So, a very interesting study was released today about LSD. It can be found at this link: Crystal Structure of an LSD-Bound Human Serotonin Receptor. As the title says, they have now mapped the structure of LSD when it is actually bound to 5-HT receptors, specifically 5-HT2A and 5-HT2B. I would recommend checking it out to anyone who's interested, but I brought it here specifically because I think it also has strong implications for the activity of ETH-LAD.
One of the primary conclusions of the study was that LSD's diethylamide group that appears to require a very strict binding orientation seems to help form a pocket for LSD in these receptors with the way it binds to them, and this gives LSD slow kinetics at these sites. They suggest that this could be a possible reason why LSD can have such a long duration of intense effects despite apparently rapid clearance from the body, like a half-life of a few hours.
I personally find this really interesting because I have always agreed with the idea that LSD comes in two phases, the first being more like a simple indole with heavy psychological effects and most of the body load if there is any, and the second being very clearheaded, cognitive, and colorful. It's really made me start to consider new reasons for why this could be now, like for instance if maybe the first phase, which does only ever last a few hours for me, gets its heavier impact from binding to many other receptors similar to an indole, and then the second phase becomes more like a phenethylamine, remaining only on the 5-HT2 receptors long after having detached from its other sites. Of course, this would also have to assume that this same finding doesn't also apply to those sites.
Anyway, I know that people have found ETH-LAD to have this two phase effect as well, and that it does have a longer duration at full doses and the diethylamide group of course, so I figured that if this applies to LSD then it may very well apply to ETH-LAD as well, so I brought it here to see what you guys think. This definitely makes me want to take ETH-LAD again soon.... The pharmacology of these substances is so fascinating.
Pretty interesting paper indeed, and an impressively thorough work. Surprised it made it into Cell.
I don't think I follow you, though, Kaleida. Not sure what you mean by "It's really made me start to consider new reasons for why this could be now, like for instance if maybe the first phase, which does only ever last a few hours for me, gets its heavier impact from binding to many other receptors similar to an indole, and then the second phase becomes more like a phenethylamine, remaining only on the 5-HT2 receptors long after having detached from its other sites. Of course, this would also have to assume that this same finding doesn't also apply to those sites." nor how you relate that to the steric hindrance from the external loop of the 5HT2AR they describe in the paper. Also, extrapolating the finding about the diethyl moiety to ETH-LAD would probably explain similarities, but hardly the differences between it's subjective effects. I just skimmed through the paper, though, I will need to give it a read when I have the time. Interesting stuff, thanks a lot for sharing.
So, a very interesting study was released today about LSD. It can be found at this link: Crystal Structure of an LSD-Bound Human Serotonin Receptor. As the title says, they have now mapped the structure of LSD when it is actually bound to 5-HT receptors, specifically 5-HT2A and 5-HT2B. I would recommend checking it out to anyone who's interested, but I brought it here specifically because I think it also has strong implications for the activity of ETH-LAD.
One of the primary conclusions of the study was that LSD's diethylamide group that appears to require a very strict binding orientation seems to help form a pocket for LSD in these receptors with the way it binds to them, and this gives LSD slow kinetics at these sites. They suggest that this could be a possible reason why LSD can have such a long duration of intense effects despite apparently rapid clearance from the body, like a half-life of a few hours.
I personally find this really interesting because I have always agreed with the idea that LSD comes in two phases, the first being more like a simple indole with heavy psychological effects and most of the body load if there is any, and the second being very clearheaded, cognitive, and colorful. It's really made me start to consider new reasons for why this could be now, like for instance if maybe the first phase, which does only ever last a few hours for me, gets its heavier impact from binding to many other receptors similar to an indole, and then the second phase becomes more like a phenethylamine, remaining only on the 5-HT2 receptors long after having detached from its other sites. Of course, this would also have to assume that this same finding doesn't also apply to those sites.
Anyway, I know that people have found ETH-LAD to have this two phase effect as well, and that it does have a longer duration at full doses and the diethylamide group of course, so I figured that if this applies to LSD then it may very well apply to ETH-LAD as well, so I brought it here to see what you guys think. This definitely makes me want to take ETH-LAD again soon.... The pharmacology of these substances is so fascinating.
I find that this applies more to ETH-LAD, as you're peaking in a world of psychedelia for 4-5 hours and then the next 4-5 hours are followed by an extremely lucid cognitive headspace, like an binary on/off switch. With classic LSD or ALD-52, it feels more gradual.
Pretty interesting paper indeed, and an impressively thorough work. Surprised it made it into Cell.
