3-HO-PCE (revisited)

Age: 24

Weight: 125 lbs

Dosage: 25 mg intranasal

Setting: My bedroom

Preface: When 3-HO-PCE first became widely available in 2017 I picked up one of the first batches that hit the market. My experiences with this substance back then were lackluster, a barely discernible and odd empty mental dissociation that barely felt like a dissociative at all, but rather some other strange, neutral altered state. I quickly dismissed this drug after a few trials as being fairly unremarkable. As time progressed positive reviews crept in and demand increased, which confounded me, but I just chalked it up to the subjectivity of drugs. It was only recently, in May of 2020, that I heard a rumor that that first batch was particularly weak or impure. I decided to see for myself and obtained some from a more recently produced batch. I initially experimented at doses similar to those I had taken with the first batch, ranging from 10-20 mg. The difference was remarkable- this later batch had indisputable dissociative effects at doses that only brought about threshold effects in the old batch. I prefer higher doses and more intense experiences with dissociatives and I feel that such experiences allow me to better understand the character of a particular substance, so I ran an experiment with 25 mg, higher than doses I had even taken with the old batch. That experience is as follows.

T0:00- Dose taken intranasally. Typical rancid petroleum odor of arylcyclohexylamines. Not much sting or discomfort to note beyond the bitter flavor.

T0:20- Begin to feel the first notes as being giddy and lightheaded and slightly dizzy. Already a presence of euphoria. This already seems better defined than the experiments with the older batch. Drip is moderately unpleasant but certainly tolerable.

T0:37- Feeling more and more dissociated, it is distinctly ringed around my head like I am wearing a tight diadem. My head begins to feel like an immense weight on my skinny neck. There is a steady feeling like I am rising- it is a gentle, soft, smooth and gradual dissociation that slowly immerses me. My fingertips feel numb and my visual field feels neutralized and subtly refracted like I am viewing it through thick glass. Open eyed visuals begin to form as smudges and blurs like some photoshop tool has been run through my field of view. Things begin to shudder and flicker ever so slightly. My eyelids feel heavier. Everything starts to feel heavy in fact, I am sitting very still at my desk and any motion feels like a massive undertaking. This is accompanied by a sense of accommodating warmth.

Cognitively, I find myself at first sitting with my eyes closed and tracing my way through pleasant memories, turning them over and analyzing every angle of them like one would analyze the shape and textures of an interesting rock. This begins to fade as a sense of stupefied numbness creeps into my brain, as though its creases are being smoothed over like clay. My thoughts begin to unravel from my head in great empty streamers that flop over and fall soft and flaccid as they peel off into nothingness, like great gooey streams of putty. I feel like I am forgetting to breathe occasionally.

T0:47- Spontaneous sensations begin to feel their way across my body like great empty hands made of wet clay. There is a pleasant pressure on my temples and it feels like my teeth are buzzing with numbness. This anesthetic buzzing passes across my skin, tickling and tingling up my neck and into my facial nerves.

T0:52- The dissociation wells up more and more, pulsing through my body like a dome of magma rupturing the earth’s crust, radiating a pleasant warmth into the shell of my being. I feel so incredibly heavy and steady and slow like I myself am made of heavy stone. Every motion requires so much effort and I am more than content to just sit perfectly still. Open eyed visuals become more and more defined, as spots, ripples, twitches and shakes. Everything is flashing and arcing off into infinity.

T1:00- It’s so hard to do anything and the trip is evolving and accelerating so quickly. My mind wanders off from my catatonic body, flaring and dancing in the empty space of my room. That body, so still, is a melting lump of clay, its weight pooling with gravity. It feels like it is being smoothed over by wind or a steady ocean current, not sudden and violent but steady and unwavering. Every motion I can muster feels slow and deliberate like I am a puppet being operated with the utmost care. My skin feels cold, glassy, and artificial.

Breathing is shallower. Visuals are flowing, in constant sinking motion, like water running down cave formations, smoothing them out. Waves of color wash over me, deep navy blues and heavy maroons. My jaw hangs agape and my teeth continue tingle.

T1:15- It feels like time has slowed down so much. It feels like everything has slowed down really. Only the music I have playing, perceived at normal speed, anchors me in a proper conception of time.

This trip is remarkably warm, not the manic fiery warmth that other arylcyclohexylamines like 3-MeO-PCP or 3-MeO-PCE can impart, but a gentle, immersive smothering warmth like sinking into a mud bath. My body continually feels like it is melting and sagging to gravity despite nothing happening physically. It is a continuous and fairly pleasant sensation. I can particularly feel the weight of my skull, and in that, particularly the weight of my mandible.

The whole world begins to look slanted and askew, especially the text on my screen. I remark to a friend that I am chatting with that it seems like everything is suddenly written in italics. I am so lazy and sedated, I don’t want to move from this spot, but I know my bed would feel even more comfortable. I want to lie down and listen to big walls of sound, let them grind down on me.

I had a bowl of cannabis packed beforehand, I muster up the motivation to smoke a few hits. It doesn’t add much to the experience other than a slight intensification of the buzzing sensation. The buzzing runs up my spine into my skull, expelling its excess energy through my teeth. This is pleasant, blissful and fun, so slow and heavy. It feels like convection, like I am constantly bubbling and floating up, then succumbing to gravity and sinking down, like a ping pong ball caught in a waterfall. The closed eyed visuals are dark, geometric, and monolithic and imposing, quickly fading into distant dark obscurity. Everything is tinged by a deep green. They are very still with only the slowest discernible motion and energy.

T1:20- I have managed to muster up everything I have and haul myself onto my bed. I immediately melt into the mattress like a big gooey puddle. Vibrations wriggle and ripple across the surface of this perceived puddle that is my being. My eyes are watering and it feels like my fingers don’t belong to me anymore. They are alabaster specters that act of their own will, a will that just coincidentally aligns with mine.

Lying down now I feel like I am an empty corpse, just a dead body in a heavy glassy casket. It is pleasant and peaceful. The only sign of life I can feel is the motile sensations that crawl up and down my body in waves, radiating and pulsing. There is a remarkable anesthesia too. Nothing feels better right now than just lying still. I can’t imagine wanting to possibly do anything else. Anything other than the bliss and tranquility of stillness seems trivial and pointless. The trip has decided its own motion and I am more than content to succumb to it, like tubing on a lazy river, a river made of viscous syrup.

