Valdoxan (Agomelatine) during recovery from MDMA-induced long-term come down

[dpd_mnk92]

Hi all,

I am a 20 year old male that has recently destroyed his brain during a disgusting MDMA binge (1.5 grams over the course of a few hours). Unfortunately, I wasn't even aware that I was continuing to consume the stuff past the 0.5 mark and had no friends around to stop me at the time. I have more than learnt my lesson (to not have lots of drugs on me at any point in time because i'm an unreliable c***) and I'm still dealing with the symtoms a month on, which include: depression, anxiety, HPPD, mild DR, sleeping problems, memory problems and severe decline in general cognitive ability (particularly spoken verbal fluency).

My doctor has prescribed me a relatively new anti-depressant called agomelatine (Valdoxan) in the hope that it might deal with some of these symptoms (sleeping problems, anxiety + depression) but I wanted to first double-check on here to get some second opinions on whether or not I should be putting this stuff into my body at a time when my brain is recovering/ rewiring itself after the damage that has occurred. I know you guys probably won't have any definitive answers based on the fact that it is a relatively new type of medication and that very few people have been in this situation before, but I was hoping some of you dudes in the advanced drug discussion forum might be able to draw some conclusions based on its mechanism of action. In short, I would very much like to start this medication to help deal with some of my problems but I am hesitant as I have no idea whether or not it would interfere with my recovery. Obviously, the long-term goal is to reverse as much of the damage caused as possible...

Any ideas, whether right or wrong, would be seriously appreciated right now!!

From wikipedia --> Mechanism of action
Agomelatine is a melatonergic agonist (MT1 (Ki=0.10nM±0.01nM) and MT2 receptors (Ki=0.12nM±0.02nM)) and 5-HT2C antagonist (IC50=270nM; pKi=6.15±0.04). Binding studies indicate that it has no effect on monoamine uptake and no affinity for adrenergic, histaminergic, cholinergic, dopaminergic and benzodiazepine receptors, nor other serotonergic receptors.[2]

 

[MollyFein74]

Dont know for sure but having a quick look on how it valdoxan works it says it doesnt affect the three monoamines, either receptors or transporters, just agonises the melatonin receptors... I strongly believe SSRIs will itnerfere with MDMA-induced damage recovery and make it worse in the long term again thats my opinion others will share and be different however I think that this could probably be taken safely without interfering with MDMA recovery.

In therory taking a look at the way it works I think this could if anything aid in MDMA-induced damage recovery as it only affects melatonin receptors, youd be able to sleep which is important for serotonin recovery.

 

[dpd_mnk92]

just agonises the melatonin receptors... I strongly believe SSRIs will itnerfere with MDMA-induced damage recovery and make it worse in the long term

Thank you so much for the reply guys! I have just found this description on another website --> Agomelatine doesn't just work by improving sleep because if did, then melatonin itself would be a cracking antidepressant, which it isn't. Agomelatine also blocks some serotonin receptors, which may boost noradrenaline and dopamine.

Does this change what you've said in any way? Would the blocking of seratonin receptors interfere with MDMA recovery? Again, your guesses are far better than mine would be as my understanding of neurology is basic at best.

Thanks!!!

 

[pofacedhoe]

a lot of mdma damage is to do with serotonin receptor downregulation

and this is also what long term ssri therapy leads to

 

[dpd_mnk92]

I agree that this is a difficult question to answer, but for me, even speculation/ guesses are better than nothing, so don't hold back for fear of giving me false information people!

I have already been through tonnes of threads on the ectasy discussion forum, and have taken on board a lot of the advice that have been given to people in similar situations, in order to deal with my symptoms + recover at an optimal rate (first bad comedown's posts have been of particular help). It just so happens that I have this box of antidepressants, prescribed by a "professional", which appears to potentially be the solution to a lot of my problems - so what do i do?

I have little knowledge about this medication other than the fact that it combats several of my symptoms and is relatively benign (probably far less likely to prolong/ worsen my recovery compared to SSRIs, which I've been warned about with specific regard to MDMA recovery more than once). Unfortunately my doctor doesn't even know what MDMA is, never mind the neurological rewiring process that occurs after MDMA damage, so it is difficult to decide whether or not I should start this medication.

