Frontal lobes; BDNF expression: Tianeptine vs SSRI's vs SJW

[somedud]

Ok quick synopsis, MDMA use/abuse induced depressive states, loss of emotions, hard time reading/relating to people, and loss intellect (memory/learning problems, minor speech problems and can't express myself/thoughts clearly). Somewhat zombieish.

Now, I've read many articles relating to BDNF gene expression, and it's immense reparative properties, most intriguingly in the frontal lobes.

Here's one study, showing immense repair after a almost complete destruction of the 5 HT network from a neurotoxic regimen of PCA.

Source: http://www.jneurosci.org/content/20/2/771.full.pdf

My aim, of course is to repair/relieve the damage/symptoms caused by my (ab)use.

This is where I need a hand, if you folks don't mind lending one. Accordingly to many theories, SSRIs have shown to emit their antidepressive effects long after synaptic levels of 5 HT have been accomplished. This is due to the "rewiring" (denser axonal networks) of key areas of the brain involved in thinking and emotions, which is proposed to be due to increase/decrease in 5 HT, which increases the BDNF expression in depressed patients, which modulates cyclic AMP signaling, which in itself is very reparative.

Ive heard ALOT of praise about Tianeptine and it's neuroprotective, memory enchacing and regenerative properties, along with minimal reports of side effects. Aswell, it's been linked to raised serum BDNF levels, which is what I'm looking for. It's also been shown to have an up-regulating effect on 5 HT receptors.

On the contray, I've read much about St johns wort upregulating 5ht1a and 5ht2a receptors. Currently I'm 2 weeks into treatment, with no effect.

In your opinion, which would be the smartest way to go about recovery/repair, and spiking BDNF levels? Unfortunately none of the studies I've read have shown a measurement of exactly how much BDNF is increased, leaving me to guess if you will.

My goal, is the best remission of these symptoms, with a stable mood, along with no debilitating side effects. I MAINLY want to be able to feel emotions again, especially when it comes to my friends, I literally have none, I'm FLAT.

I've read much about SSRIs and MDMA induced depression being contradicted, and slowing/stoping recovery, which I don't understand, because it seems to spike bdnf levels and induce axonal sprouting in regions MDMA damages.

During this time, and currently I'm taking curcumin, with other nootropics and daily exercise.

Someone, please, give me some insight, I REALLY don't want to fuck this thing up, I've only got 3 months til school, and can't complete it in this state.

P.S. For whom this may concern, my period of use was 1-2 pills a night, 11 times in 3 1/2 months.

 

[afternoonglory]

Upping the BDNF protein would not repair damage because it cannot sustain the survival of new axons, as the study quite rightly points out, it can merely encourage sprouting, which would not prevent its eventual death in the cell cycle. They use this protein in stem cell research and in the early 90s a lot of doctors thought it was the answer, however, it was shown to only induce repair on tissue in vitro and not in vivo.

 

[negrogesic]

This is the danger of the internet......

 

[mgmt&mdma]

jeez somedud haha, mad props for all the work yer doin on the 5ht system

st. johns wort didnt do anything mood-wise for me. i actually think it's what gave me anxiety which lead to worse depression

i started SSRI's 13 days ago and for the first week, i was an emotional zombie, and now i get like waves of contentment that last for an hour or 2, followed by normal mood (like how normal people normally feel, and in rare cases ill get waves of sadness where all i can think of is how much i regret being born -_- (im on citalopram ((celexa)), and will be starting lamictal for manic depression tuesday) but yeah i wouldnt recommend SSRI's. fake emotions =

anyways you should try the tieneptine, and if that doesnt work than i'd say just give yer brain a rest. stop trying to fuck with the 5ht system and let it try to work things out on its' own.

 

[somedud]

Oh really? Fuck. Then how do they propose the efficiency of SSRIs long term benefit?

Thanks mgmt I can't afford it just yet, so I think I'll try an SSRI, then switch to Tianeptine when school starts up, seeing how it's mentally stimulating with proposed benefical stress-induced memory problems.

