How do you recover Serotonin Transporter proteins (SERT)?

[Speculosity]

Hi everyone,

Okay, to keep this from being a wall of text, Someone I know took MDMA, and they have working memory problems now.

I learned through reading various studies that the main reason this problems occurs, is because MDMA significantly and (from what it says) almost irreversibly lowers the amount of the serotonin transporter (SERT), in the brain.

This correlates with why Bacopa temporarily increased my friend's memory while he was on it. Bacopa upregulates SERT.

Google's spitting out mild results, so I wanted to ask if anyone here knows how SERT is made (Might provide a clue/lead for increasing it), and if there is anyway to recover them to normal levels?

And if you don't know, or just know other ways to temporarily upregulate SERT, I'd love to see what you have to share if that's alright.

I'd really appreciate your help, thank you!

 

[anubis23]

Personally I find ashwagandha to be extremely useful to "feel normal" after any sort of stimulant use, however I have only done MDA once and never MDMA. Bacopa seems like a good choice as well, I will have to look further into it, thanks for the suggestion.

After reading this section "Physiological actions of serotonin and its regulation by serotonin reuptake transporter (SERT)" from http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3852299/ I have a feeling acetyl l carnitine and alpha lipoic acid may be beneficial, after use and abstinence. Keep in in dietary sources offer improved bioavailability than just taking expensive supplements. See also:
(Sorry I couldn't find any primate studies.)

http://www.ncbi.nlm.nih.gov/pubmed/19015003

There is some discussion regarding your question here.

http://www.bluelight.org/vb/threads/609672-Supplements-Shown-to-COMPLETELY-BLOCK-Serotonin-Depletion-from-MDMA

 

[serotonin2A]

MDMA is thought to deplete serotonin and to increase oxidative stress in serotonergic terminals. These effects may lead to reductions in SERT, potentially because of loss of serotonergic terminals, because SERT is denatured, or because of SERT downregulation to compensate for low levels of serotonin release. In any event, the loss of SERT that may occur after MDMA use is only a marker for changes to serotonergic axons, and is not the cause of the deficits that you are describing. Any post-MDMA memory problems would be due to loss of serotonin. Upregulating the transporter would actually make the problem worse because the extra SERT would lower synaptic serotonin levels even further.

You can think this through another way -- if the deficits are due to loss of SERT function then SSRIs would cause the same effect, but that is not the case.

 

[mb-909]

The only way to "reverse" the deficits you might suffer is to abstain from all drugs, eat a healthy diet and exercise. MDMA exposure inhibits the production of serotonin for a week, reduces the CYP2D6 metabolismn for up to 10 days significantly and produces a reduced blood flow in the frontal brain areas for up to 4 weeks. This changes can last way longer and therefor MDMA can lead to many adverse reactions. Not only that, but you are at a way higher risk to develope sleepping problems with reduced REM sleep leading to memory deficits. If compared to SSRI's you have to consider that MDMA leads to immediatly changes being noticeable.

Sport increases the total blood flow in your brain, which can help to get better results. This is probably the reason why it is worthy to do sports, also if you use SSRI's and antipsychotics. Physical movement seems to be very important to reduce the effects of aging.

And to your question about SERT (heavily dose and general exposure dependent):


"Vollenweider and colleagues recently measured serotonin transporter density using positron emission tomography (PET) with [11C]McN5652 before and after a single clinical MDMA exposure (Vollenweider et al. 2000, data presented at the 2000 conference of the German Society for Psychiatry, Psychotherapy and Neuromedicine). Vollenweider and colleagues were unable to detect any lasting effect of 1.5 or 1.7 mg/kg MDMA in a pilot study with six MDMA-naive healthy volunteers and in a second study with additional volunteers (n = 8 ). This ligand and measurement technique had been previously reported by another group to be sensitive to apparent serotonin transporter changes in illicit ecstasy users with at least 70 drug exposures (McCann et al. 1998 ). This measurement technique was validated in a study using a baboon exposed to a neurotoxic MDMA regimen (Scheffel et al. 1998 ), and this validation study found that PET tended to overestimate serotonin transporter changes in most cases. A more recent study in humans that employed this ligand also found reduced levels of serotonin transporter in current ecstasy users, but did not report as large a reduction in serotonin transporter as did the original study (Buchert et al. 2003; Buchert et al. 2004). Given the small sample size in the study by Vollenweider et al., it is possible that a modest change in SERT density could have gone undetected. However, very little variance in ligand binding was found in baseline measures of ligand binding.

Imaging studies in repeated ecstasy users have consistently found lower serotonin transporter levels, but these findings are also qualified by degree of exposure and period of abstinence. One study using the same ligand used by McCann and colleagues (Buchert et al. 2003; Buchert et al. 2004) and one study using a different ligand (Reneman et al. 2001) both found that serotonin transporter levels returned to normal in people who abstained from ecstasy for a year to a year and a half. Both studies also found greater reductions in serotonin transporter, greater numbers of affected areas, in women. Reneman and colleagues (2001) also compared people reporting at least 50 exposures with people who reported fewer than 50 exposures, and they found that moderate ecstasy users (those reporting use on fewer than 50 occasions) did not have significant reductions in serotonin transporter sites. These findings suggest that effects on serotonin transporter may be at least partly dependent on degree of use and time since last exposure. Because of findings in humans and non-human animals, the possibility of neurotoxicity will be discussed with all volunteers, even though strong evidence from studies in humans and non-human animals suggests that the risk of neurotoxicity posed by participating in this study is low."


