beautiful and the buildings around me sigh and heave in gentle repose. This is wonderful.
I haven’t been talking much and when I do try to talk it is awkward, I am not too articulate and I have a hard time getting my thoughts across. I am usually quite articulate on psychedelics actually, so this impairment is a testament to the intensity of the experience. I am the de facto guide for this area since I’m the only one who has been here in recent memory, but I struggle to articulate directions to the rest of the group. We end up hanging around an abandoned substation for a bit, picking through the wet trash, loitering about on the rusty machinery, joking and chiding. I smoke a bit of cannabis. Everyone seems happy with where we are, I am happy with where we are.

T:245- We sit on a pile of railroad ties at the end of the line. We’re al laughing and joking now about God knows what. We’re all cracking up, I am laughing until tears are streaming down my face. Always such a good feeling on psychedelics, always glad to have humor in an experience. After this we set out, immersing ourselves in the city’s Chinatown. It is hectic and I have to push around the crowded sidewalks. All of the people I see around me look so odd in different ways in their various groups and social circles and gaggles, and I’m sure we look strange too. It feels like the experience has subdued itself so I can navigate this setting competently. We decide to stop by E’s house for a breather and just to check it out, since it’s right on the way back.

3:10- Being back inside is disorienting. I am sweating a lot. Colored patterns sear and pulse into every wall around me, steaming like they are being baked in, just raw crackling high heat psionic energy. Textures drift and move up and down the hallways. I am enthralled standing in the tiled elevator and staring at the swirling patterns on the floor. I lay down and let my pitiful muscles and bones rest. The apartment is cozy with a beautiful view north towards the city. I still feel like I am pretty reliably peaking. The quiet in the space is heavy and glowing, contrasted to the hustle and bustle and noise of the city outside. Every little thought I have I want to engage and examine and follow through to wherever it leads me, but I also just do not feel the energy for that. After catching our breath, we set out again.

3:20- Uh oh. E can’t find his keys. Me and C and M sit in the hallway outside the elevator while E and J look. The visuals sit heavy while I sit there still and quiet. The pattern on the carpet drifts and shifts, forms twirl and intertwine, splatters of color flash into the walls. I am filled with a sharp articulate euphoria, I can talk easier now and socialize better. There is still this innate sense of being where I need to be. After about 15 minutes of waiting we realize the situation may be more dire than we first thought- E’s keys are nowhere to be found. Him and J have searched the apartment up and down, in and on and under every surface, We all join the frantic search, searching the same places 5, 6 times. Brainstorming new places to look. It becomes an engaging activity for all, we interrogate this man like the police but it is to no avail. We eventually have to make the heartbreaking decision to leave him behind as he wouldn’t be able to get back into his apartment until Monday. Adding insult to injury, it is now pouring rain outside.

(E would find his keys in his trash the next day somehow)

T4:00- We set out to walk the rest of the way back to my house. Rain is coming down in curtains, the streets are aglow with neon lights and reflected puddles, bright lights illuminate the markets and storefronts as the rain cascades off their awnings in in glowing glassy beams. We are instantly soaked to the bone, we trudge forth, all we can do is laugh at how ridiculous our circumstances are, we lost a friend, we are soaked, what a bummer. The rain and the lights are beautiful in this state, but we are drowned rats. Our path is interrupted by a goddamn parade of all things, extremely bright lights catching the raindrops, marchers who seem unsure of whether to continue in the deluge, it is all such a surreal scene, a perfect compliment to the bizarre headspace I am inhabiting. It is all chaos and deluge and a storm of god tossing us about for heaven knows what incomprehensible prank. We just try to rush home.

T4:30- Back home, we are soaked to the bone. I quickly coordinate dry clothes and towels for my friends and a pile to dry their wet clothes. It feels nice to be competent and in control, to be a good host, to make my space hospitable. I am definitely much further down in my experience now. The room is stuffy and I throw the doors open to let in fresh cool air. After the whirlwind of activity and sweat and water and mess, it is blissful to be in my own home again, my two wily cats slinking around in their own ways, it’s a warm bustle of activity vibrating the room with orange energy. We loiter around and recover from our long walk. Another friend arrives.

 

T5:00- We smoke 2 joints in the back yard. I am down enough that this doesn’t stir the dust of the experience much. My spouse arrives home shortly after this. We lie around talking about our lives, Warhammer 40k lore, gentle and joking.

T7:00- Mostly down. My friends have all left.

T10:00- Feeling a residual euphoric glow in the absence of other effects. I am filled with adoration for my spouse. It is a pleasant and coherent headspace.

T12:00- Back to baseline.