The closed eyed visuals begin to assemble more and more, a void with massive pillars begins to tighten up and form into endless expanses of vast dark, cavernous halls, heavy and meaty and moving in response to my slow and steady breaths. Indeed a sense of tightness and tension grows, like the experience is slowly constricting me. The glow of my computer screen casts my body in a sterile light, perhaps it’s just a visual hallucination but I feel like I am decidedly pallid and corpselike in appearance. But damn does being a corpse feel nice, carefree and peaceful. I feel so content to just lie down forever, heavy curtains falling on me to close out my time alive. I am almost certain that my body was not actually in any danger of shutting down, rather it was a perceptual illusion in response to every cognitive process slowing down asymptotically to a near stop.

Physical motion has already been stricken from any possible activities, and now thinking is next on the chopping block. Forming thoughts feels tedious and laborious and I no longer want to put effort into it. As I like to think way too much, this inhibition is somewhat frustrating to contend with. I lose my sense of direction, I have no idea which way I am facing and if I close my eyes I lose all sense of where my body is in relation to the space of my room. The only thing that feels worthwhile is surrendering to the steady flow of this experience, driven by the weight of gravity, like rocks grinding together. I am yawning a lot, and while I am breathing normally, albeit slowly and shallowly, I keep feeling like I consciously need to catch my breath. There is a slight nausea reminiscent of motion sickness.

Above all else, I am a golem made of wet clay.

T1:45- My notes for this part of the experience are heavily laden with typos. I am trying to still talk to some friends in a discord chat but I feel like I have to fight my way through an impenetrable denseness. I am bearing down on this inhibition like a massive glacier, slowly pressing my weight into it, but to no avail. I am simply dumbfounded, unable to effectively process anything.

There are bubbles of light rising through my visual field now. I am stone titan gazing on what now looks like a tiny screen. When I close my eyes I am greeted by the same monoliths, now contained in a room that is saturated with heavy colors. There is no feeling anymore- no anxiety or euphoria or disdain or discomfort or anything. The idea of discrete thoughts is incomprehensible, it has all been smoothed over. I feel like I am experiencing the world in the way a rock would, one that has been eroded round by a river.

2:00- I feel like I am possessed by the spirit of a cave, so neutral and empty yet tight and confined. I am not yet lucid, I am slow like paste being poured between gears, like corn syrup dumped into a computer. Visuals dance in a steady red and blue and all I can do is passively regard them. My bed feels so soft and it’s so nice. A lot of the all-consuming anesthesia and physical sensations have now passed into a ceaseless weight around my head. My cheeks and jaws tingle and twitch. My eyelids are still heavy and it feels natural to just keep them closed.

The realm of being a clay golem no longer feels forcefully thrust upon me, by now it feels like something I can passively allow to creep over me. It still reigns above all else though. This is the precipice of the comedown, and I feel content to let this experience and its stupefying inhibition pass into the night. For now it is nice to simply sit with its dying light, to regard mindfully and matter-of-factly. The sensation in my limbs as feeling returns to them is smooth and pleasant, unctuous and undulatory like a warm bath being sloshed around inside of me.

T2:28- As time passes I begin to come back into my body and mind more and more. Lucid thoughts begin to form again, thoughts about big numbers and unstoppable voids, of vastnesses and forces beyond known limits. There is a euphoric relief in becoming myself again, though I imagine the feeling would be opposite had I entered this experience in the midst of a depressive episode. This comedown is euphoric and enjoyable, almost worth the debilitating stillness of the peak. I still feel slanted and drenched in the heavy fluid of the drug, still at its gentle mercy like plastic toys floating down creek riffles. Vision is still so askew that things resemble cubism, I feel like I am viewing things from multiple impossible angles simultaneously. The visual effects are still very noteworthy despite many of the other effects tailing off, they bear down with the weight of a heavy pane of glass that seems as though it would take a great deal of effort to alter or remove. My tongue tingles like I have just swished with mouthwash.

T2:37- A lot of the weight feels like it’s been lifted from the experience, I now feel floaty like a stray balloon. I still don’t feel any motivation to move my body at all-I am content to remain a statue, albeit a one made of entirely different material than before- perhaps fiberglass or hollow plastic. Closed eyed visuals are still marked, as towers and tombs towering into the dark heavens. It’s all bending and twisting and steadily coming apart, succumbing to the formlessness of the void. I am a wobbled ghost in a dance of the dead, nursing a drink in the corner. Everything still feels slow, labored, wet and massive.

T2:56- I am getting tired of this sedation now. I want to move and do things again, but it still feels like so much effort. Though it’s only been 3 hours, the experience feels like its overstayed its welcome. I am generally an antsy person and I don’t have time for debilitating sedation. The tactile effects and numbness are now confined exclusively to my head, which still feels impossibly heavy. I feel like I will not be able to abandon this experience until the feeling in my head passes, and that currently shows no signs of abating. I am trapped in its mass.

T3:11- Still feeling dumb and heavy, though I can process thoughts and read and understand things much better than before, it is still far off from baseline and I am still distinctly incapacitated. I just feel off in a not particularly pleasant way. The experience at this point feels similar to the peaks of my experiences with the older and weaker batch.

T3:24- I note the consistent tickling in my face. It is like little caterpillars crawling up my facial nerves.

T3:52- I am feeling more and more lucid thankfully. I am able to converse with people much easier. There is still a slight numbness in my body and a lesser but still notable tightness and weight in my head.

T4:30- Still feeling something but it’s mostly just an afterglow now. I mostly ruminate on how nice it is to be able to think again.

T5:04- All that remains of the experience is a tightness in my head, like I am wearing a tight imaginary hat.

T6:00- Back to baseline by now. I go to sleep a few hours later without issue.

