How Long Should One Wait Before Taking An NBOMe After Taking St. Johns Wort?

[#Intothemdrugs]

I am currently taking St. Johns Wart for depression right now (content: 300mg 0.3% hypercin (0.9 mg)), And I read online that it can cause or at least conribulte to serotonin poisoning if coupled with certain psychedelics. Because NBOMe is a full receptor agonist of 5-HT2A receptors, the same as with LSD and shroom's active ingredient, but they are only partial, meaning that they will not cause overdose if too much is taken. So because NBOMe is full, and can cause overdose as such, I thought it might be prudent to ask this question, because dying is not something I want to do in the future anytime soon.

 

[pasha]

Basic Drug Discussion -> Psychedelic Drugs

 

[kidklmx]

Wikipedia says this about the alkaloids: "These three active substituents have plasma elimination half-lives within a range of 15–60 hours in humans"

With that in mind, I'd say 3-4 days should be fine.

[Edit] Actually searching a bit on MDMA and SJW, I'd say it's best to wait a "while"

 

[#Intothemdrugs]

Thank you very much, I appreciate it. I must have skipped over that.

 

[Solipsis]

A half-life does not indicate when a drug has been eliminated entirely but only half of it... kid, did you assume an average of 15 and 60 hours? Because if you happen to be a person that takes 60 hours, 3 days may not be enough. A week would be better.

Just like with other examples (I had to wait between tramadol and other drugs in the past), this is not a question with a simple answer. In these situations there is an absolute minimum waiting time, but then with bad luck you could still have issues, only less dramatically.

I highly doubt that we can judge adequately how risky taking NBOMe compounds is with residual SJW in your system, so do the 'math'.

 

[kidklmx]

That mostly came from others' advice on MDMA actually though I read a bit more on the subject, realized my mistake and edited my post. (didn't leave the page, so you don't see the edited subnote) How is that not good enough?

p.s Any particular reason why the 2Cs and NBOMes are a bad idea with an MAOI, but Mescaline isn't?

 

[Transform]

I would say not that long since SJW is an SRI and 25I is an agonist so any interactions will be minimal.

However, given that SJW can be a bit unpredictable and has a long half life, I would wait at least one week.

FYI, the rule of thumb for half lives is that a drug is considered eliminated after six half lives.

 

[Solipsis]

The observation that a compound like 25I-NBOMe can cause MDMA-like effects and side-effects in a lot of people does not bode well for it IMO. If it acts as a full agonist it comes closer to having excess serotonin in action (very crude and oversimplified comparison but still), while with partial agonists this may be a bit more attenuated.. so I would always still be on the lookout for additional factors that cause more synaptic serotonin to exist.

 

[Deinonychus]

I am currently taking St. Johns Wart for depression right now (content: 300mg 0.3% hypercin (0.9 mg)), And I read online that it can cause or at least conribulte to serotonin poisoning if coupled with certain psychedelics. Because NBOMe is a full receptor agonist of 5-HT2A receptors, the same as with LSD and shroom's active ingredient, but they are only partial, meaning that they will not cause overdose if too much is taken. So because NBOMe is full, and can cause overdose as such, I thought it might be prudent to ask this question, because dying is not something I want to do in the future anytime soon.

Just for reference, the status of a drug as a partial or full agonist is a measure of how strong of a reaction a drug produces inside of a cell when it binds to a receptor on that cell in relation to the effect that the natural substrate for that receptor type produces. So for 5-HT2A receptors, a full agonist produces as much of an intracellular response as serotonin itself. A partial agonist produces less of an effect than serotonin itself, and a superagonist produces a greater response than the endogenous ligand, serotonin in this case. The strength of the reaction to a partial agonist in relation to serotonin measured as a percentage determines how effective of a partial agonist a compound is.

But none of that relates to whether or not you can overdose on a compound or whether a compound can contribute to serotonin syndrome. Serotonin syndrome is a result of total levels of serotonin in the CNS, which is not dependent in any way on whether a compound is a full agonist, partial agonist, inverse agonist, antagonist, or even superagonist.

So in summary, the fact that NBOMes are full agonists whereas traditional psychedelics are not (which you're spot on correct about) doesn't have any bearing on overdose potential or likelyhood of serotonin syndrome.

 

[Solipsis]

Then why can compounds like 25I-NBOMe cause symptoms associated with poorly managed (too high) levels of serotonin, like fever, sweating, confusion, headaches, twitching and shaking and maybe other unconfirmed ones like mania?

If a compound is an antagonist for all serotonin receptor subtypes it can occupy those receptors without eliciting activation - if a compound binds strongly and for a long time which is often what antagonists do because they can bind extremely well (even more than full agonists) at least those occupied serotonin receptors don't contribute to SS that may be happening from other causes.
It is not entirely sure if it is a good idea to recommend that people administer antagonists with a suspected case of SS, but it is possible..

Antagonists that are selective for only some receptor subtypes can also sometimes form a problem because action at the subtypes they don't bind to like an antagonist is enhanced and therefore you can be more sensitive to what happens there, maybe similar to how a deaf person has enhanced vision. Some drugs apparently act based on this principle.

