Psychopharmacology of hallucinations/dissociation mediated by "other" receptor sites

[Mongrel]

Psychopharmacology of hallucinations/dissociation mediated by "other" receptor sites

Other than the 5-HT receptor agonists & NMDA receptor antagonists, both of which have a pretty well understood method of neurochemical action in the brain, what is to be said of the GABAergic hallucinogens, the Kappa Opiod receptor agonists, CB1 agonists, Muscarinic acetylcholine receptor antagonists, Sigma receptor agonists, & D2 receptor agonists?

What mediates the hallucinogenic effects of each of these receptor sites?

Have any of you expierenced any effects from any of these classes of drugs, & if so can they be described?

What causes dissociative effects from KOr agonists & Sigma receptor agonists?

What do hallucinations from GABA agonists consist of?

& Does anybody know anything about the hallucinogenic activity mediated by D2 receptor agonism, from such chemicals as Apomorphine, Bromocriptine, Cabergoline, Lisuride, Memantine, Pergolide, Piribedil, Pramipexole, Ropinirole, Rotigotine, etc. Is this class of "hallucinogen" inseperable from stimulant psychosis as expierenced with prolonged cocaine or amphetamine use?

If anybody has any knowledge on the subject, or expierence with any of these things, please share your insights.

 

[amapola]

We'll try this over in Psychedelic Drugs (PD) for the moment to get some views. If the mods there think this is complex enough to belong in ADD (Advanced Drug Discussion) then they can send it along.

homeless >>> PD

 

[sekio]

"What mediates the hallucinogenic effects at these receptor sites?" I don't know, how about you hire a team of graduate students. Figuring out how receptors influence our perception has been a long-standing problem in neurobiology.

AFAIK -

D2 agonism is non-hallucinogenic as far as I know (neither apomorphine nor lisuride is a hallucinogen - in fact apomorphine induces vomiting) though it may produce major changes in mood (hypersexuality, compulsive gambling and so on). It's interesting to note that dissociatives like ketamine and salvinorin share affinity for this site - maybe it is hallucinogenic with high enough affinity ligands.
Sigma receptor is a very complex protien that (to me) seems to be correlated with dissociative/euphoric effects and antitussive activity, though that's just from a quick and dirty SAR of drugs that act there.
Anticholinergics work by seriously disrupting the normal signalling of your brain and muscles, probably disengaging different parts of your brain from each other.
Kappa opioid agonism produces dysphoria pretty consistently along with anethesia and extreme dissociation - I bet dynorphins are tied into sensory signallng and "ego" somehow.
CB1 agonism is studied fairly well, but I couldn't tell you how it works off the top of my head - there are a variety of processes that are activated with the activation of CB1.
GABA-agonistic hallucinogens (e.g. muscimol) are very strange and may be related to the selective inhibition of normal "filters" that keep our dreams "out of sight" so to speak.


Hope this helps.

 

[OpioPhyllis]

In regards to the GABAergic hallucinations, I found that there is some research being done, post-mortem, on the brains of those who had schizophrenia, bipolar disorder, and major depression. According to the summary, the University of Minnesota's hypothesis is "that expression of molecules involved in the Reelin and GABAergic signaling pathways are altered in subjects with schizophrenia, bipolar disorder, and major depression resulting in dysfunctional signaling and consequent brain abnormalities in these disorders."
But otherwise, I wasn't aware that GABA was significantly implicated for hallucinations in healthy individuals.

 

[Thorns Have Roses]

What do hallucinations from GABA agonists consist of?

I believe the GABAergic hallucinogens all have an affinity for the GABA alpha-rho subunit (once believed to be a distinct GABA-C receptor).

Also, possibly of interest to you, a description of my first (of two) and highest dosed experience with zaleplon:

NSFW:

I consumed 40mg zaleplon the other night, I had had a stressful day involving gang members, cops, and heated familial confrontation, so I decided to take some sonata samples I found around to fall asleep quickly. I chewed up the capsules and swished the material around in my mouth with water until I began to feel effects, I decided to go with sublingual administration due to the fact the drug only has 30% oral BA, though given the fact that it's insoluble in water, I don't know how effective this method was. (note: the inner paper described the only adult overdose known to have inolved 100mg zaleplon and 1.25mg triazolam, so I figured I was well within the safety margin).

