How do you know if a weak MAOI or Serotonergic drug is safe to take with an SSRI?

[Mycophile]

So I only recently came to understand that it isn't only MAOIs which can be unsafe to mix with SSRIs, but I guess it's also unsafe to mix SSRIs with other SSRIs, or basically anything which creates too much serotonin in one way or another because it could cause Serotonin syndrome.

However, I have heard people say that certain MAOIs are "weak" MAOIs like Passion Flower and Damiana for example, and this leads me to believe that most people think they can probably be mixed with an SSRI.

Likewise, I thought I heard that Scullcap effects serotonin in some way, but I don't know if it's an SSRI.

There seem to be so many drugs which MIGHT be weak MAOIs or weak SSRIs or in some way effect serotonin but which are still safe to mix with SSRIs while others aren't and I'm wondering how a person could ever know if another serotonergic drug or weak MAOI is safe to mix with one's SSRI?

For example, I recently read on here that Marijuanna effects serotonin, and I don't know if this is true, but of course weed is safe to mix with an SSRI.

But other things like Kanna, St. John's Wort and DXM are strictly forbidden to be mixed with an SSRI yet unless I'm incorrect I don't think any are MAOIs.

So if one is on an SSRI but interested in experimenting with various things, how could one ever know which drugs effect serotonin too much to be safe and which don't?

You could say simply to stay away from ALL MAOIs if you take an SSRI, which I don't know if that is 100% necessary to do, but then what about when it comes to all these other things which effect serotonin?

How does one know for example, that Kanna and St. John's Wort effect serotonin more than Marijuanna to the extent that they cannot be mixed with an SSRI while the latter can?

Thanks

 

[AlphaMethylPhenyl]

I'd bet that most drugs of abuse affect serotonin levels (if not from a primary, than from a secondary or tertiary mechanism). I've read the same thing about marijuana but can you source that? I want to see if we have the same one or not. Usually one source isn't enough to prove very much.

You probably could've just asked in BDD or OD if you could mix those drugs.

As for weak MAOIs I'm aware of amp.

The best way to go about not hurting yourself if you're going to to take the drugs is to dose in slow increments until one is comfortable enough to stop.

 

[Hiei Loner]

I don't know if this helps or will answer part of your question, but I know the first SSRI my doc put me on was a bit high and I couldn't sit still and always has to be doing something. Yeah it worked, but it pretty much sped me up, to the point that I couldn't sleep for 2-3 days at a time. He switched me to another SSRI, lower dosage of course, abd agree everything leveled out things went back to normal. I'm not sure if it was a side effect of to much serotonin out something in the drug though.

 

[Mycophile]

I'd bet that most drugs of abuse affect serotonin levels (if not from a primary, than from a secondary or tertiary mechanism). I've read the same thing about marijuana but can you source that? I want to see if we have the same one or not. Usually one source isn't enough to prove very much.

You probably could've just asked in BDD or OD if you could mix those drugs.

As for weak MAOIs I'm aware of amp.

The best way to go about not hurting yourself if you're going to to take the drugs is to dose in slow increments until one is comfortable enough to stop.

What does the bolded part mean?

I don't have a source on weed, it was someone on here who did a lot of MDMA plus a few other drugs and then smoked weed and said that the combo gave him serotonin syndrome and someone else said weed effects it a little but probably only in combo with those drugs.

I wonder if just very slowly dosing with certain drugs that might be of danger and not going to high is safe while on an SSRI, obviously it isn't 100% safe, but I wish that more people knew which herbs in general like scullcap, Damiana, Mugwort and more obscure ones like Indian Warrior are safe to experiment with while on SSRIs.

 

[ebola?]

In short, it's difficult to tell for sure: we lack an adequate and specific theory about development of the disorder. Serotonin syndrome is a rare complication of SSRIs taken alone, and the symptoms of SSRI overdose are very similar to serotonin syndrome. But in general, mixing drugs that increase synaptic serotonin, particularly when they work via different but compatible mechanisms, increases the risk of SS. It is unclear whether direct serotonergic agonists can decrease the margin of safety for releasers or reputake inhibitors, but their contribution is minimal regardless. CBD does exert direct agonism at 5ht1a (I forget whether partial or full), but this effect is weak enough that it doesn't interact with serotonergics dangerously. When we say something is a "weak" SSRI, we mean that its activity is so minor that it's questionable whether it's relevant at all.

