LONGECITY

Hello guys. I've been wondering with all the herbs and stuff I've been trying for nootropic purposes, what is the possible chance for one to acquire serotonin syndrome. I know it has something to do with individual tolerance but still. For example is it possible to get it from a combo like this:
- 50mg 5-HTP
- 3 g Fo-Ti (MAOI properties)
- 300 mg St. John's Wort (MAOI properties)
- 100mg L-Theanine
- Possibly a Cannabis Indica hit ? (Yeah.. I live in Amsterdam)

I used to have pretty wild teenage years I've taken 2-3 tabs MDMA once which I know has a very high potential for serotonin syndrome, and the effect was pretty hardcore. It was just too powerful to either enjoy or think. I just jumped on a coach and waited for it to end and eventually fell asleep. I have no idea if this was an ss but it definitely didn't feel like life threatening.
I really want to know how much serotonin is too much and what's the easiest way to get an ss (probably mixing a strong MAOI with a strong SSRI). I think it would be really nice if we could make a Serotonin Syndrome table with points for each ingredients. Like for example if 10 gets you an ss then 5-HTP would be +2 or stuff like that.

Thanks in advance.

Herbs alone rarely cause serotonin syndrome. You generally need a pharmaceutical drug, an MAOI, SNRI, or SSRI. Then you have to combine it with another pharmaceutical drug, or with a very powerful herbal/supplemental medication.

Pretty much all cases of serotonin syndrome in the literature come from combining different antidepressants, or overdosing on a single antidepressant (e.g. in a suicide attempt). Fo-To and St. John's Wort just aren't going to do it.

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Oh that's awesome thank you so much.
However 5-HTP is listed in Wiki as one of the possible reasons for serotonin syndrome. Do you have any idea how much 5-HTP is safe during the course of a day ? Or how much L-Theanine for that matter ?

5-HTP might cause Serotonin toxicity but only when combined with an SSRI or MAOI, by itself I would really doubt your body is ever going to convert enough into Serotonin for it to be a problem (but there are other dangers with 5-HTP that make me shy away from supplementing it, anyhow)

Oh really ? Can you please mention some of them ? I never knew about that.

IIRC, it has some potential for cardio vascular side-effects, but I never investigated it in-depth

It's possible at high doses, since you've got a precursor and a oxidase inhibitor in there, but yours don't look that high. I'd say taper up the 5-HTP from 0 to 50, if you still feel like you want it after getting used to the others. You shouldn't be short on serotonin under regular maoi unfluence.

I've experienced early SS a few times, from taking MDMA on days when I'd already had tryptophan. Mostly the usual high-serotonin feelings shift suddenly to strong anxiety, and you get warmer than usual. There's a buffer zone between noticing something is wrong and the point where it gets dangerous to your health.

Attaching points to every serotonin prodrug is difficult, but I do know you have to multiply values from different categories (reuptake inhibitor, releasing agent, MAOI and precursors). Taking MDMA with an SSRI or two MAOIs won't get you SS, but taking either with 5-HTP or a MAOI might. Consuming something from only a single category doesn't seem likely to lead to SS, even at very high doses; MDMA is an exception because it's both a releasing agent and a reuptake inhibitor.
Edited by Raza, 12 June 2012 - 08:15 PM.

Taking MDMA with an SSRI or two MAOIs won't get you SS, but taking either with 5-HTP or a MAOI might. Consuming something from only a single category doesn't seem likely to lead to SS, even at very high doses;

First of all - thank you for the great input, but please explain. As far as I understand from the forementioned sentence it goes like this:
1. MDMA + SSRI = not likely to SS
2. MDMA + 2 MAOI = not likely to SS
However the next sentence says that:
3. MDMA + 5-HTP = likely to cause SS
4. MDMA + MAOI = likely to cause SS (contradicts 2.)

And the last sentence actually states that MDMA alone can cause SS (Contradicts 1-4). Please explain this to me cuz I seem to be too stupid to understand it.

Also do you have any idea if Cannabis can cause SS when combined with MAOI, 5-HTP or something else ?

Thank you.

I think he mis-spoke; the "Two MAOIs" must certainly mean the herbal medicines you mentioned. Herbal "MAOIs" are generally not strong enough to do anything unless you overdose on them. On the contrary, if you took a pharmaceutical MAOI at antidepressant doses, you would be at risk for serotonin syndrome if you took any other serotonergic drug, whether it was 5HTP, SSRI, MDMA, whatever. (Though low doses of 5HTP seem fine. It's only the high doses that are worrisome.)

Cannabis is not a factor in serotonin syndrome. It has very few known interactions, mostly with dopamine-increasing stimulants where it raises the risk for hallucinations and other psychotic symptoms.

Oh I get it now. Thank you.

