antlion

Tuesday, October 27, 2020

Why why why why why? The Realignment: A Statement on Substance Use

Why, why why why? Why am I doing this? What is to be gained at this point? This is a plea I often make to myself when faced with particularly challenging experiences, the uncomfortable or terrifying or downright painful. It is a prayer I cast into my brain when I am bled upon my bed, muscles clenched, limbs and extremities crooked, fingers clutching at nothing praying for release. The experience recedes, sometimes with a chemical counter-balance, and I find myself raw and burnt-out in its wake, and I ask myself why I did this, why have I subjected myself to this? Drugs are not always fun. For me, they are in fact explicitly not fun in most cases, replete with an arsenal of side effects and negative physical or psychosocial stipulations.

 

So why am I doing any of this?

            I wrote a post a while ago, at the ripe young age of 20, to attempt to justify my drug use, in preemptive response to the “haters” (Those who love me and see my drug use as a form of suffering, as something to be suppressed and annihilated and stricken from my existence entirely, or those who have a cautious concern for my lifestyle). Things have changed a good bit since then- no longer does there feel a need to truly justify this existence to other people, I can just simply do it independently. I am resolute in my intentions and my sense of self. This is more a declaration than a justification. I should not need to convince anyone of anything, this is my personal reasons for my personal mission.

To alter one’s mind is a right that should not be restricted. The alteration of the human mind is normal, common, and exists on a spectrum. Altered states that affect our performance in our roles amongst others arise in so many ways, and when we must confront them without our consent they are often considered pathologies. The surprising frequency of hallucinations in the general populace, the horrendous toll of sleep deprivation and the illogical puzzlebox of suicidal ideation are all divergences from normalcy that fill us with alarm, but are a fact of our existence. Alterations of our consciousness can strike at any time, why should we not be allowed to control them, contain them, utilize them, send them forth? Further, without our consent, we can find ourselves in positive states too: stricken with spiritual ecstasy, a lovedrunkenness that clouds judgement, a state of fundamental bliss triggered by experiencing immaculate beauty or the transcendence of meditation. And we accept this. Alteration can come in so many forms in so many ways. Spiritual practices particularly have for millennia sought transcendence of the confines of our mind. Chemically induced alterations certainly stand far and above as the most acute and extreme end of the spectrum, but they should be seen holistically within the entirety of what a person can do to their mind.

The prevailing perceptions of substance use do not correspond to any objective reality, but are tangled through millennia of shifting cultural mores, like layers of sediment fractured by the creeping of the earth. For our world to have a healthy relationship with mind-altering substances, for our world to approach them in a just and productive manner, for our world to address these troublesome chemicals with an objective eye, requires a fundamental restructuring of everything. Conditioning is an unstoppable force and the currents of human culture through time, filtered through our blessed yet ignorant ancestors, make what should be a simple relationship into something quite complex. Everyone has heard the rant about how the most normalized drug in our society is one of the most intensely and uniquely incapacitating. A drug that can kill from overdose, that drives a physical dependence with potentially lethal withdrawal, one that stokes fires of violence and comorbid mental illnesses to great social detriment. I don’t intend to make a whipping boy of our normalized alcohol but it stands as an idol to cast upon us how absurd and out of touch our perceptions of alteration are. It is absurd and utopian to ask that people simply step back and view substances for the individual alteration they provide, as that disregards the tangible material harm that so many suffer. So much of this suffering is intimately entangled in the culture of prohibition and disproportionate normalization, but that is a whole other path to tread. We cannot view drugs through a lens of being wholly beneficial, as we cannot view them through a lens of being wholly detrimental. Our world  exacerbates the vicious qualities of so many chemicals, but it would be remiss to ignore the presence of those qualities in the first place. It is best to approach drugs in a manner that is both level headed but also acutely aware of how they are currently caught in the dusty cobwebs of conditioning and prohibition. In a just world, it would be acknowledged that altering the mind is a human right that carries inherent risk, but we are of course, nowhere near there yet.

            These words bring no relief to those who struggle under the burden of dependence and the psychological and emotional trauma that drug use can inflict on users and their loved ones. We should never forget this and let it stand as a sobering boundary to what is possible.

 

            Second, there are so many ways to alter one’s mind, there are so many possibilities out there, and it would be a betrayal of the human spirit to disregard that. Our perceptions of drugs are ruled by a handful of the available possibilities that have, through natural occurrence, ease of production, and cultural significance come to dominate the discourse. These are familiar anchoring compounds for their respective classes, you have amphetamine, cocaine, methamphetamine as the stand ins for stimulants, Ketamine and PCP represent the entire dissociative class, as do the classical psychedelics like LSD, DMT, or Psychedelic mushrooms. Opioids hold morphine as the standard, though they now dwell in the long shadow cast by heroin, and more recently, fentanyl. Benzodiazepines are guided by Alprazolam, the rapper’s delight. These are but a handful of molecules, and a robust body of work has shown that these compounds are not unique- there is a lot to be said for tweaking the various qualities of the experience into a unique constellation of effects from just a few minor modifications to a molecule. With this in mind, the field before us is near infinite in terms of drug development. Basic structures lend themselves to a mind boggling array of modifications that yield unique experiences with unique properties, and a massive amount of basic research must be done to characterize these possibilities. There could be so many surprises distributed throughout- revolutionary therapeutics, groundbreaking psychiatric medications, compounds of immense introspective or perhaps spiritual value, compounds that are just fun, along with ones that may be heinously addictive, devastatingly potent with an extremely narrow safety margin, or are otherwise lackluster and without purpose. But the fact is- we don’t know until we try. When humans explored their wildernesses, to learn what plants to eat, how to track which creatures, how to find proper shelter and develop beneficial social structures, this was fraught with risk and terror and devastating consequences, as is any exploration. The realm of modulating human consciousness through a seemingly infinite library of possible compounds is an oft forgotten frontier for exploration. I believe exploring and developing the infinite variety of compounds at our disposal, precisely characterizing their effects, and applying them in a way that sees net benefit for users, is a worthwhile venture into a broader development of the broader human psyche.

With this daunting field before me, one in which I do not stand alone but still separate from the others who gaze upon it, what am I to do?

In the realm of testing new substances, there are several noble goals- Those who wile away in labs and poring through obscure papers, blazing the trail of what is possible with varieties of compounds. Those who aim to develop a utilitarian framework for which substances may personally benefit their life the best. Those who want to understand the entirety of the possible experiences at our disposal and will taste everything possible. Those who stalk the communities looking for a new way to get high but may possibly return indispensable data.

We simply do not have the culture or resources to dedicate to a systematic characterization of the vast possibilities of mind altering substances out there, and the responsibility falls on those driven by the passion of exploration or self-improvement or otherwise a world adorned with chemical chandeliers.

This is where I and many others come in, this is where I state my personal mission statement for my personal brand of exploration, why I think it may be necessary, why I think this could someday serve our species.

For my own sake, I have found it helps to have a clear mission in my substance use. I will list out my personal goals and intentions here.

1.     To use substances to serve my life, whether it be to serve me therapeutically, serve me creatively, and/or enrich my life with exciting and novel experiences or enhance existing experiences. This includes pure recreation and use that could possibly be characterized as abuse.

2.     To comprehensively explore the wide variety of substances that exist for the purpose of understanding different altered states and to determine which can be used to fulfill the above goals best.

3.     To contribute to humanity’s knowledge on substances, either by firsthand experience or research and data collation based on those firsthand experiences, and to help further develop and contribute to the communities based around such knowledge.