There are some unexplained complications to our picture. For the vast majority of SSRIs, their binding affinity is much stronger than common releasers, so they will block entactogens' effects by blocking its ability to bind at SERT. Yet DXM's action blocking activity at SERT can synergize dangerously with MDMA. I'm not sure why this would be.

ebola

 

[AlphaMethylPhenyl]

^I only had a couple of minutes but I couldn't find the answer.

I think he was asking more about weak maois. And OP I meant amphetamine. By the way did I read right in a previous thread that all anti-psychotics are weak SSRIs? I know aripiprazole at least has significant affinity for SERT, at least I think so. Feel free to correct me ebola? or whoever.

DXMs pharmacodynamics/kinetics seems pretty complicated. Perhaps it has to do with downstream effects of nmda antagonism. Just a guess.

 

[endotropic]

There are some unexplained complications to our picture. For the vast majority of SSRIs, their binding affinity is much stronger than common releasers, so they will block entactogens' effects by blocking its ability to bind at SERT. Yet DXM's action blocking activity at SERT can synergize dangerously with MDMA. I'm not sure why this would be.

ebola

I bet DXM's sigma agonism doesn't help, since that activity increases hyperthermia with monoamine releasing stimulants.

 

[Mycophile]

In short, it's difficult to tell for sure: we lack an adequate and specific theory about development of the disorder. Serotonin syndrome is a rare complication of SSRIs taken alone, and the symptoms of SSRI overdose are very similar to serotonin syndrome. But in general, mixing drugs that increase synaptic serotonin, particularly when they work via different but compatible mechanisms, increases the risk of SS. It is unclear whether direct serotonergic agonists can decrease the margin of safety for releasers or reputake inhibitors, but their contribution is minimal regardless. CBD does exert direct agonism at 5ht1a (I forget whether partial or full), but this effect is weak enough that it doesn't interact with serotonergics dangerously. When we say something is a "weak" SSRI, we mean that its activity is so minor that it's questionable whether it's relevant at all.

There are some unexplained complications to our picture. For the vast majority of SSRIs, their binding affinity is much stronger than common releasers, so they will block entactogens' effects by blocking its ability to bind at SERT. Yet DXM's action blocking activity at SERT can synergize dangerously with MDMA. I'm not sure why this would be.

ebola

I'm sorry but some of the scientific terms you are using here are beyond me as I don't know much about neuroscience or pharmacology.

I just take Prozac and I'm interested in knowing if there's any way I can be more sure about which weak SSRIs or weak MAOIs or weak serotonegic drugs might be safe to mix with it?

I've heard things like Scullcap, Passionaflower, Damiana, Scotch Broom and many others being suggested as possibly unsafe to mix with SSRIs, but I'd like to know whether or not they and many others truly are, and whether or not this is possible to figure out on my own through research, or whether asking a mod like you or even a doctor (if I had access to one who would answer such questions...) would clear it up...or if there's really no way of knowing.)

Perhaps it is a case by case basis, depending on which specific drug I am asking about and how much knowledge there is out there about it??

Several I am wondering about in particular and whether or not I safely could mix them with my SSRI (Prozac) are Wild Dagga, Klip Dagga, Mugwort, Passion Flower, Damiana, Scotch Broom, Khat, Blue Lotus, Sinicuichi, Marijuanilla, Calamus, Bacopa, Sam-E, Rhodila, Relora and Calea (also Indian Warrior and Xhosa Dream herb but such little is known about those I am not sure the question can be answered.

If this is an overwhelming number of herbs to ask about then lets just say I am particularly curious about Wild Dagga, Klip Dagga, Marijuanilla, Scullcap, Mugwort and Damiana.

I am also wondering if these can be mixed with my Benzo (Klonopin) but I am guessing that's less of a problem because it usually only interacts badly with serious CNS depressants.

Thanks

 

[endotropic]

I think you should ask your doctor what he thinks. A lot of people take herbal supplements, so there's a chance your doctor knows whether some of those herbs can be mixed safely (or not) based on his personal experiences with his other patients. Don't be afraid to ask for a second opinion if your doctor doesn't have any firsthand knowledge though.

