Naturally occurring dissociative compounds?

[TheAppleCore]

We know that nature produces an abundance of serotonergic psychedelics, tryptamines in particular.

But are there any naturally-occurring compounds which exert a dissociative effect a la ketamine, PCP, DXM, methoxetamine, et al.? Any plants that produce NMDA antagonists?

Also, are any of the above listed drugs semi-synthetic -- synthesized by manipulating a naturally-occurring base compound -- or are they fully synthetic? If so, which are semi-synthetic?

 

[delta_9]

Ibogaine would probably be the most well known example, and it's the only one that comes immediately comes to mind. It's entirely possible that there are some related alkaloids produced in the iboga or similar plants that we simply haven't yet isolated.

 

[kitsunedemon]

But are there any naturally-occurring compounds which exert a dissociative effect a la ketamine, PCP, DXM, methoxetamine, et al.? Any plants that produce NMDA antagonists?

Although not dissociative in any shape or form Kratom and many of it's alkaloids are NDMA antagonists, as previously mentioned by Delta 9 the only other one I can think of is Ibogaine.

However Amanita Muscaria (Fly Agaric) and Datura (Scopolamine being the active alkaloid) could be comparable due to the delirious and detatched state they put you in, although they can also be extremely dangerous due to dosage and freaking out due to delirium and I've heard the trips can be awful... 8(
More so with Datura than Fly Agaric though.

As far as I'm aware all of the above drugs you listed are fully-synthetic, but I'm no expert and haven't really researched it.

 

[Survived Abortion]

I've been wondering the exact same thing TAC. I think there must be.

Firstly, we know that there are NMDA antagonists in nature, such as alcohol, ethnobotanicals, and various ayurvedic and chinese herbs. It's just we haven't isolated any particular compound with the demonstrable effect of producing a dissociative effect comparable to the drugs you listed.

Perhaps there are many which can. It may be a case of trying to find those compounds with similar SARs, extracting them, and seeing if they have a favourable entheogenic/toxicity profile. The ability to elicit a "hole" or "plateau" state without too many physical side effects would be the important thing to look for. The reason ketamine is such a good compound both for anaesthesia and entheogenic exploration is because it is so physically benign in acute doses. Even DXM and PCP are physically safe (in acute doses, not long term!) when compared to something like ibogaine or alcohol.

I too would be fascinated if we stumbled upon a herb which provides a significant yield (in comparison to any other alkaloids it may contain) of a potent NMDA antagonist dissociative.

 

[lulzkiller]

Salvia?

 

[OTGee]

Salvia?

And I believe fly agaric are classed as a dissociative, they are the only well documented ones to my knowledge the other mentioned here are deleriants although I do not know what ibogaine is classed as.

 

[Roger&Me]

But are there any naturally-occurring compounds which exert a dissociative effect a la ketamine, PCP, DXM, methoxetamine, et al.? Any plants that produce NMDA antagonists?

It is, of course, not comparable to ketamine and the like -- but NMDA antagonism plays a significant role in ethanol's pharmacological profile. So grapes and such that are symbiont with yeasts necessary for fermentation could be considered a natural source of an NMDA antagonist.

Its unlikely that we'll find arylcyclohexylamines occuring spontaneously in nature because they can't be biosynthetically derived from amino acids through enzymatic pathways that are common to many forms of life (such as in the case of tryptamines and phenethylamines).

 

[delta_9]

Salvia has no activity at nmda as far as I know. Datura alkaloids are anticholinergic, and amanitas only have 1 compound(ibotenic acid) with activity at nmda.

and various ayurvedic and chinese herbs.

I'm curious to know what these are

 

[Survived Abortion]

Its unlikely that we'll find arylcyclohexylamines occuring spontaneously in nature because they can't be biosynthetically derived from amino acids through enzymatic pathways that are common to many forms of life (such as in the case of tryptamines and phenethylamines).

But could they be produced through other pathways? As you may be able to tell, I'm not a biochemist. But if we can produce them in a lab, there is surely every possiblity that a biological life form could synthesize it, especially considering the superior efficiency and capability of DNA-based life to synthesize new chemicals.

 

[delta_9]

But if we can produce them in a lab, there is surely every possiblity that a biological life form could synthesize it,

Not necessarily. There are some incredibly complex molecules that we have synthesized in a lab that would be down right impossible for a plant/fungi to synthesize. For one thing, it would cost too much energy, and the organism might not even have the necessary mechanisms and precursor compounds needed to create it(as Roger explains) In addition, plants/fungi/etc only produce compounds that serve them some purpose (as per evolution)

Organisms don't just start synthesizing new compounds willy-nilly.

That being said, there are certainly other molecular structures that show activity at nmda and are synthesized in nature.

 

[Survived Abortion]

That's the point: there may be some plant/fungi whatever somewhere which synthesizes arylcyclohexylamines because it serves them some purpose. It's like cannabinoids in hemp, or 4-HO-DMT in the psilocybe mushrooms; what function does psilocin serve the mushroom that the portabella mushrooms doesn't require? It must be something innate to the physiology of that particular species.