4.     To determine ways to circumvent drug prohibition, both for the benefit of those who suffer under the oppression of the drug war and to demonstrate the intractable incoherency of prohibition laws.

 

These are lofty goals, and any meaningful accomplishment of them is beyond the scope of one person, especially one such as myself. . Perhaps to address them in this way is vain, arrogant, hubristic. Nevertheless, they serve as a guidepost for me to orient myself as I use substance frequently and to not lose sight of what is possible in the throes of the undeniable pleasure that drugs can provide.

What are the stipulations of these goals? And what do they mean in practice? I sure love writing words let’s dive right in 😊

1.   To use substances to serve my life, whether it be to serve me therapeutically, serve me creatively, and/or enrich my life with exciting and novel experiences or enhance existing experiences. This includes pure recreation and use that could possibly be characterized as abuse.

 

            This is the primary goal, and the one that encompasses the most possible uses for substance. It could be described as a utilitarian approach- even appreciating altered states for the intrinsic value of novelty falls under the utility of exploration. It is here where we must recognize several potential utilities for psychoactive substances. The first is pure utility- this is things such as using stimulants to stay awake or focus on tasks (indispensable as I am very prone to dozing off at inappropriate times), using depressants to help fall asleep, using nootropics to enhance general cognitive function/wellbeing (I haven’t quite taken the plunge on this yet), using dissociatives and psychedelics as therapeutics, using cannabis as an appetite stimulant, using opioids to manage pain, all are possibilities for sensible non-abusive ways for drugs to be used in my day to day life. Abuse however, is a fine and indistinct line that I will address further in a bit.

            There is one angle of this that is particularly worth mentioning, and that is the therapeutic and creative potential of hallucinogens. Both dissociatives and psychedelics have increasingly shown massive promise in helping to alleviate mental illness in specific situations. There is still a lot of work to be done but the rate of new studies on the use of hallucinogens in therapeutic contexts is increasing exponentially and shows no sign of slowing down, an exciting revolution in the face of decades of prohibition that held the science back. The NMDAr antagonist ketamine is indicated as a neurological treatment for depression, while substances like psychedelics and MDMA are indicated as aids to talk therapy. There is plenty of anecdotal evidence for people seeing major shifts in their lives and mental health as a result of particularly intense experiences across a range of substances. Anecdotally, I have found dissociatives, particularly 3-MeO-PCE and 3-MeO-PCP to be of immense value for introspection, formation of identity, reflection on mistakes or difficult choices, creativity, and overall cognitive enhancement and improvement of long term memory, introspection, and the ability to synthesize and assemble information. Psychedelics, particularly LSD and a variety of 4-substituted tryptamines have proven extremely useful in guiding a broader trajectory of life and long-term self development, overall outlook, and interpretation of reality. It would be a lie to say I would be the same person without ever trying substances. I would like to think it has improved who I am as a person, in how I process information and interact with others and deal with my own poor mental health. Even the challenging experiences have proven extremely valuable for development.

The creative potential of hallucinogens is also immense- I make it apparent in much of my visual art that a great deal of inspiration is drawn from my hallucinogenic experiences. I do not need to delve into the psychology behind this and waste your time with that, but it boils down to the exhilaration of stepping beyond the boundaries of what’s immediately before me. Simple enough I guess.

            What of novelty and recreation? For me, this is a complex interplay- there is a great deal of recreational value in the fulfillment that comes from novel experiences, the excitement of feeling something new, even if the experience itself isn’t necessarily pleasant. And there is also a great deal of recreational value in revisiting the same mainstays again and again, hammering them into different situations for the excitement of it. In my mind recreation is defined simply and broadly as an experience that feels like a worthwhile use of my time, that brings me either short term enjoyment, long term fulfillment, or both. Recreation is present in both the cognitive reflection of a drug experience and in the euphoric, stimulating, disinhibiting, sensory, and otherwise interesting or pleasant effects of a drug itself. It has often proven difficult to demonstrate to those not familiar with this hobby that I find value in the former and not just the latter, as the draw of drugs is often only attributed to the latter. And that may in fact be the case for many people, and there is nothing wrong with that! I think it is worth mentioning though that these experiences are not always fun- and this may sound like the talk of dependence, to be driven to consume substance despite a lack of any clear reward. But the unpleasantries arise mostly from novel substances that I choose not to revisit due to the discomforts. There are certainly many substances, especially psychedelics, where I choose to weather the negative effects because the returns seem worthwhile. I would characterize the majority of my psychedelic experiences as quite uncomfortable in fact, I seem to have become increasingly sensitive to intense bodyload as time has passed. However, they are completely and utterly fascinating, and that has me returning again and again, experimenting with combinations, different substances in new settings, or new substances altogether. There is so much value in novelty, it is truly its own virtue, and each new foray into the boundaries of both my familiar consciousness and familiar altered states feels like a worthwhile endeavor. This is not to discount pure recreation. The exploratory novelty phase is often a prelude to the phase of pure recreation, it is exploration to determine that which has therapeutic or recreational value. Pure recreation is a rush, it is like meeting an old friend for a smoke and some video games, it is like a date with a significant other, comfort and familiarity brought to subtly novel boundaries each time. With substances I have become reliably familiar and intimate with such as LSD or 3-MeO-PCP or 2C-B or 4-AcO-MiPT, I find myself expanding upon their effects by dosing them in as many different settings as possible- on an airplane, at the zoo, at the aquarium, at various parties and musical performances, on hikes into nature or through the city, in the house I grew up in (sorry Mom and Dad…), across the country or with a new movie or videogame. It is a wonderful angle on the virtue of novelty to enhance what is already an interesting sober experience with substance. It is not that I need drugs to have fun or enjoy these experiences, it is just that if I have the choice to enhance them with substance, I will. Comfort and familiarity serve an important baseline for me too, to fall back into habits of using the same substances in the same settings and doing similar activities, chasing the nostalgia of what was once a pleasant and nostalgic experience. As much as I love doing this (like the gorgeous interplay of 3-MeO-PCP + 2F-DCK and the game Chivalry: Medieval Warfare), it is admittedly an angle that can lead to habitual behavior and eventually abuse. It is undeniably a slippery slope.

Which leads to an extremely important aspect of drug use- drug abuse. Drug abuse is a vaguely defined term but the most agreed upon definition is using substance in a way or amount that creates recognizable harm to oneself and others. This encompasses dependence, both psychological and physical, reckless dosing or combinations, and harmful behaviors and personality traits that are exacerbated by substances. I should say, as mentioned in the last sentence, I definitely have and currently do participate in substance use patterns that could be characterized as abusive. It’s easy to tell myself I’m in control, I am being as responsible as possible, that it’s okay when specifically I do it- when I’m using benzos regularly, or mixing depressants or depressants + stims, or shooting for ‘heroic doses’ of hallucinogens, or recklessly using street drugs without proper precautions, or behaving oddly in drug induced manic states, or recklessly throwing myself into extremely involved settings at irresponsible and difficult to control doses of drugs. Adverse effects that cycle into patterns of substance abuse are by far the biggest stumbling block even for those who attempt simple exploration. It generates a frankly justified attitude of aversion and caution to drugs in much of the populace, though this can quickly spiral into dangerous ignorance. I am here to say no one is immune to it, I believe almost everyone has their poison, and many have fortunately not discovered theirs yet. I am urged to approach this dilemma with a reframing of what defines abuse, to scrap it together in some way that absolves me of responsible use. But this is a worthless and even counterproductive measure- it is good to define when substance use becomes detrimental to a prosperous life, as can happen with any substance and any person. It is good to be able to soberly recognize use slipping into abuse. It is good to draw a distinction between healthy and unhealthy use of substance, a distinction beyond “the way I do it is healthy no matter what”. To actually desire a change in patterns of use however, is another major component that must be considered. All the world’s harm reduction practices are only as useful as the will of the user to practice them dictates. So what is to be done if your use is recognizably unhealthy but you feel as though you function as necessary and are willing to face the consequences of it for the time being without reducing use? This, I do not have the answer to. Perhaps I will come back and update this when I come to a steeper crossroads on that matter and am forced to figure it out. I sure do like getting high.