We can't give you any definite answers unless the drugs you want to use have been tested together specifically in a clinical trial. I can't be positive, but I would be very surprised if any of those combos have been tested specifically. When it comes to issues of safety the kinds of hints we could otherwise pull together from the medical literature probably aren't appropriate.

Failing information from your doctor, or a clinical trial, your best bet is to talk to people who have combined those drugs themselves. Since you're talking about legal, non-recreational herbs, I would try my doctor first though.

 

[Mycophile]

I think you should ask your doctor what he thinks. A lot of people take herbal supplements, so there's a chance your doctor knows whether some of those herbs can be mixed safely (or not) based on his personal experiences with his other patients. Don't be afraid to ask for a second opinion if your doctor doesn't have any firsthand knowledge though.

We can't give you any definite answers unless the drugs you want to use have been tested together specifically in a clinical trial. I can't be positive, but I would be very surprised if any of those combos have been tested specifically. When it comes to issues of safety the kinds of hints we could otherwise pull together from the medical literature probably aren't appropriate.

Failing information from your doctor, or a clinical trial, your best bet is to talk to people who have combined those drugs themselves. Since you're talking about legal, non-recreational herbs, I would try my doctor first though.

Yeah, asking my doctor isn't really an option because you know that doctors are not interested in helping their patients safely experiment with mind altering substances.

They SHOULD be, but they aren't.

So yeah, any answers I want would have to be obtained on this forum.

In the case of one or two substances that didn't have extensive testing done on them, simply hearing enough opinions from those who combined it with similar medications to mine proved sufficient for my own safe experimentation.

However, some will say that hearing that others mixed substances safely is really only ancedotal and surves as no real proof that the mixture is safe.

Do you agree with this statement?

I mean, there is some truth to it I think, because people have mixed some very dangerous substances and managed to survive for some reason, but I think the greater number of people you hear of who have combined certain substances with no ill-effects the more likely that the combo is probably not extremely dangerous.

I really don't know...I guess it's a slippery slope.

 

[ebola?]

But really, you listed a series of legal supplements and are concerned about combining them with an SSRI you were prescribed. Most physicians would be happy to answer this question.
...
In general, you should still respond okay to serotonergic psychedelics, as they are direct agonists. Psychedelics might have mildly reduced activity, but this is pretty inconsistent person to person. As for drugs that interact with the serotonin transporter, there will be either reduced effects as with mdma, where the Prozac blocks the other drug's interaction with the transporter, or an additive effect. This varies case by case, and you should examine each potential combination with a serotonergic individually. You should avoid 5htp. While not as likely to induce serotonin syndrome as other combinations, it's still risky.

 

[endotropic]

Yeah, asking my doctor isn't really an option because you know that doctors are not interested in helping their patients safely experiment with mind altering substances.

They SHOULD be, but they aren't.

So yeah, any answers I want would have to be obtained on this forum.

Many doctors will be willing to help you if you approach it from the viewpoint that you're trying to find supplements to augment your therapy. I know actual physicians that use herbal remedies themselves to combat depression, so it really depends on who you ask, and how you frame it.

However, some will say that hearing that others mixed substances safely is really only ancedotal and surves as no real proof that the mixture is safe.

Do you agree with this statement?

I mean, there is some truth to it I think, because people have mixed some very dangerous substances and managed to survive for some reason, but I think the greater number of people you hear of who have combined certain substances with no ill-effects the more likely that the combo is probably not extremely dangerous.

I agree with everything you wrote here. Relying solely on one person's experience can get you into a lot of trouble, the more experiences you can compare the better. No matter how many people you ask you can never reduce that risk to 0 though. That's why real (good) clinical trials use 1000's of people, there's no other way to uncover that 1 in 1000 negative reaction.

 

[ebola?]

Basically, in situations where a thin therapeutic window is suggested, or an unknown therapeutic window, Shulginesque titration becomes necessary.

ebola

 

[Mycophile]

Basically, in situations where a thin therapeutic window is suggested, or an unknown therapeutic window, Shulginesque titration becomes necessary.

ebola

Just curious, what exactly does this mean?

Would you say that perhaps careful experimentation with substances like Wild Dagga, Klip Dagga, Scullcap, Mugwort, Damiana and Passion Flower might be safe in small amounts even on my SSRI and my benzo?

Should I stay away from more obscure substances about which nothing seems to be known like Indian Warrior, Blue Lotus and Sinicuichi?