 

Conclusion: 1D-LSD is another fine addition to the growing ledger of 1-substituted LSD analogues. This is by far the most potent 1-substituted LSD analogue I have tried. To answer the biggest questions- yes it will yield an experience similar to LSD, and the tabs dosed at 150 µg offer a substantial experience that is not to be taken lightly- in fact for the inexperienced I would recommend not even consuming an entire tab. It bore all the hallmarks of a lysergamide- patterned intentional visuals, teal-pink color schemes, a long duration with a drawn out euphoric stimulating afterglow, analytical, sentimental, profound and joyous headspace. This is certainly a compound that offers a worthwhile experience.

The global war on drugs cuts the head off of another hydra, and for now it seems the possibilities for 1-substituted carbonyl alkanes that metabolize into LSD are near endless- one simply needs to mix and match the carbons as they see fit. There seems to be no upper limit on bulk- in fact it seems bulk increases potency. To constant adaptation, and to freedom for friends near and far.

 

 

POxP

 Age: 26

Weight: 130 lbs

Dosage: 350 mg oral

Setting: My house

 

POxP is a complete novelty that I had the pleasure of being one of the first people in history to try, with no prior documentation either in literature or in the realm of online research chemical users. POxP was a suggestion born out of the very similar PThP, which was mentioned in a bluelight thread where a user claimed to have seen the compound PThP mentioned as being active as an NMDA antagonist in an article published in the European Journal of Medical Chemistry. No one was able to recover this article, though the suggestion it bore- of an arylcyclohexylamine with the sulfur bearing 4-Thiane ring as opposed to the cyclohexane ring, was interesting. In psychoactive molecules, R-bonded oxygen can often be exchanged for a sulfur and retain activity, so it stands that an 4-Oxane ring would show similar activity.

Like PThP, POxP would not be an arylcyclohexylamine. Where PThP is an Arylthianylamine, POxP would be an Aryloxanylamine. Traditionally, with the arylcyclohexylamines, fundamental changes to the 6-carbon cyclohexane ring see a steep drop in activity- using a 5-carbon cyclopentane or 7-carbon cycloheptane ring makes a compound which is wholly inactive. However, its seems that swapping some of those carbons out for oxygen or sulfur is also tolerated- though there is a stark drop in activity, they certainly are still active to an appreciable degree. It seems that maintaining the approximate shape of the six member ring is key to conserving dissociative properties.

I first began to titrate doses up from .5 mg. I would later discover this is quite far off the mark! Pushing doses higher and higher, I would eventually only experience threshold effects at a dose of 150 mg orally. It did not appear to be active intranasally up to at least 100 mg, though I have not tried doses higher than that. Because the dose is so high I eventually ran out of my tester sample, and would have to wait several months for a new sample to arrive. When it had finally arrived, I immediately shot for a fairly high dose- 350 mg. This yielded an fascinating experience that perhaps shows interesting promise for this compound- underlying a brief but heavy and still dissociative experience was a stimulating empathogenic undercurrent, reminiscent of a cathinone and replete with all the social delight and euphoric energy of that class of compound. I think compounds with the oxane ring replacing the cyclohexane are definitely worth investigating further, perhaps modulated by substitutions or structural changes that may increase their potency or duration. An N-ethyl POxE for example, may by interesting. As would a structure with a 3-methyl substitution, or one with a thiophene instead of a phenyl ring.

The following report details an experience with 350 mg taken orally.

T0:00-Dose taken

 

T0:30- Onset, feleing a bit soft and Dizzy, like I am a floppy stuffed animal.

 

T1:00- Dissociation and dizziness builds. The stuffed animal grows ever softer and ever floppier.

 

T1:05- It suddenly hits like a tsunami, washing over me and disorienting me. I am taken aback by the sudden steep increase in effects. It literally hid mid-sentence. I was watching my fiancé play Katamari Damacy on our PS2 and was remarking on something when I just trailed off, whatever I was saying completely lost in my newfound mental state. The predominant feature of this dissociation is dizziness and softness. No rush, no stimulation, not much sense of motion or weight, just soft and dizzy. It is pleasant and relaxing and gentle; it is that feeling of immersion into a still pool despite the sudden spike in intensity. I feel as though I may be levitating. I am a little bit nauseous, though it feels like it may be along the lines of a dizzy motion sickness than some reaction to the chemical itself. The couch has become a boat floating about on air currents.

The headspace is neutral, not much in the way of emotional or perceptual changes beyond what is immediately happening in my body. I don’t feel manic or sociable, just neutral, content to continue as I was doing, minding my own business and occasionally chatting with my fiancé. My mind is lucid and I am still able to process and articulate thoughts as I normally would. There are no issues with maintaining conversation.