So even if answers are purely speculative (and perhaps derived from over-simplified reasoning)...

based on theories of MDMA damage (what likely occurs in the brain), does agomelatine (from the descriptions I have provided above + any knowledge anyone might have abt the drug's mechanism of action) ring any alarm bells or does it seem like it could be a good move?

The second description of valdoxan particularly worries me, espcially this line: Agomelatine also blocks some serotonin receptors, which may boost noradrenaline and dopamine, seeing as MDMA's effects are very much to do with the way it affects these receptors/ neurotransmitters.

Pofacedho mentions (above) that mdma damage is to do with serotonin receptor downregulation. What might this imply for a drug that blocks these very receptors? I wish I could decipher this problem myself but I'd much rather leave it up to ppl in the advanced discussion forum who know their stuff - EVEN IF all i can hope for are some educated guesses about the risks vs benefits of taking the Valdoxan.

Thanks so much for the time + responses so far guys!! I know I've thrown a pretty obscure question at you guys and can't expect too much, but it's worth a try since this MDMA binge has left me in a pretty way and i'm rather desperate at the moment.

 

[sekio]

MDMA damage is caused by two principal things
1. Humongous amounts of serotonin, norepinephrine, dopamine are released, and have to be broken down or disposed of somehow. (usually MAO)
2. Overheating, exertion, and water/salt imbalance.

Blocking postsynaptic serotonin receptors will do a grand total of nothing in terms of damage. At best, it would reduce the subjective effects of MDMA somewhat because it blocks all the released serotonin from having an effect.

Pofacedho mentions (above) that mdma damage is to do with serotonin receptor downregulation. What might this imply for a drug that blocks these very receptors?

Basically, nothing you need to be concerned about, and a loss of MDMA's efficacy in the worst case (e.g. treatment with antipsychotics)

given that agomelatine only blocks one of the 13+ serotonin receptors - 5ht2c - and even then it is not a high affinity ligand, I would expect it to be benign.

also, by the way, don't put too much stock in "1.5 grams of MDMA destroyed my brain". MDMA is actually amazingly physically benign, most users damage themselves psychologically much more than physically. (given that you still retain the capacity to feel emotions, and reason, and you can recognize you have deficits in your life, you're on good standing)

 

[pofacedhoe]

yeah i've cained 1.5 grams ish (lots of lines and bombs of 200mg repeated and we had 7 grams so its hard to tell how much everyone had) before in a binge and in time you recover.

what i meant is that downregulation and the effects that this causes are often mistaken for "i've broken my brain with neurotoxicity"

i honestly think one off binges do less damage than moderate weekly use as you can recover from a binge and see the effects as your mood improves. with weekly use your on a permanent comedown

 

[Epsilon Alpha]

Everyone is different, but before everyone goes all out on drugs to treat an issue have you looked at working out and improving your diet? MDMA is FAR from benign, I'm not sure where that notion even comes from sekio. Damage may be due to destruction of the serotogenic axons; they're extremely long and wrap from the raphe nuclei around the frontal lobe and then to the back of the brain.

Supposing something got fried along those lines then downregulation is only an ancillary consequence.

 

[sekio]

I'm not sure where that notion even comes from sekio

call it wishful thinking... Of course I'm not saying that doing grams and grams of MDMA daily is a good thing, but I don't think single-dose exposures will cause massive serotonergic axon loss like some people expect.
really I have not seen much evidence of long-term damage to the serotonin system from responsible usage of MDxx. c.f. Ricaurte's fucked up meth monkeys. what I have seen is a lot of people who become psychologically damaged from a bad trip/comedown, and then fixate on the MDMA as a traumatic event, rather than moving on and letting their mind recover. especially those that fixate on the nitty-gritty biochemical details, convinced that one neurotransmitter or the other must be malfunctioning, without any real evidence except high-level nonspecific psychological malaise. and usually also without consulting any sort of medical personell.

