SSRIs + 5-HTP

[Brian Oblivion]

I have seen people raise questions regarding this combination in conjunction with taking MDMA (the 5-HTP to pre and post-load, and the SSRI as a post-load protective for SERTs). The concern regarding SSRIs + 5-HTP is a rational one, specifically with the idea that serotonin syndrome could potentially resulting from it.

There is very little hard scientific information available (that I am aware of) regarding taking 5-HTP in conjunction with SSRIs. The only reference that I know of is anecdotal (i.e., could be due to unrelated factors), and is located here on Lycaeum. It warns that it is possible to develop serotonin syndrome when taking them together.

One of the things sited in that article puzzles me is that it mentioned a vitamin B-6 warning printed on the bottle of 5-HTP:

...nothing on the 5-HTP bottle said anything about contraindictions with antidepressants. It just said don't eat vitamin B-6 until atleast 3 hours before or afterward...

I question both the notion of potential serotonin syndrome and the warning about avoiding vitamin B-6.

First, vitamin B-6 contributes to passing 5-HTP across the blood/brain barrier and converting it into 5-HT or serotonin (see references: *1*, *2* and *3*). If anything, it would seem that one would want to take B-6 along with 5-HTP to increase absorption effectiveness and conversion into 5-HT, rather than avoid it. (Inconsistencies like this are what make me constantly weary of "alternative" health sources.)

Second, and this is my hunch, NOT a scientifically proven fact, I don't believe that the brain will absorb more 5-HTP than it requires. My suspicion is that once brain levels of 5-HT reaches a maximum saturation, any additional 5-HTP will remain in suspension in the blood (or will be utilized elsewhere in the body). In other words, taking more 5-HTP will not increase 5-HT concentrations within the brain past a natural saturation ceiling. Again, I could very well be wrong about this, so I DO NOT recommend that anyone stake their health on this opinion. In the absence of solid laboratory data, this is nothing more than a hypothesis.

I am submitting this post in the hopes that someone else may have better scientifically authoritative references regarding taking 5-HTP with SSRIs. Or at least precursor studies that might shed more light on the potential (or non-potential) health risks involved. If anyone has any ideas please do feel free to suggest them.

Thanks

 

[neurotoxic]

I'm pretty damn sure
SSRIs + 5htp = serotonin syndrome

 

[Brian Oblivion]

Hi neurotoxic,

Do you have any idea why you'd be sure of this? I'm just trying to establish the science behind it.

 

[Adam X]

I have seen people raise questions regarding this combination in conjunction with taking MDMA (the 5-HTP to pre and post-load, and the SSRI as a post-load protective for SERTs). The concern regarding SSRIs + 5-HTP is a rational one, specifically with the idea that serotonin syndrome could potentially resulting from it.

Agreed. The combination of two or more agents which increase net serotonin neurotransmission is the primary cause of serotonin syndrome.

There is very little hard scientific information available (that I am aware of) regarding taking 5-HTP in conjunction with SSRIs.

No, but there is plenty of anecdotal evidence. Furthermore, the combination of L-tryptophan and certain tricyclic antidepressants with a heavy serotonergic function has resulted in serotonin syndrome. Most commonly, serotonin syndrome results from the combination of a MAOI (excluding Deprenyl in selective dosages) and SSRI. Serotonin syndrome is most commonly fatal with this combination. However, there are literally dozens of combinations of drugs documented in medical literature which the combination of has resulted in serotonin symdrome.

The only reference that I know of is anecdotal (i.e., could be due to unrelated factors), and is located here on Lycaeum. It warns that it is possible to develop serotonin syndrome when taking them together.

Of course it's possible, even though the majority of 5-HTP is decarboxylated before reaching the brain, appreciable amounts of serotonin will be formed in the brain following administration of 5-HTP. This is compounded in the presense of an SSRI, especially since many SSRIs (fluoxetine) are also mild to moderate MAOIs.

One of the things sited in that article puzzles me is that it mentioned a vitamin B-6 warning printed on the bottle of 5-HTP:
...nothing on the 5-HTP bottle said anything about contraindictions with antidepressants. It just said don't eat vitamin B-6 until atleast 3 hours before or afterward...