What about GABA + 5-HTP combos. I've read somewhere that it's not the safest combination and I don't think it had anything to do with SS.

I meant that either [MDMA + SSRI] or [MAOI + MAOI] were not likely to cause SS, due to mechanism overlap/competition.

MDMA plus one or more MAOIs definitely could, and I wouldn't take it with any herbal ones either, since it can come pretty damn close on its own.

Sorry for the ambiguity.
Edited by Raza, 14 June 2012 - 09:19 AM.

I get it now. Thank you.

What about benzodiazepines, barbiturates, opioids and basically the Psych Ward stuff though ? Can they increase the chance for, or cause SS alone or in combination with other drugs ? I know there's probably no single answer to such a stupidly asked question as drugs even in the same class greatly vary in terms of properties. Anyhow it'd be nice to have some basic understanding of SS likelihood for all people using a variety of drugs to achieve various mental modifications.Especially now that we are starting to discover the great benefits ot 5-HT2a agonists like LSD/Psilocin/DMT for drastic nootropic improvements. It'd be really nice to have a topic covering the absolute basics of SS potential for the common agents such as the forementioned plus stuff like supplements - L-Theanine, GABA, Melatonin, L-Tryptophan etc.
After there's enough info I'll make sure to summarize it in a more friendly fashion and post it up in the section.
Edited by Tatsumaru, 17 June 2012 - 01:00 AM.

I can answer this for some of your list (take with large grains of salt though)
Benzos: potent GABAergic drugs and are commonly combined with SSRI and other anti depressants so no risk there.
GABA itself is a somewhat useless supplement as it does not even cross the blood-brain barrier so unlikely to cause any SS related issues.
L-Theanine probably has a relatively low risk but it is not entirely clear whether it might have Serotonergic effects to some degree
L-Tryptophan is a 5-HTP pre-cursor so I would avoid supranatural doses (its a fairly common amino acid in food, though) when using SSRIs or MAOIs
Melatonin is a Serotonin metabolite so probably safe

Nupi got most of them right.

Benzos, barbituates, opiates, melatonin and GABA won't add up towards SS.

Theanine "increases levels of serotonin in the brain", but doesn't seem to do so much at conventional doses. It almost certainly adds up to SS, but almost certainly only very little. Probably not enough to cause SS in combination with any single potent contributor (MAOI, precursor, releasing agent, reupkeep inhibitor), but it might add up if you're pushing your luck combining some of these already.

Tryptophan is a precursor, and very much adds to SS potential. Food sources are fine in moderation, but taking it as a supplement away from competing amino acids can easily pave the way for MAOIs or MDMA to put you over the edge.

Partial serotonin agonists are an uncertainty; I don't know which 5-HT receptors cause the SS symptoms upon overstimulation. They could add a little towards the threshold, but not much since they don't multiply with anything else.

One noteworthy factor is Saint John's Wort, which aside from very weak SSRI and MAOI activity upregulates and sensitizes 5-HT receptors on the long term. People who've undergone chronic treatment with this probably have lowered SS thresholds, even when not actively dosed.
Edited by Raza, 25 June 2012 - 09:00 PM.

So if one took St. John's Wort in conventional doses for say 1 year and then takes some LSD in conventional doses too (LSD is supposed to be a powerful 5-HT2a agonist) does he risk SS ? Thanks.

I think that's highly unlikely. Serotonin agonists aren't known to cause SS under any conditions and LSD is only decently potent at maybe three receptor types.

With a year's worth of St John's Wort treatment my guesstimate is that you may want to dose lower on MDMA (I'd start at 60% and work my way up to determine my new dosage, if I hadn't used since before the SJW treatment), and pay extra close attention to your dietary intake of tryptophan (as in, ration it below common intake) when taking pharmaceutical MAOIs. I don't see low-to-medium potency contributors like SSRIs, serotonin agonists or regular dosed herbal MAOIs pushing you across by themselves even with that lowered threshold.
Edited by Raza, 25 June 2012 - 09:55 PM.

That's good stuff. Thanks a lot. Basically it turns out that SS is a rather rare condition unless you aren't mixing too much pharmaceutical grade substances.

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One noteworthy factor is Saint John's Wort, which aside from very weak SSRI and MAOI activity upregulates and sensitizes 5-HT receptors on the long term. People who've undergone chronic treatment with this probably have lowered SS thresholds, even when not actively dosed.

I'm going a little off-topic but I was wondering if you had any information on the dosage levels required to upregulate and resensitize 5HT receptors. i am wondering does it upregulate specific 5HT receptors? I would like to resensitize my receptors as I am assuming drug abuse in the past [mdma] has damaged mine. But I was curious as to whether I could take a fairly low dose because I don't want to take the common full therepeutic dose, just something low.