 

2. To comprehensively explore the wide variety of substances that exist for the purpose of understanding different altered states and to determine which can be used to fulfill the above goals best.

 

I more or less covered the bases here in talking about the virtue of novelty- how it can be rewarding to experience something new just for the sake of experiencing something new. To expand on this in the utilitarian sense- I mentioned before how certain drugs serve to benefit and enrich my life in various ways. How am I to discover which drugs will serve me in that capacity without even trying them in the first place? As a matter of personal interest, I am enthralled with the interplay between structure and effects, the ways in which changing just a few atoms on a molecule can vastly change the nature of an experience. There is simply no way to understand this quite as well as experiencing those changes firsthand. Trying as much as possible also leads into my next point:

 

3. To contribute to humanity’s knowledge on substances, either by firsthand experience or research and data collation based on those firsthand experiences, and to help further develop and contribute to the communities based around such knowledge.

 

            I do it for the fans! Kinda. One of the biggest motivations in researching novel psychoactive substances has been writing about them and sharing that information with likeminded communities. What is the purpose of obtaining any of this knowledge if I’m not willing to share it? If I have the ability to consume all these substances without lasting adverse effects, why not give back to the community that in turn, helped educate me on many of them in the first place? This also engenders meaningful discussion and connections within and without the community! I’ve made many friends who I hold dear just through doing a lot of drugs and writing about them. I pray that the contributions I make to this community may help someone in some way in harm reductive terms, or better yet inspire someone to take things a step further and generate new knowledge in the realm of psychoactive substance. Granted, very little of what I work on is “new knowledge”. Many of the novel psychoactive substances and more “classical” substances I’ve tried are paths that have been well trodden by other researchers. I am simply adding one more data point to the vast banks of knowledge that exist already. Combinations are also another fascinating outlet to testing new substances- there are near infinite permutations in the ways one can mix and match them, and this provides a whole host of novel experiences in and of itself! So much to do so little time.

 

4. To determine ways to circumvent drug prohibition, both for the benefit of those who suffer under the oppression of the drug war and to demonstrate the intractable incoherency of prohibition laws.

 

I’ve already said my piece on how fucked up and nonsensical prohibition is in the introduction. I don’t need to repeat my rant, as much as I love writing words. On a broader scale- do novel psychoactive substances provide a viable alternative to prohibition? Honestly, not really, except for very niche and exceptional instances. The demographics of the research chemical community are quite small and tightly knit, as opposed to the larger and wider demographics of “street drug” users. In some cases, novel substances can break out of those tight online circles and become street drugs, either as adulterants for more popular drugs or by themselves. Recall the bath salts scare of the early 2010s, where cathinone research chemicals became all the rage worldwide. Oftentimes, when a drug breaks into the mainstream like that, it is quickly prohibited by law. Though to be fair, this often follows dire consequences such as strings of overdose deaths or dangerous behaviors. Thus many research chemical users do well to keep their substances of choice on a low profile, walking a careful balance of spreading the good word on exciting new substances while also avoiding too much scrutiny from various world governments. If you’re someone with a certain fix, switching from street drugs of choice to grey area legality analogues can be easier, safer, and more cost effective, though it requires certain skillsets and knowledge bases to be fun safely and effectively. This holds true particularly for benzodiazepines, in which a renaissance of available substances is occurring right now. There is a whole cornucopia to choose from! I believe this serves to benefit individuals who are trying to circumvent prohibition, but such an idea simply cannot be applied on a larger scale.

 

 

So there it is, now we both know why I do what I do. The last time I wrote a piece like this was 5 years ago, I figured it was a simple and lasting declaration, and much of that does still apply. Things have changed since then though, perceptions expanded, and I would say I have a clearer and more coherent idea on how I want to approach substances. I am no longer feeling bound to the the confines of pure hallucinogens, I no longer feel a need to stick my nose up at “hard drugs” or those who use them, and nobody should be doing that. Have I incurred negative consequences from my explorations? I seem to have developed a permanent body load through repeated and frequent use of psychedelics- while I could once upon a time handle them well it has reached a point where almost every experience is stricken with digestive distress, excess stimulation, and physical pain. This got increasingly worse over time before eventually levelling off, probably after about 2 years of weekly use. I believe this may be connected to a permanent nausea and digestive issues that developed over time and has plagued me in my adulthood, though this could also be attributed to poor diet and certain food intolerances that I haven’t taken the time to investigate. Specific incidents of vasoconstriction I believe are responsible for a tingling and pain I will sometimes get in my legs. I believe frequent use of dissociatives has had some effect on my urinary system, including urinary retention, frequent urination and er… a weak stream. I have what appears to be a permanent visual HPPD, presenting as visual snow, flashes of colors, patterning and drifting textures (especially on mottled surfaces), ripples and heat wave type visuals. It seems to fluctuate pretty randomly, and flares up when I take non-hallucinogenic drugs, particularly stimulants and benzodiazepines. Taking my prescribed doses of buproprion particularly ramped up these effects. I don’t necessarily consider this a negative as I quite enjoyed it. I also at one point developed a physical dependence to benzodiazepines. Although the withdrawal I experienced was extremely mild relative to what others have been through,

This is to say- it is naïve to think drugs are all good, or that they can supply pure benefits. It’s always a tradeoff and there is always risk. Ironically they must be approached with as much sobriety and level-headedness as possible. It is always best to do your research, make informed decisions, and know the risks when you go in. It is best to consciously accept those risks if you choose to do that. The war on drugs is bullshit. Get high, love your life for it, and by god be as responsible as you can.

 

 

 

Wednesday, October 14, 2020

3-Me-PCP

Age: 25

Weight: 130 lbs

Dosage: 16 mg intranasal

Setting: My house

 

[NOTE: This is not a typo for 3-MeO-PCP, this is a report for the semi-novel dissociative 3-Methyl-PCP, the only extant alkane substituted phenyl ring PCP analogue (for now).]

 

Per usual, skip to the conclusion if you don’t want all the fluff.

 

Preface: I attempted 2 trials prior to this to get a sense of this compound’s character, at 10 and 12 mg intranasal. I also took a small sublingual booster dose during one of the trials. Physically the powder is pretty caustic, burning a lot when dosed intranasally and leaving a raw spot on mucous membranes when dosed sublingually, similar to 3-MeO-PCP (though without the local anesthesia that 3-MeO-PCP has). Some brief notes on its general properties at those doses were that it was lucid and functional, similar to 3-MeO-PCP or unsubstituted PCP, with a notably greater loss of motor skills. I was able to socialize without issue, and the experiences were both fairly short in duration with a pleasant drawn-out afterglow featuring an elevated mood and increased articulation, especially when combined with etizolam and cannabis in one instance. Overall at those doses, the experience was characterized by a mental stimulation with mild physical sedation, euphoria, disinhibition, light open eye visuals, and a fairly shallow headspace in terms of introspection and meditation. It was delightfully social, though this diminished as I pushed the dose up more. The short duration also lent itself to an urge to redose. The following report is the highest dose I have attempted so far, though I will say that there appear to be diminishing returns as the dose is nudged higher. It is also probably worth mentioning the steep dose/response curve, with substantial observable differences with just a 6 mg discrepancy in dose (and this is trusting my scale, so there is some wiggle room there!). Be careful with this one!

