Post-roll 5-HTP, guidelines and pitfalls to avoid

[LabRat74]

5HT-P and its application in post-roll scenarios / if it can prevent damage is something that comes up a lot. I wrote a thing a while back:

Generally speaking if you dose sensibly, and dont dose too often, you shouldnt be causing a great deal of damage. Theres a difference between damage done by mdma, and the temporary deficit of serotonin you experience post roll. Just because youre on a comedown doesnt mean a lot of neurotoxic damage was done, in the same vein just because you feel fine after a heavy one doesnt infer damage wasnt.

Overuse of mdma gradually damages (though its probably more accurate i dont like the term "burnt out" cos it has similar connotations to "fried" in how people describe users) the transport axons responsible for generating/transmitting new serotonin. Using mdma doesnt badly damage these, abusing it does. However after a roll, you will have less 5HT floating about purely cos you just dumped a lot of your "store". 5HT-P does NOT prevent or reverse damage to the axons, it only lets the axons that are still working add more 5HT back to the reserve quicker.

In short, 5htp will increase your mood sooner than usual post-roll and counteract some of the comedown as you will get back on your feet after a shorter period of time due to there being more 5HT being made to replenish reserves. 5htp will not reverse or protect against MDMA induced neurotoxicity.

The issue with how people use 5htp is that it often amounts to no more than an expensive placebo due to it binding peripherally. A large portion (~90 percent) of your serotonin system is in the gastrointestinal tract (5ht3 being the primary mediator of nausea in the gut and emesis response in the brain), so 5htp will natrually bind to these sites first, next followed by binding to receptors in cardiac tissue (and thus 5ht2b agonism). The former can cause nausea and vomiting as mentioned, the latter will gradually cause valve hardining. To avoid this, and send the 5htp to your brain where it needs to be to make brain serotoin, you should also supplement ECGC, which can be found in green tea extract amongst other things, this inhibits it from binding peripherally.

Also iirc you need to not be suffering from a vitamin b6 deficit, otherwise the 5htp cant effectively convert into 5ht.

5htp should NOT be used to treat depression, or on an ongoing basis without consulting a decent bit of research, or a professional. Regular use of one amino precursor without balancing it out with others, will impact nondominant systems. In the case of 5htp, it will gradually downregulate your dopamine, causing potential further mood issues. Look to L-Tyrosine for somewhere to start with this.

You should avoid taking 5htp within 24hours before dosing MDMA. even though it has never contributed to serotonin syndrome (except once in a golden retriever, where it was the only drug accidentally administered), 5htp will still potentially increase serotonin levels uncomfortably alongside a releaser. Taking it for up to a week following a roll wont harm you. Avoid high doses as they are unneccessary and will only add extra side effects.
www.rollsafe.org is a better resource than any bottle of 5htp imo.

Further reading on 5htp:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3415362/

 

[andyturbo]

5HT-P and its application in post-roll scenarios / if it can prevent damage is something that comes up a lot. I wrote a thing a while back:

Generally speaking if you dose sensibly, and dont dose too often, you shouldnt be causing a great deal of damage. Theres a difference between damage done by mdma, and the temporary deficit of serotonin you experience post roll. Just because youre on a comedown doesnt mean a lot of neurotoxic damage was done, in the same vein just because you feel fine after a heavy one doesnt infer damage wasnt.

Overuse of mdma gradually damages (though its probably more accurate i dont like the term "burnt out" cos it has similar connotations to "fried" in how people describe users) the transport axons responsible for generating/transmitting new serotonin. Using mdma doesnt badly damage these, abusing it does. However after a roll, you will have less 5HT floating about purely cos you just dumped a lot of your "store". 5HT-P does NOT prevent or reverse damage to the axons, it only lets the axons that are still working add more 5HT back to the reserve quicker.

In short, 5htp will increase your mood sooner than usual post-roll and counteract some of the comedown as you will get back on your feet after a shorter period of time due to there being more 5HT being made to replenish reserves. 5htp will not reverse or protect against MDMA induced neurotoxicity.