Conclusion: With a newer and better batch, 3-HO-PCE has truly shown itself as a powerful and remarkable dissociative. It is too sedating and inhibitory for my preferences nonetheless, though now that I have more thoroughly felt the substance out I can absolutely understand how others might enjoy this, as opposed to my total dismissal of it before. It is definitely warm, comfortable, and anesthetic, with pleasurable physical sensations. Less enjoyable is the total smothering of thought processes, of everything slowing to a halt, of the act of existing turning into a tedious and laborious burden. This drug is extremely incapacitating in the sense that it just drains any motivation to do anything, to even think much less move. This is perhaps the most sedating dissociative I’ve ever consumed, even moreso than a ketamine hole but without the rushing intensity. The visual effects are notable and theoretically enjoyable, though their vividness is stunted by an inability to process them. This drug is nice for just lying around, I can’t really imagine doing much else on it. It probably is great for pain relief too. The dissociation is heavy and floppy, I mostly felt like I was made of wet clay drooping to gravity. There was a persistent weight and tightness in my head- the first sensation to present and the last to leave. The comedown was pleasurable in the sense that it was a release from the frustrating incapacitation. I felt dead and catatonic and it felt so very neutral. A good way to kill a night with nothing to do I suppose.

Obscure and Unknown: Benzomorphans

*WARNING* The substances mentioned in this entry actually have an extensive history of human use and a robust body of knowledge on their effects. Nonetheless, they have little history of recreational use, and their effects in that contexts with higher than pharmaceutical doses is still not fully understood. Some, like Phenazocine, have unique methods of action that present unexpected risks such as respiratory depression. Two of them are also explicitly illegal. Tread very carefully with these substances. Nonetheless I think they are very interesting and would love to collate the body of knowledge regarding them from the context of viewing them as hallucinogens. 

The Benzomorphans are a family of tricyclic opioid drugs that also highly likely to be NMDA antagonists (dissociatives) at the same time1 2 3. They have been recorded to yield hallucinations with several qualities of the experience consistent with the familiar hallucinatory dissociative experience (in addition to their opioid effects). Benzomorphans have a spotty history of human use, though two have been marketed and sold as prescription medications for treatment of pain. They are very rarely prescribed in western countries nowadays. The two that made it to the market are Pentazocine and Phenazocine, under the brand names Talwin and Prinadol/Narphen respectively. Hallucinations have also been observed in more experimental drugs like Cyclazocine and Alazocine.

The generalized structure of a hallucinogenic Benzomorphan (stereochemistry may vary)

Structurally, the Benzomorphans bear a strong resemblance to the Opiate family of drugs, containing a phenyl ring joined directly to a cyclohexane ring, which is in turn joined to a piperidine, both of these lower rings mashed up against each other. All of the familiar opiate drugs (Morphine, Codeine, Heroin (Diacetylmorphine), Oxymorphone, Oxycodone etc.) have an additional six member ring (either a cyclohexane or cyclohexene) and a tetrahydrofuran between the phenyl and the lowermost ring. The hallucinogenic benzomorphans are all equipped with an -OH group on 4 position of the phenyl ring, methyl groups (of varying stereochemistry) on the 1 and 13 positions of the lower rings, and a variable functional group on attached to the nitrogen in the piperidine ring.

The exact receptor profile of Benzomorphans is variable. As a whole family they are mixed agonists/antagonists of the various CNS opioid receptors, which yields a variety of effects4. Agonism of the μ-opioid receptor yields most of the familiar opioid effects like analgesia and sedation. Most familiar opioids primarily act on this receptor. Agonism of the other two receptors is much less common. Agonism of the δ-opioid receptor also yields therapeutic pain relief but is very rare as a primary method of action. Agonism of the κ-opioid meanwhile, triggers interesting effects like dysphoria and hallucinations in addition to some standard opioid effects. A very familiar and notorious κ-opioid agonist is Salvinorin A, the active constituent in Salvia divinorum. Also noteworthy is the fact that activation of the κ-opioid receptor seems to suppress activity of the μ-opioid receptor5. This turns the degree to which different drugs act as agonists for the different receptors into a complex balancing act, juggling effects between the receptors selectively. Subtle changes to these molecules can yield shifts in this delicate opioid receptor balance6. However, most hallucinogenic Benzomorphans are primarily regarded as κ-opioid agonists, and thus to some degree μ-opioid antagonists (though this varies, Phenazocine for example, is a μ-opioid agonist). 

Some benzomorphans are observed to be NMDA antagonists, though it is unknown if all of the hallucinogenic benzomorphans have this effect, it is highly likely that they do1 2 3. Cyclazocine is at the very least confirmed to be an NMDA antagonist7. Many of them are also very likely σ receptor agonists, a property shared with a wide variety of stimulants and dissociatives including PCP, Ketamine, DXM, Cocaine, and Methamphetamine8. It is still unknown what exactly σ agonism specifically entails or what the effects are, as most agonists also act on a variety of other receptors. It nonetheless probably plays some role in the effects of these various drugs, perhaps as a psychotomimetic?

The picture this paints of Benzomorphans is that of a hallucinogenic opioid with notable analgesic effects in addition to hallucinatory κ-opioid effects, similar to Salvia. On top of this is probable NMDA antagonism, which would give an extra degree of dissociative hallucinatory effects on top of that. This would be an extremely unique hallucinatory experience, quite unlike that of any known hallucinogens- a great deal of physical dissociation and anesthesia with intense and vivid open and closed eyed visuals.

It should be noted that hallucinations have been attributed to a wide variety of opioids9-however most other opioids have seen significantly more widespread use than pentazocine, thus a much larger body of data. Hallucinations from other opioids are still considered relatively rare, despite the much larger data set. What stands out about Benzomorphans is their unique receptor profile and the frequency in which hallucinations are reported despite a comparatively minuscule data set. 

