Often, hallucinogens are catagorized in two main types: the tryptamine's and phenenthylamine's.
This has repeatedly led to discussions on whether a substance like LSD falls under one of these categories or not, or whether it resembles one of these categories more than the other.

The typical thing though, is that as well the tryptamines, the phenethylamines and the lysergamide's all work on the 5-ht-2 receptor.
Between all of these substances there are variances in other receptors they work on as well and you could see an overlap in the receptors that are being activated for most of these substances. for instance, many of these substances also affect taar-receptors.

I would say that instead of categorizing into tryptamines, phenethylamines and other chemical families, it makes more sense, categorizing the all of the known hallucinogens into 5-ht-2 entheogens and substances that bind to other receptor's. The only substance that falls in neither of the two categories is ibogaine, since ibogaine has the working mechanisms of as well a 5-ht-2 entheogen as a dissosciative, that binds to glutamate receptors.

Besides the fact that there is an overlap in receptors these 5-ht-2 substances bind to, there is also an overlap in effects.

Everybody who has experience with a view of them, will recognize the typical 5-ht-2 effect. Even if you would be introduced to a new hallucinogen, you would immediately be able to recognize whether it's a 5-ht-2 entheogen or not.

This would lead me to the conclusion that, although you could probably not exclusively atribute all of the main effects purely to 5-ht-2 activity because there is for instance a strong overlap between 5-ht-2 binding and taar binding, an experienced user could recognize the 5-ht-2 effects of a substance, itself.
It would mean that you could distinguish the effects of various receptor bindings, by experience.

I think that this would open many possibility's for neuropsychological research. Imagine that you could, by experience, tell what the effects where of binding to each individual receptor, because your test subjects would be able to distinguish the different effects of various substances.

For the first time, you could actually say something as "activity on the X-receptor will make you feel like this" and for the first time you could actually say something like this objectively, if you would have enough experienced testsubjects to compare.

If there wouldn't be such a tabboo on psychedelic research, not olny would we be able to far better understand how the brain works, but it would also be possible to make huge inprovements in the development of medications for all kind of psychiatric dissorders.

At least, this is what i believe.

There are some difficulties though.

For one, the psychedelic experience is highly subjective. Set & setting, and suggestion from self or others play a huge part in the effects of any psychedelic. It's just not that simple. Also everyone reacts differently to all chemicals. It wouldn't be very accurate to map receptor binding by subjective experiences of the ligand's psychoactive effects.

Also, in order to map the effects of single receptors you would need to create ligands that would bind only to a certain receptor, and for each receptor you need as many ligands as there are ways to activate that receptor.

That would quite frankly be impossible. The receptor proteins are in many cases so similar, that their ligands overlap a lot. Even psychedelics bind to many receptors at once.

Maybe in the future we will develop nanobots that can seek out a certain receptor and activate it. Imagine how cool it would be, you could download all your drugs from the internet as nanobot software...

Interesting post polytrip!..very knowledgeable..

I agree there is an overlap between substances like LSD, DMT, psilocybin, mescaline etc..but I feel like I can tell the difference between a phenethylamine and tryptamines..though I have limited experience with phens..

I have often wondered about the effects of ibogaine, and how the dissociative effects of it compare and contrast the effects of dissociatives such as salvinorin alpha..I would guess though that overall ibogaine is more euphoric/pleasurable than salvinorin for most people..

Lots of people place salvia in the category existentia..which makes sense..I wouldnt quite call it a hallucinogen..although it can def cause hallucinations!

I always thought that LSD hit both the seratonin and dopamine receptors..is that right?

I hope I am alive to see that day!!..sign me up!

In my opinion, it is a good idea to keep the dividing between phenetylamines and tryptamines, as they are metabolized by different kind of MAO. Tryptamines are mainly broken down by MAO-A, Phenetylamines mainly by MAO-B. Most MAOIs are selective in nature, for example does Harmala-alkaloids primarily affect MAO-A. As they only affect MAO-B to a small degree, Harmala-alkaloids will not give an extreme boost in effects from a phenetylamine.

man oh man have i been thinking a LOT about ibogaine lately....anyone try it? ever since i read Breaking Open the Head i've had a fascination with it. the fact that the pigmy tribe in africa that has an entire society centered around the stuff makes me think of an african ayahuasca of sorts. that they have a name for those who've done it that translates out to "awakened" and a name for those who have not that is the equivalent of "sleeper"....makes my brain meat quiver with excitement...

L&G!!

indeed, if 5HT2A were the sole psychedelic neurotransmitter, aniracetam would make you trip; it's a modulator of both AMPA and 5HT2A.

ibogaine is an interesting animal; it binds several receptors, including sigma and nicotinic acetylcholine

Yes, you are right.
But ofcourse i was thinking of exactly those objections you make, befrore i posted this. So why did i post it anyway?