This is gay, I never even used that hardcore and I've got a lifetime worth of bullshit to deal with.

 

[mgmt&mdma]

OHYEAHH!!! I FORGOT TO MENTION:
SSRI's have so many WONDERFUL side effects. the most WONDERFUL ive experienced so far is the sexual dysfunction. do you know how fucking frustrating it is?!!?!?!?!?
im 16 and used to have NO problem with my [[junk]]. now- i cant get turned on when i want to, or when im supposed to. and it takes me like 75minutes to [[finish]] my business. im gonna ask my psych if i can taper next time i see her. hopefully this isnt permanent...

the only benefit i can see (and maybe its placebo) is that i have a little less anxiety.

i deffinitley wouldnt recommend it. sorry brahski i know how you feel though. the depression...sucks fucking balllsssss. do you have anxiety too?

 

[somedud]

I did until rolled again? Then I got ED problems, along with fucked up speech, but no anxiety now? It's fucked up.

Ive got minor Ed problems now :/ maybe I should stay away from them then. The. Again I'll give it a try, and see how it works out. If I get problems I'll bounce off em

 

[First Bad Comedown]

Hey guys...

Some quick advice...

SSRIs are simply helping to plug up some of the receptors.
The effect of this is that the available serotonin goes a LOT further.
It likely affects receptors that shouldn't be receiving serotonin.
Well, how can that be?

Because quite a few of these receptors are meant to be lost to the re-wiring process.
The branches have to re-organize in an ascending pattern...from the back to the front.

By filling up receptors that are meant to be 'lost', you are stalling the healing process. In fact, you may down-regulate some receptors that 'should be' or 'could have been'.

Does this make any sense?
You are shoving serotonin into crevices that have 'run dry'.
This distracts the brain from 'forcing' new ones to pop up elsewhere - which is meant to result in a lasting 're-organization' of the extended branches of the network.

I know these are crude metaphors, considering my propensity to pontificate...but I thought this would make the most sense.

Look up SSRIsex on yahoo groups or go to paxilprogress.com
You can find many stories of people that began having sexual and ejaculatory anhedonia very quickly after beginning an SSRI. I have heard many stories of LONG-term recoveries, but some of the PERMANENT victims (10-20 years) declare fast-onset problems after beginning medication. Some even stopped after two doses, and still claim permanent status!

For this sexual dysfunction, it is theorized that SSRIs, and likely MDMA, cause a permanent down-regulation of dopamine receptors in the nucleus acumbens due to extended elevation of prolactin. This results in a change in gene expression - another way of saying mitochondrial damage. Again, this is theory - many doctors don't even know this condition exists!

PSSD, or Post-SSRI Sexual Dysfunction, is rare.
However, dysfunction during use is VERY COMMON. 60-80% of men and women experience sexual side-effects.

For most, it subsides within weeks or months of discontinuation.
Then there is the sad group that fears permanence.
I have seen a trend of recovery after the 1-1.5 year mark, much like that found in MDMA general recovery. Some take more than 2 years, and there seems to be another group that takes up to 4, maybe a little longer.
Beyond this, I have not personally seen any success stories.
By year 10, it is considered permanent - however I have heard anecdotal reports about success in this group with the use of penile injections. The proponents do claim that sensation and libido return briefly during its use.

I need to do more research on Tianeptine. It is relatively new, as I understand it.
It does sound a little safer than SSRIs, but I am personally cautious.

St. John's Wort does show some promise.
Like many other 'natural' compounds, it has a very multi-faceted effect upon the brain. It plays with dopamine, serotonin, and norepinephrine. Its interaction is more difficult to study, as a result.

It is a very mild antagonist of the 5-HT system, but it seems to impact Dopamine, especially in the prefrontal cortex. This is believed to be responsible for its beneficial effects. Dopamine may actually cause some 'anxiety' - there is an association between high dopamine levels and mental disorders. Dopamine is not always associated with just pleasure. Perhaps the increase in dopamine/anxiety in the PFC results in more 5-HT axons...