 

 

T0:00- Powder snorted- it is chalky with an odor of naphtha and burning rubber. There is an instant searing pain. My eyes water, it stings like an acrid petroleum spear up my nose. Thankfully it’s a small quantity of powder but damn is it unpleasant.

 

T0:05- Rapid onset, feeling a bit faint and dizzy, fingertips numb, it’s a warm and sweaty numbness washing over me reminiscent of nitrite inhalants (poppers). A marked cognitive dissociation has already set in, creeping up on me unannounced. The passage of time suddenly strikes me as an alien and novel concept, its passage tracked through the music I’m listening to. It strikes me as odd that parts of the song will be sensed by me and then disappear forever, even though this is my default state of experiencing anything.

My head is empty yet very heavy. It is full of warm, wet syrup, smothering my attachments to this world, leaving me feeling distant.

 

T0:10- I am so dizzy all of a sudden. A powerful spinning dizziness seems to be a remarkable early symptom of ingesting this drug, moreso than any other dissociative I’ve tried. It is a sense of suddenly being very drunk or trying to walk on a violently rocking boat. The drip begins to travel down the back of my throat, acrid and gross and burning most of the way down.

I get up to get some water and my movement is extremely uncoordinated. I have a very hard time standing up straight or walking in a straight line, having to hold onto objects as I walk past. It is interesting to be so heavily incapacitated just 10 minutes into the experience. This doesn’t feel like the loss of coordination and equilibrium that comes with the full-body anesthesia of other dissociatives- rather this just feels like my limbs are not behaving how I want them to. I am still certainly aware of my body and the space it occupies.

 

T0:15- I still feel warm, relatively, but a sudden chill runs up my spine, through my bones, not like a biting wind on a frigid winter night but like a cold stone that’s been sitting in a dreary rain. I feel queasy, wavy, nauseous, blissful, and a bit itchy and warm at my joints. My breathing feels slower and shallower. I have limited experience with opioids but this is fairly reminiscent of them.

The experience intensifies by the second, and as time ticks down I feel that initial warmth drain away bit by bit. There is stimulation and mania running through my mind, I am thinking so much about nothing in particular, my thoughts don’t feel especially profound or useful, it’s just a machine running faster than it is supposed to. Physically I feel absolutely still, almost corpselike- as mentioned before, I am not rendered immobile by a full anesthesia. It is certainly not a hole, but a different sort of sedation, there is simply zero desire to move. Everything feels jilted out of place and all I can do is watch. There is a certain joviality and euphoria to it as it continues to build and build and as I continue to sink and sink, it is like riding a speeding boat and catching the cold spray and whipping wind with my face. Exhilarating. I really don’t know what to do with this body, it feels excessive, heavy and unnecessary. So warm yet so cold at the same time. I flick my lighter on and after letting it run for a bit, press the hot metal on my skin, curious about how numb my body is becoming. My reflexive response to the stimulus is certainly reduced. Go figure.

Perhaps the other most noteworthy physical feature is how soft the numbness is-my fingertips feel spongy, or like they are sheathed in undulating clouds, squishing into my body with each keystroke.

 

T0:20- Though there has been a constant acceleration, there is now a sudden and greater rush, like some great intangible weight smothering my face. The building rush of some dissociatives can sometimes feel like sticking my head in a stream of cold rushing water. This however, is like a lazy outflow from thermal spring, warm and gentle but with an undeniable force behind it. This builds and builds though, from a trickle to a flash flood, gobsmacking me upside the head. I am steady and still and unwavering in the face of its power, it feels like the only thing I can do. The rush of say, 3-MeO-PCP, has a biting edge, a sparkling energy. This has a similar degree of crackling flame behind it, but it is slower, softer, smoother.

There are pulsing waves of flashing visuals, subtle but apparent, like refreshment bands running the length of an old TV screen. There are spots and blotches in regular hexagonal tessellated patterns slowly and quietly blooming where I can hardly notice them. With my eyes closed I am greeted by nothing but a blue darkness.

There are clouds streaming out of my skull, towers and pillars, soft and gooey and ever expanding, I feel like I am fading more and more by the second. Such energy courses through my nerves, but it is cold and still , not a manic electrical storm, but a wad of ball lightning.

Ultimately I would still say this is quite similar to 3-MeO-PCP- similar in terms of overall lucidity and mental stimulation, but with a heavy streaming dissociation running through my extremities, and less of a pointed rush.

 

T0:30- I go outside to check a light sheet I have set up- this is a trap used in entomology where a bright light (in this case a UV light) is shone at a white cloth to reflect it at night, attracting large numbers of nocturnal insects.  I love insects so much. It doesn’t feel like I’ve stepped outside, just into a larger inside. Everything feels so distant, yet at the same time unreasonably flat and close. Exerting myself makes it feel hard to breathe, the sky is heavy and my limbs are heavy, the night is gentle and distant. I trip over my feet just walking a short distance outside. The world is spinning around me and I cannot really figure out how to place my feet. I feel shorter than I really am. I am a bit nauseous. It is hard to focus or examine the insects, which I can normally readily spot ID. They are blurry and indistinct unless I really close one eye and focus on them, and the subtle strobing of my entire field of vision only makes it more disorienting. Some stand out- some large moths, a giant water bug, a great wolf spider stalking the grass. I go back inside after a short while.

 

T0:35- It is still getting stronger by the second, visuals flash with deeper and deeper contrast, my body feels melty, not entirely melty but melty for something so lucid and functional. Every movement is stuck in syrup, but just a little bit. It’s hard to move, my limbs just feel heavy and I feel no desire to do anything exciting with them. When I close my eyes the visuals are faint and stationary, no specific forms or images stand out beyond broad bands of dull colors. I am developing a double vision that is making it increasingly difficult to read. I find I can read better with one eye closed.

The experience kicks up in squalls, sudden raging swirling gales, blowing in swells of dissociative fog, blurring and smudging everything they drag their nebulous forms across. I keep drifting off, my eyelids keep sinking shut, my default directive seems to be to just sit here and drool on myself. My mind is awake and active, buzzing away and trying its best to process the disjointed and subdued information it is receiving- my body wants no part of such energy however. I am lazy and sitting in a warm swirling cloud, my head is a big mass of cotton candy spinning from a blue-grey abyss, it is no longer a rush but a constant pressure, building and building by the minute, though it is resolutely comfortable and pleasant.

 

T0:45- I feel so disoriented, cold metal bars spring from my skull and encase my body before turning to liquid and drifting away with the relentless wind.  I am wrapped in plastic, I am spinning and sinking. What am I even to do? I have just been sitting still listening to music, it is hard to engage in other tasks. I feel quite nauseous which is uncharacteristic for dissociatives for me. This is static and draining and powerful. My breathing still feels shallow- I would exercise caution with pushing this one towards any higher doses.

 

T1:00- The experience seems to have capped off- the steady pressure and gentle but definite acceleration have all slowed- the spinning and whipping clouds and dense masses of wind have had the life breathed out of them, they now are carried along only by their momentum. My motor control is still messy, it is still hard to walk properly. I go out and look at my bug light again- all sorts of beetles and an interesting wasp have taken up residence. I smoke a few hits of cannabis while I’m out. The stars glisten in the sky above, great masses of them clustered together into a great sparkling dance, the darkness of space twisting and undulating. It’s a beautifully clear yet humid night. This doesn’t feel particularly manic or energetic- I wish I could just flop down on the grass and gaze into the sky but it’s all wet.