And should I stay away from all MAOIs or are "weak" MAOIs safe and how can I know whether or not a substance is a "weak MAOI?

Simply by what others say?

 

[sekio]

To understand if a herb is going to be safe you have to know what components are expected to have MAOI activity, the strength of those compounds and whether they select for MAO-A or MAO-B, and how concentrated they are. Brush up on your biochemistry and look on PubMed. You need to know your SI scale (nano, micro, milli) and a few other things like what it means for a compound to have a higher affinity than another.

Off the top of my head, the only readily availiable effective natural non-pharmaceutical MAOI of note I can name are the harmala alkaloids. They're present in B. caapi, syrian rue, passionflower, and cigarette smoke (not very much in smoke but they're present). Harmaline is what you take in ayahuasca to make DMT orally active.

Dagga, skullcap, mugwort, damiana, indian warrior, blue lotus, sinicuichi in typical usage do not have a MAOI activity of note unless heavily concentrated or you take insane doses. Same with shit like Rhodiola, sceletium, kava. The compounds that have been observed to inhibit MAO enzymes only do so at very high concentrations in petri dish-cultured cells, and should not be taken as evidence they are effective clinical MAOIs. That does not mean these compounds are not centrally active and it sure doesn't mean they can't have bad interactions. All it means is that they aren't going to inhibit MAO enzymes noticeably if you take them.

Shulgin titration involves starting with a dose hundreds to thousands of times smaller than activity is expected at, and increasing your dosage every few days, taking breaks in between, and being very attentive to effects.

TL;DR: Figure out what the active compounds in the herbs you take are, using PubMed or Google Scholar. Look up the Ki (affinity) for binding to MAO enzymes. Anything that's greater than about 1 micromolar (1000 nanomolar), is pretty much useless as a MAOI unless you take huge doses. Clinically used MAOIs have affinities in the single to tens of nanomoles. (Harmine is about 16nM at MAO-A. Selegiline is in the single-digit nanomolar range. Rosiridin from Rhodiola rosacea is like 15,000 nM, on the other hand.)

 

[Mycophile]

To understand if a herb is going to be safe you have to know what components are expected to have MAOI activity, the strength of those compounds and whether they select for MAO-A or MAO-B, and how concentrated they are. Brush up on your biochemistry and look on PubMed. You need to know your SI scale (nano, micro, milli) and a few other things like what it means for a compound to have a higher affinity than another.

Off the top of my head, the only readily availiable effective natural non-pharmaceutical MAOI of note I can name are the harmala alkaloids. They're present in B. caapi, syrian rue, passionflower, and cigarette smoke (not very much in smoke but they're present). Harmaline is what you take in ayahuasca to make DMT orally active.

Dagga, skullcap, mugwort, damiana, indian warrior, blue lotus, sinicuichi in typical usage do not have a MAOI activity of note unless heavily concentrated or you take insane doses. Same with shit like Rhodiola, sceletium, kava. The compounds that have been observed to inhibit MAO enzymes only do so at very high concentrations in petri dish-cultured cells, and should not be taken as evidence they are effective clinical MAOIs. That does not mean these compounds are not centrally active and it sure doesn't mean they can't have bad interactions. All it means is that they aren't going to inhibit MAO enzymes noticeably if you take them.

Shulgin titration involves starting with a dose hundreds to thousands of times smaller than activity is expected at, and increasing your dosage every few days, taking breaks in between, and being very attentive to effects.

TL;DR: Figure out what the active compounds in the herbs you take are, using PubMed or Google Scholar. Look up the Ki (affinity) for binding to MAO enzymes. Anything that's greater than about 1 micromolar (1000 nanomolar), is pretty much useless as a MAOI unless you take huge doses. Clinically used MAOIs have affinities in the single to tens of nanomoles. (Harmine is about 16nM at MAO-A. Selegiline is in the single-digit nanomolar range. Rosiridin from Rhodiola rosacea is like 15,000 nM, on the other hand.)

Thanks,

Very confusing for someone like me because I never even took chemistry in school and don't have any background in science at all or know what an SI scale is, but I'll try to research this stuff and hopefully come to understand some of it over time.

If it involves a lot of math I don't know if I could understand it on my own...