Regardless, SJW is known to have almost NO side-effects.
Not all people respond greatly, though.
Studies show that the most depressed people derive the greatest benefit from it, a remarkable result.

Important - the research with the most reliable success used an extract of SJW that contained 5% hyperforin. This is not easily found, as most SJW that is sold is marketed for its hypercin content. I have come across 3% hyperforin online, but I have yet to try SJW for myself. There is a good chance that I will.

Finally, I have an unusual method to share.
I normally shy away from things that seem 'out there', but this one is described as having a 'small to medium' effect in treatment of major depression.
It has also shown modest results in treatment of schizophrenia, a disorder associated with serotonin and dopamine dysfunction.

Transcranial Magnetic Stimulation involves a powerful electromagnet that can be aimed at different brain regions through the scalp, including the PFC. It releases very strong bursts of magnetic force, in a single pop or in quick succession.
It is believed to work by polarizing and de-polarizing different neurons, which can result in endocrine and neurotransmitter activity.

Repeated treatments were more effective, as well as abstaining from medication during treatment.

Again, this one has a lot more study needed, but it seems to have few risks and some potential. Look into it.

Somedud, I really hope you start feeling sharper, soon.
Its good to hear you aren't suffering as much.
I strongly recommend against everything other than SJW.
Make sure you get the best kind you can find, and please let us know how it turns out. It may take many weeks/months to feel a great difference. It shouldn't carry the risk of setting you back like the others. If it causes anxiety, good.

If you give a good report, I will be very likely to try it to. I will probably start soon, regardless.

Even if you really did set yourself back, thats all it is.
You are not going to stay this way permanently - of this I am highly confident. Worst-case scenario, it takes another year.

Remember - recovery from SSRI use often takes MONTHS. Sometimes years. Even if your last pill set it off, it doesn't mean this wasn't going to happen regardless. Maybe you just sped up the damn process.

And you know what?
Go to school anyways. I can almost guarantee that forcing yourself to function in that way will generate some of the anxiety you want back. You can take just one or two easy classes, but the point is to push yourself. The worst that can happen is you drop or fail.
No...the worst would be you missed out on stimulating your brain.

I know it feels impossible right now.
But others have crossed impossible barriers as well.
The only way you will fail for sure is to not try.

When, not if, you start making progress again - please let all of us know.
This information will be important to others.
Good luck, brother.

 

[mgmt&mdma]

^^another great post by FirstBadComedown
so if SSRI's cause dopamine downregulation does that mean my adderall wont be as fun?

@somedud:
my comp isnt complying with BL and none of my pm's are opening so i cant respond, sorry.
let me know if you find anything that works, or anything you want me to try

 

[somedud]

As usual, another brilliant post by FBC.

I've made up my mind, I'm taking SJW, the Kira brand standardizes for 5-6% Hyperforin, and it also potently boosts BDNF, even compared to SSRIs.

Its cool man don't stress it, I'm about a week into SJW now, and I started doubling up my dose today. I'm taking 1800 my daily, I'll let you know how that goes.

 

[mgmt&mdma]

^^sounds good

 

[First Bad Comedown]

SSRIs will cause serotonin down-regulation, not dopamine.

However, disabling SERT receptors seems to have a direct effect upon dopamine pathways - serotonin is the great modulator of all pathways, due to its profound impact upon blood distribution.

Somedud - good call on the Kira. Please keep me updated.

Suggestion for the ED: try yohimbine bark extract.
I did, with shocking results.

Let me clarify - I have had NO problems with erections during my entire recovery.
I have had lack of libido, early on, along with absence of sensation during orgasm, although this is improving considerably. It seems that repeated release on consecutive nights delivers the most sensation.

I just wanted to try the yohimbine, since I have been in recovery for 7 months.
I was slightly nervous because it affects the androgenic receptors and releases adrenaline. It warns against use by those with psychiatric conditions especially panic attacks.

So I took a small dose - about 30 drops of alcohol based tincture. This was the maximum daily use suggested on the bottle. This seems much more reserved than taking pills. I experienced NO anxiety at all, but after two hours of waiting, it started working. BIG time.