It's quite understandable that people are afraid of brain damage when they experience this sort of mental disruption; the average person has never been told that there were any other possible explanations, in spite of virtually all of us being familiar with the basic phenomenon in the form of 'needing that first cup of coffee in the morning to get going' and the like. My position is not that people don't get seriously screwed up by frequent use of MDMA; only that the cause is unlikely to be actual permanent damage. Given a break from use of a few months, even the most severely 'e-tarded' user should find themselves greatly improved as the brain slowly returns to its normal 'volume settings.'

http://thedea.org/neurotoxicity.html

maybe I am just overconfident in the brain's ability to adapt to damage and stress. people recover from strokes and brain tumors all the time, i cannot believe the damage of a moderate dose of MDMA is greater than that of a stroke?

basically what i am saying is that "mdma brain damage" (in humans), to me, is nothing more than korean fan death... most all of the toxicity I have seen comes from 2ndary symptoms of mdma toxidrome like overheating.

 

[pasha]

Sekio you may be right. I was watching a segment on discovery channel all about MDMA. They did scientific studies (I can't recall the scan but I think it was called functional magnetic resonance imaging) and they found clear evidence of damage on long term ecstasy users and they weren't using nearly as much as OP. They also found evidence that when opioid addicts think about using they trigger large amounts of dopamine. Just something to consider.

EDIT: regarding agomelatine, a friend of mine started it two years ago and he swears by it for sleep and social anxiety. However, many of us have noticed that he can't keep a secret. It's really odd but he says its a side effect of the medication. Also, after he recommended it I asked my psychiatrist about it. He says there's clear evidence that it causes liver damage.

 

[sekio]

According to information disclosed by Les Laboratoires Servier on October the 10th, 2012, guidelines for the follow-up of patients treated with Valdoxan have been modified in concert with the European Medicines Agency. As some patients may experience increased levels of liver enzymes in their blood during treatment with Valdoxan, doctors have to run laboratory tests to check that the liver is working properly at the initiation of the treatment and then periodically during treatment, and subsequently decided whether pursue the treatment or not

I think that's far from "clear evidence it causes liver damage". The benefits seem like they outweigh the risks too.

 

[cope]

Hi dpd,

sorry, havent been much on BL lately.

i cannot say if its a good med for recovery but it sure did not hurt when i took it.

personally i found stablon much more effective for recovery, but its only available in some countries of the EU.

but rest assured that you will recover(!) , took a lot of time for me but i am at 85% now and still improving.


best of luck

 

[Tussmann]

I was under the assumption MDMA damage is due to extreme levels of oxidative stress. This occurs when all 5-HT has been expelled, and instead DA is recycled back into the synapse. This explains the role of taking SSRIs post-MDMA -- to simply block this re-uptake from happening.

 

[Epsilon Alpha]

I was under the assumption MDMA damage is due to extreme levels of oxidative stress. This occurs when all 5-HT has been expelled, and instead DA is recycled back into the synapse. This explains the role of taking SSRIs post-MDMA -- to simply block this re-uptake from happening.

Its got several mechanisms, but it appears to share a kind of general trend with the rest of the psychedelic amphetamines that they activate 5HT2A in such a manner that apoptosis inducing factor is activated. I actually haven't seen much convincing data that the more classical tryptamine compounds do so at relevant concentrations.

http://www.sciencedirect.com/science/article/pii/S0161813X0700071X

But, back to OP if you have sleep troubles maybe this drug would be worth trying. I wish I could say more but the data doesn't seem to be there.

 

[sekio]

In conclusion, direct MDMA 5-HT2A-receptor stimulation produces intracellular oxidative stress that leads to neuronal apoptosis accompanied by caspase 3 activation.

So, oxidative stress?

 

[Epsilon Alpha]

So, oxidative stress?

Yep, granted its one of the many pathways to cell death via oxidative stress. Its interesting as its apoptosis rather than necrosis however, as oxidative stress can cause both.