I don't think I follow you, though, Kaleida. Not sure what you mean by "It's really made me start to consider new reasons for why this could be now, like for instance if maybe the first phase, which does only ever last a few hours for me, gets its heavier impact from binding to many other receptors similar to an indole, and then the second phase becomes more like a phenethylamine, remaining only on the 5-HT2 receptors long after having detached from its other sites. Of course, this would also have to assume that this same finding doesn't also apply to those sites." nor how you relate that to the steric hindrance from the external loop of the 5HT2AR they describe in the paper. Also, extrapolating the finding about the diethyl moiety to ETH-LAD would probably explain similarities, but hardly the differences between it's subjective effects. I just skimmed through the paper, though, I will need to give it a read when I have the time. Interesting stuff, thanks a lot for sharing.
Sorry if I wasn't clear on anything, let me try to fix it. First I'll just tackle this: "Also, extrapolating the finding about the diethyl moiety to ETH-LAD would probably explain similarities, but hardly the differences between it's subjective effects." I'm not sure what it seemed like I was saying, but I wasn't trying to say anything at all about the differences between LSD's and ETH-LAD's subjective effects. I do have plenty of my own ideas about that, but not related to this. The only implication I was addressing here applied to possible similarities between their binding properties and the resulting consequences thereof.
About what I said in the first part and how it relates to the paper, it's because one of the main things they suggested in the paper was that the way that LSD bound to the 5-HT2A and 5-HT2B receptors could be an explanation for why it seems to produce a duration of effects a good deal longer than it appears to remain in the body in general before being metabolized, because the pocket it forms would keep it held in for a good long time. If that is true then that would be entirely sufficient to explain its long-lasting psychedelic effect, even while the rest of the LSD that's not bound to these receptors appears to be metabolized and washed out. However, a possible implication of that is that the duration of LSD's neurochemical effects may be shorter for any receptor from which it can dissociate more rapidly, which would mean that the non-5-HT2 receptor activity it brought in at the beginning of the experience would be shaved down until it was essentially 5-HT2-selective by the end of the experience.
Due to going from non-selective to selective for 5-HT2 receptors, if this were true it would mean that the beginning of the experience would be built on a pharmacological profile more alike tryptamine psychedelics, whereas the end would be built more like a phenethylamine psychedelic. While I know it is a topic of much debate what role other receptors really do or don't play in the effects of psychedelics as 5-HT2A receptors do seem to be necessary and, with few exceptions, sufficient to produce the psychedelic state in general, I still believe that they very likely do play some sort of modulatory role on the overall experience that could contribute to things like overall mood extending to hallucinogenic content, euphoria or dysphoria, how clearheaded or not the experience is, and aspects of the body load. And a few things in particular already are very well-established to have direct interactions with 5-HT2A receptors, like 5-HT1A receptors. In the few studies available on human combinations I am aware of it appears that 5-HT1A agonism reduces the hallucinogenic effects of psychedelics and some of their expansive euphoria, but it does seem quite notable as well that 5-HT1A agonists have their own behavioral effects, and psychedelics with high 5-HT1A receptor activity tend to feel unique or intense in ways that ones without it don't, with the most extreme example of 5-MeO-DMT obviously standing out. So, for instance, LSD also binds strongly to 5-HT1A receptors as an agonist, so if the diethylamide group did not behave the same way at this receptor and LSD only bound to it for maybe half as long at most, then halfway through the experience it would shift from being a dual 5-HT1A/5-HT2A agonist to just being a 5-HT2A agonist, and that could reduce some of 5-HT1A's potential subjective contribution that makes for the heavier trippy aspect of the first phase, but at the same time liberate some of 5-HT2A's colorful and loving euphoric effects for the second phase.
There is this graphic I'm aware of, though unfortunately I don't know what study it's supposed to have come from and cannot verify its authenticity. If someone is familiar with this, I would be grateful if you could speak up! But, regardless, I shall post it as an acceptable enough example for now.
So, let's take a look at LSD and ETH-LAD here. If this data actually can be trusted, then by this measure LSD would be just slightly more potent at 5-HT1A than 5-HT2A, with 10 at the former and 14 at the latter. ETH-LAD, on the other hand, has a value of 2.5 at the former and 42 at the latter, which would make it over 16(!) times selective for 5-HT1A. If that is actually the case and it's also the case that ETH-LAD benefits from slow dissociation kinetics due to the diethylamide group and that the above idea about LSD is correct, then ultimately it would seem like this change could be even more relevant due to things like this, as going from 16x selectivity for 5-HT1A to 5-HT2A selectivity over the course of one trip could understandably make for some pretty variable reactions based on how much time has passed.