My brain is jelly, I am probing into depths I shouldn’t be, my brain feels like melted ice cream, when I nod out and close my eyes I am still greeted by the same dull fields and pulses of color. I am reading stuff on the internet but I am not really taking it in, there is no urge or desire to dive into it or read more. The information just bounces off my glassy eyes. My teeth feel heavy and wet and soft.

 

T1:07- I decide to turn out my lights and listen to music on my bed with a blindfold on. This is usually an exhilarating activity to do while on dissociatives- It can feel like a roller coaster or a vibrant twisting ride into another realm- this however is much more nondescript. I’m still here, on my bed, and I am acutely aware of that the entire time. Instead of a roller coaster I am quietly and gently sailing down a warm viscous river, my field of vision just some quiet color splotches. I try to meditate, to think about memories or dreams, as that often serves as an analytical jumping off point for streams of adventures into the subconscious with other dissociatives. While I would consider this a fairly intense experience, it yields nothing to me in that regard- it crosses its arms and purses its lips and keeps its secrets. Or perhaps it has none to share at all. I would certainly regard this as shallow, an experience grounded more in sensation than in cognition. Lying still on my extra soft mattress pad feels extravagant though. This is a drug for doing things, for enhancing other experiences, for socializing or dancing or just relaxing under some heavy air. It is not the kind of dissociative that is exploratory in its own right, at least not for me.

 

T1:20- After only trying for a short time to sink into the depths of the experience, I decide to go back to what I was doing before, which was nothing while gazing at a computer screen. My toes and fingers are still very numb and feel like they are made of soft mud. Everything is decelerating and cooling down now, there is a definite comedown. I am still pretty uncoordinated when I try to move, but it is more manageable than before. The peak has certainly passed at this point.

 

T1:20- Motor skills returning more and more. I can walk in a straight line for the most part, though I will occasionally stumble. Well into the afterburn now. There are flashes of visuals playing in the white of my laptop screen. The double vision is fusing back into one now.

 

T1:30- Nothing feels quite real, It’s all still cold and weird. The cognitive dissociation lingers. It’s not the sort of empty neutrality that certain substances present though- it’s something brighter, warmer, more pleasant, but ultimately alienating and confusing. So many basic and familiar things seem foreign now, I feel like I have to make a conscious effort to adjust back to the world of sobriety.

 

T1:40- A glowy dizzy drunky feeling, not sharp or manic, a bit of residual stimulation run through my mind and exits quietly in my muscles as some fidgeting and twitching. I would still broadly characterize this drug as a depressant though, at least physically.

 

T2:05- I go out to socialize with my roommates, they are watching Seinfeld in the living room. We are all currently under isolation because two of us were exposed to someone who was COVID positive. Talking feels weird and distant, I haven’t attempted to say anything out loud this entire experience so far and now it feels like I’m stumbling on my words as much as I was stumbling on my own feet. I thought I had come down pretty far, that I was inching back towards sobriety, but being around other people made me realize how distant I really was. I am not entirely sure what I am even saying, the words aren’t properly registering in my memory. I am tossing them blindly into the void, hoping they are coherent. My roommates really truly look like I am viewing them on a screen, entirely divorced from their actual presence. This is kind of scary- it makes me feel like I may not realize the full weight of social consequences, that I may not properly regulate or moderate what I am saying. I am truly treading water over some deep depths. I go outside and grab a giant water bug to show them. Talking about an insect I love helps to ground me and feel more in touch, along with coming down more as time passes. After about half an hour I feel like I am socializing normally, better than normal in fact. I take them outside to show them what came to the light sheet and talk about bugs with them, this also helps to ground me. We turn the light off and pack it in, the darkness is heavy and swallowing. They go to bed.

 

T2:47- I feel mostly down by this point. The experience is only present when I stop and think about it.

 

T3:11- Still feeling a bit numb and off balance, but otherwise pretty close to baseline. There is a subtle euphoric afterglow that I am not 100% certain I can attribute to the drug but it is definitely there.

 

T3:30- Mostly just feel tired and sedated and a bit dizzy still. Lying still and doing nothing feels like a sacred activity.

 

T5:00- Back to baseline.

 

Conclusion: Such an interesting and promising compound that just begs further exploration by intrepid souls! This is, as far as I’ve experienced, one that sees diminishing returns as you increase the dose. The sedation and incapacitation builds as the dose creeps up, eventually glaring out the more pleasant dissociative effects that stand at the forefront at lower doses. At 10-12 mg it feels an immaculate party drug- a euphoric rush with soft edges and a steady pace, reminiscent of unsubstituted PCP or GHB or alcohol. The dissociation of this drug is characterized by dizziness above all else, a sense of spinning and perpetual motion and steady flow. It doesn’t fully anesthetize the body or plunge the user into a hole like other dissociatives, rather it leaves one with a inhibited, off-kilter, but still fully functional and present body, with numbness and distortion rooted in the extremities and skull and seeping inwards from there. Physically, it is sedating, especially at a higher dose, a GABAergic sedation replete with heavy eyelids and slow shallow breathing. There were also odd thermal sensations, an almost feverish being hot and cold at the same time. I do not have much experience with opioids for reference but at the higher dose, sensations similar to how stronger doses of opioids are described were present. This warrants investigation from someone with more familiarity in that area! The headspace is one of stimulation and very slight mania at lower doses. As the dose increases, this is replaced with a dumbfounded neutrality, like just being stunned and unable to properly process thoughts or stimuli. Visual effects are slight, and mostly only with eyes open. With eyes closed, any visuals were barely discernible at any dose. It is not the most introspective and doesn’t seem to lend itself much to therapeutic use. It is however, delightfully hedonistic and euphoric (especially at lower doses) and would be an excellent party drug. What I found it most similar to in fact was alcohol, just being a little past buzzed at 10 mg (or perhaps like I said before, GHB, but a bit stimmier). These returns deplete as the dose increases however, and it quickly turns into a disorienting and less rewarding experience that simply incapacitates the user. The short duration is also noteworthy, though there is a drawn out afterglow, it is subtle and not the typical stimulation that lasts after a dissociative and keeps a user awake in the dark. This does however, lend itself to a desire to redose, which could be problematic with the compounding effects as dosage increases. As mentioned before, this is one for fans of PCP, Alcohol, Poppers, or GHB. This is a fun and worthwhile compound, so long as you aren’t expecting too much depth from it! 

Monday, October 12, 2020

Obscure and Unknown: Heterocyclic amine/Competitive antagonist Dissociatives

*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.

Hello I have been caught in a firestorm of different activities but I didn't forget about this series! I certainly have not updated in a while. But I have something new for everyone- Today we will be looking at a series of dissociatives based on the structure of a heterocyclic amine. Heterocyclic amines are unique in how they cause dissociative effects- quite different from all of the familiar NMDA antagonists!

Heterocylclic amine? What does that mean? Let's break it down! A cyclic molecule is a bunch of carbons bonded to each other in a ring. Hetero-means different, so that means something other than a carbon is sitting in that ring. Amine is an amine, nitrogen, etc. so a heterocyclic amine is a ring shaped molecule with a nitrogen in there somewhere! In this case these are saturated heterocyclic rings, which means we just see single bonds between the carbons.