That sounds like a messy cocktail of effects nonetheless- are Benzomorphans safe? Especially considering the notorious lethal respiratory depression effects seen in opioids? Studies on the safety profiles of Benzomorphans are mostly focused on Pentazocine, as it is the most commonly prescribed one. Pentazocine acts primarily as an agonist of the κ- and δ-opioid receptors and is a weak antagonist of the μ-opioid receptor10. Respiratory depression has indeed been observed in Pentazocine, though not to the same degree of frequency and severity as with typical opioids. However, a 20 mg mg dose in a clinical study was equivalent in (still safe and tolerable) respiratory depressive effects of a 10 mg dose of morphine in a 70 kg individual11. It is worth noting that morphine is generally considered one of the "safer" opioids in terms of overdose danger, with a higher dose required to incur dangerous effects. Pentazocine also did not have a cumulative effect on respiratory depression with repeated doses11. There do exist case reports of severe respiratory depression from Pentazocine, though they cite the old age of the patients as a major risk factor and conclude that while possible, dangerous respiratory depression is rare (though this report is very early in the drug's history)12. In fact, it is believed that Pentazocine has a "ceiling effect", whereas the respiratory depressant effects max out at a certain point and no longer increase with increasing dosage. The only reported deaths from Pentazocine were from intentional overdose as a method of suicide15, or when potentiated with an antihistamine15. Respiratory depression has also been observed in Phenazocine, which saw equivalent respiratory depressant effects to Morphine16. A set of case reports stated that the dangers of respiratory depression in Phenazocine were negligible, though this was also a very early study in the drug's history17. Phenaozcine however, unlike Pentazocine is understood to be a μ-opioid agonist, so respiratory depression similar to other opioids is expected (more on that later). Curiously, dangerous respiratory effects typically arise from μ-opioid agonists, κ-opioid agonists are not understood to cause respiratory depression, and δ-opioid agonists only do it to a minor degree18. So where is this activity arising from in the Benzomorphans, when they are mostly understood to be both κ-opioid agonists and mild μ-opioid antagonists? As μ-opioid antagonists, it is likely that Benzomorphans would suppress the effects of other typical opioids if they were administered simultaneously. Indeed Pentazocine is not known to fully suppress respiratory depression from morphine when taken concurrently19. Certain Benzomorphans have also been researched extensively for their potential for treating opioid addiction through their μ-opioid receptor antagonist activity.

What about other physical side effects that opioids are known to cause- things such as itching, hypotension (low blood pressure), bradycardia (slow heart rate), sedation, nausea, and constipation? Pentazocine was observed to actually raise blood pressure and increase heart rate, similar to a stimulant11. This may be because of possible underlying NMDA antagonist effects. It also causes constipation and nausea, but does not cause the "pinpoint pupils" typical of other opioids11. Other side effects are less understood. In general, best harm reduction practices would be to avoid combining Benzomorphans with any other depressants, particularly benzodiazepines or alcohol (which aside from respiratory depression risk inducing sleep and nausea at the same time, which risks choking on vomit while sleeping). They also should not be combined with anticholinergics as this risks potentiating the drug past predictable effects for a given dose.

What about the other big danger associated with opioids: Dependence and addiction? There are few records of addiction due to Benzomorphans, though this may just be because their use is so rare. For what its worth, with a large population pool you inevitably find people becoming dependent on any drug, even ones that seem impossible to develop reinforcing behavior like high doses of DPH. One case study cites a woman who became dependent on injecting Pentazocine after being prescribed an intravenous formulation for Migraine (which resulted in severe infections of the injection sites and eventual necrosis of the hand that required amputation)20. Another case study cited a woman with bone pain who began abusing Pentazocine injections for its "Euphoric effect"21. Thus Benzomorphans do certainly have addictive potential. This fact seems to be stated that the main formulation of Pentazocine in fact contains naloxone so that it cannot be injected for abuse. The degree of addictive potential relative to other opioids however, is not yet understood.

So if Benzomorphans are understood as drugs of abuse, what is their legal status? Well only Pentazocine and Phenazocine are explicitly scheduled as they are the only ones that were manufactured and sold. Pentazocine is a Schedule IV drug in most states in the U.S., scheduled substances with an accepted medical use and low potential for abuse (it shares this place with Prescription benzodiazepines, Tramadol, and Modafinil among others). In Illinois and South Carolina however, it is Schedule II (accepted medical use but high potential for abuse, including Cocaine and Heroin), and in Kentucky it is Schedule III (Moderate potential for abuse, including Ketamine and Anabolic Steroids). It is schedule III in international UN conventions too. Phenazocine meanwhile is broadly classified as a schedule II drug. So unfortunately, the two best known and most tested hallucinogenic Benzomorphans are pretty illegal, with very low demand and near 0 street presence. It is unlikely they will ever be encountered by most people (though Pentazocine is still widely prescribed outside the U.S., with abuse reported particularly in Nigeria). 

Anyways, 21 citations in, lets finally look at the hallucinogenic effects of these unique drugs in detail.

Pentazocine

l-Pentazocine

Yes, yes I've already said so much about Pentazocine. If you skipped the intro, here it is, quick and dirty:

Pentazocine is the most widely prescribed and used benzomorphan, prescribed for pain in situations where other opioids are indicated against. It was invented in the 1950's and saw usage in the U.S. throughout the 1970's until it eventually fell into obscurity. It is now mostly prescribed only outside of western nations. Pentazocine is a mixed opioid receptor agonist/antagonist- it is an agonist of the κ- and δ-opioid receptors and is a weak antagonist of the μ-opioid receptor9. It is also likely an NMDA antagonist. Where its prescribed more commonly, most notably in Nigeria, it is known as a drug of abuse, documented in a number of case studies that demonstrate symptoms typical of opioid dependence20 21. Pentazocine is normally administered either in 30 mg injections or as a 50 mg oral tablet (This is a formulation of Pentazocine/Naloxone called Talwin- the inclusion of Naloxone is to discourage abuse by intravenous administration, Naloxone is not active orally)

An example of an oral Pentazocine/Naloxone tablet (50 mg/0.5 mg) under the brand name Talwin

Injectable Pentazocine formulation from Pakistan (from https://blogger.googleusercontent.com/img/b/R29vZ2xl/AVvXsEhIzRGl8izquBEeUNFGSBVWhCSGy0tto11gHgPV1of3gnu2xUCJ-rYgP3Q64-JmCccl6y0LzmNRmK9CvYkn3pCA02vRW4nn3Bzyemus6plORfc0SKdeEn-dGUGIbU1KJ12o8FaKzLTb2So/s1600/picture-733274.jpg)

Structurewise, Pentazocine is the basic Benzomorphan structure with a 3-methyl-2-butene attached to the open functional site on the nitrogen in the piperidine ring. It is sold as a racemic mixture, however the enantiomer to which most of its opioid activity is attributed is the (-) isomer, aka l-pentazocine11. 

