Wandering Girl
Bluelighter
Before I start, this is not a thread to come in and talk about the dangers of 5-HT2B activation. For all intents and purposes here I am talking about the effects of acute administration, not chronic. Furthermore, I am relating it most significantly to drugs that are known to not have problems because of this. Some more questionable ones will be mentioned as well, but that's not why they are being talked about and I don't think it really applies much here.
So on to the point.... I am a strong proponent of the idea that most receptors in the brain can have a significant impact on the hallucinogenic effects caused by 5-HT2A agonists, even if those receptors didn't seem to be significantly hallucinogenic on their own. Because of this I am always trying to look more into other monoamine receptors specifically so that I can make an attempt to understand the effects of various psychedelics. Following in line with this, one of my biggest interests has been the 5-HT2B receptor.
When I use the term delirium in the title of this thread, I am trying to relate it specifically to the effects caused by anticholinergic deliriants. Not many of the physical effects such as stimulation and dysphoria so much, but the effects on consciousness and perception. In my more reckless days, I experimented with diphenhydramine on occasion.... For those who aren't familiar with the general progression of deliriant hallucinations as doses increase, I will detail my personal experiences and information that I've gathered from the accounts of others here. A lot of people say that deliriants don't have visuals like psychedelics, but I tend to find that the people who say this are the ones who only ever had one strong deliriant trip and never tried them again, and I feel that I can explain this. In lower doses, they definitely do have some more "typical" visual effects; patterning, distortion, and more abstract hallucinations are common. At higher doses, the strength of these effects increases to the point where they cover a much more significant area of your visual perception, reaching fully panoramic scenes at very high doses. I personally believe that that's why those who have only experienced high doses don't believe that normal visuals are common, because they spend their entire trips fully immersed in these strongly-generated imitations of reality rather than riding the line in between "clearheadedness" (I use the term lightly) and full delirium. An example of this with diphenhydramine would be how at full doses people talk about seeing spiders and having full conversations with people. At only moderate doses, I've experienced effects that are quite clearly the same kinds of distortions at work, but to a lesser degree; colorful, translucent form constant patterns with shapes that certainly do resemble the movement of spider legs but don't quite reach that full hallucinations, and hearing random hallucinated words here and there that never amount to full sentences, instead sounding more like sound distortions on something like mushrooms like... which will actually play into what I'm trying to get at in a bit. It's also quite common at least for me on deliriants to stare at certain objects and not realize until looking closer that they're something very different from what I originally thought, but full delirium is not necessarily required for that.
Then there's MDMA. It seems like one in at least every few drug users with much experience is aware of the fact that MDMA can cause a fairly powerful delirium upon either redosing or adding something such as cannabis or ketamine into the mix, particularly on the tail end of the experience. I have also read many reports where people mixed MDMA with full psychedelics, such as one about mescaline that comes to mind especially, and found that the abstract hallucinations of the psychedelic became much more "real" from that point on, generally being pushed into the visionary or out-of-body state. I don't have nearly as much experience with combining MDMA with psychedelics as I would like, but I have redosed and mixed it with cannabis on several occasions to achieve this effect. While the visual effects are slightly differing in their art style in some ways, the overall effects are strikingly similar to what I have experienced on deliriants. The realism of the visuals is out of this world, and it basically feels like a deliriant with some psychedelic flavoring added in. For a long time it was actually a common practice in my group of friends to get this effect going as strongly as possible, and I have friends who managed to trip much harder on it than I did. One in particular stands out who got the furthest of any of us on two separate occasions, and I would say that his behaviors were indistinguishable from someone in the throes of anticholinergic delirium. While the rest of us were mostly achieving the abstract patterning and maybe moments of fleeting full delirium every now and then, he was completely submerged in that panoramic state. The way he responded to use and mumbled to himself and people who weren't there, and kept thinking that we were in his house instead of mine, or thought he was playing Xbox in front of a TV that was off... it was all perfect. I've never even seen someone trip as hard on an actual deliriant as he did on that MDMA and cannabis combination both times, it was like something out of a heavy datura trip report.