The issue with how people use 5htp is that it often amounts to no more than an expensive placebo due to it binding peripherally. A large portion (~90 percent) of your serotonin system is in the gastrointestinal tract (5ht3 being the primary mediator of nausea in the gut and emesis response in the brain), so 5htp will natrually bind to these sites first, next followed by binding to receptors in cardiac tissue (and thus 5ht2b agonism). The former can cause nausea and vomiting as mentioned, the latter will gradually cause valve hardining. To avoid this, and send the 5htp to your brain where it needs to be to make brain serotoin, you should also supplement ECGC, which can be found in green tea extract amongst other things, this inhibits it from binding peripherally.

Also iirc you need to not be suffering from a vitamin b6 deficit, otherwise the 5htp cant effectively convert into 5ht.

5htp should NOT be used to treat depression, or on an ongoing basis without consulting a decent bit of research, or a professional. Regular use of one amino precursor without balancing it out with others, will impact nondominant systems. In the case of 5htp, it will gradually downregulate your dopamine, causing potential further mood issues. Look to L-Tyrosine for somewhere to start with this.

You should avoid taking 5htp within 24hours before dosing MDMA. even though it has never contributed to serotonin syndrome (except once in a golden retriever, where it was the only drug accidentally administered), 5htp will still potentially increase serotonin levels uncomfortably alongside a releaser. Taking it for up to a week following a roll wont harm you. Avoid high doses as they are unneccessary and will only add extra side effects.
www.rollsafe.org is a better resource than any bottle of 5htp imo.

Further reading on 5htp:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3415362/

What a ripper post!! Thanks Labrat!

 

[TheYellowMoon]

Wow thank you

 

[cosmosmariner]

I would just add to take EGCG with your 5htp to help it convert to serotonin in the brain, rather than the periphery.

 

[negrogesic]

I would just add to take EGCG with your 5htp to help it convert to serotonin in the brain, rather than the periphery.

Looks like they already mentioned that:

To avoid this, and send the 5htp to your brain where it needs to be to make brain serotoin, you should also supplement ECGC, which can be found in green tea extract amongst other things, this inhibits it from binding peripherally.

Question is...does ECGC really make 5HTP more centrally active/available?

 

[SpiralusSancti]

Not sure how much 5htp use as a mean to lower damage done by MDMA is based on reality. Yeah, OP wrote how it isn't really repairing anything but for proposed use I lean on the side that there are better options. Ones that aren't connected to serotonin per se.
I say leave you brain recover naturally and if you really feel that bad after MDMA take something that helps you feel better, and take a pause or stop doing it after.

Imo it's much more important to take antioxidants, eat good, be in good company and doing stuff you love at least in days prior and following roll.

I wrote that elsewhere and I'll repeat it here, proper use of MDMA results in afterglow and not suicide Monday or whatever.

 

[cosmosmariner]

Not sure how much 5htp use as a mean to lower damage done by MDMA is based on reality. Yeah, OP wrote how it isn't really repairing anything but for proposed use I lean on the side that there are better options. Ones that aren't connected to serotonin per se.
I say leave you brain recover naturally and if you really feel that bad after MDMA take something that helps you feel better, and take a pause or stop doing it after.

Imo it's much more important to take antioxidants, eat good, be in good company and doing stuff you love at least in days prior and following roll.

I wrote that elsewhere and I'll repeat it here, proper use of MDMA results in afterglow and not suicide Monday or whatever.

You make a good point. After my last roll, I did not take 5htp on night 1 and 2, and I felt pretty low. I took 100 mg on night 3 with EGCG and woke up the next day feeling significantly better. I skipped night four and woke up feeling low again. That night, I again took 5htp and woke up feeling good the next morning. I repeated this patter three times.

So, for me, I am concluding that it does help in the weeks following a roll to restore serotonin levels.

 

[SpiralusSancti]

You make a good point. After my last roll, I did not take 5htp on night 1 and 2, and I felt pretty low. I took 100 mg on night 3 with EGCG and woke up the next day feeling significantly better. I skipped night four and woke up feeling low again. That night, I again took 5htp and woke up feeling good the next morning. I repeated this patter three times.

So, for me, I am concluding that it does help in the weeks following a roll to restore serotonin levels.

5htp works wonders for depression generally in some people so that's to be considered too.

Questionable thing concerning this practice (not if it makes you feel better as it does work fine for many) is if screwing around with serotonin balance, even with direct precursor, be it post or pre loading might in the long run do more harm than good.