Now I am just curious though, because you say harmaline is the only major MAOI that interacts badly with SSRIs that is readily available without prescription, where things like DXM and St. John's Wort fall into the equation because I have heard that with them, ESPECIALLY DXM in Robitussion, are very dangerous to mix with SSRIs like Prozac and I have heard the same of Kanna which is something else I was curious about but told never to touch on an SSRI.

This is where I get confused, when people talk about MAOIs being so bad to mix with SSRIs because they could induce serotonin syndrome, when there are also things like DXM and Kanna and St. Johns Wort which are NOT MAOIs to the best of my knowledge, which also cannot be mixed with SSRIs.

This is why I get so confused when I consider what I can and can't mix with Prozac but I guess maybe these other things can't be mixed because they are also SSRIs? Is it dangerous to mix 2 SSRIs?

On the other end of the equation, am I correct in assuming that the only things that mix badly with Klonopin/benzos are other extremely powerful CNS depressants?

Thanks

 

[sekio]

know what an SI scale is

I should have been a little clearer, I meant metric system.

If it involves a lot of math I don't know if I could understand it on my own...

There isn't much math beyond comparing the sizes of numbers.

Is it dangerous to mix 2 SSRIs?

The reason people say you shouln't mix SSRIs with more SSRIs is for three reasons. Depending on your dose of SSRI, taking other SSRIs or serotonin releasers could act like a dose increase for your SSRI. This results in likely side effects typical of SSRI overdose (aka serotonin syndrome). Taking other SSRIs could also mess with metabolism of your prescribed drugs, or vice versa - so you end up with a SSRI overdose that lasts a long damn time. The third reason is because even if you didn't get side effects (a more likely situation if you're on high dose SSRI... if that exists?) you would basically get no effect then, because all your serotonin transporters are taken up already.

So at best it's pointless and at worst it's dangerous.

On the other end of the equation, am I correct in assuming that the only things that mix badly with Klonopin/benzos are other extremely powerful CNS depressants?

Basically. CNS depressants, alcohol, some anticonvulsants and stuff like that. If you are chronically dependent on low doses of klonopin it's less of a concern than if you take it once in a while for recreation, but still you shouldn't go binge drinking. Other drugs that cause amnesia like Z-drugs and cannabis in combination with benzos can result in blacking out if you're not careful.

 

[Mycophile]

^^^

So does that comment about the uselessness of serotonergic drugs while on SSRIs mean that certain drugs like Kanna, DXM and MDMA might not even get me high?

And are any of the herbs I asked about like Wild Dagga, Scullcap, Mugwort, Damiana, Blue Lotus, Indian Warrior, etc serotonergic or (CNS depressant) in a sense that they'd be dangerous to mix with Prozac (or Klonopin?)

 

[sekio]

So does that comment about the uselessness of serotonergic drugs while on SSRIs mean that certain drugs like Kanna, DXM and MDMA might not even get me high?

It means don't take them at all. Put the thought out of your mind.

And are any of the herbs I asked about like Wild Dagga, Scullcap, Mugwort, Damiana, Blue Lotus, Indian Warrior, etc serotonergic or (CNS depressant) in a sense that they'd be dangerous to mix with Prozac (or Klonopin?)

Look up their mechanisms of action and figure it out. Or ask your doctor. Or do some searching on places like Erowid. It depends largely on dosage, quality of plant material, set, setting, and how you respond to drugs as an individual.

Just go slow with dosing any of these and you should be fine. The only one to be concerned about that you've mentioned is lotus flower, it contains apomorphine and other dopamine receptor agonists that are used as veterinary emetics (make you vomit), if you take too much.

 

[Toz]

Can I borrow this thread a bit and ask about NMDA antagonists + SSRI medication? I am considering accepting a script for citalopram from my doctor but if that means no ketamine or phencyclidine, then I have to think about it some more. I know these drugs affect serotonin as well but if it's something you've used quite frequently in the past and have tolerance, wouldn't this decrease the risk? Most of them seem to have fairly weak SRI effects anyway.

Wikipedia says this: "Other neurotransmitters may also play a role; NMDA receptor antagonists and GABA have been suggested as affecting the development of the syndrome.[1] Serotonin toxicity is more pronounced following supra-therapeutic doses and overdoses, and they merge in a continuum with the toxic effects of overdose.[35][40]"

Affecting development of the syndrome, how? I got a bit confused by this line.