Is this starting to make sense now or am I missing the point...?
I find that this applies more to ETH-LAD, as you're peaking in a world of psychedelia for 4-5 hours and then the next 4-5 hours are followed by an extremely lucid cognitive headspace, like an binary on/off switch. With classic LSD or ALD-52, it feels more gradual.
That's very interesting, thanks for speaking up. I've still only taken it once so far, at 100 ug, and that wasn't really enough for an overly strong effect yet, so I'm not that knowledgeable on it. I would love to experience that shift though, both to understand this better and just because I tend to enjoy particularly dynamic psychedelic experiences.
Makes perfect sense, it was me that wasn't getting your point
Would be interesting to have the dissociation kinetics of each receptor involved in LSD's pharmacological profile to make definite claims about the "Biphasic" effect. But I think you might be onto something with your reasoning.
To keep the thread in topic, I've also noticed "two phases" to the ETH-LAD trip. Or rather, a very sudden drop from the peak to the rest of the trip. The peak of effects feels a little bit short and intense, and then very suddenly I'm left with some residual psychedelia.
Yeah, I would love to have that kind of data, and about more than just LSD. This has really gotten me thinking about how much these kinds of things might come into play for any of the drugs we use on a regular basis.... I mean, logically these molecules probably aren't always binding to each totally different receptor for the exact same amount of time, right? They all involve unique physical interactions, not just the more basic computational relationships that are generally captured in binding studies.
Out of curiosity, how long are your ETH-LAD trips generally in total? I'm wondering if the difference might be more significant with particularly high doses, which is the case for me with LSD. If I take a low to moderate dose the first phase lasts a few hours and then the second phase is only another few hours max, and mostly feels like a slow comedown. With higher doses, the first phase still only lasts a few hours but then entirely changes to a still full-strength but different character trip for at least another eight hours, or even like another twelve hours with really strong trips. The difference is extreme and obvious.
I find my eth lad trips last approximately 8-11 hours depending on how large the dose is but I do think in general the trip is shorter than lsd. Perhaps it's just that lsd, from what I remember, was far more stimulating and going to sleep was harder.
I would say your comment about dose changing the two stage experience applies to eth lad, for me anyway. One difference (again, from what I recall from lsd taken years ago) is that I find the second peak of eth lad far deeper and more powerful than the first. In my most recent and by far my strongest trip I recounted in a previous post I was experiencing ego loss 'nod-offs' in the second peak. The visuals were easily 2 or 3x stronger as well in the second phase of the trip. At its height my entire visual field was overrun with every type of oev imaginable. At half this dose I still experienced a two stage trip but the subjective feel of the experience was less starkley differentiated...More of a gentle 'bump' with the second peak followed a few hours later with a pretty sharp come down.
1) I find it less stimulating and hipomanic than lsd, nearly sober mindstate at normal or low doses, so for me it doesn't produce that hipomanic crazy funny LSD mindstate (which for me is awesome, as some times I pefer to be in a more relaxed mindstate than that of LSD)
2) Yes, it's layed in blotters like LSD
3) I find it crazy visual but without the mindfuck, not having the LSD stimulation makes the trip less spiritual, which, again, for me is a bonus. I'm done with all that hippy universal love shit, the world is fucked up and I don't enjoy beeing in a fake pink world anymore.
I find my eth lad trips last approximately 8-11 hours depending on how large the dose is but I do think in general the trip is shorter than lsd. Perhaps it's just that lsd, from what I remember, was far more stimulating and going to sleep was harder.
I would say your comment about dose changing the two stage experience applies to eth lad, for me anyway. One difference (again, from what I recall from lsd taken years ago) is that I find the second peak of eth lad far deeper and more powerful than the first. In my most recent and by far my strongest trip I recounted in a previous post I was experiencing ego loss 'nod-offs' in the second peak. The visuals were easily 2 or 3x stronger as well in the second phase of the trip. At its height my entire visual field was overrun with every type of oev imaginable. At half this dose I still experienced a two stage trip but the subjective feel of the experience was less starkley differentiated...More of a gentle 'bump' with the second peak followed a few hours later with a pretty sharp come down.
Interesting, thanks for the input. Yeah, I could see the residual simulation of LSD contributing to the perceived duration as well, it can keep you going for quite a while. If my ETH-LAD trips were 8-11 hours that would still definitely be shorter than a full dose of LSD for me even without the simulation though, which generally has me going for at least twelve.