There are a lot of reasons why it might be bad idea and one is that following MDMA use, instead letting your body to get back to balance naturally (and learn to deal with MDMA toxicity) you add something that might program your body with time in a way that it recovers longer and less efficient with every such use. Making your brain lazy so to speak. Like with benzos/booze and gaba.

With drugs feeling good or bad isn't always great indicator of harm, sometimes not at all.

 

[cosmosmariner]

5htp works wonders for depression generally in some people so that's to be considered too.

Questionable thing concerning this practice (not if it makes you feel better as it does work fine for many) is if screwing around with serotonin balance, even with direct precursor, be it post or pre loading might in the long run do more harm than good.

There are a lot of reasons why it might be bad idea and one is that following MDMA use, instead letting your body to get back to balance naturally (and learn to deal with MDMA toxicity) you add something that might program your body with time in a way that it recovers longer and less efficient with every such use. Making your brain lazy so to speak. Like with benzos/booze and gaba.

With drugs feeling good or bad isn't always great indicator of harm, sometimes not at all.

I hear you. And I only use 5htp in the two weeks following a roll. During that time, your body can’t restore serotonin levels “naturally” because the enzyme that produces serotonin has been destroyed and takes a couple of weeks roughly to return to normal. During that time, 5htp makes sense for me.

 

[snmfmy]

5HT-P and its application in post-roll scenarios / if it can prevent damage is something that comes up a lot. I wrote a thing a while back:

Generally speaking if you dose sensibly, and dont dose too often, you shouldnt be causing a great deal of damage. Theres a difference between damage done by mdma, and the temporary deficit of serotonin you experience post roll. Just because youre on a comedown doesnt mean a lot of neurotoxic damage was done, in the same vein just because you feel fine after a heavy one doesnt infer damage wasnt.

Overuse of mdma gradually damages (though its probably more accurate i dont like the term "burnt out" cos it has similar connotations to "fried" in how people describe users) the transport axons responsible for generating/transmitting new serotonin. Using mdma doesnt badly damage these, abusing it does. However after a roll, you will have less 5HT floating about purely cos you just dumped a lot of your "store". 5HT-P does NOT prevent or reverse damage to the axons, it only lets the axons that are still working add more 5HT back to the reserve quicker.

In short, 5htp will increase your mood sooner than usual post-roll and counteract some of the comedown as you will get back on your feet after a shorter period of time due to there being more 5HT being made to replenish reserves. 5htp will not reverse or protect against MDMA induced neurotoxicity.

The issue with how people use 5htp is that it often amounts to no more than an expensive placebo due to it binding peripherally. A large portion (~90 percent) of your serotonin system is in the gastrointestinal tract (5ht3 being the primary mediator of nausea in the gut and emesis response in the brain), so 5htp will natrually bind to these sites first, next followed by binding to receptors in cardiac tissue (and thus 5ht2b agonism). The former can cause nausea and vomiting as mentioned, the latter will gradually cause valve hardining. To avoid this, and send the 5htp to your brain where it needs to be to make brain serotoin, you should also supplement ECGC, which can be found in green tea extract amongst other things, this inhibits it from binding peripherally.

Also iirc you need to not be suffering from a vitamin b6 deficit, otherwise the 5htp cant effectively convert into 5ht.

5htp should NOT be used to treat depression, or on an ongoing basis without consulting a decent bit of research, or a professional. Regular use of one amino precursor without balancing it out with others, will impact nondominant systems. In the case of 5htp, it will gradually downregulate your dopamine, causing potential further mood issues. Look to L-Tyrosine for somewhere to start with this.

You should avoid taking 5htp within 24hours before dosing MDMA. even though it has never contributed to serotonin syndrome (except once in a golden retriever, where it was the only drug accidentally administered), 5htp will still potentially increase serotonin levels uncomfortably alongside a releaser. Taking it for up to a week following a roll wont harm you. Avoid high doses as they are unneccessary and will only add extra side effects.
www.rollsafe.org is a better resource than any bottle of 5htp imo.

Further reading on 5htp:
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3415362/

The only issue with this is that MDMA inhibits Tryptophan Hydroxylase. Which is absolutely required to turn 5HTP into serotonin. Which is the reason you have low serotonin - your body doesn't run out of 5htp it temporarily loses the ability to convert it to serotonin.