And I mean BIG.
It did not have any effect on libido, per se.
Sensation was slightly improved, due to increases in blood flow.
However, the release of nitric oxide was amazing. There was so much blood flow down there it almost hurt. This was a raging hard-on that could last for hours. When I finally climaxed, the volume of semen was obscene. There was so much, it hurt coming out. I have heard of lecithin use causing this, but DAMN...yohimbine is amazing!

Again, no euphoria or major changes in libido, but I achieved a hard-on that should only be possible with the use of major drugs. And yes - it works for women as well. It causes all the tissues to engorge with blood, which will have modest effects upon improving sensation. Perhaps, for you guys, sensation will go up much higher.

It is worth looking into, but use with caution. High doses have been associated with major panic attacks as well as priapism.
After I was finished, my 'painful' hard-on took twenty minutes to go away! I could have kept going, if so inclined. I imagine this is what Viagra is like...

Moving on...

I wanted to tell you that your research paper about BDNF is a major find, IMO.
It is now part of my arsenal, but I should point out why.

This paper clearly shows the profound effect that BDNF has upon 5-HT axonal sprouting. Although the effect is not permanent, it is not exactly transient, either. The re-innervation seen around the infusion pump sites is impressive - shockingly so. Great fucking pictures in this one.

If we ignore the highly localized and temporary effect....ignore the pump that is being used - imagine that all the BDNF being introduced is from internal processes only.

Now, lets revisit the concluding sentences in the study:

"Our findings expand the role of BDNF as a regulator of 5-HT neuron function and include the demonstration of a remarkable structural plasticity of these neurons, whether intact or injured, in response to BDNF. We hypothesize that, in the adult brain, BDNF-TrkB signaling primarily serves to modulate the physiology and plasticity of 5-HT neurons, as opposed to being a major protective factor for these neurons during stress or insult."

I'm shitting myself, as we speak. :D

Ok, enough said - impressive find, my friend.

This is the best direct evidence I have seen that exercise and other forms of BDNF production are indeed having a profoundly beneficial effect upon recovery. I have always been a proponent of working out, but I have never had evidence this clear - thank you somedud.

Regardless of whether or not all re-innervation is permanent, or nearly as impressive as the localized effect seen in this research, repeated release of BDNF by our OWN infusion pumps should have an impressive global effect.

Keep up the daily exercise - I am going to increase my routine.
Don't forget tumeric extract with black pepper - it is amazing and may further provide BDNF.

The stronger SJW may indeed do the job, my friend, but be careful mixing it with anything else. Even the tumeric extract, in high repeated doses, could interact.

If you feel any type of panic attack or internal pain, pay attention.
Serotonin Syndrome from SJW should be mild if you aren't taking other pharmaceuticals, if it happens at all. In the event you DO have symptoms, lowering your body temperature is the best way to fight the process. A fever of 101 is a sign of severe SS, ok?

Put ice/water in a container and repeatedly apply wet towels to your face, head, and neck. This should turn down the anxiety, by several notches. Try to remain calm, but I don't necessarily believe in laying down. Remember - serotonin is the 'brain-gut' connection, so walking around may allow gravity to help the digestion process. Try to keep benzos on hand, just in case. Drinking electrolytes is also recommended. Quickly lowering body temp is your most affective tool.

This is the exact same treatment recommended for MDMA toxicity, of course.
No surprise, as MDMA toxicity and Serotonin Syndrome are closely related.

Thanks for the research link, again.
Keep up the good fight - your resolve is impressive.
And keep us updated - you provide valuable information about recovery.

 

[mgmt&mdma]

^^

For this sexual dysfunction, it is theorized that SSRIs, and likely MDMA, cause a permanent down-regulation of dopamine receptors in the nucleus acumbens due to extended elevation of prolactin. This results in a change in gene expression - another way of saying mitochondrial damage. Again, this is theory - many doctors don't even know this condition exists!

alright because you said dopamine in yer last post.

 

[lenses]

Tianeptine looks super promising from the reports and research papers I have read ...