It seems logical to me that if you have a drug acting in your brain that is a full agonist, you have generally increased serotonergic action as your 'baseline' and relatively speaking you are closer to the SS threshold.

The best explanation we have now for NBOMe compounds being potentially dangerous or lethal is because of the action at serotonergic receptors - initially people thought at the 2B receptor, but it may just be 2A. It may not necessarily have anything to do with serotonin syndrome but I think you are wrong about it not mattering whether they are full agonists or not.

We may not fully understand this yet, and consequently not the interactions either, but until we do we'd better be safe than sorry if there is a plausible rationale behind it.
This is a harm reduction forum, so the point of departure is being careful.

 

[Deinonychus]

Then why can compounds like 25I-NBOMe cause symptoms associated with poorly managed (too high) levels of serotonin, like fever, sweating, confusion, headaches, twitching and shaking and maybe other unconfirmed ones like mania?

If a compound is an antagonist for all serotonin receptor subtypes it can occupy those receptors without eliciting activation - if a compound binds strongly and for a long time which is often what antagonists do because they can bind extremely well (even more than full agonists) at least those occupied serotonin receptors don't contribute to SS that may be happening from other causes.
It is not entirely sure if it is a good idea to recommend that people administer antagonists with a suspected case of SS, but it is possible..

Antagonists that are selective for only some receptor subtypes can also sometimes form a problem because action at the subtypes they don't bind to like an antagonist is enhanced and therefore you can be more sensitive to what happens there, maybe similar to how a deaf person has enhanced vision. Some drugs apparently act based on this principle.

It seems logical to me that if you have a drug acting in your brain that is a full agonist, you have generally increased serotonergic action as your 'baseline' and relatively speaking you are closer to the SS threshold.

The best explanation we have now for NBOMe compounds being potentially dangerous or lethal is because of the action at serotonergic receptors - initially people thought at the 2B receptor, but it may just be 2A. It may not necessarily have anything to do with serotonin syndrome but I think you are wrong about it not mattering whether they are full agonists or not.

We may not fully understand this yet, and consequently not the interactions either, but until we do we'd better be safe than sorry if there is a plausible rationale behind it.
This is a harm reduction forum, so the point of departure is being careful.

Sure, good points all around. My point is that overdose or serotonin storm is dose dependent. The activity of psychedelics is AFAIK reliant upon the molecules themselves acting as an alternative, competitive substrate for the 5-HT receptor system. So it is possible that since some receptors are occupied by drug molecules, there may be more extracellular / inter-synaptic serotonin, since some of the receptors that serotonin would occupy would be blocked. But that quantity – how much excess extracellular unbound serotonin there is that would ordinarily be busy acting on receptors – would be based on how many receptors have drug molecules bound. Which in turn would be a function of receptor affinity, not level of agonism, as agonism level is relevant only to intracellular response once a substrate is bound into a receptor.

Now if NBOMes and other psychedelics were serotonin releasing agents, or blocked reuptake, then the level of effect produced by a molecule of drug binding to a receptor – in a word the level of agonism – on the transport system or on receptors that initiate serotonin release would be more relevant to whether or not serotonin syndrome occurs. But my understanding is that psychedelics are alternate substrates for the serotonin receptors instead of transport/reuptake-inhibitors or serotonin releasing agents themselves.

Also I wasn't sure whether the OP meant that agonism was related to overdose potential or potential for serotonin storm, so I sorta assumed he meant both. I'm pretty sure that agonism doesn't have a ton to do with overdose potential independent of dose either, but I'm less sure about that than I am about the relevance of agonism to serotonin syndrome. And I'm not 100% on that either obviously, but I do at least have a reasonable rationale for my thoughts on that specific subject, which are given above.

Cheers to constructive, rational debate and discussion then!

 

[ParappaTheRapper]

is there any proof that st. johns wort is actually an SSRI? I'm just basing this off google/wikipedia unless someone has citation, but I thought its only known to mimic the effects of SSRIs. And is more of an MAOI/ dopamine uptake inhibiitor.

 

[forgoodnesssakes]

Do not dose nbome's, with mao-b selective inhibitor's

Listen to how scary this is, I dosed nbome's one night and caught the fear like no other, the fear of death that is. Dig this, Daddy-O was taking Mr. Fo-ti daily (same mao-i effects as Miss St. Johns Wart). He didn't realize his mistake until he found out number 1) the nbome's can be fatal 2) Fo-ti exhibits mao-b inhibitor effects, just the mao that the nbome's require extreme caution with, mao-a not so much it seems).

What we should have done was take a 1/3 of the normal dose and left a note for the coroner. One can only be so healthy and strong and not expect a not-so-much researched RC to KILL them, but if I believe in the power of prayer and meditation, it would be that those 2 TOOLS saved my very life, and GET THIS I dosed an even higher dose of 25i and 25c the next night, still ignorant of the maoi effects of Fo-ti that i was taking daily. (I did not find out until months after the trip, and this most likely explains why my conscious mind became so worried for my life, it seems survival instincts are turned on even when one does not know why or how death is lurking around the next corner, but something inside knows you are in danger).