Unfortunately 5HTP post roll is a waste of money.

 

[cosmosmariner]

The only issue with this is that MDMA inhibits Tryptophan Hydroxylase. Which is absolutely required to turn 5HTP into serotonin. Which is the reason you have low serotonin - your body doesn't run out of 5htp it temporarily loses the ability to convert it to serotonin.

Unfortunately 5HTP post roll is a waste of money.

I think this is incorrect. Tryptophan Hydroxylase is needed to convert tryptophan to 5htp, not 5htp to serotonin. Taking tryptophan post roll would be a waste of money, but 5htp should bypass TPH to become serotonin.

5htp with EGCG taken after 24 hours post roll should be a viable way to replenish serotonin for the first week to two after rolling.

 

[snmfmy]

I think this is incorrect. Tryptophan Hydroxylase is needed to convert tryptophan to 5htp, not 5htp to serotonin. Taking tryptophan post roll would be a waste of money, but 5htp should bypass TPH to become serotonin.

5htp with EGCG taken after 24 hours post roll should be a viable way to replenish serotonin for the first week to two after rolling.

Actually MDMA does inhibit tryptophan-hydroxylase.

But you are correct AADC converts 5HTP to 5HT, and that was the enzyme that I meant to be talking about because I remember finding this paper a few years ago.

However, MDMA at neurotoxic doses (which have never been defined for humans) causes a multifold increase in tyrosine which can non-enzomatically convert to DOPA which is a precursor for dopamine. The massive dopamine release plus the imbalance in dopamine synthesis and overload of the organic cation transporter with phenylalanine, tyrosine, DOPA, and dopamine CAUSES THE 5-HT depletion.

This paper describes how blocking the AADC which is the enzyme necessary for 5-HT synthesis, actually prevents the serotonergic damage because it limits the synthesis of dopamine.

There's this really interesting balance between the catecholamines and actually the organic cation transporter system.

Basically the AADC which is necessary to convert 5-HTP to 5HT is being used up by the massive excess of tyrosine, DOPA, and dopamine itself because dopamine converts to norepinephrine.

Regardless of taking 5-HTP It's not going to help.

Now the real truth of the matter.

Recreational doses of MDMA do not induce neurotoxicity or anything more than transient lower levels of serotonin which have been seen to recover in less than a week.

In fact:

"Outcomes of MDMA use are context‐dependent, as seen by elevations in BDNF in both recreational settings and fear extinction studies, as well as phase II trial results."

Potential Psychiatric Uses for MDMA

Phase II trials of 3,4‐methylenedioxymethamphetamine (MDMA)‐assisted psychotherapy have demonstrated initial safety and efficacy for treatment of posttraumatic stress disorder (PTSD), with potential for expansion to depression and anxiety ...

www.ncbi.nlm.nih.gov

Brain derived neurotrophic factor is the exact opposite of neurotoxicity.

It's a brain growth factor and it is elevated after therapeutic/ recreational doses of MDMA.

Every single paper written by good scientists will tell you that lower SERT binding could simply have been from downregulation of the serotonin transporter (SERT).

THE SAME EXACT THING HAPPENS DURING SSRI AND OTHER SEROTONERGIC ANTIDEPRESSANT THERAPY.

Effects on SERT density
"It is apparent that treatment with the SSRIs markedly reduced binding, "

Effects of Chronic Antidepressant Treatments on Serotonin Transporter Function, Density, and mRNA Level

To investigate functional changes in the brain serotonin transporter (SERT) after chronic antidepressant treatment, several techniques were used to assess SERT activity, density, or its mRNA content. Rats were treated by osmotic minipump for 21 d with ...

www.ncbi.nlm.nih.gov

So why when sert binding is lower associated with MDMA Use all of a sudden it's neurotoxicity, yet, we know lower SERT binding is a hallmark of SSRI and long-term antidepressant therapy and we don't call that neurotoxicity.

I call bullshit on the entire premise that recreational doses or even a few times, the recreational dose of MDMA causes any significant neurotoxic effects in humans.

Absent polydrug use or malignant hyperthermia, there's not one documented case of axonal or neuronal damage from recreational doses of MDMA.