Ressources: section "neurotoxicity"

- http://www.maps.org/research-archive/mdma/canceranxiety/fda-protocol/pandt.html

 

[sekio]

MDMA significantly and (from what it says) almost irreversibly lowers the amount of the serotonin transporter (SERT), in the brain.

I think you need to be using very high doses (grams or more per session) before you get long lasting serotonergic damage. A more likely cause of feeling "down" after moderate recreational usage is simply depleted levels of monoamine neurotransmitters. MDMA actually releases dopamine and norepinephrine too. It can also mess with cortisol (stress horomone) among other things, too.

Time, restful sleep, and a balanced diet will help speed recovery. Avoid using cannabis or alcohol in the meantime too.

 

[Fractality]

A more likely cause of feeling "down" after moderate recreational usage is simply depleted levels of monoamine neurotransmitters.

Also, let's not forget the use of MDMA is associated with little to no sleep, little to no (nourishing) food, and high amounts of strenuous physicial activity.

Just this past weekend I rolled and engaged in A LOT of moving around with essentially no sleep but I did consume a couple of green smoothies with fruits/vegetables during the roll and found that the only issue was a sore body and even that was ameliorated after staying still for a short while.

 

[serotonin2A]

Also, let's not forget the use of MDMA is associated with little to no sleep, little to no (nourishing) food, and high amounts of strenuous physicial activity.

Just this past weekend I rolled and engaged in A LOT of moving around with essentially no sleep but I did consume a couple of green smoothies with fruits/vegetables during the roll and found that the only issue was a sore body and even that was ameliorated after staying still for a short while.

The usage pattern that you are describing is not an inherent property of MDMA. Not everyone uses it that way.

 

[Speculosity]

Sorry for being late but thanks for the responses everyone.

I actually did find out that SERT was not the reason for the deficeit. I found out that Methyl Folate increases SERT expression, but it did not make my memory better.

The search continues...

PS. I am exercising constantly, and take multivitamins. There has been no improvement. I've tried ALCAR and it did nothing. And I'm gonna try ashganwandra.

 

[Cotcha Yankinov]

Hi Speculosity, I'm surprised no one has mentioned 5-HTP yet. I believe that taking the serotonin precursor 5-HTP can help replenish serotonin long term, and in the rodent models 5-HTP has been shown to help prevent serotonin loss if given within a short enough time frame (I think it was like two weeks). Normally you get serotonin from your diet (L-tryptophan) but the enzyme that converts L-tryptophan in your diet to (5-HTP) serotonin in your brain can be reduced for a couple of weeks after MDMA use, so skip a step and go 5-HTP . In the study it was also with another drug carbidopa that helps the 5-htp reach the brain but since that's a parkinsons drug you would really want something called ECGC (green tea extract) that has a similar effect. It will help get the 5-HTP into your brain and not just in your periphery. I would take around 200mg 5-HTP (If feeling heroic could go 300mg or whatever I guess) a day (spread out, but most before you workout preferably early in the day) and with 400mg EGCG to help the serotonin reach the brain. Depending on how much you want to spend or what problems you're having you could also invest in L-theanine to help your GABA to help with sleep (SLEEP IS ESSENTIAL, SPECIFICALLY FOR MEMORY), L-tryrosine and L-taurine for your focus, if you multi vitamin doesn't have b6 (Pyridoxine) I would take b6 with the 5-HTP because it is a cofactor and helps absorption. Melatonin is very important to try if you're not sleeping well, normally your brain makes serotonin out of melatonin. I recommend extended release, and experiment with dosages, you might not need much (1mg or less even).

But yeah if your multi doesn't suck then basically 5-htp, EGCG, L-theanine, can try L-tryrosine and L-taurine (helps make dopamine/adrenaline for focus) but they could possibly keep you up and bad sleep ain't worth it. Melatonin for sleep. An antioxidant you could take is alpha lipoic acid with acetyl-l-carnitine. I take curcumin (turmeric). I wouldn't take much of this stuff for very long, after a month I would drop it down to just 5-HTP at like 25mg twice a day or something like that (though L-theanine/turmeric is good forever IMO, I will always take). HOW IS YOUR SLEEP DOING??? BTW 30 minutes of cardio as early in the day as you can get it has been shown to help neurogenesis specifically in the dentate gyrus which is a really important area for memory (Where most serotonin is and projects to the rest of the brain from). So keep at the cardio! It helps make new brain cells. BTW don't take 5-htp or anything with an SSRI! and if you feel like its causing problems just try a low dose like 25-50 mg. If you've got any questions fire away, I'd love to help.