Well, on it being a subjective experience wich veries from person, set and setting (if person is not already included in both set and setting).
-I am absolutely shure that you could feed me with any, to me unknown chemical, and that i would still be able to tell whether it's a 5-ht-2 entheogen or not. I am absolutely confident about this. No matter what the set and setting would be, i would be able to say coumpound 'A' is '5-ht-2' binding and compound 'B' is not.
-if you would have a test group that's large enough, the individual differences would fall away and you would get a picture of basic psychedelic properties related to the combination of receptor's that a compound binds to.
For instance: everybody more or less agree's that (for most people) 5-MeO-DMT is not a very visual substance, but that it's psychological effects are very strong compared to other psychedelics. So many people agree on this, that individual variations can be compensated. Ofcourse you could find someone for who it's exactly the other way round: lot's of visuals and hardly a change on the mental part.
But it wouldn't be unlikely that this individual would have different receptors, just like for instance people with ADHD have different receptors and respond differently to many substances.

The thing about there not being substances that only bind to specific receptors.
-You could also distinguish the effect of individual receptors by looking at the picture of combined receptor activity of different substances. There must be a significant difference in receptor affinity between 5-MeO-DMT, for instance, and psilocin.
If you collect tripreports of all known substances that fall in the same group (for instance 5-ht-2 entheogens or cannabinoids) then you can focus on the differences between those substances.
You could also make objective predictions on the basis of this.

It is innevitable that if you look at the greater picture of all the major 5-ht-2 entheogens, you will get an objective impression of the subjective effects of at least some individual receptors, or at least some specific combinations of receptors.

To me, it's interesting that there is a clear link between objective effects and subjective effects.
Establishing this link is exactly what's so exciting about this concept.

There are cases in wich a tryptamine and phenethylamine distinction is apropriate.
Yet it is also apropriate to aknowledge that also a substance like LSD, falls into the category of 'typical' psychedelic's while it's neither a tryptamine nor a phenethylamine.

At the same time MDMA is a phenethylamine, yet it is not psychedelic in the same manner as mescalin is. The effects of psychedelic doses of mescalin have more resemblences with psilocin or LSD then with MDMA.

So there is a whole group of substances that have something very basic in common. Something that, no matter what chemical family they belong to, set's them apart as psychedelic's, from substances like ketamine, salvia, fly-agaric or cannabis.

Making a difference between 5-ht-2 entheogens and non-5-ht-2 entheogens is practically the same as making a distinction between 'typical/classic' hallucinogens and atypical hallucinogens, but with the difference that you have a basis on wich you can make this distinction. A basis on wich you can explain as well the physiological as subjective differences.

Many compounds bind to 5-HT2a that are not hallucinogenic. Additionally both visual and non-visual hallucinogens bind. This is interesting however two compounds can bind to the same receptor and induce different responses. This is a relatively novel topic in pharmacology and is called agonist directed trafficking. This is when an agonist binds to a receptor and induces a specific second messenger response whereas a different ligand may bind and induce a different response. Diff compounds can have different relative ratios for the diff second messengers. 5-HT2a has been associated with PKC - IP3, DAG, and PKA-AA production among others. However neither seem to be correlated with Hallucinogenic activity. This area is understudied, and the activity of these compounds at the TAARs and other sites needs further investigation. Furthermore more selective antagonists are needed to help elucidate the role of given receptors.

The fact that one can have a strong psychedelic experience without visuals is fascinating (5-MeO-DMT, MIPT, AMT). The visual effects then must arise from some accessory activity. This activity does not appear to be the 5-HT2a receptor. However exactly "what effects" are 5-HT2a mediated is unclear. The only evidence is from antagonist studies with psilocybin using respiridone and ketanserin. Although the selectivity of these compounds for TAAR sites and other sites of action has NOT been performed. As a result of the the structural similarity of the TAAR sites and 5-HT2a receptor the activity of these antagonists at both is likely. Thus it is premature to say what role 5-HT2a plays in the subjective effects of these drugs in humans. Especially since non-HA 5-HT2a agonists exist. Although agonist directed trafficking could explain this observation.

Other non-5-HT2a sites are absolutely involved in the effects of these compounds. While 5-HT2a likely plays a role in the "similar" effects of hallucinogens other sites definitely are involved in the "unique" effects of the different compounds. It will be great to begin to analyze these compounds for their different subjective effects and begin to correlate this with activity at different receptors. Hallucinogen rating scales are very valuable in this regard. It is a shame their is such a barrier to this type of research in humans for the animal work can tell us very little if anything about subjective effects. Even though some research can occur it is only with established compounds. No clinical trial will be able to occur with the non-classical hallucinogens as their "safety" has not been determined in the eyes of the authorities. The underground community should begin to collect data in a effective consistent scientific manner on the subjective effects of these compounds. This data can than be used by researchers much as TIHKAL and PIHKAL are today.

I saw you posted a link to an interesting article on this subject.
The research you're refering at and the nuances you make are exactly what i'm talking about.

Ofcourse i don't hold 5-ht-2 activity solely responsible for the effects of the classic entheogens. It is just that 5-ht-2 entheogens often tend to bind to other receptors as well and that there is a strong overlap between in receptor agonism between these compounds. (ibogaine is the only exception to this family) Furthermore, i find that 5-MeO-DMT is not completely void of visual activity, it has very little in relation to it's other effects, wich might point at ratio's of relative receptor affinity as well.