Both compounds listed here are what are called "Allosteric modulators" of the NMDA receptor. What does this mean? Well, first lets talk about what an NMDA receptor does- you can envision the NMDA receptor as a sort of gate made of several different components, a gate that separates the inside of a nerve cell (aka the neuron) from the synapse, a small space that insulates it from an adjacent nerve cell. By default, the gate is closed. However, this gate has keys, that must be used in tandem to unlock it. When the neurotransmitters glutamate or NMDA bind to this gate at the same time as the amino acid glycine, the receptor changes its configuration and opens up, allowing ions to flow from the synapse into the cell, allowing an electric impulse to be passed from neuron to neuron. When something interferes with this process, you have a breakdown of communication between cells, giving us the familiar "dissociative" effects of NMDA antagonists. Most familiar NMDA antagonists like PCP and ketamine work by simply wedging themselves into the channel that was opened by Glutamate/NMDA,  and physically blocking ions from passing through. Allosteric modulators however, bind elsewhere to the molecule, triggering a reaction that affects its shape and function. Glutamate/NMDA and glycine are allosteric modulators of the receptor in that they triggers it to change to an open position. Other allosteric modulators however will interfere with that reaction and keep it closed. A competitive antagonist will rush in and block the spot that either Glutamate/NMDA or glycine are supposed to bind to before they can get there, meaning the receptor will never open in the first place. Noncompetitive antagonists will bond to a different part of the receptor, simply not allowing it to open. With our gate analogy, channel blockers are like sticking a boulder in the opening of the gate after it's been opened, competitive antagonists are like filling one of the keyholes with superglue so that the keys can't be used, and noncompetitive antagonists are like gluing the hinges still, so that even when all the components are there the gate still won't open. Both compounds we will look at today are different kinds of competitive antagonist.

The specific compounds we will be looking at here are two pharmaceutical candidates that were, per usual, abandoned due to their "undesirable side effects". These compounds are called Selfotel and HA-966.

Let's just dive right in.

HA-966

The structure of HA-966

HA-966 is an NMDA antagonist that consists of a pyrrolidine ring with a number of substitutions- 1-HO, 2-Oxo, and 3-amino. It is structurally similar to the neurotransmitter GABA, the main depressive neurotransmitter, though GABA occurs as a straight chain, while HA-966 comes in the form of a ring.

HA-966 was first developed in the 1960s and published in 1971, where its structural similarity to GABA was noted. Thus, the effects it had on animals, such as catalepsy and sedation, were attributed to that mode of action and it was for a time regarded as a run of the mill depressant [1]. It was later determined to be an NMDA antagonist, the specific mechanism of which being fully characterized in vitro in 1989, as a glycine binding antagonist, different from the familiar NMDA antagonists [2]. I explain what this means in the next paragraph. Another study went on to demonstrate that the different enantiomers had different effects, where the (+) enantiomer was an NMDA antagonist while the (-) enantiomer was something more of a sedative similar to GBL [3]. Thus a racemic mixture of the drug would present an interesting combination of sedative and dissociative activity.

Foster and Kemp demonstrated in [2] that HA-966 was a different sort of NMDA antagonist than we're used to. As mentioned before, drugs like PCP and ketamine are channel blockers, that physically wedge into the channel of the NMDA receptor, blocking it [4]. HA-966 is a bit different however- it is an allosteric inhibitor. In the intro, there was an analogy that the NMDA receptor is like a gate, opened with 2 keys, NMDA and glycine. HA-966 is a glycine antagonist, meaning it wedges itself into the keyhole glycine is supposed to enter, preventing the fate from opening. We have almost no examples of what sort of experience this kind of NMDA antagonist yields in humans for reference. A study with rats however showed that when trained to discriminate between different drugs, they treated HA-966 different from PCP, indicating some sort of qualitative difference [5]. It's been in fact demonstrated that HA-966 will actively inhibit the action of PCP or MK-801 when administered concurrently [6].

So all of this dense data goes on to say: HA-966 is an NMDA antagonist, and will likely act as a dissociative, but with a mechanism of action unlike any dissociative that's been ingested by humans, save for the noble gas Xenon. So what happens when you give it to a person? Well the reason I know about it in the first place is that intrepid reddit users recently blazed this trail. 

I source these descriptions from a series reddit posts. The first is from u/Strangetimer, who shared a live report of their experience [7].

A dose of 100 mg + 50 mg + 100 mg sublingually proved to be as such:

(At 100 mg) "Certainly feeling dissociated but not in a dreamlike/euphoric way like with opiates or alcohol. It almost feels like I'm a bit anesthetized. Extreme reduction in pain sensation, unsteady gait, feeling somewhat mentally/physically dampened, and my peripheral vision has become incredibly dark and blurry. I can only read something when I'm looking directly at it. So far it is incredibly unique."

(At 150 mg)  "Second dose is now kicked in. Feeling heavily sedated. If I close my eyes for too long I could easily fall asleep. This now feels remarkably similar to alcohol physically, however mentally there is much less disinhibition/euphoria. My mind almost feels "cleared" similar to antipsychotics and it's hard for me to focus on one thing for too long."

(At 250 mg) "Physical impairment is now severe, mental impairment however is relatively low. Can still think fairly clearly, however acting on anything is difficult...Right there is a notable difference from alcohol/benzos. Unlike benzos I’m very aware that I’m pretty messed up and unlike alcohol I don’t have the “fuck it” attitude that makes long treks through the snow and cold more bearable."

A second report from u/StoopSign with a presumably oral dose of 120 mg stated [8]:

"thought I'd close my eyes for mild dissociation and of course I holed TF out completely and totally. I only know the amount of time it lasted because of songs on a list playing throughout. I may have been fully unconscious for a few mins. It wasn't until I realized I couldn't move and fully anaesthesiiazed off some unknown shit and about to OD from some bad drug combo"

(It should be stated that this user had also consumed a number of GABAergic sedatives throughout the day prior to this experience)

This information seems to indicate that HA-966 is a uniquely sedating and physically incapacitating dissociative with a fairly lucid headspace. It appears to be a relatively short duration experience, in the range of about 3-5 hours. It shows great promise and it would be interesting to explore further, especially from those well versed in typical ion-blocker type dissociatives who could draw comparisons between the different mechanisms of action!

There were a few cursory explorations into its potential in human as a neuroprotective, sedative, and anticonvulsant, though these were never explored much further in humans. It has found new legs in the nootropics market. 

Selfotel
Structure of Selfotel

Selfotel (aka CGS-19755) is another heterocyclic amine, like HA-966, though there are a number of superficial differences between the two. For one- Selfotel is a 6 member ring, while HA-966 is a 5 member ring! HA-966 is a tertiary amine (there are things other than hydrogen bonded to all 3 spots of the nitrogen), while Selfotel is a secondary amine (there is one hydrogen bonded to the nitrogen). Selfotel also has various substitutions around its ring, namely a 2-Carboxyl group and a 4-phosphonate. However, HA-966 has the distinction of being a direct variant of the neurotransmitter GABA, while Selfotel is just kinda its own thing.

Like HA-966, Selfotel is a competitive NMDA antagonist, meaning it also clogs one of the keyholes on the receptor, preventing it from opening. While HA-966 blocks the Gylcine keyhole, Selfotel blocks the other one, the hole for the neurotransmitter NMDA that the receptor is named for [9]. This would also suggest that it has unique qualitative properties relative to the familiar ion channel antagonists.