Pentazocine is perhaps the best documented Benzomorphan for hallucinations, given its relatively widespread use. The most detailed study is a series of case reports from 1969 that give an interesting insight into this experience. It looks at a body of 7 people who experienced hallucinations out of a group of 20 people reporting adverse effects from Pentazocine. Some of the more interesting reports are as follows:

"A 74-year-old man (race not specified) was given 30 mg of pentazocine intramuscularly for pain. The patient began hallucinating and dreaming that he was being restrained."22

"A 69-year-old white man was given 60 mg of pentazocine for severe sciatica. Ten minutes later, he became groggy and complained of a "crazy feeling in the head" which was followed by severe nausea. Shortly thereafter a jerking of the muscles of his whole body developed and he said he felt that the walls of the room were beginning to move and that they were covered with multicolored designs, which he eventually recognized as a tropical forest with ferns and large white birds and peacocks which faded out and were replaced by several lions. The lions gradually faded out and were followed by geometric patterns in various colors that changed from squares to stripes and finally disappeared"22

"A 49-year-old white woman, who was given propoxyphene hydrochloride (Darvon) and aspirin but had no relief of the pain caused by infected teeth, was then given 30 mg of pentazocine intramuscularly. Vertigo and dizziness developed within 10 minutes, drowsiness in 20 minutes, and severe vomiting 40 minutes later. About 90 minutes after injection, the patient became hallucinatory and described the feeling that her ghost left her body, walked around her prone figure, and stayed with her three to four hours. She felt as if she was trying to climb the side of a huge rubber balloon, but repeatedly fell to the floor. She recalled seeing strange animals and faces but was not frightened because of the feeling of general euphoria. The next morning the patient had an apparent lack of coordination; she was unable to think clearly and was quite exhausted."22

"A white woman, age not given, received 30 mg of pentazocine intramuscularly for severe headache and experienced a floating, swirling sensation, drowsiness, and increased acuteness of hearing when her eyes were closed."22

It should be noted that there was little vocabulary to describe hallucinatory experiences beyond psychedelics in the 1960s. In previous analyses of descriptions of known dissociative hallucinogens from that era, I have taken references to "dreams" and "nightmares" as sometimes actually describing closed eyed hallucinatory experiences rather than actual sleeping dreams. They simply were not aware of  the nature dissociative hallucinations at the time. Another case study from 1969 yields the following experience:

"An intramuscular injection of 30 mg of pentazocine was then given to relieve pain. Within five minutes of injection she started shaking and sweating and while waiting for a taxicab began to feel depersonalized and "freaky". En route home, she thought that the cab driver looked like a frog. For the next three hours she had visual, soundless, slow-motion hallucinations whether her eyes were open or closed. To be more accurate these were pseudohallucinations since she was aware that they were not grounded in reality. She went to bed feeling numb all over and unable to move. Five hours after the injection the hallucinations had ceased"23

This case study mentions that there was a persistent period of emotional depression for 24 hours after the hallucinations had stopped, along with uncomfortable physical effects and anxiety. It mentions other case studies where psychotic effects were observed in response to Pentazocine, such as panic, confusion, and paranoia, but not necessarily with hallucinations.

One other patient who had taken an oral dose of 75 mg described his hallucinations as:

"nice dreams, lots of sandwiches, bottles of wine, beautiful red lips"24

A seminal summary of case reports (which I believe to probably be the best paper to read on Pentazocine hallucinations) is provided by Coursey 201625. This summary offers a description of vivid auditory hallucinations too, "Visual hallucinations often consisted of various colored objects or patterns. Auditory hallucinations consisted of either voices or loud ticking of watches or clocks."25
This report also offers insight into other effects: "Closely related to tactile hallucinations are "strange feelings" reported by pentazocine-treated patients. The most frequently reported "strange feeling" was a floating or swirling sensation" "Delusional thinking was also reported with some frequency and almost invariably involved a sensation of impending death or doom. Distorted body images and feelings of depersonalization have also been noted."25

So what does this say about the nature of Pentazocine hallucinations? A lot of the effects described appear to be consistent with what is felt with dissociatives- Vertigo, dizziness, "feeling that her ghost left her body, walked around her prone figure", "She felt as if she was trying to climb the side of a huge rubber balloon, but repeatedly fell to the floor.", "apparent lack of coordination", "floating, swirling sensation", " feeling numb all over", and "distorted body images". What is most remarkable however, is the prevalence of extremely vivid open eyed hallucinations, particularly the vivid images of animals and natural scenes. One patient also cited clearly seeing intricate color geometry on the walls. This points to similarities with the best known κ-opioid hallucinogen, Salvinorin A, which can induce vivid open eyed visuals (in addition to its extreme other effects). Whether the incredibly powerful effects of Salvinorin A and hallucinations of a similar nature would present with higher doses of Pentazocine is still unknown, but it is possible that higher doses would also produce stronger dissociative or dissociative-resembling effects. 

It is noteworthy that all of these case reports are for standard prescribed doses of Pentazocine, which suggests that these patients are in some way sensitive or have some underlying risk factor. It is not fully known whether increasing dosage would increase the frequency of hallucinogenic effects, but it may be possible. One study cited hallucinations in 0.6% of patients who were prescribed Pentazocine25. Another later study observes an incidence between 1-2% of patients receiving medical doses25.  It noted they were most common in patients receiving oral doses of 50 mg 3-4 times a day, so this certainly suggests that higher doses increases the likelihood of hallucinations26. The only problem with pushing doses higher is that these are opioids, and that risks dangerous respiratory depression. As mentioned before, concerning respiratory depression was only noted in elderly patients with Pentazocine. While there have been overdose deaths attributed to Pentazocine, they were administered intentionally. The LD50 is given at 1000 mg/kg in rats and 205 mg/kg in mice when given orally27. In general it is understood to have a much lower risk of severe respiratory depression than typical μ-opioid agonist opioids (Morphine, Heroin, Oxycodone, Codeine etc), though the risk isn't nonexistent. Nevertheless, the study that collected case studies into one handy chart cites an oral dose of 50-240 mg as resulting in hallucinations25. One other troubling fact is that the duration is highly variable- some patients reported an onset immediately after administration, while others felt it hours later. Some only experienced hallucinations for an hour or so, while others experienced them for days or even weeks25. The majority of experiences however saw a duration of 1-5 hours25. While some found the experience euphoric, more people reported a sense of dysphoria, and a number reported a lasting sense of depression even after the hallucinatory effects had worn off, sometimes for several days25. Tread carefully.