I question both the notion of potential serotonin syndrome and the warning about avoiding vitamin B-6.

First, vitamin B-6 contributes to passing 5-HTP across the blood/brain barrier and converting it into 5-HT or serotonin (see references: *1*, *2* and *3*). If anything, it would seem that one would want to take B-6 along with 5-HTP to increase absorption effectiveness and conversion into 5-HT, rather than avoid it. (Inconsistencies like this are what make me constantly weary of "alternative" health sources.)

B6 does nothing to increase the passage of anything through the blood/brain barrier. The tryptophan hydroxylase and tyrosine hydroxylase enymes require adequate amounts of B6 to convert to 5-HTP or L-dopa respectively. Taking vitamin B6 with 5-HTP would have little to no effect, since unlike TPH/TH, the L-AAAD (L-aromatic amino acid decarboxylase) enzyme is not dependant on B6 and is not a rate limiting step in synthesis.

Second, and this is my hunch, NOT a scientifically proven fact, I don't believe that the brain will absorb more 5-HTP than it requires.

This is just about ludicrous. Can you tell me what caused you to form this 'theory'? Unlike amino acids such as L-tryptophan and L-tysosine, 5-HTP does not require active transport and does not compete with other amino acids. The brain does not turn off the blood/brain barrier when it becomes saturated with a particular neurotransmitter precursor, it simply turns of the rate limitng enzymes which are needed to complete this synthesis.

Furthemore, if saturation resulted in the "turning off" of the ability of 5-HTP to enter the brain, L-dopa overdosages would not result in central toxicity or amphetamine like reactions. L-dopa is analogous to 5-HTP in that it's the same step in the pathway to dopamine as 5-HTP is to serotonin.

L-tysosine --[TH]--> l-dopa --[L-AAAD]--> dopamine
L-tryptophan --[TPH]---> 5-HTP --[L-AAAD]--> serotonin

My suspicion is that once brain levels of 5-HT reaches a maximum saturation, any additional 5-HTP will remain in suspension in the blood (or will be utilized elsewhere in the body). In other words, taking more 5-HTP will not increase 5-HT concentrations within the brain past a natural saturation ceiling. Again, I could very well be wrong about this, so I DO NOT recommend that anyone stake their health on this opinion. In the absence of solid laboratory data, this is nothing more than a hypothesis.

I'm not trying to sound like an ass here, but honestly I've never read a more flawed hypothesis on 5-HTP/serotonin and uptake into the brain. It apparant you lack a basic understanding of the mechanisms of neurotransmitter function/synthesis within the brain. I would suggest you satisfactorily acquaint yourself with "The Biochemical Basis of Neuropharmacology", this book will provide answers to questions you never even knew you had. I encourge you to learn more about this facinating field of study.


X

 

[pinwheel]

Brian Oblivion, I thought it was a good theory that the brain will not absorb more 5-H than needed, but then I thought about it and if there really are deaths resulting from serotonin syndrome then I think there is really no way to stop the brain from feeding just like we can't stop the stomach from feeding on the food it has just been given.

Not that the absorption of 5-HTP is responsible for any of the deaths...but apparently serotonin syndrome is a real thing...and I do have to be careful if I really want to go on a MAO inhibiting-anti-depressant...
I could always just smoke uncured tobacco...

 

[VelocideX]

The theory that the brain will not absorb more serotonin than needed it ludicrous.

The brain has no way of stopping the enzymatic conversion; you cant just switch the enzymes off.

The enzymatic conversion is determined entirely by chemical means - the availabilty of l-AAAD, the availability of 5-HTP and nothing more. thats the whole point in enzymes... they catalyse a reaction. The only other number that makes a difference is the equilibrium coefficients.

and as was said, serotonin syndrome has occurred from 5-htp + antidepressant combinations. i myself accidentally induced a mild form of serotonin syndrome. I was on 75mg/day venlafaxine and had a 5-htp capsule (i'd forgot i'd taken the venlafaxine), and felt mildly nauseous... my eyes were huge.

the brain is not as smart as you give it credit for. it must ultimately succumb to chemistry.