I've heard a lot of people suggest that these hallucinogenic effects of MDMA are mediated by its eventual metabolism into MDA, which makes enough sense to me. However, I've also seen research studies that suggest that many of the empathogenic qualities of these drugs (particularly involved in serotonin and dopamine release) come from activation of the 5-HT2B receptor. The same seems to hold true for the more recent research chemical analogues of these drugs as well. I'm going to tie this into a bigger picture, but at first, this is what made me really become interested in it. If we just assume for now that this is the case, that 5-HT2B adds some delirium to the effects of 5-HT2A activation, it would fit quite well, wouldn't it? All of these MDMA analogues that have psychedelic effects are known to cause particularly realistic and delirious hallucinations on top of their normal effects, and though MDMA doesn't on its own because it's lacking in significant 5-HT2A affinity in normal doses, anecdotal reports would seem to suggest that it has the same or at least a similar effect when it is combined with a 5-HT2A agonist. One that especially stands out to me though is MMDA. Reports of this drug are pretty hard to come by, but the most significant one to me is the one here by morninggloryseed. MMDA is said to be a fairly specific serotonin releasing agent, and given its similarity to MDMA I don't think it's absurd to suggest that 5-HT2B plays a role, as well as a 5-HT2A agonist, and it's said to create incredibly realistic visuals with closed eyes. In morninggloryseed's reports, many of the effects he details as part of the experience are extremely similar to those caused by anticholinergic deliriants such as what I mentioned above, and I've even gotten something similar to what he describes about seeing the vivid internet browser with clear but meaningless text on it on diphenhydramine before. I think this is a particularly important example to follow, however you don't have to use something so rare to see this either... many, many people report delirious hallucinations from MDA such as seeing objects or people on the dance floors of clubs that aren't actually there. The more you read about these experiences, I think the harder it gets to differentiate them from many that are reported from anticholinergic deliriants.
Here's what I'm really trying to get at though.... Those MDMA analogues are strong 5-HT2B agonists but presumably not incredibly potent 5-HT2A agonists, as psychedelic effects are not the main part of what they're used for. So what about 5-HT2B activation by something that is used primarily for its psychedelic properties? Well, that leads me here.... Let's consider the four best known psychedelics: LSD, mescaline, psilocin, and DMT. The former two are known for being more stimulating in a dopaminergic way and causing trips that, while they can be very powerful and hallucinogenic, tend to take place more "in reality", even if reality seems pretty difficult to comprehend at the time. The latter two are known for much more easily causing those breakthrough experiences filled with entities that transport you to a completely different realm. LSD has been shown to bind to 5-HT2B only at very high doses, above what would be considered in the normal range of use. As far as I'm aware, mescaline has never been shown to have any significant affinity for 5-HT2B. At least one study I found, on the other hand, has shown psilocin to bind quite strongly to 5-HT2B, maybe even much more so than to 5-HT2A. DMT has been known to bind to 5-HT2B for some time, relatively unselectively in comparison to most other serotonin receptors it binds to. This is quite significant to me, because psilocin has also, in my experience, been the one to cause much more brain fog (not necessarily meant in a bad way), memory disruption, and general dissociation of mind from behaviors than DMT at least at normal doses, which would be supported well by my theory of 5-HT2B delirium if it works as part of a ratio to 5-HT2A effects. The reason all of this is so important though is because those "breakthrough" experiences to me completely resemble the effect of deliriants where abstract hallucinations steadily increasing in realism reach a point of panoramic effect where they overtake your consciousness and bring you to a totally other place. The significant difference here would be that on a deliriant you see things that are, relatively speaking, much more normal, but on a psychedelic the hallucinations would mix with the already very powerful hallucinogenic effects of 5-HT2A activation to create the bizarre dream worlds that users of tryptamines are familiar with.
Many tryptamines, synthetics included, are described as having an empathogenic effect, and it wouldn't surprise me if 5-HT2B activation was the culprit to that too. After all, they're all so similar to serotonin that it really wouldn't be that shocking if most or all of them had some affinity for it.... Tryptamines aren't the only thing that's really making me think this though. Going back to LSD and mescaline... I often see the two related to each other in effect, and both of them to the phenethylamine psychedelics. LSD is of course a bit more tryptamine-y likely due to hitting a few more serotonin receptors, but I generally assumed that dopaminergic effects likely play a role in why these drugs all feel pretty similar to each other. Now I'm thinking though that there's more to it too.... I'd still like to see some affinity data of course, but if mescaline doesn't bind to 5-HT2B then I don't think it would be nuts to expect that many of the 2C-x compounds don't significantly activate it either. If that was the case, wouldn't it make sense to lump then in more with mescaline and LSD? On the other hand, as far as I'm aware many of the DOx compounds have been shown to bind to 5-HT2B, along with bromo-dragonfly and several of the 25x-NBOMe compounds as well. Are those psychedelics not all known for being able to cause particularly powerful hallucinations even leading to possibly psychosis (aka... delirium) at higher doses? The difference would be that they also have significant physical effects, and so you probably wouldn't want to take them at the point of trying to reach breakthrough like you would for a tryptamine; however, I still think the similarities are notable....