I challenge somebody to prove me wrong and find an actual voxel-based PET scan supported clinical before
-and-after study showing actual axonal and neuronal damage in a human caused by recreational doses of MDMA.

Guess what? You're not going to be able to do it because if you could, MDMA wouldn't have gotten its phase 2 approval for use as a therapeutic drug.

 

[cosmosmariner]

Thanks for all this info, Couple questions:
1. Did you post a paper about AADC? I don’t see one.
2. Can you say why you think 5htp won’t help replenish serotonin post roll? Or rather, why that won’t help? I didn’t understand what you were saying.

 

[snmfmy]

Thanks for all this info, Couple questions:
1. Did you post a paper about AADC? I don’t see one.
2. Can you say why you think 5htp won’t help replenish serotonin post roll? Or rather, why that won’t help? I didn’t understand what you were saying.

Here's the abstract

L-tyrosine contributes to (+)-3,4-methylenedioxymethamphetamine-induced serotonin depletions - PubMed

The specific mechanisms underlying (+)-3,4-methylenedioxymethamphetamine (MDMA)-induced damage to 5-HT terminals are unknown. Despite the hypothesized role for dopamine (DA) and DA-derived free radicals in mediating this damage, it remains unclear why MDMA produces long-term depletions of 5-HT...

pubmed.ncbi.nlm.nih.gov

You can search for the full paper.

Basically, tyrosine which is the precursor to dopamine can convert to DOPA on its own, MDMA elevates tyrosine multiple times upon administration.

AADC is required for serotonin synthesis. Even if you have a bunch of 5-HTP floating around, serotonin, dopamine, and norepinephrine all require AADC for synthesis. They all 'compete' for AADC. Using that term compete is incorrect. But I really don't know how better to say it.

When there 's an excess of tyrosine and DOPA, that results in an excess of dopamine and by extension norepinephrine because norepinephrine is synthesized from dopamine. MDMA is also a monoamine oxidase inhibitor which means the dopamine and norepinephrine will be hanging around for a while.

They literally hog up the use of AADC so serotonin can't be synthesized no matter how much 5-HTP you try and consume
Obviously serotonin synthesis doesn't completely stop or you would die.

 

[cosmosmariner]

Here's the abstract

L-tyrosine contributes to (+)-3,4-methylenedioxymethamphetamine-induced serotonin depletions - PubMed

The specific mechanisms underlying (+)-3,4-methylenedioxymethamphetamine (MDMA)-induced damage to 5-HT terminals are unknown. Despite the hypothesized role for dopamine (DA) and DA-derived free radicals in mediating this damage, it remains unclear why MDMA produces long-term depletions of 5-HT...

pubmed.ncbi.nlm.nih.gov

You can search for the full paper.

Basically, tyrosine which is the precursor to dopamine can convert to DOPA on its own, MDMA elevates tyrosine multiple times upon administration.

AADC is required for serotonin synthesis. Even if you have a bunch of 5-HTP floating around, serotonin, dopamine, and norepinephrine all require AADC for synthesis. They all 'compete' for AADC. Using that term compete is incorrect. But I really don't know how better to say it.

When there 's an excess of tyrosine and DOPA, that results in an excess of dopamine and by extension norepinephrine because norepinephrine is synthesized from dopamine. MDMA is also a monoamine oxidase inhibitor which means the dopamine and norepinephrine will be hanging around for a while.

They literally hog up the use of AADC so serotonin can't be synthesized no matter how much 5-HTP you try and consume
Obviously serotonin synthesis doesn't completely stop or you would die.

Thanks for providing the link. If you’re saying that 5htp won’t convert to serotonin post MDMA use, because AADC is being used up converting L-DOPA to dopamine, I think you’re going further than the paper. I mean, it might be true, but it might not. Does dopamine conversion actually outcompete serotonin conversion? Are enzyme stores completely depleted? I couldn’t find these answers in the abstract, but perhaps you know this.

 

[snmfmy]

Thanks for providing the link. If you’re saying that 5htp won’t convert to serotonin post MDMA use, because AADC is being used up converting L-DOPA to dopamine, I think you’re going further than the paper. I mean, it might be true, but it might not. Does dopamine conversion actually outcompete serotonin conversion? Are enzyme stores completely depleted? I couldn’t find these answers in the abstract, but perhaps you know this.

Yes.

