You have the mu-opioid receptors which are responsible for mediating all the wonderful, classical opiate effects; you just generally feel extremely comfortable and content when it's activated. Then you have delta-opioid receptors which I guess are responsible for mediating some portion of the pain relieving qualities of opioids.
But then there is the kappa-opioid receptor which the active drug contained within Salvia Divinorum binds to. Like what? Lmao that's kinda bizarre that an opioid receptor is mediating such wild effects. People don't generally think an opioid receptor being activated can make you believe you're in the humans-are-chairs dimension, but here we are. Also the weird, extreme feelings of dysphoria kappa activation can cause, like a feeling of impending doom. Polar opposite to the mu-receptors in possibly every way.
What's weirder is the body has a natural endogenous agonist for the kappa receptor. It's called dynorphin. Kind of like the opposite of endorphins. Like wtf, why would my body want to be activating the kappa opioid receptor ever at all. I feel like this thing needs more research.
Buprenorphine, the active drug in Suboxone, is actually a mixed opioid agonist/antagonist. It's a partial agonist at the mu-opioid receptor. This means it activates it to the extent it will stop withdrawals and cravings, but if you have an opioid tolerance it won't activate it enough to get you high. But it's also an antagonist at the kappa-opioid receptor.
You know the drug Naloxone? It's used to revive people from an opioid overdose. It works by being an antagonist at the mu receptors. That means it binds to the receptor but doesn't activate it. In doing so it reverses the effects of any opioids in your system such as respiratory depression. Since it is then taking up space on the receptor, the other opioid molecules in your body are then unable to bind to it themselves. This reverses the overdose.
As I said, Buprenorphine does this at the kappa receptor. That means people on Buprenorphine have blocked kappa-opioid receptors that their natural endogenous dynorphin can't bind to. What is the opposite of thinking you're a piece of furniture? Idk, but this suggests to me that if someone is having a bad Salvia trip, you could probably reverse it by quickly giving them Buprenorphine. The same way that Naloxone reverse mu-opioid overdoses.
But what's more interesting to me is wondering about the long term effects of never having Dynorphins binding to my kappa-opioid receptors. Why would I ever want Dynorphins to bind to it? People don't generally describe the Salvia experience as pleasant. Idk
Just wondering out loud here, the way drugs interact with your brain to significantly alter your consciousness is very fascinating to me
Kappa is there to allow feelings of impending doom when you really need it- about to have a heart attack, stung by a deadly jellyfish, getting the wrong kind of blood transfusion or whatever. Not something you want to hear from but even worse if you don't have it.
Yes that's a very good point. Makes me wonder if kappa antagonism needs more study to determine if Buprenorphine dulls that sense too much. It's benefit as anxiolytic probably outweighs the negatives, though.
this is a fascinating avenue i've never considered and a great write-up. this is why i love neurochemistry. it seems to be one of those dark, unexplored frontiers of science that doesn't require insane math or massive, NASA budgets to explore.
as an aside my own personal, strong saliva trip was the worst experience i ever had with any substance. reality itself broke down, i was convinced i was dead, and was basically sent to some kind of hell dimension and flayed with burning pain. this was after the world flushed like a toliet. it was just intense, abject fear for what felt like hours. i was only in for 4 minutes, and my friends said i just sat there with my eyes wide and sweating. yeah, part of me wonders what the hell those receptors are actually for. if glutamate and NMDA can get you to "heaven" or an afterlife at least (ketamine, other dissos) then are these the receptors to send you to hell?
I haven't tried Salvia myself yet, but I have a morbid curiosity for it that I think will one day lead me to using it. I've always loved traditional psychedelics like LSD. I even loved the funky dissociative trips brought about by DXM. But everything I've heard about Salvia suggests it's another animal entirely.
Bizarrely, it's an opioid. Four years ago I got clean from opioids, though I still have a strong nostalgia when remembering their effects. It seems so alien to me that an opioid can do what Salvia does. I've read some research that suggests the kappa opioid receptor is involved in some way with making us feel fear. That makes a lot of sense I think.
I wish I could find some trip report from someone on Buprenorphine using Salvia. I'm on Buprenorphine, an antagonist of the kappa receptor. So I have some doubts Salvia would even work on me. If it does, then it would need to have a stronger binding affinity at the receptor then Buprenorphine, which is a tall order because Buprenorphine is known for holding onto receptors with absolutely wicked force. The only opioids that can casually push Buprenorphine off the mu-opioid receptor are those in the fentanyl family. Though, that isn't a guarantee it has the same strong binding affinity for antagonism at the kappa opioid receptors.
I feel like a strong part of the high that Buprenorphine can possibly produce isn't mediated by the mu opioid receptor at all. When I first got off opium, I tried using Buprenorphine instead, but it didn't work too well because of my insane tolerance to opiates. At this point, four years into daily Buprenorphine use though, I'm still getting a significant mood lift every time I take it. I think a lot of this might be due to antagonism of the kappa opioid receptor, basically producing the opposite effects as Salvia.