And that is very fascinsting about the two phases too, thanks again! That certainly does deepen my curiosity about it.... Intriguing that you found the second phase so much stronger too, considering the possibly valid binding data. I really need to try pushing higher with this one soon! Crazy that you got that much out of the jump up to 120 ug.... I took 100 ug the first time, I think next time I might just go for 200 ug and see what happens.
I just wanted to say to this, while I do agree with MSK about the lack of simulation or mindfuck in ETH-LAD compared to LSD, I did still actually find it to feel quite spiritual and could definitely see it being able to tap into that same cosmic connection feeling, even just from my one experience on 100 ug. This was actually one of my favorite things about it.... A psychedelic that is simultaneously visual and deep while still being calm and lucid is nearing perfection in my book. Like, on that 100 ug dose I closed my eyes and was presented with a huge field of what I perceived to be ravers dancing in a cosmic void, and I was able to float down and move around with them and start to see from their perspective, and I suspect that a higher dose could take me even deeper. On LSD I can get to a similar space, but by the time I do I will usually be too distracted to focus it like that, and the empathetic connections will be more chaotic and hedonism-based. They both have their ups and downs too, but I wouldn't say I found one weaker than the other in this way so far.
My two trips with ETH-LAD have been quite "spiritual".
Not necessarily in the cosmic sense, maybe introspective would be more suiting. But kind of falls short because it's not necessarily a self-center perspective.
Meh, some things are just hard to talk about.
All I can say is it enhanced "philosophical" thinking, in a way not limited to rational though but including "thinking with and about the emotions".
I did felt all lovey dovey on my first go with it but I think it was set and setting.
I was saying goodbye to my girl for a four month period.
Img_9999 I think you described the "spiritual" nature of an ETH-LAD trip well. I felt the same about it, but couldn't find the words to describe it, like you said it's hard to talk about.
It's not the same perspective as acid, maybe not so high and mighty, there is more of an emotional tint to it. It's less ego-bound.
I found it to be lovey dovey too, but it's hard to separate from set and setting. In any case I found that it enhances feelings of attraction and beauty, and appreciation for the love in your life.
edit: regarding humor - I think that's super context dependent, but I found it to be extremely hilarious at times, in the best way. Really good for seeing the hilarity of life, and putting a ridiculous spin on some dark paranoid ideas.. AL-LAD might be even goofier though.
I find AL-LAD to be the best hilarity-enhancer I have ever taken, honestly. Sides and face hurting the next day from so much laughter. I found it not very deep mentally, but the thing it did do really well was to make my friends and I find really ironic and ludicrous humor is the connections between concepts and in the structure of language. Such a great time. But it was the kind of stuff we often couldn't remember later. ETH-LAD also showed me humor in things but my entire state of mind was calmer, it was more of a zen-like humor (if that even makes sense). I didn't get carried away on tangents and being crazy and silly, instead I found deep amusement in something and quietly experienced a great, warm pleasure at that.
Alright, so this little devil is on the mail! Next to a couple of AL-LAD blotters hehe :D which one do you think it's ideal to try first? And would you dose alone the first time, or is it fine to take it with my girl, and/or friends?
Al-lad would be the better choice to try first, it's easier on the mind and the body.
About dosing alone or with people I don't know about your experience and preferences.
I tripped alone since my first blotter and loved it, while tripping with other people is not my cup of tea at all, as I'm a lone wolf that feels unconfortable arround human beeings.
Al-LAD is the easiest and friendliesr lysergamide I've tried. I would recommend being with at least one friend during it, as for me, it really makes me want to socialize and laugh, it's not so much for introspection. ETH-LAD is much more powerful and introspective.
I recently had a second eth-lad trip at 200ug.
The thing I noticed is that at almost exactly the 4 hour mark the visuals suddenly really peak. On both my 200ug trips I have had what I can only describe as fireworks going off in my vision, so realistic that on my first experience I actually thought they were real!
This really ties in with the mentioned two stages. I've found that the first stage is fairly introspective; on this occasion I figured out that I need to look after myself better. I've lost a lot of weight recently (deliberately, at first certainly) and believe I have become too thin. I wanted to lose weight and then exercise to get in better shape so I now need to follow through.
The second phase is pure euphoric hedonism. On recent trips I have been revisiting some old albums: I have to say that Leftism by Leftfield is astounding whilst tripping (even straight). Song of Life had me gyrating wildly and shaking my boots like crazy. Also listened to The Go! Team's 'Thunder, Lightning, Strike'. Rarely has a more uplifting album been made and the track Ladyflash is possibly the pinnacle. Also a track called 'Hold yr Terror Close' is one of the most beautiful ever recorded.
This stuff is disappearing soon. I recently received 25 tabs and will order another 100 to keep for special times.