"MDMA decreased 5-HT content compared with saline-injected controls (q = 8.403; p < 0.05). This decrease was significantly enhanced by the local perfusion of l-tyrosine but not l-valine (significant interaction, F(3,24) = 30.461; p < 0.05). Specifically, the reverse dialysis of l-tyrosine (500 μm) exacerbated the MDMA-induced 5-HT depletion in striatum by 30% (q = 4.328; p < 0.05) (Fig. 3A)."

I tracked down the actual paper in the journal of neuroscience. There's a lot more than Just what I posted above.

L-Tyrosine Contributes to (+)-3,4-Methylenedioxymethamphetamine-Induced Serotonin Depletions

The specific mechanisms underlying (+)-3,4-methylenedioxymethamphetamine (MDMA)-induced damage to 5-HT terminals are unknown. Despite the hypothesized role for dopamine (DA) and DA-derived free radicals in mediating this damage, it remains unclear why MDMA produces long-term depletions of 5-HT...

www.jneurosci.org

 

[snmfmy]

Thanks for providing the link. If you’re saying that 5htp won’t convert to serotonin post MDMA use, because AADC is being used up converting L-DOPA to dopamine, I think you’re going further than the paper. I mean, it might be true, but it might not. Does dopamine conversion actually outcompete serotonin conversion? Are enzyme stores completely depleted? I couldn’t find these answers in the abstract, but perhaps you know this.

"Consistent with Figure 6, MDMA alone did not change striatal 5-HT content. In contrast, the effect of the infusion of MDMA on 5-HT content was dependent on the presence of l-tyrosine (F(1,29) = 6.221; p < 0.05) (Fig. 7A). The combined infusion of MDMA and l-tyrosine significantly decreased 5-HT tissue content compared with the infusion of MDMA alone (q = 4.360; p < 0.05) and l-tyrosine alone (q = 3.985; p < 0.05). The combination of NSD 1015 with MDMA and l-tyrosine blocked the depletion of 5-HT produced by the MDMA and l-tyrosine combination (t(14) = 4.032; p < 0.05)."

NSD 1015 is an AADC inhibitor. When tyrosine is present, but AADC is not inhibited. 5-HT is severely depleted.

 

[snmfmy]

Thanks for providing the link. If you’re saying that 5htp won’t convert to serotonin post MDMA use, because AADC is being used up converting L-DOPA to dopamine, I think you’re going further than the paper. I mean, it might be true, but it might not. Does dopamine conversion actually outcompete serotonin conversion? Are enzyme stores completely depleted? I couldn’t find these answers in the abstract, but perhaps you know this.

It's also well known that supplementation of the precursor for any individual monoamine or catecholamine neurotransmitter will cause an imbalance with respect to neurotransmitters in the brain.

 

[snmfmy]

Thanks for providing the link. If you’re saying that 5htp won’t convert to serotonin post MDMA use, because AADC is being used up converting L-DOPA to dopamine, I think you’re going further than the paper. I mean, it might be true, but it might not. Does dopamine conversion actually outcompete serotonin conversion? Are enzyme stores completely depleted? I couldn’t find these answers in the abstract, but perhaps you know this.

What's even more crazy is that I found evidence and posted in another link that oversupplementation of tryptophan and 5 HTP can cause a deficit of serotonin.

Over supplementation of tryptophan can result in it. Converting to a different enzyme and actually blocking absorption of tryptophan through the blood-brain barrier. This results in a 5-HT deficiency.

The mechanism for oversupplementation of 5-HTP is a little bit more complex and I forget exactly what occurs.

 

[cosmosmariner]

What's even more crazy is that I found evidence and posted in another link that oversupplementation of tryptophan and 5 HTP can cause a deficit of serotonin.

Over supplementation of tryptophan can result in it. Converting to a different enzyme and actually blocking absorption of tryptophan through the blood-brain barrier. This results in a 5-HT deficiency.

The mechanism for oversupplementation of 5-HTP is a little bit more complex and I forget exactly what occurs.

Got it. I wasn’t saying, by the way, that one should supplement with 5htp all the time. I don’t think that is safe. I was only suggesting it as a way to restore serotonin after a roll when tryptophan hydroxylase has been depleted. However, I may change my mind about that based on your posts. So, thanks for the info.