 

[VelocideX]

a quick search on google for
5-htp "serotonin syndrome" reveals a plethora of links, including one very high up on erowid experiences:
http://www.erowid.org/experiences/exp.php?ID=12878

 

[VelocideX]

A quick search on bluelight (i was very fast) turns up the following possible instance of serotonin syndrome from 5-htp and a SSRI:
http://www.bluelight.ru/vb/showthread.php?s=&threadid=28376&highlight=5htp+serotonin+syndrome

 

[Brian Oblivion]

The theory that the brain will not absorb more serotonin than needed it ludicrous.

I'm starting to think that "ludicrous" is the word of the week or something. What ever happened to responses like "that's not an accurate model because..." or something to that effect? (*sheesh*) 8(

Does anyone have any clinical references to reports where someone acquired serotonin syndrome from combining 5-HTP and a SSRI?

I don't mean to sound critical. But I have not been able to find one single clinical case study of serotonin syndrome resulting from someone taking 5-HTP and a SSRI together. I am not arguing that this is not the case. But there are a LOT of people taking SSRIs, and there is a wide distribution of 5-HTP available (and unregulated at that). Yet, the only reports of suggested serotonin syndrome coming in are non-clinical, and from people taking these in combination with recreational drugs.

Surely, there sould be a base of clinical experience confirming that this has occurred.

 

[Brian Oblivion]

a quick search on google for
5-htp "serotonin syndrome" reveals a plethora of links, including one very high up on erowid experiences:
http://www.erowid.org/experiences/exp.php?ID=12878

The problem is that almost every one of these links leads to a non-authoritative source (i.e., health stores, alternative health, etc.). I'm not finding anything originating from a scientific journal, or a university. I've been all over the Centers for Disease Control's database and haven't come up with one case.

I would highly expect that problems with this combination would be showing up in traditional medical settings (i.e., clinics, ERs, private practise, public health services, etc.).

 

[Brian Oblivion]

Hi pinwheel,

Brian Oblivion, I thought it was a good theory that the brain will not absorb more 5-H than needed, but then I thought about it and if there really are deaths resulting from serotonin syndrome then I think there is really no way to stop the brain from feeding just like we can't stop the stomach from feeding on the food it has just been given.

Not that the absorption of 5-HTP is responsible for any of the deaths...but apparently serotonin syndrome is a real thing...and I do have to be careful if I really want to go on a MAO inhibiting-anti-depressant...
I could always just smoke uncured tobacco...

Thanks

I was just toying with the idea 5-HT saturation as a regulating factor. But I knew full well with that I didn't have a real working understanding of the process. Just playing with the model.

As I've been looking into this, it appears that serotonin syndrome is a very rare condition. Even in cases where people have taken rather large doses of 5-HTP (without any other drug combinations).

Definitely be careful about going on an MAOI. I'm sure that you are aware of the implications if you do.

 

[Brian Oblivion]

Adam,

This is just about ludicrous. Can you tell me what caused you to form this 'theory'?

Chill :D
I never said that I was married to the idea, I've simply been toying with the notion of serotonin saturation and stasis. I don't think it is ludicrous (there are a lot of other processes which work that way), it was just a bad model. That's all.

If I am understanding you correctly, there is absolutely no regulation of 5-HTP build up in serotonin cells. That 5-HTP distribution is essentially random, and that 5-HTP freely passes through the cell membrane. So, assuming that I have that correct, of someone ingested 1 gm. (a large dose) of 5-HTP they could have an abnormally large concentration of 5-HTP in the majority of serotonin cells.

Is that correct, or have I missed something.

 

[Adam X]

I never said that I was married to the idea, I've simply been toying with the notion of serotonin saturation and stasis. I don't think it is ludicrous (there are a lot of other processes which work that way), it was just a bad model. That's all.

I really wasn't trying to rip you personally on your theory, it just defied everything I've ever learned about how the CNS operates.

If I am understanding you correctly, there is absolutely no regulation of 5-HTP build up in serotonin cells. That 5-HTP distribution is essentially random, and that 5-HTP freely passes through the cell membrane.