It bears reminding that Pentazocine is a schedule IV drug in much of the U.S., making possession without a prescription illegal. It is placed in a higher schedule, schedule II, in North Carolina and Illinois, and schedule III in Kentucky. It is also internationally scheduled as a schedule III drug according to UN conventions. It's illegality in addition to its obscurity and scant history of abuse means it is highly unlikely this drug will ever be encountered by most people.

Phenazocine

l-Phenazocine

Phenazocine is the other benzomorphan that has been seen on the pharmaceutical market, under the trade names Prinadol and Narphen. It is also used to treat pain. It is for the most part not seen much in western countries, and even in "less developed" countries, Pentazocine is much more commonly prescribed in its stead. Phenazocine was one of the first Benzomorphans developed, being invented in the early 1950's. Most prescription use of Phenazocine overall was before 2000, with prescription in the U.S. mostly only in the 1960's, and it seems unlikely that it is even prescribed anywhere anymore, except perhaps in exceptional cases where Pentazocine can't be used.

An interesting advertisement for Phenazocine from a 1960 issue of the British Journal of Anaesthesia

Phenazocine has a phenethyl group as the N substitution. It is notable for being significantly more potent than Pentazocine, being sold medically in the form of 5 mg oral tablets. It is believed that the phenethyl group is responsible for this steep increase in potency28. It is also administered as a racemic mixture, though the main enantiomer to which its opioid activity is attributed to is l-Phenazocine29.

There exists no information online detailing the hallucinogenic properties of Phenazocine. Rather, there is a single line on Wikipedia that states high doses may induce hallucinations. This line is parroted word for word across a variety of drug database websites that clog up any attempts to search for information about this. This claim cites a paper by Harris LS and Pearson AK from 1964, titled "Some Narcotic Antagonists in the Benzomorphan Series"30. However, reading this paper, there is no mention of hallucinations at all, for any of the drugs listed. In fact the paper is just a series of animal studies to determine analgesic effects.

So that is a dead end. The next step is to compare the receptor affinities of Phenazocine to that of known hallucinogen l-Pentazocine, to see how similar they are. l-Pentazocine has the following receptor affinity profile:

Receptor	Ki (nM)
μ-opioid (antagonist)	3.9 ± 0.731
δ-opioid	49.3 ± 15.131
κ-opioid	2.2 ± 0.231
σ	56.6 ± 7.432

While l-Phenazocine has the following profile:

Receptor	Ki (nM)
μ-opioid (agonist)	0.2 ± 0.0429
δ-opioid	5.0 ± 0.8829
κ-opioid	2 ± 0.1329
σ	61.7 ± 10.0929

So what does this tell us? Well the most noteworthy difference in affinities here is with the μ-opioid receptor- Phenazocine is a μ-opioid agonist, while Pentazocine is a μ-opioid antagonist. Not only is Phenazocine a μ-opioid agonist, it is an very potent one, several times more potent than morphine. This suggests that Phenazocine would present normal opioid effects, to a high degree (hence the very low doses of its pharmaceutical formulations). Phenazocine has a significantly higher affinity for the δ-opioid receptor too, which would also contribute to opioid analgesic effects. Most important though, Phenazocine and Pentazocine have almost the same affinity for the κ-opioid receptor. This is particularly interesting when you look at the κ-opioid affinity of typical opioids, which is lower by several magnitudes. It is postulated that the hallucinogenic properties of Pentazocine arise from its high affinity for the κ-opioid receptor, something it shares with Pentazocine (They may also arise from NMDA antagonist activity but affinity for that receptor is as of now unknown for both drugs). So this tells us that it is highly likely that Phenazocine has similar hallucinogenic properties to Pentazocine. However, higher hallucinogenic doses of Phenazocine may be prohibitively dangerous courtesy of its higher affinity for the μ-opioid receptor. Simply put, you may not be able to reach a dose of Phenazocine that would induce hallucinations because it may very well kill you through respiratory depression. Perhaps this could be alleviated in a way that still allows for the hallucinogenic effects to present if a highly selective and competitive μ-opioid antagonist was administered at the same time, but this is just conjecture. This is not a risk any psychonaut should be willing to take until more information has been determined in a safe, stringent clinical setting. Meanwhile, they have a similar affinity for the σ receptor. I'm not sure what this means in terms of psychological effects, I don't know if anyone does, but it may be significant.

Of course, receptor affinities can only tell us so much, they don't account for pharmacokinetic effects and how that may affect things, but the remarkably low clinical dosages of Phenazocine indicate that these conjectures have some validity to them. But once again, the effects in humans aren't fully known until they are tested in humans, and despite the pharmaceutical use of Phenazocine, a lot of that data simply doesn't exist because its usage was so sparse and rare. 

Given the illegality of Phenazocine, (It is a schedule III drug), it is unlikely any kind of development along those lines will ever occur. I would recommend staying away from this one for now, but it's certainly interesting to think about!

Cyclazocine

l-Cyclazocine

Cyclazocine never made it to the market. It was initially tested for its potential as a treatment for mental illnesses such as bipolar disorder and depression. It was later tested as an anesthetic, but was ultimately abandoned in the 1970's for the prevalence of hallucinogenic and psychotomimetic effects. 

Structurally, Cyclazocine has a cyclopropyl as the N-substitution. Like other Benzomorphans studied,  l-Cyclazocine carries the opioid receptor effects while, notably, d-Cyclazocine apparently has PCP mimicking properties in animals33. This suggests possible NMDA activity in d-Cyclazocine, which raises the question if that's also the case for the d-enantiomer of other Benzomorphans. Nonetheless, similar to the other Benzomorphans, it would probably be most useful to study a racemic mixture for Cyclazocine. Indeed human trials were performed with a racemate.