I realize that there are no sources in this, but that's just because this is information that I've been building up over time, not something I just worked all on recently. I would be happy to dig up my sources again if anyone needs to see them. I may have left something out too... but if I forgot anything then I'll add it in later in newer posts. In the meantime, does anyone else have anything to add to this, whether it helps or hurts this theory? I'm interested in what anyone has to say!
So on to the point.... I am a strong proponent of the idea that most receptors in the brain can have a significant impact on the hallucinogenic effects caused by 5-HT2A agonists, even if those receptors didn't seem to be significantly hallucinogenic on their own. Because of this I am always trying to look more into other monoamine receptors specifically so that I can make an attempt to understand the effects of various psychedelics. Following in line with this, one of my biggest interests has been the 5-HT2B receptor.
When I use the term delirium in the title of this thread, I am trying to relate it specifically to the effects caused by anticholinergic deliriants. Not many of the physical effects such as stimulation and dysphoria so much, but the effects on consciousness and perception. In my more reckless days, I experimented with diphenhydramine on occasion.... For those who aren't familiar with the general progression of deliriant hallucinations as doses increase, I will detail my personal experiences and information that I've gathered from the accounts of others here. A lot of people say that deliriants don't have visuals like psychedelics, but I tend to find that the people who say this are the ones who only ever had one strong deliriant trip and never tried them again, and I feel that I can explain this. In lower doses, they definitely do have some more "typical" visual effects; patterning, distortion, and more abstract hallucinations are common. At higher doses, the strength of these effects increases to the point where they cover a much more significant area of your visual perception, reaching fully panoramic scenes at very high doses. I personally believe that that's why those who have only experienced high doses don't believe that normal visuals are common, because they spend their entire trips fully immersed in these strongly-generated imitations of reality rather than riding the line in between "clearheadedness" (I use the term lightly) and full delirium. An example of this with diphenhydramine would be how at full doses people talk about seeing spiders and having full conversations with people. At only moderate doses, I've experienced effects that are quite clearly the same kinds of distortions at work, but to a lesser degree; colorful, translucent form constant patterns with shapes that certainly do resemble the movement of spider legs but don't quite reach that full hallucinations, and hearing random hallucinated words here and there that never amount to full sentences, instead sounding more like sound distortions on something like mushrooms like... which will actually play into what I'm trying to get at in a bit. It's also quite common at least for me on deliriants to stare at certain objects and not realize until looking closer that they're something very different from what I originally thought, but full delirium is not necessarily required for that.
Then there's MDMA. It seems like one in at least every few drug users with much experience is aware of the fact that MDMA can cause a fairly powerful delirium upon either redosing or adding something such as cannabis or ketamine into the mix, particularly on the tail end of the experience. I have also read many reports where people mixed MDMA with full psychedelics, such as one about mescaline that comes to mind especially, and found that the abstract hallucinations of the psychedelic became much more "real" from that point on, generally being pushed into the visionary or out-of-body state. I don't have nearly as much experience with combining MDMA with psychedelics as I would like, but I have redosed and mixed it with cannabis on several occasions to achieve this effect. While the visual effects are slightly differing in their art style in some ways, the overall effects are strikingly similar to what I have experienced on deliriants. The realism of the visuals is out of this world, and it basically feels like a deliriant with some psychedelic flavoring added in. For a long time it was actually a common practice in my group of friends to get this effect going as strongly as possible, and I have friends who managed to trip much harder on it than I did. One in particular stands out who got the furthest of any of us on two separate occasions, and I would say that his behaviors were indistinguishable from someone in the throes of anticholinergic delirium. While the rest of us were mostly achieving the abstract patterning and maybe moments of fleeting full delirium every now and then, he was completely submerged in that panoramic state. The way he responded to use and mumbled to himself and people who weren't there, and kept thinking that we were in his house instead of mine, or thought he was playing Xbox in front of a TV that was off... it was all perfect. I've never even seen someone trip as hard on an actual deliriant as he did on that MDMA and cannabis combination both times, it was like something out of a heavy datura trip report.