 

T1:10- It builds exponentially, a rising weight heaving through me. I feel heavy, so much heavier, this has passed into the realm of the great dense syrupy sinking dissociation. There is a great deal of euphoria and comfort lurking about here, I feel extremely content to be right here, in this moment. I am chatty and bubbly, there is a social warmth among the heavy dizzy dissociation. Not a manic stimulated warmth, but something akin to the bubbles rising up to the surface of water that has just begun to boil. I am certainly reaching a rapid boil now.

It builds and builds and it becomes harder to think or speak, there is just so much of the experience to engage with. Not much in the way of visual or sensory effects, but any attempts at moving or walking make it deeply apparent how heavily dissociated I am.

Another curious effect begins to creep in at this point- I am swallowing more, my heart flutters, my fingertips are stimming and grabbing at things, and above all else, I am just awash with a fiery explosion of pure euphoria- The dizzying fog is cut through with a galleon of empathogenic effects, bright flares setting my neurons alight. I am suddenly very talkative and gushy, easily treading past the normal dissociative inhibitions to socializing. I just do not care, I want to talk, to love, to be friendly. I am jittery and jumpy, but oddly enough there still isn’t much of a sense of underlying stimulation. It is as though I am presenting the outward façade of an empathogen without the underlying systemic effects. Very curious. I am excited and short of breath. The edges of my vision flash in pale magenta and teal.

 

T1:20- Anything that gives me empathogenic effects will normally leave me tense, strung, and shaky, but not this. I am just melted on the couch, adrift in my dizzy dissociation, a pool of dense oil sloshing and dripping as the world turns. A rainbow sheen of energetic euphoria traces across the surface of this oil, not penetrating any deeper into it. I am alert but not stimulated. I definitely could not sleep right now. I am dissociated and content with it and all of its implications. My heart and brain feel flighty like a bird flitting through the warmth of sunbeams. There is visual static washing over everything I can see, multicolored visual snow, at times trying to form itself into vague amorphous patterns but ultimately failing and collapsing under their own instability and half-formedness. I close my eyes to try and immerse in that visual space, but I am greeted with little more than concentric ripples in dull colors. Not much to say, it is as if the drug wants me to open my eyes and engage with the waking world. I want to talk to people and be social but I cannot yet publicly talk about this compound so I keep it to myself. No matter what happens though, I am blissful and content.

 

T1:46- Effects have held the same pattern for a steady peak. Not many differences to note, I am playing video games on my laptop while my fiancé still plays other video games in the same room. It is a comfortable coexistence and this is particularly highlighted by a drug that emphasizes contentedness, peace and tranquility with ones current conditions. I am feeling great, I am numb at my extremities and it is like a gentle wind blows across me. The sense of dizziness and floppiness seems to well through me in waves. A vast deep-sea upwelling that tangles my proprioception with each pass. My limbs slowly settle back into place just as another wave hits and scrambles them again. The gentle lapping tides of a moonlit night. I am still a bit nauseous but nothing too concerning or annoying. This is not a dissociative for getting up and doing things. I am glued to the couch. Despite the energetic euphoria, nothing overcomes the floppy weight of this drug. Perhaps I could get up and dance if someone forced me but I am content to just lay here and think pleasant thoughts.

 

T2:06- The experience begins to recede a bit- a brief but exciting peak. I am mostly just feeling alert and distractable. There is clearly a physical dissociation and numbness still trailing through my limbs, but the headspace has remained lucid throughout. Beyond the generated euphoria and the dissociative afterglow, I am perfectly functional. I lie back and enjoy the ride. I am distractible and keenly interested in whatever grabs ahold of me, like being very stoned.

 

T2:20 – Trickling down more. The empathogenic effects have for the most part passed, there is no stimulated interest in anything. Just a lingering sense of dizziness and dissociation.

 

T3:00- Completely back to baseline.

 

Conclusion: POxP is a really exciting development in the world of dissociatives- that immutable cyclohexane ring in the arylcyclohexylamine is now quite mutable, though it doesn’t really yield potent compounds. It will just barely tolerate another atom in the ring, so long as it remains six members.  This is seen in POxP and PThP. PThP is fairly boring- doses high, short duration, not a particularly intense or interesting experience. POxP is something a little more special though- though it is even less potent and shorter acting than PThP, there is this fascinating empathogenic rush, a delightful serotonergic euphoria. There is still an edge of dissociative intensity lurking there too, though the dissociation itself is fairly nondescript. I only tried this one orally, so I am not sure if different effects would be found with other routes of administration, perhaps intranasal or vaporized.
I have no idea to what it owes these seeming serotonergic effects, or if that was even just some weird fluke for me. I have not heard of anybody else’s experience with this compound so I cannot have this corroborated. It is definitely something worth investigating further- though I do wonder if it is a compound that lends itself to compulsive redosing- the short duration coupled with the intense euphoria. Perhaps someday it will exist in the world in someday to learn more about it.