It is well documented that Cyclazocine has hallucinogenic psychotomimetic effects with enough frequency that vague statements on the matter have made their way into most writing on the drug. It is mentioned in passing in two summaries on the potential for Cyclazocine to be used in treating opioid addiction, similar to how Buprenorphine would be used. One mentions "Two patients reported visual hallucinations, although one had been hallucinating before cyclazocine treatment"34, while another states

"Some persons have disturbing side effects from cyclazocine, manifesting dysphoria and vivid imagery approaching hallucinatory proportions. However, tolerance does develop for the subjective effects which can be largely eliminated by small increments in dosage, but no tolerance develops to the antagonism to opiates"35

This comment is interesting in that it states that even effects like hallucinations are mitigated with a tolerance developed from repeated dosing. The characteristics of Cyclazocine hallucinations are often defined along parameters of being "psychotomimetic". One study that recognizes them as such stated that "Some psychotomimetic phenomena such as depersonalization, peculiar, and weird experiences were as frequent for [Cyclazocine]... as for LSD."36 The fact that the tested doses induced hallucinatory effects with the same consistency of LSD is a very interesting, though possibly exaggerated statement. Nonetheless, the experience is also largely described as being dysphoric, though a few patients found it euphoric36. It notes that Cyclazocine is more incapacitating than LSD, Barbiturates, Alcohol, or Typical Opioids- attributed to its broad similarities between all of these groups of drugs, combined into one. This author however, draws parallels to scopolamine, stating "The total pattern of subjective effects was most similar to that found for scopolamine. Dry mouth, metallic taste, difficulty in swallowing, increased appetite for ice cream, impairment of memory for recent events, and restlessness occurred more frequently in scopolamine,"36 The similarities to anticholinergics listed in this example are indeed remarkable, though some of these qualia can be attributed to other hallucinatory methods of action. Another study remarked on the similarities of LSD and Cyclazocine by means of the behavioral response in rats, though it's worth mentioning that in pharmacological contexts, LSD is often regarded as a pscyhotomimetic37. This continues to hammer home the point that Cyclazocine is consistently hallucinogenic.

As far as doses are concerned, Cyclazocine is extremely potent. At an oral dose of 4 mg it is an effective μ-opioid antagonist for 24 hours, while an analgesic dose is cited at just .5 mg38. This study also states that side effects were mitigated by building tolerance, which could be driven up to 13 mg daily38. It states that hallucinatory and psychological side effects most often presented with sudden steep increases of dose- indeed one patient noted that a single 1 mg dose made them feel "unreal"38.

Safety? Cyclazocine is understood to be a clear μ-opioid antagonist38, so it definitely wouldn't have the same respiratory depressive effects as Phenazocine, but rather would probably have a similar safety profile to Pentazocine, though adjusted for its extreme potency. The potency presents the biggest hazard in using this drug, and if ever used in a recreational context, it should only be administered volumetrically or in tabs or tablets precipitated from solution. 

Alazocine

(l)-Alazocine

Alazocine, also known as N-Allylnormetazocine, is an experimental Benzomorphan with an allyl group attached to the Nitrogen. It has also mainly been studied as a racemic mixture. Alazocine has mostly been tested in animals, where it is regarded as a psychotomimetic with behavioral effects consistent with other hallucinogenic Benzomorphans. In humans it is also broadly regarded as a psychotomimetic.

In animals, Alazocine produced marked psychotomimetic effects. One study noted that d-Alazocine, along with a racemate, produced behavioral responses similar to PCP in rats and squirrel monkeys, as also seen with the d-enantiomer of Cyclazocine39. This continues to point towards my hypothesis that the d-enantiomer of Benzomorphans has NMDA antagonist activity. Another study in mice (which also conjectures NMDA antagonism as a possible mechanism for what it calls Alazocine's clear hallucinogenic and psychotomimetic effects) found that Alazocine disrupts the prepulse inhibition of startle in mice, a behavioral effect seen in dissociatives40. Another study in rats found similar behavioral effects to Cyclazocine, including circling, spontaneous rearing, and bizarre side-to-side head movements41.

There is only one record of human tests of Alazocine- These tests describe Alazocine as intensely psychomimetic, to the degree that studies had to be discontinued due to the "severity" of the effects, which were likely hallucinatory. The given dose for these severe effects was 15 mg orally, for a 70 kg human42.

All of this points to Alazocine as perhaps having the highest frequency of hallucinogenic effects out of all the Benzomorphans, as most mentions of it regard it as a psychotomimetic. It is more potent than Pentazocine, with a dose probably in the range of 10-20 mg. Alazocine is also regarded as an opioid antagonist, so it likely wouldn't carry as much risk of respiratory depression.