Anyway, I had my eyes closed and something like a movie was playing on the back of my eyelids, dreaming while awake if you will, this was rather interesting. But within a few minutes I started to feel my bed floating, and had the sensations that something like snakes were slithering under my sheets. Now, I knew hallucinations were a side effect, so I was merely excited by this, rather than frightened, and I started looking around my room (which was dark). My pieces of furniture looked not at all like furniture, but living things that were interacting with one another, producing some amount of audible sound, (the appearance was a mix of Dr. Seuss and the Mos Eisley cantina, with some Lovecraft and old school fantasy thrown in). Rinkles in my sheet appeared to be moving lizards, the darker floral parts of my pillow case windows, and my depth perception was quite off. And not only were existing objects distorted, but non-existant things manifested quite clearly, there were cobwebs in the air that I could wrap around my finger, and blow off into the wind, and several beings (something with a trenchcoat and beak, and a faerie, among others) appeared where there were no objects to distort. I was not delirious however, I was lucid and aware of the fact that I was hallucinating the entire time.

This is quite remarkable to me, a truly hallucinogenic drug (unlike 5ht and nmda mediated "hallucinations" which are more just caused by over and underactivity in the whatever parts of the mind create objects on visual data, IME. Well, high dose 4-meo-pcp and DXM binges seemed to transorm objects quite effectively. I remember one time my desk appeared to be a torii in the sea, and once my computer held up by a forklift, but my mind was too barely functional to truly appreciate it, but this was quite vivid. Though I think this is merely an extreme example of my mind trying to paint objects on visual data but being too fucked up to do it with any semblance of accuracy) that isn't merely the waking dreams of delirium.

 

[Mongrel]

What are some Sigma receptor agonists one can expierence dissociation off of? Any OTC drugs? And are these effects memorable or worthwhile?

This is quite remarkable to me, a truly hallucinogenic drug that isn't merely the waking dreams of delirium.

That truly is insane, It sounds wonderous. Most people who are drug naive would think that mushrooms or acid would do something like that. I'm surprised that state is both attainable & lucid, I figured such expierences were only will & whim to deliriants.
Would amanita muscaria have any effects comparable to zaleplon? I once had a whole ounce but thanks to too little information & lots of misinformation I never really touched the things out of fear they would be a deliriant.

 

[Thorns Have Roses]

That truly is insane, It sounds wonderous. Most people who are drug naive would think that mushrooms or acid would do something like that. I'm surprised that state is both attainable & lucid, I figured such expierences were only will & whim to deliriants.
Would amanita muscaria have any effects comparable to zaleplon? I once had a whole ounce but thanks to too little information & lots of

I only tried A. Muscaria once, years ago, and didn't prepare it correctly, all I got was a loss of short term memory. In theory it should produce comparable effects. I should note however that from the pharmacological fact sheet that came with the sonata samples (Incidence of treatment-emergent adverse effects in the long term (28 and 35 nights) placebo controlled clinical trials of sonata*), out of 297 people taking 20mg zaleplon, only 1% reported hallucinations as a side effect, and less than 1% reported them at doses of 5mg, and 10mg. Amnesia was reported at 1% in the 5mg group (344 people), 2% at 10mg (569 people), and 4% at 20mg. Confusion was reported with the same instance as hallucinations.

I'm one of the <1% who get hallucinations at 10mg (though they increase in intensity and complexity with increased dosage), so it may be that the GABAergic hallucinogens only show their full potential to a lucky few. Since it seems amnesia has greater incidence than hallucinations, simply increasing the dosage may lead to experiencing the desired effects and simply not remembering them. Of course, I'm not sure that the properties of this drug are extendable to other drugs of the class.