I've heard a lot of people suggest that these hallucinogenic effects of MDMA are mediated by its eventual metabolism into MDA, which makes enough sense to me. However, I've also seen research studies that suggest that many of the empathogenic qualities of these drugs (particularly involved in serotonin and dopamine release) come from activation of the 5-HT2B receptor. The same seems to hold true for the more recent research chemical analogues of these drugs as well. I'm going to tie this into a bigger picture, but at first, this is what made me really become interested in it. If we just assume for now that this is the case, that 5-HT2B adds some delirium to the effects of 5-HT2A activation, it would fit quite well, wouldn't it? All of these MDMA analogues that have psychedelic effects are known to cause particularly realistic and delirious hallucinations on top of their normal effects, and though MDMA doesn't on its own because it's lacking in significant 5-HT2A affinity in normal doses, anecdotal reports would seem to suggest that it has the same or at least a similar effect when it is combined with a 5-HT2A agonist. One that especially stands out to me though is MMDA. Reports of this drug are pretty hard to come by, but the most significant one to me is the one here by morninggloryseed. MMDA is said to be a fairly specific serotonin releasing agent, and given its similarity to MDMA I don't think it's absurd to suggest that 5-HT2B plays a role, as well as a 5-HT2A agonist, and it's said to create incredibly realistic visuals with closed eyes. In morninggloryseed's reports, many of the effects he details as part of the experience are extremely similar to those caused by anticholinergic deliriants such as what I mentioned above, and I've even gotten something similar to what he describes about seeing the vivid internet browser with clear but meaningless text on it on diphenhydramine before. I think this is a particularly important example to follow, however you don't have to use something so rare to see this either... many, many people report delirious hallucinations from MDA such as seeing objects or people on the dance floors of clubs that aren't actually there. The more you read about these experiences, I think the harder it gets to differentiate them from many that are reported from anticholinergic deliriants.
Here's what I'm really trying to get at though.... Those MDMA analogues are strong 5-HT2B agonists but presumably not incredibly potent 5-HT2A agonists, as psychedelic effects are not the main part of what they're used for. So what about 5-HT2B activation by something that is used primarily for its psychedelic properties? Well, that leads me here.... Let's consider the four best known psychedelics: LSD, mescaline, psilocin, and DMT. The former two are known for being more stimulating in a dopaminergic way and causing trips that, while they can be very powerful and hallucinogenic, tend to take place more "in reality", even if reality seems pretty difficult to comprehend at the time. The latter two are known for much more easily causing those breakthrough experiences filled with entities that transport you to a completely different realm. LSD has been shown to bind to 5-HT2B only at very high doses, above what would be considered in the normal range of use. As far as I'm aware, mescaline has never been shown to have any significant affinity for 5-HT2B. At least one study I found, on the other hand, has shown psilocin to bind quite strongly to 5-HT2B, maybe even much more so than to 5-HT2A. DMT has been known to bind to 5-HT2B for some time, relatively unselectively in comparison to most other serotonin receptors it binds to. This is quite significant to me, because psilocin has also, in my experience, been the one to cause much more brain fog (not necessarily meant in a bad way), memory disruption, and general dissociation of mind from behaviors than DMT at least at normal doses, which would be supported well by my theory of 5-HT2B delirium if it works as part of a ratio to 5-HT2A effects. The reason all of this is so important though is because those "breakthrough" experiences to me completely resemble the effect of deliriants where abstract hallucinations steadily increasing in realism reach a point of panoramic effect where they overtake your consciousness and bring you to a totally other place. The significant difference here would be that on a deliriant you see things that are, relatively speaking, much more normal, but on a psychedelic the hallucinations would mix with the already very powerful hallucinogenic effects of 5-HT2A activation to create the bizarre dream worlds that users of tryptamines are familiar with.
Many tryptamines, synthetics included, are described as having an empathogenic effect, and it wouldn't surprise me if 5-HT2B activation was the culprit to that too. After all, they're all so similar to serotonin that it really wouldn't be that shocking if most or all of them had some affinity for it.... Tryptamines aren't the only thing that's really making me think this though. Going back to LSD and mescaline... I often see the two related to each other in effect, and both of them to the phenethylamine psychedelics. LSD is of course a bit more tryptamine-y likely due to hitting a few more serotonin receptors, but I generally assumed that dopaminergic effects likely play a role in why these drugs all feel pretty similar to each other. Now I'm thinking though that there's more to it too.... I'd still like to see some affinity data of course, but if mescaline doesn't bind to 5-HT2B then I don't think it would be nuts to expect that many of the 2C-x compounds don't significantly activate it either. If that was the case, wouldn't it make sense to lump then in more with mescaline and LSD? On the other hand, as far as I'm aware many of the DOx compounds have been shown to bind to 5-HT2B, along with bromo-dragonfly and several of the 25x-NBOMe compounds as well. Are those psychedelics not all known for being able to cause particularly powerful hallucinations even leading to possibly psychosis (aka... delirium) at higher doses? The difference would be that they also have significant physical effects, and so you probably wouldn't want to take them at the point of trying to reach breakthrough like you would for a tryptamine; however, I still think the similarities are notable....
I realize that there are no sources in this, but that's just because this is information that I've been building up over time, not something I just worked all on recently. I would be happy to dig up my sources again if anyone needs to see them. I may have left something out too... but if I forgot anything then I'll add it in later in newer posts. In the meantime, does anyone else have anything to add to this, whether it helps or hurts this theory? I'm interested in what anyone has to say!