Selfotel was, similar to Aptiganel, developed for treatment of situations that caused an excessive and toxic release of glutamate, like stroke or head injury. Also like Aptiganel, certain "side effects" led to the eventual abandonment of development.

It was first studied in 1988, where it was identified as an NMDA antagonist [10]. Further investigation into its potential as an anticonvulsant/anxiolytic/anti-ischemic raised it into the world of pharmacological development [11]. An animal study elaborated on its analgesic and motor effects, an indicator of a potentially interesting NMDA antagonist [12]. One other study corroborated an observation with HA-966: that competitive antagonists produce an experience in animals that is unique from the typical channel blockers, and that they can be reliably expected to produce a unique subjective experience in humans [13]. 

All of this goes to say- scientists found this drug very interesting and sought further development. Unfortunately, it would follow a very similar trajectory to that of Aptiganel. Similar to Aptiganel, Selfotel ran up against the absurd issue that it was actually potentially deadlier than administering nothing at all [14]. A drug that may be toxic in stroke victims is certainly the opposite of a treatment for stroke. This is explored in further detail in the aptly named analysis "Failure of the competitive N-methyl-D-aspartate antagonist Selfotel (CGS 19755) in the treatment of severe head injury: results of two Phase III clinical trials" by Morris M.D. et al, 1999 [15]. 

Other very interesting effects also detracted from its candidacy as a pharmaceutical. Most notably, what one study referred to as "PCP-like behavioral effects" in animals [16]. I cannot find the full version of this paper for free unfortunately so I am not sure on the details of that, but the abstract states that such effects presented only from exceptionally high doses of Selfotel, well beyond the therapeutic range. Unfortunately, as stated before, I can't access this paper so I am not sure what dose that is. A therapeutic dose is indicated ~2 mg/kg or 140 mg in a 150 lb (70 kg) person. No subjective descriptions of the effects in humans seem to exist. Similar to Aptiganel, it is determinedly probably not safe to take Selfotel if you have recently had a stroke or head injury, as it seems to be specifically counterindicated in those cases (even though that is what it was developed for! oops.)

Development of Selfotel never really went any further. Perhaps researchers were leary with the concurrent failures of Aptiganel. Unlike Aptiganel, Selfotel never went on to tank its development company. Much less of a problem child. 

It also probably bears mentioning Midafotel, (aka CPPene or SDZ EAA 494) which bears a similar structure and activity to Selfotel, though it utilizes a Piperazine ring instead of a Piperidine (that means there's 2 nitrogens).
Structure of Midafotel

Midafotel has a similar pharmacological action to Selfotel and perhaps suggests some ways in which the structure of Selfotel can be modified to retain activity- The phosphonate occurs as a trans-phosponate across a butene chain which is an interesting modification- it is also bonded to a nitrogen, forming a tertiary amine that's absent in selfotel. Midafotel was developed for similar reasons as Selfotel, and has a similar highly selective competitive NMDA antagonist activity. Its development was ultimately abandoned as it showed no efficacy for its intended purpose, though there were no reports of dissociative effects. The closest were some patients citing memory problems during trials. [18]

----------------------------


So there we have it, these are 2 examples of heterocyclic amines that act as dissociatives. It is interesting that they share a different mechanism of action than the usual channel blockers. Seeing as they are active, this opens the door perhaps to other competitive antagonists as interesting and active compounds. Whether all single heterocyclic amine ring based dissociatives are competitive antagonists is unknown- various mixing and matching of the substitutions has not yet been attempted- HA-966 seems to be a unique GABA-adjacent structure and probably can't risk much modification. As for selfotel- it seems the phosphonate group carries some essential function in binding to the NMDA receptor, as can be seen in other similar non-analgesic NMDA antagonists like Perzinfotel [17]. However, the Carboxylic acid bonded to the amine mimics a portion of the neurotransmitter NMDA, so perhaps that is indispensable too. So maybe there isn't much wiggle room to modify these unique compounds, though someone else may know better than me,

Sources and Further Reading:
[1]- Bonta IL, De Vos CJ, Grijsen H, Hillen FC, Noach EL, Sim AW (1971) 1-Hydroxy-3-amino-pyrrolidone-2(HA-966): a new GABA-like compound, with potential use in extrapyramidal diseases. Br J Pharmacol. 43(3):514-35
[2]- Foster A, Kemp J (1989). HA-966 antagonizes N-methyl-D-aspartate receptors through a selective interaction with the glycine modulatory site. The Journal of neuroscience : the official journal of the Society for Neuroscience 
[3]- Singh L, Donald AE, Foster AC, Hutson PH, Iversen LL, Iversen SD, Kemp JA, Leeson PD, Marshall GR, Oles RJ, Priestly T, Thorn L, Tricklebank MD, Vass CA, Williams BJ (1990) Enantiomers of HA-966 (3-amino-1-hydroxypyrrolid-2-one) exhibit distinct central nervous system effects: (+)-HA-966 is a selective glycine/N-methyl-D-aspartate receptor antagonist, but (-)-HA-966 is a potent gamma-butyrolactone-like sedative. Proc Natl Acad Sci U S A. 87(1):347-51
[4]- Waterhouse RN (2003) Imaging the PCP site of the NMDA ion channel. Nucl Med Biol. 30(8):869-78.
[5]- Singh L, Menzies R, Tricklebank MD (1990) The discriminative stimulus properties of (+)-HA-966, an antagonist of the glycine/N-methyl-D-aspartate receptor. European Journal of Pharmacology 186(1):129-132
[6]- Bristow LJ, Hutson PH, Thorn L, Tricklebank MD (1996) The glycine/NMDA receptor antagonist, R-(+)-HA-966, blocks activation of the mesolimbic dopaminergic system induced by phencyclidine and dizocilpine (MK-801) in rodents. Br J Pharmacol.108(4):1156-63
[7]- https://www.reddit.com/r/researchchemicals/comments/es2z2a/ha966_live_experience_report/
[8]- https://www.reddit.com/r/researchchemicals/comments/g3cz3k/ha966_experience_full_unexpected_30min_k_hole/
[9]- Baron SP, Woods JH (1995) Competitive and uncompetitive N-methyl-D-aspartate antagonist discriminations in pigeons: CGS 19755 and phencyclidine. Psychopharmacology 118:42–51
[10]- Lehmann J, Hutchison AJ, McPherson SE, Mondadori C, Schmutz M, Sinton CM, Tsai C, Murphy DE, Steel DJ, Williams M, et al. (1988) CGS 19755, a selective and competitive N-methyl-D-aspartate-type excitatory amino acid receptor antagonist. J Pharmacol Exp Ther. 246(1):65-75
[11]- Bennett DA, Lehmann J, Bernard PS, Liebman JM, Williams M, Wood PL, Boast CA, Hutchison AJ (1990) CGS 19755: a novel competitive N-methyl-D-aspartate (NMDA) receptor antagonist with anticonvulsant, anxiolytic and anti-ischemic properties. Prog Clin Biol Res. 361:519-24
[12]- France CP, Winger GD, Woods JH (1990) Analgesic, anesthetic, and respiratory effects of the competitiveN-methyl-d-aspartate (NMDA) antagonist CGS 19755 in rhesus monkeys. Brain Research 526(2):355-358
[13]- Baron SP, Woods JH (1995) Competitive and uncompetitive N-methyl-D-aspartate antagonist discriminations in pigeons: CGS 19755 and phencyclidine. Psychopharmacology 118: 42-51
[14]- Davis SM, Lees KR, Albers GW, Diener HC, Markabi S, Karlsson G, Norris J (2000) Selfotel in acute ischemic stroke : possible neurotoxic effects of an NMDA antagonist. Stroke 31(2):347-54
[15]- Morris GF, Bullock R, Marshall SB, Marmarou A, Maas A, Marshall LF (1999) Failure of the competitive N-methyl-D-aspartate antagonist Selfotel (CGS 19755) in the treatment of severe head injury: results of two phase III clinical trials. The Selfotel Investigators. J Neurosurg 91(5):737-43
[16]- Bennett DA, Bernard PS, Amrick CL, Wilson DE, Liebman JM, Hutchinson AJ (1989) Behavioral pharmacological profile of CGS 19755, a competitive antagonist at N-methyl-D-aspartate receptors. Journal of Pharmacology and Experimental Therapeutics 250(2):454-460
[17]- Kinney WA, Abou-Gharbia M, Garrison DT, Schmid J, Kowal DM, Bramlett DR, Miller TL, Tasse RP, Zaleska MM, Moyer JA (1998) Design and Synthesis of [2-(8,9-Dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl)- ethyl]phosphonic Acid (EAA-090), a Potent N-Methyl-d-aspartate Antagonist, via the Use of 3-Cyclobutene-1,2-dione as an Achiral α-Amino Acid Bioisostere. J. Med. Chem. 41(2):236-246
[18]- Rockstroh S, Emre M, Pokorny R, Tarral A (1996) Effects of the novel NMDA-receptor antagonist SDZ EAA 494 on memory and attention in humans. Psychopharmacology 124:261-266