This is why I do not like 5-HTP as a supplement for anything but post-MDMA. 5-HTP causes serotonin formation anywhere that L-AAAD is found. This could be serotonergic neurons, dopaminergic neurons or the bloodstream. L-tryptophan does not produce this haphazard serotonin formation, as the enzymes needed to convert it to 5-HTP are found nearly exclusively in serotonergic neurons.

So, assuming that I have that correct, of someone ingested 1 gm. (a large dose) of 5-HTP they could have an abnormally large concentration of 5-HTP in the majority of serotonin cells.

No, they'd have an abnormally large distribution of serotonin, it would not be limited to serotonergic neurons. Remember that serotonin forms anytime 5-HTP comes in contact with the extremely active L-AAAD enzyme. This enzyme is so active in fact that 5-HTP/L-dopa cannot be found in the brain (post mortem). The conversion from 5-HTP to 5-HT is very nearly instantaneous, as the removal of a carboxyl group (as opposed to the addition of a hydroxyl) obviously does not require any effort and is catalyzed by a very active enzme. The brain is better at breaking things down than building them, Parkinson's Disease is probably the prime example.


X

 

[VelocideX]

If I am understanding you correctly, there is absolutely no regulation of 5-HTP build up in serotonin cells.

Serotonin production is rate-regulated by tryptophan hydroxylase.... serotonin is the ONLY neurotransmitter ( to the best of my knowlege) not subject to end-step inhibition. This is why many people feel that 5-htp supplementation is unwise; there's probably a very good reason that you dont want to bypass the rate-limiting step.

 

[VelocideX]

CDC is the wrong place to look. You want to search medline.

Here's a case (21 in fact) involving dogs: http://www.ncbi.nlm.nih.gov:80/entr...ve&db=PubMed&list_uids=10863592&dopt=Abstract

Here's an abstract from the Department of Emergency Medicine, University of Pittsburgh, which suggests that "The main pathophysiologic mechanism appears to be excessive 5-hydroxytryptophan stimulation"
http://www.ncbi.nlm.nih.gov:80/entr...eve&db=PubMed&list_uids=8909274&dopt=Abstract

There's an implied serotonin syndrome induced in rats here: http://www.ncbi.nlm.nih.gov:80/entr...eve&db=PubMed&list_uids=9692731&dopt=Abstract

A MAOI and 5-htp induced serotonin syndrome in these rats: http://www.ncbi.nlm.nih.gov:80/entr...ve&db=PubMed&list_uids=10867971&dopt=Abstract

Low level serotonin syndrome was induced in rats with ONLY 5-htp: http://www.ncbi.nlm.nih.gov:80/entr...eve&db=PubMed&list_uids=1409774&dopt=Abstract

 

[dr. greenthumb]

i would assume if taken in lrage amounts, this combo could potentiate seritonin sydrome ephasis on the word "assume".

^^^velcidex your on mksydney arent you?

-cyto

 

[VelocideX]

yeah i do post on mk. i cant imagine there'd be anyone else with as unique a dj name as velocidex

 

[Brian Oblivion]

Hi VelocideX,

CDC is the wrong place to look. You want to search medline.

Here's a case (21 in fact) involving dogs: http://www.ncbi.nlm.nih.gov:80/entr...ve&db=PubMed&list_uids=10863592&dopt=Abstract

Here's an abstract from the Department of Emergency Medicine, University of Pittsburgh, which suggests that "The main pathophysiologic mechanism appears to be excessive 5-hydroxytryptophan stimulation"
http://www.ncbi.nlm.nih.gov:80/entr...eve&db=PubMed&list_uids=8909274&dopt=Abstract

There's an implied serotonin syndrome induced in rats here: http://www.ncbi.nlm.nih.gov:80/entr...eve&db=PubMed&list_uids=9692731&dopt=Abstract

A MAOI and 5-htp induced serotonin syndrome in these rats: http://www.ncbi.nlm.nih.gov:80/entr...ve&db=PubMed&list_uids=10867971&dopt=Abstract

Low level serotonin syndrome was induced in rats with ONLY 5-htp: http://www.ncbi.nlm.nih.gov:80/entr...eve&db=PubMed&list_uids=1409774&dopt=Abstract

I've already seen these. None of them are related to actual clinical studies. One of them "supposes" the potential problem in emergency medicine, and the rest are serotonin syndrome induced in lab animals (i.e., forcefully inducing the condition in an animal with a much higher metabolic rate than a normal human).