I am also not sugesting that the effects of entheogens is simply a matter of addition. It might be that activity on various receptors combined is different than the simple addition of the effects of separate receptors activity.

Yet, the more we know about the physiological effects of each hallucinogenic and the subjective effects of them, the more we will be able to draw a link between subjective and objective effects, between psychological and physiological effects.

That is something science very much needs. There is no grand unifying theory in the field of neuropsychology yet. In physic's, scientists are working hard to construct such a theory, while in physics these attempts are much more likely to fail then in the sciences that study the mind.
Relating subjective phenomena to objective ones is a tabboo in science, for various legitimate reasons, yet, it is at the end the ultimate goal in science to be able to do so. I would even dare to say that as long as the sciences of the mind are not able to do this even slightky, they fail to come up with a proper explanation on what the mind is and how it works.
There hardly is any other doorway more suited for study's to establish exactly this link, then the combined research of pharmacological as well as subjective effects of these substances.

Anyway i think, taking all nuances in acount, that '5-ht-2 entheogens' is just a proper name for this categorie of substances because everybody immediately knows what kind of subjective and objective effects we are talking about. It's a name that stands for substances that not just bind to 5-ht-2 receptors, but a whole group of receptors. Yet this is a selective group, so it is a bit contradictory to call this group after one of the receptors it binds to, but there is no name for the cluster of receptors they work on, as far as i know, and the 5-ht-2 affinity was the just the first receptor of wich this was known.

There even might be entheogens that do not bind to 5-ht-2, of wich it would be still justifyable to categorize them in the 5-ht-2 entheogens, because of the total of the cluster of receptors they bind to.

This is no objection for categorizing entheogens in groups of clusters of receptors they bind to.
This is also the reason why we call morphine and fentanyl as well as methadon opiates in spite of their chemical unrelatedness.

And Salvinorin A

And THC, DXM, ketamine, ethanol, harmine, harmaline, and THH!

No, this is not true, since i meant the categories A- '5-ht2 entheogens' and B- 'non-5-ht2 entheogens', wich basically are all other entheogens.

Ibogaine however, has working mechanisms that resemble as well the typical 5-ht2 entheogens as the typical dissosciatives that mainly affect glutamate receptors; DXM, ketamine, PCP, PCC, etc.

This makes ibogaine a hybrid substance and unique.

If you categorize substances according to receptor activity, then indeed salvinorin becomes a new category or subcategory.

It affects the kappa-opioïd receptor. Yet it is not an opiate like morphine, heroïn or fentanyl.
It doesn't affect the cluster of receptors like the other opiates do, but only this specific receptor.

Maybe we should place this substance in the new subcategory 'psychedelic opiates'.

But that would lead to false associations. I mean, it feels nothing like opiates and after doing it, you usually don't want or need to do it again. It's a strange little creature.

BTW, I find this thread interesting, but can't really constribute due to lack of personal experience.

There is a term in the literature for describing chemicals with effects similar to psilocybin, LSD and mescaline (which is what we are talking about) and it is called classical hallucinogens. I think this is a more effective term than calling them after a receptor which many show affinity for. I see your point however I think it is dangerous to call it a 5-HT2a effect only because it will be misleading to so many. It is important to keep an open mind in this type of research and a name implies a lot. I think we all know what is meant by the term classical hallucinogen. PCP and ketamine (NMDA antagonists) are called dissociative hallucinogens. These types of chemicals have distinct effects on the mind subjectively and physiologically on the brain.

5-MeO-DMT has some mild visual distortion especially at high doses however in relation to compounds like DMT, and psilocin it can be considered a non-visual hallucinogen. You make a good point that it is likely the ratio of activity. 5-MeO-DMT has reduced efficacy at TAAR1 showing that these receptors are capable of exhibiting selective affinity. A simple change in the active site of a receptor enables this site to distinguish between very similar compounds. Other non TAAR non-5-HT2a sites could also easily be involved. This area is in dire need of effective research. So much effort has been spent on 5-HT sites in exclusion of others. While 5-HT is likely involved the similarity of the ligands for receptors confounds a simple interpretation until all activities are characterized.

How many categories of entheogen do we actually have?

1-the classic hallucinogens, that i suggested calling 5-ht2 hallucinogens: LSD, mescalin, psilocybin, DMT, (ibogaine),etc.

2-the classic dissosciatives: PCP, ketamin, DXM, (ibogaine), etc.

3-cannabinoids: cannabis, jw- compounds, etc.

4-'psychedelic opiates': salvinorin and other possible kappa-opioid agonists

5-XTC's: MDMA, MDEA, MDPA, MBDB, metylone, mephedrone, BZP, etc.

6-muscarinic receptor agonists: fly-agaric...

what else?

Anticholinergic Delirants

isn't salvinorin A an opioid?..or is there a difference between opiates and opioids?
edit..NM I see you already stated it was a kappa opioid agonist..but would it then be a psychedelic opioid instead of psychedelic opiate?..

..I guess some would concider nicotine poisoning entheogenic ...