Sources and Further Reading:
1- Grauert M, Bechdel WD, Ensinger HA, Merz H, Carter AJ (1997) Synthesis and Structure−Activity Relationships of 6,7-Benzomorphan Derivatives as Antagonists of the NMDA Receptor−Channel Complex. Journal of medicinal chemistry 40:2922-30. 
2- Pasquinucci L, Parenti C, Amata E, Georgoussi Z, Pallaki P, Camarda V, Calò G, Arena E, Montenegro L, Turnaturi R (2018) Synthesis and Structure-Activity Relationships of (-)-cis-N-Normetazocine-Based LP1 Derivatives. Pharmaceuticals (Basel) 11(2):40
3- Grauert M, Rho JM, Subramaniam S, Rogawski MA (1998) N-methyl-D-aspartate receptor channel block by the enantiomeric 6,7-benzomorphans BIII 277 CL and BIII 281 CL. J Pharmacol Exp Ther. 285(2):767-776.
4- Turnaturi R, Marrazzo A, Parenti C, Pasquinucci L (2018) Benzomorphan scaffold for opioid analgesics and pharmacological tools development: A comprehensive review. Eur J Med Chem. 148:410-422.
5- Pan ZZ, (1998) μ-Opposing actions of the κ-opioid receptor. Trends in Pharmacological Sciences 19(3):94-98
6- Bidlack JM, Cohen DJ, McLaughlin JP, Lou R, Ye Y, Wentland MP (2002) 8-Carboxamidocyclazocine: a long-acting, novel benzomorphan. J Pharmacol Exp Ther. 302(1):374-380.
7- Sawyer DC, McLarnon JG, Church J (1995) The effects of (-)- and (+)-β-cyclazocine on NMDA-evoked responses and NMDA-mediated cell damage in cultured rat hippocampal neurons. Brain Research 698(1-2):30-38
8- Zhao J, Ha Y, Liou GI, Gonsalvez GB, Smith SB, Bollinger KE (2014) Sigma receptor ligand, (+)-pentazocine, suppresses inflammatory responses of retinal microglia. Invest Ophthalmol Vis Sci. 55(6):3375-3384
9- Sivanesan E, Gitlin MC, Candiotti KA (2016) Opioid-induced Hallucinations: A Review of the Literature, Pathophysiology, Diagnosis, and Treatment. Anesth Analg. 123(4):836-43
10- https://www.guidetopharmacology.org/GRAC/LigandDisplayForward?ligandId=1606
11- Brogden RN, Speight TM, Avery GS (2012) Pentazocine: A Review of its Pharmacological Properties, Therapeutic Efficacy and Dependence Liability. Drugs 5:6–91
12- Rigas SC (1970) Severe respiratory depression after pentazocine administration: two case reports. Br J Anaesth. 42(6):547
13- Engineer S, Jennett S (1972) Respiratory depression following single and repeated doses of pentazocine and pethidine. Br J Anaesth. 44(8):795-802
14- Poklis A, Mackell MA (1982) Toxicological findings in deaths due to ingestion of pentazocine: a report of two cases. Forensic Sci Int. 20(1):89-95
15- Monforte JR, Gault R, Smialek J, Goodin T (1983) Toxicological and pathological findings in fatalities involving pentazocine and tripelennamine. J Forensic Sci. 28(1):90-101.
16- Papadopoulos CN, Keats AS (1961) VI. Comparative respiratory depressant activity of phenazocine and morphine. Clinical Pharmacology and Therapeutics 2(1):8-12
17- Thomas KB (1961) Phenazocine and Respiratory Depression. Br Med J. 1(5235):1318–9
18- Shook JE, Watkins WD, Camporesi EM (1990) Differential roles of opioid receptors in respiration, respiratory disease, and opiate-induced respiratory depression. Am Rev Respir Dis.142(4):895-909
19- Koyyalagunta D (2007) Chapter 113 - Opioid Analgesics. Pain Management 2:939-964
20- Mudrick C, Isaacs J, Frankenhoff J (2011) Case Report: Injectable pentazocine abuse leading to necrotizing soft tissue infection and florid osteomyelitis. Hand (N Y) 6(4):457-9
21- Makanjuola AB, Olatunji PO (2010). Pentazocine abuse in sickle cell anaemia patients: A report of two case vignettes. African Journal of Drug and Alcohol Studies 8(2) 
22- DeNosaquo N (1969) The hallucinatory effect of pentazocine (Talwin). JAMA 210(3):502
23- Edison GR (1969) Hallucinations associated with pentazocine. N Engl J Med. 281(8):447-448.
24- Economou G, Monson R, Ward-McQuaid JN (1971) Oral pentazocine and Phenazocine: A comparison in postoperative pain. British Journal of Anaesthesia 43(5):486-495
25- Coursey CE (1978). The Psychotomimetic Side Effects of Pentazocine. Drug Intelligence & Clinical Pharmacy 12(6), 341–346.
26- Terris B, Jick S, Beeman D, Jick H (1994). Frequency of adverse events among users of Talwin Nx. Pharmacoepidemiology and Drug Safety 3:351-354.  
27- Lewis RJ. Sax's Dangerous Properties of Industrial Materials. 9th ed. Volumes 1-3. New York, NY: Van Nostrand Reinhold, 1996., p. 1275
28- Feinberg AP, Creese I, Snyder SH (1976) The opiate receptor: a model explaining structure-activity relationships of opiate agonists and antagonists. Proc Natl Acad Sci U S A. 73(11):4215-9.
29- Cagnotto A, Bastone A, Mennini T (1994) [3H](+)-pentazocine binding to rat brain sigma 1 receptors. Eur J Pharmacol. 266(2):131-138.
30- Harris LS, Pierson AK (1964) Some Narcotic Antagonists in the Benzomorphan Series. J Pharmacol Exp Ther.143:141-148.
31- Toll L, Berzetei-Gurske I, Polgar W, Brandt S, Adapa D, Rodriguez L, Schwartz R, Haggart D, O'Brien A, White A, Kennedy J, Craymer K, Farrington L, Auh J (1998) Standard binding and functional assays related to medications development division testing for potential cocaine and opiate narcotic treatment medications. NIDA research monograph. 178:440-66. 
32- Prezzavento O, Arena E, Sánchez-Fernández C, Turnaturi R, Parenti C, Marrazzo A, Catalano R, Amata E, Pasquinucci L, Cobos EJ (2017) (+)-and (-)-Phenazocine enantiomers: Evaluation of their dual opioid agonist/σ1 antagonist properties and antinociceptive effects. Eur J Med Chem.125 603-610. 
33- Brady KT, Balster RL (1982) Discriminative stimulus properties of stereoisomers of cyclazocine in phencyclidine-trained squirrel monkeys. Life Sci. 31(6):541-549
34- Freedman AM, Fink M, Sharoff R, Zaks A. (1967) Cyclazocine and Methadone in Narcotic Addiction. JAMA 202(3):191–194
35- Freedman AM, Fink M (1968) Basic concepts and use of cyclazocine in the treatment of narcotic addiction. Br J Addict Alcohol Other Drugs. 63(1):59-69
36- Haertzen CA (1970) Subjective effects of narcotic antagonists cyclazocine and nalorphine on the Addiction Research Center Inventory (ARCI). Psychopharmacologia 18(4):366-377
37- Wray SR (1972) A correlative evaluation of cyclazocine, LSD and naloxone on continuous discriminated avoidance in rats. Psychopharmacologia 26(1):29-43
38- Archer S, Glick SD, Bidlack JM (1996) Cyclazocine revisited. Neurochem Res. 21(11):1369-1373
39- Brady KT, Balster RL, May EL (1982) Stereoisomers of N-allylnormetazocine: phencyclidine-like behavioral effects in squirrel monkeys and rats. Science 215(4529):178-180.
40- Halberstadt AL, Hyun J, Ruderman MA, Powell SB (2016) Effects of the psychotomimetic benzomorphan N-allylnormetazocine (SKF 10,047) on prepulse inhibition of startle in mice. Pharmacol Biochem Behav. 148:69-75
41- Iwamoto ET (1980 ) Pharmacological Effects of N-Allylnormetazocine (SKF-10047). Problems of Drug Dependence 34:82-87
42- Keats AS, Telford J (1964) Narcotic Antagonists as Analgesics. Advances in Chemistry 45(14):170-176

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