This is what I'm finding frustrating about this. There do not seem to be any recorded clinical instances (which is why I was poking around the CDC database - this is exactly the kind of thing I would expect to see appear in a health surveillance archive). I've also looked at the American Academy of Emergency Medicine, Journal of Emergency Medicine and Acute Primary Care, and the European Journal of Emergency Medicine. These also produce no useful references.

The reason that I am so interested in this is because we have a community which is being advised to take 5-HTP after using MDMA. Also, there are separate recommendations to the same community to take Prozac in a prophylactic capacity about 5 hours after an MDMA experience has been started.

Let's look at this from the standpoint of a public health service for a moment.

On the one hand, we could issue an alert stating that taking both an SSRI and 5-HTP together can produce serotonin syndrome. But, in absence of clinical evidence that this combination is dangerous, we would be issuing a "false warning." Additionally, IF this combination does not actually produce serotonin syndrome, we would effectively be advising people to avoid known harm reducing activities (all based on a "hunch" which has absolutely no valid clinical experience behind it).

Even publishing a simple warning that this combination "may" produce serotonin syndrome, is irresponsible. It would likely scare people away from these harm reducing practises (and, again, without valid clinical evidence).

 

[Adam X]

I've already seen these. None of them are related to actual clinical studies. One of them "supposes" the potential problem in emergency medicine, and the rest are serotonin syndrome induced in lab animals (i.e., forcefully inducing the condition in an animal with a much higher metabolic rate than a normal human).

A higher metabolic rate would represent a lowered risk of serotonin syndrome.

This is what I'm finding frustrating about this. There do not seem to be any recorded clinical instances (which is why I was poking around the CDC database - this is exactly the kind of thing I would expect to see appear in a health surveillance archive). I've also looked at the American Academy of Emergency Medicine, Journal of Emergency Medicine and Acute Primary Care, and the European Journal of Emergency Medicine. These also produce no useful references.

You have to understand that evidence which shows that SSRI antidepressants are dangerous, in any capacity, is going to be underrepported or downright censored. There are literally hundreds of reports of suicide and homicide associated with the use of SSRI drugs, starting from the first clinical trials of Prozac in the early 1980s. Yet even today, most people are blissfully ignornat of this. I don't think many doctors, psychiatrists or researchers are going to be to eager to point their fingers at SSRIs for ANYTHING negative.

The reason that I am so interested in this is because we have a community which is being advised to take 5-HTP after using MDMA. Also, there are separate recommendations to the same community to take Prozac in a prophylactic capacity about 5 hours after an MDMA experience has been started.

This is the problem with amatuer pharmacologists. I have never recommended ANYONE take any SSRI, EVER! In fact, I have reason to believe that the usage of SSRIs after MDMA might be extremely damaging to the brain.

On the one hand, we could issue an alert stating that taking both an SSRI and 5-HTP together can produce serotonin syndrome. But, in absence of clinical evidence that this combination is dangerous, we would be issuing a "false warning."

Please. Be reasonable here. People who do not know what they're doing should not be haphazardly combining drugs. I don't know why this whole myth of SSRI = neuroprotection is even here, other than the misinterpretations of a few wanna-be psychopharmacologists. Let me be perfectly clear:

SSRI DRUGS HAVE NEVER BEEN SHOWN TO BE BENEFICIAL OR TO PREVENT NEUROTOXICITY AFTER TAKING MDMA, EVER.

Additionally, IF this combination does not actually produce serotonin syndrome, we would effectively be advising people to avoid known harm reducing activities (all based on a "hunch" which has absolutely no valid clinical experience behind it).