 

[Mongrel]

Damn dude, that sucks. I always felt bad for the people who's brain chemistry was unafflicted by Salvinorin. It's almost as if there's a window they'll never get to look through. Are the effects you described exclusive to zaleplon alone? Because THAT is a definate window I hope to one day climb through.

EDIT:

I'm not sure that the properties of this drug are extendable to other drugs of the class.

Ah, nevermind. It could be a possibility after all.

 

[sekio]

Known sigma receptor agonists that have dissociative effects include dextromethorphan/dextrorphan, ketamine, PCP, the azocine opioids, and ibogaine. Other drugs of interest that posess affinity are DMT, methamphetamine, noscapine, morphine/heroin, and a whole slew of exeprimental ligands.

I find it unlikely that certain people are "unaffected" by salvinorin, it is ridiculously potent if administered properly (which can be hard to do).

 

[Thorns Have Roses]

Damn dude, that sucks. I always felt bad for the people who's brain chemistry was unafflicted by Salvinorin. It's almost as if there's a window they'll never get to look through. Are the effects you described exclusive to zaleplon alone? Because THAT is a definate window I hope to one day climb through.

Effects should definitely be similar amongst the other Z hypnotics (zolpidem, zopiclone), it's just that zaleplon has the shortest half-life / duration, and may be slightly more effective at causing the desired effects (I believe I read another post on here somewhere where someone who had more experience with the other z drugs than I said as much). I'd also expect muscimol would be substantially similar, at least in many respects, I'd love to do some experimentation to find out (alas, finances prevent me from trying so many things I'd like to). If you get a chance to try out any GABAergic hallucinogens and experience some success, be sure to post it on here or the thread I have on the subject.

And on salvinorin, I never actually achieved breakthrough with that subtsance in my half dozen uses of salvia. Probably not a strong enough extract/less than ideal technique. The shit was weird though, I remember most vividly that odd pulling sensation.

 

[Mongrel]

I find it unlikely that certain people are "unaffected" by salvinorin, it is ridiculously potent if administered properly (which can be hard to do).

I'm pretty sure I've read of people having no success with it, but then again some people may need 40x to have a 5x trip, & some people can breakthrough on they're first time doing 5x. People have different sensibilities to it. I'm also aware it can take a few uses to actually procure any effects from it (may have to do with Reverse Tolerance, which I have observed in my own salvia use).
My friend's girlfriend tried a bunch of different extract strengths & never felt anything from it

Effects should definitely be similar amongst the other Z hypnotics (zolpidem, zopiclone), it's just that zaleplon has the shortest half-life / duration, and may be slightly more effective at causing the desired effects (I believe I read another post on here somewhere where someone who had more experience with the other z drugs than I said as much). I'd also expect muscimol would be substantially similar, at least in many respects, I'd love to do some experimentation to find out (alas, finances prevent me from trying so many things I'd like to). If you get a chance to try out any GABAergic hallucinogens and experience some success, be sure to post it on here or the thread I have on the subject.

And on salvinorin, I never actually achieved breakthrough with that subtsance in my half dozen uses of salvia. Probably not a strong enough extract/less than ideal technique. The shit was weird though, I remember most vividly that odd pulling sensation.

Thanks to these discussions GABAergic hallucinogens have become grounds I intend to cover, especially with that trip you described. When the expierences come they will be reported

In my expierence, Salvia is something you really need to invest time in if you want the most out of the relationship. I figure the ratios I've been using it I'm more bound to have a glowing expierence when I break through, rather than the expierence of going to hell. It's kind of expected with the compound though, higher the dose range, greater the dysphoria. I really enjoy it though, despite how people recieve it. I've always made the most out of it.
The one thing that sucks though is the trip is almost impossible to entirely integrate into linguistics, & that the majority of the effects are forgotten until the next time you do it. Even a month or so of doing it alot hasn't been too recallable, but I know that Sally & her Fairy kin are always waiting for my return to their world Every time I revisit that place i get a sense that "They" have missed me.
All the time investment in getting accustomed to the effects & working up a reverse tolerance has really paid off though.