Definitely one of the smart drugs at the very top of my list at the moment.

-lenses

 

[bolinas]

I've never found the sexual side effects of SSRIs to be all that bad. The loss of sensation can be a bit much, but I also find it useful, sometimes. Tianeptine has little effect on sex either way. Both SSRIs and tianeptine leave me feeling stupid and unable to concentrate or produce after continuous administration. I can't take it for more than 3 or 4 days with any SSRI. I can't think straight, my higher logic and reasoning fades noticeably (from my internal point of view, at least)

I did lots of DXM as a teenager, back in the early to mid 90s. Sometimes I even took it with prozac (obviously i didn' t take serotonin syndrome seriously). After 3 years of heavy abuse, DXM lost all effect. I had to "recover" by myself for another 3 years before I felt "ok" again. My reaction to SSRIs is IMMEDIATE now (wasn't when I was 16), I can tell prozac or lexapro coming on within 30 minutes of taking it. Tianeptine is immediate, too, but that seems standard for most people, not just DXM hags like me.

So all this stuff about SSRIs having serious, long-term consequences, obviously DXM changed my brain chemistry significantly. Mostly for the worse, in my opnion. My reactions to SSRIs now are strong. I couldn't imagine taking Prozac for months or years straight. None of these drugs were originally intended to be used chronically. Knowing how strong SSRIs were to me, I can only see long-term SSRI use as being some form of chemical brain fry.

How Tianeptine can be considered a "smart drug" or something that enhances your mental ability is beyond me. It is distracting, makes me less attentive, mild, feels nice. It's basically what you would expect from an anti-depressant. It's not all dirty and shitty like most SSRIs tend to lean towards. I do take 4g Piracetam + 4g Choline Citrate each morning and I get a significant benefit from this combo. I know how Piracetam doesn't do anything and all that, but it makes me feel as smart as I did before I started using DXM.....

 

[Limpet_Chicken]

Different reactions, different people....

As for BDNF and antidepressants, tricyclics are known to be agonists at the BDNF receptor (TRKb), at least amitryptiline is. It does have plenty of antimuscarinic and antihistaminergic activity howeve.

Couldn't possibly comment on personal experience with tianeptine, for I have none to share, I would love to try it though. Someone I talk to who also has PTSD (as do I) swears by it.

With racetams, it seems like there is an awful lot of differing reaction to them, and some people who find one not to do much find that a different drug in the class is more useful. I've had the best results from pramiracetam. Too bad its so damn expensive. I figure that might be something to do witu the cost of Hunig's base (diisopropylethylamine), commonly used as a sterically hindered non-nucleophilic base in organic syntheses, but its a part of pramiracetam, in that it actually contains a diisopropylethylamino moiety.

I recall reading a paper on AMPAkines somewhere or other, that stated piracetam was a ligand for a newly (at the time of publication of the paper of course) discovered positive modulator of the AMPA type ionotropic glutamate receptor. If this is the case, then I have a hunch it may induce the upregulation of BDNF mRNA and induce BDNF release. Other AMPAkines do. Doesn't mean all of them do, there are a number of binding sites on AMPARs for positive and negative allosteric modulators, but at least some of them are known to do so.

Wouldn't be all too surprising if piracetam caused BDNF release.

One thing that bears mention however, is that BDNF is NOT some simple catch all wetware screwdriver in the sense of 'inject it into a brain and watch everything realign itself, and everything start working as it should' (ignoring that its not a simple neurotransmitter of the monoamine flavour, ala DA, NA, 5HT etc) that can be gotten into the brain with 'simple tricks' like for instance, dopamine precursors and carbidopa to prevent peripheral decarboxylation and thus the same shitty brain penetration of dopamine itself, for parkinsons patients.

BDNF does indeed have potent effects on neuronal differentiation and an apparent antidepressant effect. But its pharmacology is complex. Interacting with amongst other targets, alpha7 type neuronal NAChRs, all over different sites within the brain, some places doing the inverse of what is expected.

Oh, and simplest drug of all to induce BDNF release, is exercise.