 

[forgoodnesssakes]

I am currently taking St. Johns Wart for depression right now (content: 300mg 0.3% hypercin (0.9 mg)), And I read online that it can cause or at least conribulte to serotonin poisoning if coupled with certain psychedelics. Because NBOMe is a full receptor agonist of 5-HT2A receptors, the same as with LSD and shroom's active ingredient, but they are only partial, meaning that they will not cause overdose if too much is taken. So because NBOMe is full, and can cause overdose as such, I thought it might be prudent to ask this question, because dying is not something I want to do in the future anytime soon.

Depends on how long you have been taking it really.

If you have been taking it daily for some time, I'd have to caution at least 1 month to be on the safer side, probably 2 months to eliminate any & all chances of interaction b/t phen's and mao-b inhibitor's (Miss SJWort is both an mao-a and mao-b inhibitor, do not be misled that it does not exhibit mao effects, it does as any clinical licensed doctor will be able to tell you).

 

[Solipsis]

how much excess extracellular unbound serotonin there is that would ordinarily be busy acting on receptors – would be based on how many receptors have drug molecules bound. Which in turn would be a function of receptor affinity, not level of agonism, as agonism level is relevant only to intracellular response once a substrate is bound into a receptor.

I think you are confused, affinity IS "level of agonism". The level of intracellular response is efficacy.

And again: I understand what you are trying to say but I don't think it is as simple as saying "psychedelics only mimic serotonin so there is no risk of getting too much serotonin since it isn't being released". You do have your own endogenous serotonin levels that may be elevated from using something like MAOIs and that may not be tolerated as well if something like NBOMe compounds is used. Just remember that NBOMe compounds may pose poorly understood risks even though they don't release serotonin. My best guess is that some people may be poor metabolizers, possibly of some CYP450 kind just like can happen with DXM.
Considering that at the doses NBOMe compounds are used the drugs don't affect much more than serotonin receptors at an appreciable level so it indicates that some form of overloading the serotonergic system is the culprit, even if we don't really understand how or why.
Which is the reason I am saying that modulating your serotonin system could very well increase the chances that shit hits the fan with NBOMe compounds.

 

[Deinonychus]

^^ Affinity =/= agonism. Affinity is measured with a dissociation constant, so just like acids and bases, the formula will look like X = A*B / (A+B). In the case of protein ligand binding, this takes the form of K = P*M / C where P is protein, M is molecule, and C is protein/molecule complex. All of those variables, including K, are measured in terms of molar concentrations. So the dissociation constant is in this case determined to be the concentration of the drug/molecule required to reach a state where the concentration of protein bound to the drug equals the concentration of protein that has no bound substrate. Alternately you can think of this as a state where half the receptors in a given set are occupied by a drug and half are not.

What that means for potency and drug mechanics is as follows: We can't directly measure the interactions between a molecule of drug and a protein, the receptor in this case, to see how strong the attraction is / how likely a drug is to bind. So we measure the dissociation constant as proxy for that value, looking at a population of receptors instead of just one. So if a drug requires a concentration of X to reach a state where half the population of receptors are bound, that value X acts as a stand-in to determine the affinity of that drug for the receptor, because a drug that needs a higher concentration to bind half the receptors obviously has less affinity for those receptors than one that can bind half the receptor population at a lower concentration.

This is why Ki values are smaller for greater affinity. The smaller value indicates that the concentration necessary to bind half of a given set of receptors is low. If the concentration is low, then the dose must be accordingly small in comparison to something that requires a higher concentration to bind the same number of receptors, since Ki values examine only receptor/ligand interactions and don't take bioavailability or BBB-crossing ability into account.

Agonism level on the other hand zooms in further, exchanging a variable concentration of drug and a population of receptors for a single cell. Agonism is all about how strong the response is *within* that cell when a receptor on its surface (technically the receptor actually extends past the membrane in both directions) is stimulated by having bound a drug molecule.

Receptor affinity is a measure then of how much drug is necessary, in terms of molar concentration, to bind half of a population of receptors. In this manner it is a proxy for how well a drug binds and how attracted the drug and the receptor binding site are to one another. Agonism is a measure of what happens to a cell when binding does happen, regardless of external concentration of that drug. So you can have a drug that is massively potent, but only a partial agonist, like LSD, or a drug that is very impotent and requires a huge dose but is still a full agonist, for which I don't have an example on the top of my mind.

But the important point is that these quantities are completely independent of one another. It is true that a given functional group or moiety in a molecule can have an effect on both binding affinity and agonism, but the two values are nonetheless not the same thing at all. Efficacy, which you mention, actually is related (inversely) to agonism, and affinity is a separate quantity altogether.

A good primer on the subject is wikipedia, see the following links:
http://en.m.wikipedia.org/wiki/Receptor_affinity
http://en.m.wikipedia.org/wiki/Agonist