 

[skillet]

I find it unlikely that certain people are "unaffected" by salvinorin, it is ridiculously potent if administered properly (which can be hard to do).

Same with zalepon hallucinations - could it not just be that 1% of the participants failed to fall asleep and noticed them, while most of the participants just fell straight asleep. I had a similar, though milder, experience to Never Knows Best with 10 mg, and I bet most people would.

 

[Mongrel]

Known sigma receptor agonists that have dissociative effects include dextromethorphan/dextrorphan, ketamine, PCP, the azocine opioids, and ibogaine. Other drugs of interest that posess affinity are DMT, methamphetamine, noscapine, morphine/heroin, and a whole slew of exeprimental ligands.

With the exception of Noscapine, the majority of these seem to have shared interactions with either the NMDA & Kappa Opiod receptors (azocine opiods). I'd like to expierence the effects of sigma agonism without the effects mediated by other receptor affinity (to get the cleanest idea of the dissociative effects mediated by sigma agonists). Suppose I'll have to find Noscapine somewhere. I've read alot of discussion about Noscapine but never any expierence reports. Hopefully I can find the stuff online.

 

[Thorns Have Roses]

Same with zalepon hallucinations - could it not just be that 1% of the participants failed to fall asleep and noticed them, while most of the participants just fell straight asleep. I had a similar, though milder, experience to Never Knows Best with 10 mg, and I bet most people would.

That experience was with 40mg sublingual/oral, my 10mg was much milder as well.

 

[skillet]

Yeah I know, I worded it really badly sorry. I meant the study was presumably into the efficacy of zalepon at inducing sleep, so they probably gave it to the participants and had them immediately lie down in bed. Maybe 99% of them fell asleep as soon as the drug took effect, the 1% that didn't were the ones who noticed the hallucinations. I bet if you gave people 10mg plus and had them do something to stay awake, most of them would get the hallucinations. Do know any more details about the study?

I'm curious to compare muscimol too, though it doesn't really sound very similar, just need to find some amanitas...

 

[Mongrel]

Thujone(salvia offinialis) is interesting but ultimately dissapointing. I figure Absinthe isn't anything special, could be though, with the combination of ethanol & thujone working on the GABA system.

 

[sekio]

A bit of a digression - the best mechanism of action for the thujone in absinthe that I have read of is that of an antinauseant agent due to its action at 5-HT3 receptors in the gut, allowing one to drink more alcohol than usual. I have serious doubts about the efficacy at central GABA sites and the resulting "psychoactivity" that people hypothesize. I don't get stoned when I eat poultry seasoning.

 

[allium]

Just for your information, erowid has some interesting reports on wormwood.

 

[Mongrel]

Just for your information, erowid has some interesting reports on wormwood.

Thanks for the info. I guess I figured Thujone was bunk because all my friends & I got from smoking sage was a headchange, & a bit of "The Dollhouse effect". Even smoking bowl after bowl after bowl didn't make the effects more pronounced. It's true that Wormwood & Sage aren't the same thing either. Read a trip report in that link of someone having success with an extract & seeing entities.

 

[SNR]

What are some Sigma receptor agonists one can expierence dissociation off of? Any OTC drugs? And are these effects memorable or worthwhile?



That truly is insane, It sounds wonderous. Most people who are drug naive would think that mushrooms or acid would do something like that. I'm surprised that state is both attainable & lucid, I figured such expierences were only will & whim to deliriants.
Would amanita muscaria have any effects comparable to zaleplon? I once had a whole ounce but thanks to too little information & lots of misinformation I never really touched the things out of fear they would be a deliriant.

Pretty damn late reply (and an older post too, sorry) but this is a simple question. Dextromethorphan (DXM) an its metabolite dextrorphan are OTC and have appreciable affinity for the sigma 1 receptor at recreational doses. DXM is dirty stuff, but I'm sure sigma activation has somethin to do with DXM's effects, as DXM and other NMDA antagonistic hallucinogens are very different in effect.

~snr