Also, regular opiates like Morphine and Heroin have the same kappa agonism ability as Salvia, just at a much lower potency. I would think opiate overdose would actually be a blissful way to die, but many people report intense feelings of extreme fear and panic when they overdose. This is probably mostly because they can't breathe, but I also suspect there is something going on with the kappa agonism at very high doses.
Yeah there a ton of weird opioids. Normally people think of just Heroin, Morphine, Oxycodone, and such, but there is a ton of variety.
Kratom is almost like an alternative and weaker Opium Poppy. Like the Poppy, it contains a large number of alkaloids active at the opioid receptors. The main one is Mitragynine, which interestingly, is a partial agonist at the mu-opioid receptor just like Buprenorphine, the opioid most commonly prescribed to treat opioid use disorder. People use it to get clean from opioids all the time due to sharing this property with Buprenorphine.
Partial agonists are extremely hard to overdose on because they don't activate the mu-opioid receptor enough to cause significant respiratory depression. However, Kratom also contains 7-Hydroxymitragynine which is a full agonist at the mu-opioid receptor, though it is contained in much smaller concentrations than Mitragynine. This is probably why people find it more recreational than Buprenorphine.
Buprenorphine is most often taken sublingually. So yeah, that's about 15 to 30 minutes before onset, in that case it would be too late.
But with other RoAs, I think it might come on fast enough to help. Nasal spray Naloxone is pretty quick at stopping opioid overdoses. So nasal spray Buprenorphine might be fast enough to be of some help with a bad Salvia trip, even if just makes the end of the trip more tolerable.
However, I think IV Buprenorphine would definitely be fast enough. It'd probably make more sense to just wait out the rather short trip than to go that far, though.
Yeah, it would not be practical if you had someone do it spur of the moment if a bad trip is becoming obvious. You'd need to prep it in advance. I'm just wondering if it is theoretically possible.
The og way to do salvia is to chew a big wad of the fresh leaves. It has a much more manageable intensity curve similar to traditional psychedelics apparently.
Salvia is like the generic "drugs" pickup in an 80s video game in it's effects.
I've had some experience with salvia, but I never considered them to be negative. I guess I had previously experienced other psychedelics like shrooms and LSD, so it didn't seem too intense in comparison. The really positive aspect of the salvia experience for me was what I call the afterglow. During the trip (over in 5 mins or less) you have a sense of disillusion of self that is equatable to stepping into a reality were you, as your self, no longer exist. This is also referred to as ego death. This is something that can be difficult to handle psychologically if you have not had similar experiences to relate to it. But, the afterglow, that's this slowly coalescing sense that you do exist in the world as a self. This made me feel very appreciative of all the kindness and connections I have with other people that actually care about me and my well being. Now, if you are terminally online or whatever, this feeling could easily take a turn into some serious self judgement with variable results. I guess just be prepared to have a very dissociative self critical struggle session if you don't have a good set and setting available.
I’ve never tried it, so my thoughts on it mostly come from reading the experiences of people who have. Those tend to mostly be negative. But there does seem to be a good portion of people like you who got something positive out of it. That’s the beautiful thing about hallucinogenic substances, every trip is unique.
Thanks for sharing your experience. The tail end of a Salvia trip essentially being the precipitation of ego sounds like a beautiful thing. It tears you down, dissolving everything about you, but then you get to experience being rebuilt from scratch piece by piece.
Have you experienced ego death on LSD and kept memories of it? If so, how would you compare the experience of ego death between it and Salvia?
Also thanks for that struggle session metaphor haha That's also exactly how I would describe a bad trip too now that you mention it, a struggle session with yourself within your own mind!
In my experience LSD ego death is more like a slow wave washing over you until you go under the surface. Salvia is much more abrupt and accelerated, more like the flip of a switch. With LSD, I usually have a sense of being a consciousness contained in within the physical vessel, kinda like piloting a mech suit. Salvia's dissociative effects can definitely verge into feeling more dislocated from your physical vessel for a short time. Now that short time can feel a lot longer than it is in real time. I think this is why it's common for folks to have bad salvia experiences. If you are not prepared to lose your corporeal self for a bit, things could easily go badly.
Once I did some 15x salvia with some folks that had never tried it before. Sitting on the floor, take the big hit, have someone take the pipe/lighter etc from the your hands as you lay back onto the floor. This protocol had pretty good results. The disorienting onset is so fast. Once the participant starts to come out of it, the after glow affect can really generate a strong sense of appreciation and bonding amongst the group. I went first as I had past experience, and I think this also helped the newbies feel more at ease with the whole thing.
I don’t really understand why I enjoy intense rollercoasters but I enjoy salvia for the same reason.
- by the time the buprenorphine kicked in, the salvia trip would be over.
Also, have you ever done a REAL solid dose of traditional opiates? That shit will blast you into space almost as reliably as salvia, although the experience is generally much more pleasant. I can actually see the throughline there.
Definitely, mainlining Heroin, you'll feel it kick in nearly instantly. In cases of overdose, people have been known to pass out before they even get the chance to remove the needle.