Sunday, October 4, 2020

5-MeO-MET

 Age: 25

Weight: 130 lbs

Dosage: 25 mg fumarate salt oral in gel cap

Setting: My house

 

T0:00-Dose taken on an empty stomach.

 

T0:15- Feeling a bit stimmy, anxious, on edge, there is bit of stirring in my gut and some undulating unease in my muscles.

 

T0:20- The unease grows, I feel uncomfortable in any position no matter how much I keep adjusting myself, all of my muscles are clenching and my jaw is grinding. I feel queasy and distant, like awaking from a drunken stupor, the world not properly registering yet. I feel like I am sitting stationary on a perpetual sickly air current, a fetid breeze over a menacing crag.

I want to move but moving feels wrong so I sit still, but that feels wrong too. I am losing confidence in my body’s ability to feed me any meaningful information. I get a sense that I am in for something of a trial. My body feels warmer. There are no sensory effects to speak of so far beyond the physical discomfort, which makes me want to curl up and clench all of my muscles like a dead insect.

I am trying to engage in a debate on the internet about evolution, because I am an insufferable nerd. I write out lengthy posts with the information I can recall, doing so feels like an immense effort with so much discomfort and stimulation running through me, a hurdle I have to overcome to think clearly.

 

T0:30- I feel so sick and uncomfortable, not like I am on any kind of drug, more like I've just been poisoned. Take a hit from my cannabis vape to take the edge off but it does nothing

I'm shaking so much now, I feel so nauseous like my brain is being violently dragged around in circles by a maddened dog.

It feels like it keeps building up to something but nothing happens. So much stimulation is firing off from all of my nerves but it just smokes and sputters into the air, it goes nowhere and does nothing, there is nothing to feel about it. This is so empty and uninteresting and uncomfortable. It is still purely physical effects- I feel no alteration of thought, no changes in sensory perception, no physical sensations beyond discomfort. I am quite bored.

 

T0:40- Every part of my body feels disjointed, desynchronized, out of order and out of touch. My heartbeat isn’t matching my blood flow, the movement of my muscles doesn't quite match what I'm ordering them to do, my breathing ins unsteady and inconsistent. Everything is just slightly off, but it is glaringly noticeable, like a cruel prank.

Why did I do this to myself? This is thoroughly unenjoyable. Everything looks and feels faint, illusory and foggy. I don’t want to perceive physical objects around me, I just want to curl up and let this pass, and so I don’t, they are virtual facsimiles for a physical reality I don’t have the energy to fully comprehend.

Standing up and moving feels uneasy and unstable, each step is confused and cacophonous, my bones and muscles and neurons bickering in perpetual disagreement. My heart is pounding.

 Time passes and all hell has broken loose, like a flash flood through my bloodstream that binds me to my bed, twisting and turning into whatever way offers the slightest relief. It is not quite painful or torturous, just a terrible wasteful and inconvenient discomfort.

I am not even thinking about or processing information in some novel unique way, there are so many weird little malcontent sensations and odd little flashes of pains, the muscles and bones in my limbs feel ashen and achy. My body does not feel like has taken any shape that my mind conceives it as being. There are still no noteworthy sensory effects. Just a dizzying discomfort.

 

T1:00- Already the discomfort seems to be receding just a bit, this is an immense relief. My muscles feel strung out and ragged but the discomfort drains from me, it feels heavenly, it feels like a nice cool rush, it feels like I've been unburdened. I step outside on my back porch for a smoke. Even still, gazing upon the beautiful natural vista before me does little to move me or stir me, it is just visual information I quietly and neutrally take in with no bearing on thoughts or emotions. It sure is nice and sunny though. I sigh and go back in.

 

T1:15- Not unpleasant anymore but fairly nondescript. I am definitely altered in some way but it is hardly discernible beyond stimulation. Nothing is especially engaging, I don't feel any strong feelings or motivations in any direction, just blank and neutral. Visuals finally start to present but they are subtle and hardly above my baseline HPPD visuals- just an increase in visual snow and vague drifting forms, with occasional flashes of color and light and motion.

 

T1:30- The awkward anxiety that was predominating has given way to feeling lovey and sweet and warm, I want to talk with my friends and interact with people, I open my blinds to watch the golden hour sunlight reach through the trees. There is a warmth in my brain and it looks like everything is run through with heat waves. I want this warmth to reach out and touch upon everything, to bless the earth with its breath. I still don’t feel particularly altered or incapacitated, it’s all subtle and hardly discernible. There is a warm sensation of numbness and disorder rippling through my body, but aside from that, the physical effects have mostly abated. What was once rippling arcs of electricity have given way to a glowing smoldering core, simple and nondescript.

 

T2:30- I facetime with a friend while working on a drug research project. They’re working on something too so we mostly just pass occasional chatter back and forth as we stay busy. It is nice to see someone’s face and hear someone’s voice. I don’t feel awkward at all and my social skills don’t seem to be impaired in any way as psychedelics can often do- where oversensitivity and rumination render interaction quite challenging.

 

T3:00- Experience is for the most part over. I can hardly discern being off baseline in any way.

 

T4:00- Definitely fully back to baseline by this point. Oh well.

 

Conclusion: This is a boring and uncomfortable drug when taken orally, underwhelming and underperforming in just about every conceivable way. The physical sensations consist primarily of discomfort and unease, with muscle aches, nausea, and excess stimulation casting dominion over the experience. There is nothing remotely pleasant or enjoyable, just a sense that no matter what I do my body is not quite right. The cognitive and mental effects are almost non-existent, rather it is a sensation of confusion and irritation driven by the physical effects. Nothing is any more interesting or stimulating than normal, as psychedelics will often do. Rather every bit of input becomes tedious and tiresome. I don’t want to perceive anything. My thoughts are for the most part rumination on the fact that it feels like I have poisoned myself. Sensory effects are also near non-existent. Slight and subtle visuals came about on the tail end of the experience but they were absolutely nothing interesting or worthwhile. The duration was extremely short too, which is normally quite disappointing for any drug, but with this substance I was glad the experience passed quickly. I do not see any reason to experiment further with this.