You're starting to get on my nerves. You really don't know what you're talking about here, yet for some reason you think you do. SSRI administration post-MDMA is a "known harm reducing activity"? Would you care to provide a source for this? There has never been a study done, on human or animals on oral use of an SSRI post-MDMA.

Even publishing a simple warning that this combination "may" produce serotonin syndrome, is irresponsible. It would likely scare people away from these harm reducing practises (and, again, without valid clinical evidence).

[EDIT]No Personal Attacks - Flex[/EDIT]

I just get really irked when people who HAVE NO IDEA WHAT THEY'RE TALKING ABOUT start speculating about "facts" and start filling in the blanks with absolutely no knowledge of which they speak. Why in the world would a person need to take 5-HTP with an SSRI? Can you explain to me why this would be beneficial and not dangerous?

X

 

[Brian Oblivion]

Adam,

You really need to stop this personal attach stuff. You have no knowledge of my background, and you don't seem willing to disclose your's.

I've worked for the Centers for Disease Control as a contract software engineer for about 8 years. (I've been developing software for scientific and medical applications in research for almost 20 years). One of the project series I've work on was a joint development project to produce several computer models of neurological processes used in antidepressant research.

I may not be a neurophysiologist, but I have worked with quite a few (both MDs and PhDs). I am also aware that SSRIs are not the 100% safe drug that many drug companies would like us to think that they are. But public health agencies like the CDC do not succumb to such pressure. CDC's culture is different from NIH's (NIH tends to be somewhat driven by politics as well as by public health concerns). CDC is solely concerned with public health (which is why many within CDC when out on a limb during the early out break of HIV - in a political climate where doing so was not conducive to doing so). Also, CDC issued a statement contradicting NIH regarding the dangers of MDMA use, based on the lack of clinical data.

So, my professional background is one of working within public health research. And I am looking at this whole problem from that point of view.


Regarding your impressions of SSRIs and their use in conjunction with MDMA: first, no matter what we think, or what we would like people to do, it is already a common practise in the MDMA community. You can have all of the opinions that you would like, it is NOT going to change the fact that people are actively doing it.

Second, I would like to see some hard scientific evidence illustrating that taking an SSRI in a prophylactic neuroprotective measure with MDMA is hazardous. If you are really a scientist, and not simply someone who reads a lot, you should have no problem producing references (this is how science is done).


Third, and this doesn't mean a damn thing except to me, I have been post-loading with Prozac for about 8 years (ever since I became aware of some findings that were made at a primate research lab in La hoya, Ca). From personal experience, it appears to help a great deal. And, this is coming from someone with a 50 year old nervous system (i.e., more sensitive to chemical assaults).

[EDIT]Personal Attack Removed - Brian[/EDIT]

That is the kind of thing that I would expect to hear from an armchair "expert," not a true scientist. You really need to get this under control. For one thing, it is a dominance technique, and intimidates people who do not deserve to be treated that way (I've seen you do this on the DanceSafe forum).

Also, science is not something that you can jump up and down and say, "my world view is right so fuck you." Anyone who does that ends up not working in science. Even the assholes are forced to be open minded (except with their grad students who they abuse, but not the rest of the scientific community).

When I see you say, "[EDIT]comment removed - Brian[/EDIT]" I conclude, "reads books, doesn't work in science, needs to use science to prove how smart he is."

I'm going to give you the benefit of a doubt. Maybe you are having a bad day? But, I've layed my cards on the table. I've worked around research science for most of my professional life. So what is your background?


Anyway, regardless of what you personally think of me, I am going to continue to try to obtain a clear idea of this practise is dangerous or not. And base it on clinical data, not opinions (this is how it is done in public health). If you would like to help, that would be great. If you don't want to help, that is fine, too. I'm concerned about the impact on folks who may be taking SSRIs and 5-HTP together, not prove to others that I am smart. 8)



EDIT: It is important to point out that I am not currently employed by the Centers for Disease Control. I am not speaking as a representative of the CDC. All opinions expressed here are solely my own, and have absolutely nothing to do officially or unofficially with positions held by the Centers for Disease Control and Prevention, nor do they represent the points of view held by any other governemnt agency.