Not that it's all about arylcyclohexylamines by any means.

 

[delta_9]

That's the point: there may be some plant/fungi whatever somewhere which synthesizes arylcyclohexylamines because it serves them some purpose.

Yes there may be, but the point is there's little if any scientific precedent for it(as far as I know).

what function does psilocin serve the mushroom that the portabella mushrooms doesn't require?

I believe we're still trying to figure this out. It may be some leftover secondary metabolite that was perviously needed for the organism but simply hasn't been phased out yet. It could also be a way to store excess phosphorus. There are plenty of theories but I don't think we've nailed it down yet.

As a side note - It's been suggested that cannabinoids help to protect the plant from UV light, but again I'm not certain that this has been confirmed.

 

[<SpaceHead>]

I have wondered about this many times. I know xenon is present in trace amounts in the atmosphere and it is a dissociative anesthetic like N2O, although does that antagonize the NMDA receptors? It does seem fitting considering the nature of the arylcylohexalamine experience that they would be entirely unnatural. I don't know too much about chemistry, but the synthetic dissociative molecules visually look unnatural with their odd symmetrical like arrangement, especially PCP. Also, interestingly, Ibogaine and some of the active chemicals in kratom seem to look alike in some ways, DXM kindof looks similar to them in shape aswell, and yohimbine sortof fits in there. I never see organic chems that look much like that, (again my chem knowlege is pretty limited to Phikhal and tihkal) Ibogaine has that same kind of physical lag feeling of DXM or ketamine where you move your head and then you actually feel your head moving a couple seconds later, although under ibogaine this creates far worse nausea than with the dissociatives. Same with alcohol I suppose. Do GHB/ GBL have the same effects on NMDA? They certainly share that physical effect.

 

[Biovail]

In addition, plants/fungi/etc only produce compounds that serve them some purpose (as per evolution)

Organisms don't just start synthesizing new compounds willy-nilly.

This is a bit misleading.. Plants don't synthesize compounds because they're helpful. They synthesize compounds willy-nilly, and if those compounds happen to be helpful, their offspring are more likely to have genes causing them to synthesize the same compounds. Even if they're not helpful, there's still a chance the gene that caused that synthesis will be passed on so long as it isn't detrimental to the plant's survival (in other words, a quirk of evolution).

 

[stormcharger]

Yea but most plants now days are the remnants of million years of evolution so it is probably correct to say most plants synthesize compounds because its helpful.

 

[Thorns Have Roses]

If by dissociative you mean NMDA antagonist, then no, we haven't found one or else you'd be aware of it already.

If by dissociative you merely mean matching the dictionary definition of dissociation, then we have salvia and amanitas muscaria, among other things (entirely different than what recreational drug users such as ourselves would consider to be a dissociative).

 

[delta_9]

This is a bit misleading.. Plants don't synthesize compounds because they're helpful. They synthesize compounds willy-nilly, and if those compounds happen to be helpful, their offspring are more likely to have genes causing them to synthesize the same compounds. Even if they're not helpful, there's still a chance the gene that caused that synthesis will be passed on so long as it isn't detrimental to the plant's survival (in other words, a quirk of evolution).

My point is that a plant/fungi/whatever has to have the necessary precursor compounds as well as the necessary mechanisms/pathways to even begin to make a new compound.
Yes, an organism can have a brand new mutation in its genes that could cause it to start to produce a new compound, but unless there is some benefit to doing this, it is unlikely that this mutation will be become commonplace for the species as a whole(eventually of course. These things take time)

 

[sn23]

I stumbled over some interesting structures a while ago, which apparently are produced in plants of the Psychotria genus and are said to be NMDAr antagonists: Psychotridine and Hodgkinsine. I'm fairly certain they have been mentioned somewhere on BL already, but no trustworthy bioassays were performed if I remember correctly.

 

[Nexus298]

Has anyone tried Psychotridine or Hodgkinsine? Hodgkinsine reportedly has mu agonism as well as NMDA antagonism. Hodgkinsine is basically 3 eseroline's stuck together minus the hydroxy group (which can make or break an opiate). Eseroline is said to be a "fairly potent" opiate. I was thinking of importing some Psychotria colorata but I'd like to here trip reports on it first.

 

[TheAppleCore]

Yes, an organism can have a brand new mutation in its genes that could cause it to start to produce a new compound, but unless there is some benefit to doing this, it is unlikely that this mutation will be become commonplace for the species as a whole(eventually of course. These things take time)

Not necessarily. Often, certain traits can become widespread in a species, simply because the genes that are responsible for the trait, and the genes responsible for another more adaptive trait, share a similar location on the same chromosome in the species' DNA, and so the two traits are carried from parent to offspring hand-in-hand. In other words, a useless trait "tags along" with a useful trait by close association in genetic code.