 

[pasha]

Agomelatine (Valdoxan/ Thymanax): risk of dose-related hepatotoxicity and liver failure – updated warnings and monitoring guidance.

Link:

http://www.mhra.gov.uk/Safetyinformation/DrugSafetyUpdate/CON199558

 

[atara]

also, by the way, don't put too much stock in "1.5 grams of MDMA destroyed my brain". MDMA is actually amazingly physically benign, most users damage themselves psychologically much more than physically. (given that you still retain the capacity to feel emotions, and reason, and you can recognize you have deficits in your life, you're on good standing)

As Dr. Nichols is fond of pointing out, fenfluramine does as much damage, and ex-fenfluramine users generally aren't trashed for life.

 

[magniloquentcunt]

I agree that this is a difficult question to answer, but for me, even speculation/ guesses are better than nothing, so don't hold back for fear of giving me false information people!

I have already been through tonnes of threads on the ectasy discussion forum, and have taken on board a lot of the advice that have been given to people in similar situations, in order to deal with my symptoms + recover at an optimal rate (first bad comedown's posts have been of particular help). It just so happens that I have this box of antidepressants, prescribed by a "professional", which appears to potentially be the solution to a lot of my problems - so what do i do?

I have little knowledge about this medication other than the fact that it combats several of my symptoms and is relatively benign (probably far less likely to prolong/ worsen my recovery compared to SSRIs, which I've been warned about with specific regard to MDMA recovery more than once). Unfortunately my doctor doesn't even know what MDMA is, never mind the neurological rewiring process that occurs after MDMA damage, so it is difficult to decide whether or not I should start this medication.

So even if answers are purely speculative (and perhaps derived from over-simplified reasoning)...

based on theories of MDMA damage (what likely occurs in the brain), does agomelatine (from the descriptions I have provided above + any knowledge anyone might have abt the drug's mechanism of action) ring any alarm bells or does it seem like it could be a good move?

The second description of valdoxan particularly worries me, espcially this line: Agomelatine also blocks some serotonin receptors, which may boost noradrenaline and dopamine, seeing as MDMA's effects are very much to do with the way it affects these receptors/ neurotransmitters.

Pofacedho mentions (above) that mdma damage is to do with serotonin receptor downregulation. What might this imply for a drug that blocks these very receptors? I wish I could decipher this problem myself but I'd much rather leave it up to ppl in the advanced discussion forum who know their stuff - EVEN IF all i can hope for are some educated guesses about the risks vs benefits of taking the Valdoxan.

Thanks so much for the time + responses so far guys!! I know I've thrown a pretty obscure question at you guys and can't expect too much, but it's worth a try since this MDMA binge has left me in a pretty way and i'm rather desperate at the moment.

So OP, a couple of weeks after: how did the valdoxan experience go? could you describe it?

 

[dpd_mnk92]

So OP, a couple of weeks after: how did the valdoxan experience go? could you describe it?

Hello cunt! I finished the 1 month course prescribed by my GP and decided not to go back for more. There were few prominent effects that I can definitively state were the result of anything more than placebo. I am relatively sure it helped normalise my sleeping patterns to some extent and enabled me to get better quality at a time when I was in need of it, however.

Its mood-lifting properties were far harder to assess in the context of my recovery. With time, exercise and a good diet, my emotional and cognitive difficulties were slowly, but surely, improving anyway. When you consider that I was more or less an incoherent, walking talking vegetable, too anxious/ depressed to leave my room, directly after abusing/ binging MDMA (predominantly), I could only have improved as time went on, regardless of whether or not I had gone down the AD route. Nevertheless, I suspect there was a very subtle mood-lifting effect which may have made a very dark period marginally brighter.

If you are considering it, I would say it is worth a try as very little can go wrong - zero noticeable side effects. On the other hand, don't expect anything dramatic. Its effects will likely be subtle at best (at least in my particular case). In the end, I terminated my usage after 4 weeks as I felt a sober recovery was probably the safest option (minus my pack-a-day cig habit......) - it's worth considering the possibility that I may have ended the treatment too soon to reap the full benefits of this medication.

Hope this helps!